Katzung, all questions

Ampicillin is eliminated by first-order kinetics. Which of the following statements best describes the process by which the plasma concentration of this drug declines? (A) There is only 1 metabolic path for drug elimination (B) The half-life is the same regardless of the plasma concentration (C) The drug is largely metabolized in the liver after oral administration and has low bioavailability (D) The rate of elimination is proportional to the rate of administration at all times (E) The drug is distributed to only 1 compartment outside the vascular system

"First-order" means that the elimination rate is proportional to the concentration perfusing the organ of elimination. The half-life is a constant. The rate of elimination is proportional to the rate of administration only at steady state. The order of elimination is independent of the number of compartments into which a drug distributes. The answer is B.

A 60-year-old woman was told she had hypertension and should be taking antihypertensive medication. She decides to take an herbal medication from an online "holistic pharmacy." One week after starting the medication, she is found unconscious in her apartment. In the emergency department, her blood pressure is 50/0 mm Hg and heart rate is 40 bpm. Respirations are 20/min; pupils are slightly constricted. Bowel sounds are present. Which of the following would be the most effective cardiovascular stimulant? (A) Amphetamine (B) Clonidine (C) Isoproterenol (D) Norepinephrine (E) Tyramine

"Herbal" medications often contain potent synthetic drugs in addition to (or instead of) the advertised constituents. This patient shows signs of sympathetic autonomic failure: hypotension, inappropriate bradycardia, constricted pupils. These signs are compatible with a large overdose of a drug that causes marked depletion of stored catecholamine transmitter such as reserpine, an obsolete but inexpensive antihypertensive agent. The indirect-acting agents (amphetamines and tyramine) act through catecholamines in (or released from) the nerve terminal and would therefore be ineffective in this patient. Clonidine acts primarily on presynaptic nerve endings although it can activate α 2 receptors located elsewhere. Isoproterenol would stimulate the heart but has no α-agonist action and might exacerbate the hypotension. Norepinephrine has the necessary combination of direct action and a spectrum that includes α1 , α2 , and β 1 effects. The answer is D.

A 12-year-old child has bacterial pharyngitis and is to receive an oral antibiotic. She complains of a sore throat and pain on swallowing. The tympanic membranes are slightly reddened bilaterally, but she does not complain of earache. Blood pressure is 105/70 mm Hg, heart rate 100/mm, temperature 37.8 °C (100.1 °F). Ampicillin is a weak organic acid with a pKa of 2.5. What percentage of a given dose will be in the lipidsoluble form in the duodenum at a pH of 4.5? (A) About 1% (B) About 10% (C) About 50% (D) About 90% (E) About 99%

(A) About 1%

A large pharmaceutical company has conducted extensive animal testing of a new drug for the treatment of advanced prostate cancer. The chief of research and development recommends that the company now submit an IND application in order to start clinical trials. Which of the following statements is most correct regarding clinical trials of new drugs? (A) Phase 1 involves the study of a small number of normal volunteers by highly trained clinical pharmacologists (B) Phase 2 involves the use of the new drug in a large number of patients (1000-5000) who have the disease to be treated under conditions of proposed use (eg,outpatients) (C) Chronic animal toxicity studies must be complete and reported in the IND (D) Phase 4 involves the detailed study of toxic effects that have been discovered in phase 3 (E) Phase 2 requires the use of a positive control (a known effective drug) and a placebo

(A) Phase 1 involves the study of a small number of normal volunteers by highly trained clinical pharmacologists

select the ONE lettered option from the following list that is most closely associated with it. (A) Bleomycin (B) Cytarabine (C) Dacarbazine (D) Doxorubicin (E) Etoposide (F) Flutamide (G) Fluorouracil (H) Leuprolide (I) Mechlorethamine (J) Mercaptopurine (K) Methotrexate (L) Paclitaxel (M) Procarbazine (N) Rituximab (O) Vincristine This antimetabolite inhibits DNA polymerase and is one of the most active drugs in leukemias. Although myelosuppression is dose limiting, the drug may also cause cerebellar dysfunction, including ataxia and dysarthria.

(B) Cytarabine

The matching questions in this section consist of a list of lettered options followed by several numbered items. For each numbered item, select the ONE lettered option that is most closely associated with it. Each lettered option may be selected once, more than once, or not at all. (A) Arsine (B) Deferoxamine (C) Dimercaprol (D) Edetate calcium disodium (E) Inorganic mercury (F) Iron (G) Methylmercury (H) Mercury vapor (I) Penicillamine (J) Succimer (K) Tetraethyl lead (L) Trivalent arsenic High doses of this agent can cause histamine release and extreme vasodilation.

(B) Deferoxamine

A 3-year-old is brought to the emergency department having just ingested a large overdose of tolbutamide, an oral antidiabetic drug. Tolbutamide is a weak acid with a pKa of 5.3. It is capable of entering most tissues, including the brain. On physical examination, the heart rate is 100/min, blood pressure 90/50 mm Hg, and respiratory rate 20/min. Which of the following statements about this case of tolbutamide overdose is most correct? (A) Urinary excretion would be accelerated by administration of NH4Cl, an acidifying agent (B) Urinary excretion would be accelerated by giving NaHCO3, an alkalinizing agent (C) Less of the drug would be ionized at blood pH than at stomach pH (D) Absorption of the drug would be slower from the stomach than from the small intestine (E) Hemodialysis is the only effective therapy

(B) Urinary excretion would be accelerated by giving NaHCO3, an alkalinizing agent

A patient who is taking verapamil for hypertension and angina has become constipated. Which of the following drugs is an osmotic laxative that could be used to treat the patient's constipation? (A) Aluminum hydroxide (B) Diphenoxylate (C) Magnesium hydroxide (D) Metoclopramide (E) Ranitidine

(C) Magnesium hydroxide A laxative that mildly stimulates the gut would be most suitable in a patient taking a smooth muscle relaxant drug such as verapamil. By holding water in the intestine, magnesium hydroxide provides additional bulk and stimulates increased contractions. A helpful mnemonic is magnesium "magnifies" stool, aluminum hALts the stool. The answer is C. Diphenoxylate is an opioid receptor agonist, metoclopramide is a prokinetic agent, ranitidine is a H 2 receptor blocker.

A 55-year-old woman with type 1 diabetes of 40 years' duration complains of severe bloating and abdominal distress, especially after meals. Evaluation is consistent with diabetic gastroparesis. Which of the following is a prokinetic drug that could be used in this situation? (A) Alosetron (B) Cimetidine (C) Loperamide (D) Metoclopramide (E) Sucralfate

(D) Metoclopramide Of the drugs listed, only metoclopramide is considered a prokinetic agent (ie, one that increases propulsive motility in the gut). The answer is D. Alosetron is a 5HT 3 receptor blocker, cimetidine is a H 2 receptor blocker, loperamide is an opioid, and sucralfate forms a protective layer over an ulcer.

You are stuck in traffic in New York City in summer for 3 or 4 h and you begin to get a headache, a feeling of tightness in the temporal region, and an increased pulse rate. What is the antidote based on the most likely cause of these effects? (A) Activated charcoal (B) Atropine (C) Fomepizole (D) Oxygen (E) Pralidoxime

(D) Oxygen The symptoms described are those of carbon monoxide inhalation. Oxygen is the antidote. The answer is D. Note atropine and pralidoxime are used in insecticide poisoning with acetylcholinesterase inhibitors, and fomepizole is used in methanol and ethylene glycol poisoning.

The matching questions in this section consist of a list of lettered options followed by several numbered items. For each numbered item, select the ONE lettered option that is most closely associated with it. Each lettered option may be selected once, more than once, or not at all. (A) Arsine (B) Deferoxamine (C) Dimercaprol (D) Edetate calcium disodium (E) Inorganic mercury (F) Iron (G) Methylmercury (H) Mercury vapor (I) Penicillamine (J) Succimer (K) Tetraethyl lead (L) Trivalent arsenic Gingivitis, discolored gums, and loose teeth are common symptoms of chronic exposure to this agent.

(E) Inorganic mercury

The matching questions in this section consist of a list of lettered options followed by several numbered items. For each numbered item, select the ONE lettered option that is most closely associated with it. Each lettered option may be selected once, more than once, or not at all. (A) Aldicarb (B) Benzene (C) Carbon monoxide (D) Carbon dioxide (E) DDT (F) Dioxin (G) Malathion (H) Nitrogen dioxide (I) Paraquat (J) Pyrethrum (K) Rotenone (L) Sulfur dioxide (M) Tetrachloroethylene (N) Toluene This compound is a potential environmental hazard that is formed as a contaminating byproduct in the manufacture of herbicides. It causes acneiform lesions and may be carcinogenic.

(F) Dioxin

The matching questions in this section consist of a list of lettered options followed by several numbered items. For each numbered item, select the ONE lettered option that is most closely associated with it. Each lettered option may be selected once, more than once, or not at all. (A) Arsine (B) Deferoxamine (C) Dimercaprol (D) Edetate calcium disodium (E) Inorganic mercury (F) Iron (G) Methylmercury (H) Mercury vapor (I) Penicillamine (J) Succimer (K) Tetraethyl lead (L) Trivalent arsenic This toxic compound can be produced in seawater by the action of bacteria and algae. It is also synthesized chemically for commercial use as a fungicide.

(G) Methylmercury

The following section consists of a list of l tered options followed by several numbered items. For each numbered item, select the ONE option that is most closely associated with it. (A) Allopurinol (B) Carbamazepine (C) Cholestyramine (D) Cimetidine (E) Clarithromycin (F) Cyclosporine (G) Digoxin (H) Erythromycin (I) Fluoxetine (J) Ibuprofen (K) Lovastatin (L) Phenelzine (M) Rifampin (N) Ritonavir (O) Theophylline Concomitant use of St. John's wort is reported to increase the effectiveness of this drug.

(I) Fluoxetine

The matching questions in this section consist of a list of lettered options followed by several numbered items. For each numbered item, select the ONE lettered option that is most closely associated with it. Each lettered option may be selected once, more than once, or not at all. (A) Arsine (B) Deferoxamine (C) Dimercaprol (D) Edetate calcium disodium (E) Inorganic mercury (F) Iron (G) Methylmercury (H) Mercury vapor (I) Penicillamine (J) Succimer (K) Tetraethyl lead (L) Trivalent arsenic This agent is used in the treatment of Wilson's disease and has been reported to cause lupus erythematosus and hemolytic anemia.

(I) Penicillamine

The following section consists of a list of l tered options followed by several numbered items. For each numbered item, select the ONE option that is most closely associated with it. (A) Allopurinol (B) Carbamazepine (C) Cholestyramine (D) Cimetidine (E) Clarithromycin (F) Cyclosporine (G) Digoxin (H) Erythromycin (I) Fluoxetine (J) Ibuprofen (K) Lovastatin (L) Phenelzine (M) Rifampin (N) Ritonavir (O) Theophylline This drug enhances the toxicity of methotrexate by decreasing its renal clearance.

(J) Ibuprofen

The following matching questions consist of a list of lettered options followed by several numbered items. For each numbered item, select the ONE option that is most closely associated with it. (A) Aluminum hydroxide (B) Balsalazide (C) Castor oil (D) Cimetidine (E) Dexamethasone (F) Methotrexate (G) Metoclopramide (H) Mineral oil (I) Omeprazole (J) Linaclotide (K) Pancrelipase (L) Sucralfate Which drug stimulates chloride secretion into the gut lumen and is used for irritable bowel syndrome?

(J) Linaclotide

select the ONE lettered option from the following list that is most closely associated with it. (A) Bleomycin (B) Cytarabine (C) Dacarbazine (D) Doxorubicin (E) Etoposide (F) Flutamide (G) Fluorouracil (H) Leuprolide (I) Mechlorethamine (J) Mercaptopurine (K) Methotrexate (L) Paclitaxel (M) Procarbazine (N) Rituximab (O) Vincristine If allopurinol is used adjunctively in cancer chemotherapy to offset hyperuricemia, the dosage of this anticancer drug should be reduced to 25% of normal.

(J) Mercaptopurine

The following matching questions consist of a list of lettered options followed by several numbered items. For each numbered item, select the ONE option that is most closely associated with it. (A) Aluminum hydroxide (B) Balsalazide (C) Castor oil (D) Cimetidine (E) Dexamethasone (F) Methotrexate (G) Metoclopramide (H) Mineral oil (I) Omeprazole (J) Linaclotide (K) Pancrelipase (L) Sucralfate This is a small molecule that polymerizes in stomach acid and coats the ulcer bed, resulting in accelerated healing and reduction of symptoms.

(L) Sucralfate

The matching questions in this section consist of a list of lettered options followed by several numbered items. For each numbered item, select the ONE lettered option that is most closely associated with it. Each lettered option may be selected once, more than once, or not at all. (A) Aldicarb (B) Benzene (C) Carbon monoxide (D) Carbon dioxide (E) DDT (F) Dioxin (G) Malathion (H) Nitrogen dioxide (I) Paraquat (J) Pyrethrum (K) Rotenone (L) Sulfur dioxide (M) Tetrachloroethylene (N) Toluene Asthma is often exacerbated in patients exposed to this reducing agent when concentrations in the air are as low as 1-2 ppm. It is formed mainly from combustion of fossil fuels.

(L) Sulfur dioxide

The matching questions in this section consist of a list of lettered options followed by several numbered items. For each numbered item, select the ONE lettered option that is most closely associated with it. Each lettered option may be selected once, more than once, or not at all. (A) Aldicarb (B) Benzene (C) Carbon monoxide (D) Carbon dioxide (E) DDT (F) Dioxin (G) Malathion (H) Nitrogen dioxide (I) Paraquat (J) Pyrethrum (K) Rotenone (L) Sulfur dioxide (M) Tetrachloroethylene (N) Toluene Acute exposure to this aliphatic hydrocarbon solvent causes CNS depression; chronic exposure has led to impairment of memory and peripheral neuropathy.

(M) Tetrachloroethylene

The following section consists of a list of l tered options followed by several numbered items. For each numbered item, select the ONE option that is most closely associated with it. (A) Allopurinol (B) Carbamazepine (C) Cholestyramine (D) Cimetidine (E) Clarithromycin (F) Cyclosporine (G) Digoxin (H) Erythromycin (I) Fluoxetine (J) Ibuprofen (K) Lovastatin (L) Phenelzine (M) Rifampin (N) Ritonavir (O) Theophylline In patients with HIV infection, the inhibitory action of this agent on drug metabolism has clinical value.

(N) Ritonavir

select the ONE lettered option from the following list that is most closely associated with it. (A) Bleomycin (B) Cytarabine (C) Dacarbazine (D) Doxorubicin (E) Etoposide (F) Flutamide (G) Fluorouracil (H) Leuprolide (I) Mechlorethamine (J) Mercaptopurine (K) Methotrexate (L) Paclitaxel (M) Procarbazine (N) Rituximab (O) Vincristine This drug is used in combination therapy for non-Hodgkin's lymphoma. Due to its selectivity, it is expected to be less myelosuppressive compared with the classic agents.

(N) Rituximab

Prior to clinical trials in patients with heart failure, an animal study was carried out to compare two new positive inotropic drugs (A and B) to a current standard agent (C). The results of cardiac output measurements are shown in the graph below. Which of the following statements is correct? (A) Drug A is most effective (B) Drug B is least potent (C) Drug C is most potent (D) Drug B is more potent than drug C and more effective than drug A (E) Drug A is more potent than drug B and more effective than drug C

*The answer is D.* Drug A produces 50% of its maximal effect at a lower dose than either B or C and thus is the most potent; drug C is the least potent. However, drug A, a partial agonist, is less efficacious than drugs B and C.

A newborn girl exhibited ambiguous genitalia, hyponatremia, hyperkalemia, and hypotension as a result of genetic deficiency of 21α-hydroxylase activity. Treatment consisted of fluid and salt replacement and hydrocortisone administration. In this type of adrenal hyperplasia in which there is excess production of cortisol precursors, which of the following describes the primary therapeutic effect of glucocorticoid administration? (A) Increased adrenal estrogen synthesis (B) Inhibition of adrenal aldosterone synthesis (C) Prevention of hypoglycemia (D) Recovery of normal immune function (E) Suppression of ACTH secretion

A 21α-hydroxylase deficiency prevents normal synthesis of cortisol and aldosterone, and causes accumulation of cortisol precursors (Figure 39-2). The hypothalamic-pituitary system responds to the abnormally low levels of cortisol by increasing ACTH release. High levels of ACTH induce adrenal hyperplasia and excess production of adrenal androgens, which can cause virilization of females and prepubertal males. Glucocorticoid is administered to replace the missing mineralocorticoid and glucocorticoid activity and to suppress ACTH release, which removes the stimulus for excess adrenal androgen production. The answer is E.

A 10-year-old boy has uncomplicated pulmonary tuberculosis. After initial hospitalization, he is now being treated at home with isoniazid, rifampin, and ethambutol. Which statement about this case is accurate? (A) A baseline test of auditory function test is essential before drug treatment is initiated (B) His mother, who takes care of him, does not need INH prophylaxis (C) His 3-year-old sibling should receive INH prophylaxis (D) Polyarthralgia is a potential adverse effect of the drugs the boy is taking (E) The potential nephrotoxicity of the prescribed drugs warrants periodic assessment of renal function

A baseline test of ocular (not auditory) function may be u ful before starting ethambutol. None of the drugs prescribed is associated with nephrotoxicity. Polyarthralgia is a common adverse effect of pyrazinamide that was not prescribed in this case. Periodic tests of liver function may be advisable in younger patients who are treated with INH plus rifampin, especially if higher doses of these drugs are used. Prophylaxis with INH is advisable for all household members and very close contacts of patients with active tuberculosis, especially young children. The answer is C.

All of the listed neurotransmitters change membrane excitability by decreasing K + conductance except (A) Acetylcholine (B) Dopamine (C) Glutamic acid (D) Norepinephrine (E) Serotonin

A decrease in K +conductance is associated with neuronal excitation. With the exception of dopamine, all of the neurotransmitters listed are able to cause excitation by this mechanism via activation of their specific receptors: acetylcholine (M 1 ), glutamate (metabotropic), norepinephrine (α1 and β1 ), and serotonin (5-HT 2A ). The answer is B.

A 32-year-old woman underwent segmental mastectomy for a breast tumor of 3 cm diameter. Lymph node sampling revealed 2 involved nodes. Because chemotherapy is of established value in her situation, she underwent postoperative treatment with antineoplastic drugs. The regimen consisted of doxorubicin followed by cyclophosphamide/methotrexate/ fluorouracil. Adjunctive drugs included tamoxifen because the tumor cells were hormone receptor-positive. After several cycles of chemotherapy, the patient was found to have a high resting pulse rate. A noninvasive radionuclide scan revealed evidence of cardiomyopathy. The drug that is most likely responsible for the cardiac toxicity is (A) Cyclophosphamide (B) Doxorubicin (C) Fluorouracil (D) Methotrexate (E) Tamoxifen

A high resting pulse rate is one of the first signs of cardiotoxicity resulting from anthracyclines, which can include arrhythmias, cardiomyopathies, and heart failure. The risk of cardiotoxicity depends on cumulative dosage, so doxorubicin should be discontinued. The answer is B.

A 35-year-old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cholesterol, LDL cholesterol, and triglyceride are elevated. Her serum concentration of HDL cholesterol is somewhat reduced. The patient is started on gemfibrozil. Which of the following is a major mechanism of gemfibrozil's action? (A) Increased excretion of bile acid salts (B) Increased expression of high-affinity LDL receptors (C) Increased secretion of VLDL by the liver (D) Increased triglyceride hydrolysis by lipoprotein lipase (E) Reduced uptake of dietary cholesterol

A major mechanism recognized for gemfibrozil is increased activity of the lipoprotein lipase associated with capillary endothelial cells. Gemfibrozil and other fibrates decrease VLDL secretion, presumably by stimulating hepatic fatty acid oxidation. The answer is D.

A 35-year-old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cholesterol, LDL cholesterol, and triglyceride are elevated. Her serum concentration of HDL cholesterol is somewhat reduced. Which of the following is a major toxicity associated with gemfibrozil therapy? (A) Bloating and constipation (B) Cholelithiasis (C) Hyperuricemia (D) Liver damage (E) Severe cardiac arrhythmia

A major toxicity of the fibrates is increased risk of gallstone formation, which may be due to enhanced biliary excretion of cholesterol. The answer is B.

A 28-year-old man living on the East Coast was transferred by his employer to California for several months. On his return, he complains of having influenza-like symptoms with fever and a cough. He also has red, tender nodules on his shins. His physician suspects that these symptoms are due to coccidioidomycosis contracted during his stay in California. This patient should be treated immediately with (A) Amphotericin B (B) Caspofungin (C) Ketoconazole (D) Terbinafine (E) None of these drugs

A travel history can be important in the diagnosis of fungal disease. If this patient has a fungal infection of the lungs, it is probably due to C immitis, which is endemic in dry regions of the western United States. Pulmonary symptoms of coccidioidomycosis are usually self-limiting, and drug therapy is not commonly required in an otherwise healthy patient. Tender red nodules on extensor surfaces constitute a good prognostic sign. Erythema nodosum is a delayed hypersensitivity response to fungal antigens. No organisms are present in the lesions, and it is not a sign of disseminated disease. The answer is E.

A 33-year-old woman attempted to induce an abortion using ergotamine. She is admitted to the emergency department with severe pain in both legs. On examination, her legs are cold and pale with absent arterial pulses. Which of the following is the most useful antidote for reversing severe ergotinduced vasospasm? (A) Bromocriptine (B) Cimetidine (C) Ergotamine (D) Ketanserin (E) LSD (F) Nitroprusside (G) Sumatriptan (H) Ondansetron

A very powerful vasodilator is necessary to reverse ergot-induced vasospasm; nitroprusside is such a drug (see Chapter 11). The answer is F.

A patient is admitted to the emergency department with severe tachycardia after a drug overdose. His family reports that he has been depressed about his hypertension. Which one of the following drugs increases the heart rate in a dosedependent manner? (A) Captopril (B) Hydrochlorothiazide (C) Losartan (D) Minoxidil (E) Verapamil

ACE inhibitors (choice A), ARBs (choice C), and diuretics (choice B) do not significantly increase heart rate. Although dihydropyridine calcium channel blockers do not usually reduce rate markedly (and may increase it), verapamil (choice E) and diltiazem do inhibit the sinoatrial node and predictably decrease rate. Other direct vasodilators (choice D) regularly increase heart rate, and minoxidil, a very efficacious vasodilator, causes severe tachycardia that must be controlled with β blockers. The answer is D.

A 58-year-old woman with chronic hypertension and diabetes mellitus was recently admitted to the hospital for congestive heart failure and new onset atrial fibrillation. She is now seeing you after discharge and, though feeling better, is still in atrial fibrillation. An echocardiogram shows an ejection fraction of 40%; there are no valvular abnormalities. An ECG reveals only atrial fibrillation. You calculate her risk using the CHADS (2) system and the score indicates that she requires anticoagulation rather than antiplatelet therapy. You are discussing the risks and benefits of anticoagulation therapy with her, including the option of using direct thrombin inhibitors. Which of the following anticoagulants is a direct inhibitor of thrombin? (A) Abciximab (B) Dabigatran (C) Rivaroxaban (D) Warfarin

Abciximab is an antiplatelet agent that binds to and inhibits GPIIb/IIIa. Rivaroxaban is an oral factor X inhibitor and warfarin inhibits vitamin K epoxide reductase (VKOR). The answer is B.

A young woman is brought to a hospital emergency department with intense abdominal pain of 2 days duration. The pain has spread to the right lower quadrant and is accompanied by nausea, vomiting, and fever. She arrives at the emergency department with a blood pressure of 85/45, pulse 120/min, and temperature 40°C. Her abdomen has a board-like rigidity with diffuse pain to palpation. Laboratory values include the following: WBC 20,000/µL and creatinine 1.5 mg/dL. After abdominal x-ray films are taken, a preliminary diagnosis of abdominal sepsis is made, possibly resulting from bowel perforation. After appropriate samples are sent to the laboratory for culture, the patient is hospitalized, and antimicrobial therapy is started with intravenous ampicillin and gentamicin. Regarding the treatment of this patient, which statement is accurate? (A) A drug active against anaerobes should be included in the antimicrobial drug regimen (B) Cultures are pointless because this is probably a mixed infection (C) Empiric antibiotic therapy of abdominal sepsis should always include a third-generation cephalosporin (D) Gram stain of the blood would provide positive identification of the specific organis

Abdominal sepsis is commonly a mixed infection; the most likely pathogens are Bacteroides fragilis, Enterobacteriaceae, and Enterococcus faecalis. An antibiotic regimen that includes only ampicillin and gentamicin does not control B fragilis. Empiric treatment in this case should include a drug active against this pathogen (eg, metronidazole, cefoxitin, cefotetan, or clindamycin). The answer is A.

Which drug, a partial agonist at nicotinic acetylcholine receptors, is used in smoking cessation programs but may cause seizures in overdose? (A) Acamprosate (B) Buprenorphine (C) Nalbuphine (D) Rimonabant (E) Varenicline

Acamprosate is an antagonist of NMDA glutamate receptors used together with counseling in alcohol treatment programs. Varenicline, a partial agonist at nicotinic receptors, blocks the rewarding effects of nicotine and is used in smoking cessation programs. However, the drug may cause psychiatric changes and in overdose has caused seizures. The answer is E.

A 63-year-old woman in the intensive care unit requires an infusion of procainamide. Its half-life is 2 h. The infusion is begun at 9 am. At 1 pm on the same day, a blood sample is taken; the drug concentration is found to be 3 mg/L. What is the probable steady-state drug concentration after 16 or more hours of infusion? (A) 3 mg/L (B) 4 mg/L (C) 6 mg/L (D) 9.9 mg/L (E) 15 mg/L

According to the curve that relates plasma concentration to infusion time, a drug reaches 50% of its final steady-state concentration in 1 half-life, 75% in 2 half-lives, etc. From 9 am to 1 pm is 4 h, or 2 half-lives. Therefore, the measured concentration at 1 pm is 75% of the steady-state value (0.75 × Cp(ss) ). The steady-state concentration is 3 mg/L divided by 0.75, or 4 mg/L. The answer is B.

A 30-year-old man is brought to the emergency department in a deep coma. Respiration is severely depressed and he has pinpoint pupils. His friends state that he self-administered a large dose of morphine 6 h earlier. An immediate blood analysis shows a morphine blood level of 0.25 mg/L. Assuming that the Vd of morphine in this patient is 200 L and the half-life is 3 h, how much morphine did the patient inject 6 h earlier? (A) 25 mg (B) 50 mg (C) 100 mg (D) 200 mg (E) Not enough data to predict

According to the curve that relates the decline of plasma concentration to time as the drug is eliminated (Figure 3-3), the plasma concentration of morphine was 4 times higher immediately after administration than at the time of the measurement, which occurred 6 h, or 2 half-lives, later. Therefore, the initial plasma concentration was 1 mg/L. Since the amount in the body at any time is equal to Vd × plasma concentration (text Equation 1), the amount injected was 200 L × 1 mg/L, or 200 mg. The answer is D.

Which of the following drugs, if used chronically, is most likely to increase the toxicity of acetaminophen? (A) Cimetidine (B) Ethanol (C) Ketoconazole (D) Procainamide (E) Quinidine (F) Ritonavir (G) Succinylcholine (H) Verapamil

Acetaminophen is normally eliminated by phase II conjugation reactions. The drug's toxicity is caused by an oxidized reactive metabolite produced by phase I oxidizing P450 enzymes. Ethanol and certain other drugs induce P450 enzymes and thus reduce the hepatotoxic dose. Alcoholic cirrhosis reduces the hepatotoxic dose even more. The answer is B.

Which of the following is an analgesic and antipyretic drug that lacks an anti-inflammatory action? (A) Acetaminophen (B) Celecoxib (C) Colchicine (D) Indomethacin (E) Probenecid

Acetaminophen is the only drug that fits this description. Indomethacin is a nonselective COX inhibitor and celecoxib is a COX-2 inhibitor; both have analgesic, antipyretic, and anti-inflammatory effects. Colchicine is a drug used for gout that also has an anti-inflammatory action. Probenecid is a uricosuric drug that promotes the excretion of uric acid. The answer is A.

Which drug is correctly associated with its actions in the following table? (+ indicates increase and - indicates decrease.) (A) Acetazolamide Urine Na+ (+++) Urine K+ (+) Alkalosis (B) Furosemide Urine Na+ (++) Urine K+ (-) Alkalosis (C)Hydrochlorothiazide Urine Na+ (+) Urine K+ (++) Acidosis (D) Spironolactone Urine Na+ (+) Urine K+ (-) Acidosis (E)Mannitol Urine Na+ (-) Urine K+ (++) Alkalosis

Acetazolamide causes metabolic acidosis. Furosemide causes a marked increase in sodium and a moderate increase in potassium excretion. Thiazides cause alkalosis and a greater increase in sodium than potassium excretion. Mannitol causes a small increase in both sodium and potassium excretion and no change in body pH. Spironolactone causes the changes indicated. The answer is D.

A patient underwent a surgical procedure of 2 h. Anesthesia was provided by isoflurane, supplemented by intravenous midazolam and a nondepolarizing muscle relaxant. At the end of the procedure, a low dose of atropine was administered followed by pyridostigmine. The main reason for administering atropine was to (A) Block cardiac muscarinic receptors (B) Enhance the action of pyridostigmine (C) Prevent spasm of gastrointestinal smooth muscle (D) Provide postoperative analgesia (E) Reverse the effects of the muscle relaxant

Acetylcholinesterase inhibitors used for reversing the effects of nondepolarizing muscle relaxants cause increases in ACh at all sites where it acts as a neurotransmitter. To offset the resulting side effects, including bradycardia, a muscarinic blocking agent is used concomitantly. Although atropine is effective, glycopyrrolate is usually preferred because it lacks CNS effects. The answer is A.

Which statement about the toxicity of local anesthetics is correct? (A) Bupivacaine is the safest local anesthetic to use in patients at risk for cardiac arrhythmias (B) In overdosage, hyperventilation (with oxygen) is helpful to correct acidosis and lower extracellular potassium (C) Intravenous injection of local anesthetics may stimulate ectopic cardiac pacemaker activity (D) Most local anesthetics cause vasoconstriction (E) Serious cardiovascular reactions are more likely to occur with tetracaine than with bupivacaine

Acidosis resulting from tissue hypoxia favors local anesthetic toxicity because these drugs bind more avidly (or dissociate more slowly) from the sodium channel binding site when they are in the charged state. (Note that onset of therapeutic effect may be slower because charged local anesthetics penetrate the membrane less rapidly; see text.) Hyperkalemia depolarizes the membrane, which also favors local anesthetic binding. Oxygenation reduces both acidosis and hyperkalemia. Bupivacaine may cause severe cardiotoxicity including arrhythmias. The answer is B.

A 32-year-old woman underwent segmental mastectomy for a breast tumor of 3 cm diameter. Lymph node sampling revealed 2 involved nodes. Because chemotherapy is of established value in her situation, she underwent postoperative treatment with antineoplastic drugs. The regimen consisted of doxorubicin followed by cyclophosphamide/methotrexate/ fluorouracil. Adjunctive drugs included tamoxifen because the tumor cells were hormone receptor-positive. The chemotherapy undertaken by this patient caused acute hemorrhagic cystitis. Which drug was most likely to be responsible for this toxicity? (A) Cyclophosphamide (B) Doxorubicin (C) Fluorouracil (D) Methotrexate (E) Tamoxifen

Acrolein, a toxic metabolite of cyclophosphamide that is concentrated in the urine, is associated with hemorrhagic cystitis. Mesna, a sulfur-containing substance that also concentrates in urine, can be administered in an attempt to prevent this complication. The answer is A.

A 23-year-old pregnant woman is referred by her obstetrician for evaluation of anemia. She is in her fourth month of pregnancy and has no history of anemia; her grandfather had pernicious anemia. Her hemoglobin is 10 g/dL (normal, 12-16 g/dL). The child in the previous question did ingest the ironcontaining supplements. What immediate treatment is necessary? Correction of acid-base and electrolyte abnormalities and (A) Activated charcoal (B) Oral deferasirox (C) Parenteral deferoxamine (D) Parenteral dantrolene

Activated charcoal does not bind iron and thus is ineffective. Oral deferasirox is effective for chronic iron toxicity. Dantrolene inhibits Ca 2+ release from the sarcoplasmic reticulum and is an antidote for malignant hyperthermia induced by inhaled anesthetics. The answer is C.

Which of the following best describes a glucocorticoid response element? (A) A protein regulator that controls the interaction between an activated steroid receptor and DNA (B) A short DNA sequence that binds tightly to RNA polymerase (C) A small protein that binds to an unoccupied steroid receptor protein and prevents it from becoming denatured (D) A specific nucleotide sequence that is recognized by a steroid hormone receptor-hormone complex (E) The portion of the steroid receptor that binds to DNA

Activated steroid hormone receptors mediate their effects on gene expression by binding to hormone response elements, which are short sequences of DNA located near steroidregulated genes. The answer is D.

Neurotransmitters may (A) Increase chloride conductance to cause hyperpolarization (B) Increase potassium conductance to cause inhibition (C) Increase sodium conductance to cause excitation (D) Inhibit calcium conductance to reduce transmitter release (E) Exert all of the above actions

Activation of chloride or potassium ion channels commonly generates inhibitory postsynaptic potentials (IPSPs) and hyperpolarization. Activation of sodium and calcium channels (and inhibition of potassium ion channels) generates excitatory postsynaptic potentials (EPSPs). Inhibition of presynaptic calcium channels may reduce transmitter release. The answer is E.

Activation of metabotropic receptors located presynaptically causes inhibition by decreasing the inward flux of (A) Calcium (B) Chloride (C) Potassium (D) Sodium (E) None of the above

Activation of metabotropic receptors located presynaptically results in the inhibition of calcium influx with a resultant decrease in the release of neurotransmitter from nerve endings. This type of presynaptic inhibition occurs after activation of dopamine D2 , norepinephrine α2 , metabotropic glutamate, and mu opioid peptide receptors. The answer is A.

A young woman recently diagnosed as schizophrenic develops severe muscle cramps with torticollis a short time after drug therapy is initiated with haloperidol. The best course of action would be to (A) Add risperidone to the drug regimen (B) Discontinue haloperidol and observe the patient (C) Give oral diphenhydramine (D) Inject benztropine (E) Switch the patient to fluphenazine

Acute dystonic reactions are usually very painful and should be treated immediately with parenteral administration of a drug that blocks muscarinic receptors such as benztropine. Adding risperidone is not protective, and fluphenazine is as likely as haloperidol to cause acute dystonia. Oral administration of diphenhydramine is a possibility, but the patient may find it difficult to swallow and it would take a longer time to act. The answer is D.

Neuropathies are more likely to occur with this agent when it is used in patients with renal dysfunction. The drug may cause acute hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. (A) Chlorhexidine (B) Halazone (C) Methenamine (D) Metronidazole (E) Nitrofurantoin

Acute hemolytic reactions in G6PD deficiency occur with drugs that are oxidizing agents, including antimalarials, sulfonamides, and nitrofurans. Severe polyneuropathies may occur with nitrofurantoin, and they are more likely to occur in patients with renal dysfunction. The answer is E.

A 23-year-old pregnant woman is referred by her obstetrician for evaluation of anemia. She is in her fourth month of pregnancy and has no history of anemia; her grandfather had pernicious anemia. Her hemoglobin is 10 g/dL (normal, 12-16 g/dL). If this patient has a young child at home and is taking ironcontaining prenatal supplements, she should be warned that they are a common source of accidental poisoning in young children and advised to make a special effort to keep these pills out of her child's reach. Toxicity associated with acute iron poisoning usually includes which of the following? (A) Dizziness, hypertension, and cerebral hemorrhage (B) Hyperthermia, delirium, and coma (C) Hypotension, cardiac arrhythmias, and seizures (D) Necrotizing gastroenteritis, shock, and metabolic acidosis (E) Severe hepatic injury, encephalitis, and coma

Acute iron poisoning often causes severe gastrointestinal damage resulting from direct corrosive effects, shock from fluid loss in the gastrointestinal tract, and metabolic acidosis from cellular dysfunction. The answer is D.

A 45-year-old woman with hyperlipidemia and frequent migraine headaches develops angina of effort. Which of the following is relatively contraindicated because of her migraines? (A) Amlodipine (B) Diltiazem (C) Metoprolol (D) Nitroglycerin (E) Verapamil

Acute migraine headache is associated with vasodilation of meningeal arteries. Of the drugs listed, only nitroglycerin is commonly associated with headache. In fact, calcium channel blockers and β blockers have been used with some success as prophylaxis for migraine. The answer is D.

A 65-year-old woman has been admitted to the coronary care unit with a left ventricular myocardial infarction. She develops acute severe heart failure with marked pulmonary edema, but no evidence of peripheral edema. Which one of the following drugs would be most useful? (A) Digoxin (B) Furosemide (C) Minoxidil (D) Propranolol (E) Spironolactone

Acute severe congestive failure with pulmonary edema often requires a vasodilator that reduces intravascular pressures in the lungs. Furosemide has such vasodilating actions in the context of acute failure in addition to its diuretic effect. Pulmonary edema also involves a shift of fluid from the intravascular compartment to the lungs. Minoxidil would decrease arterial pressure and increase the heart rate excessively. Digoxin has a slow onset of action and lacks vasodilating effects. Spironolactone is useful in chronic failure but not in acute pulmonary edema. Pulmonary vasodilation and removal of edema fluid by diuresis are accomplished by furosemide. The answer is B.

Which statement about the mechanisms of action of antiviral drugs is accurate? (A) Acyclovir has no requirement for activation by phosphorylation (B) Ganciclovir inhibits viral DNA polymerase but does not cause chain termination (C) Increased activity of host cell ribonucleases that degrade viral mRNA is one of the actions of interferon-α (D) The initial step in activation of foscarnet in HSVinfected cells is its phosphorylation by thymidine kinase (E) The reverse transcriptase of HIV is 30-50 times more sensitive to inhibition by fosamprenavir than host cell DNA polymerases

Acyclovir is activated by host cell kinases. Like acyclovir, ganciclovir inhibits viral DNA polymerase and causes chain termination. However, foscarnet inhibits viral DNA polymerase without requiring bioactivation. Fosamprenavir is the prodrug of amprenavir, an inhibitor of HIV protease; it has no significant effect on reverse transcriptase. The answer is C.

More than 90% of this drug is excreted in the urine in intact form. Because its urinary solubility is low, patients should be well hydrated to prevent nephrotoxicity. Which drug is described? (A) Acyclovir (B) Efavirenz (C) Indinavir (D) Trifluridine (E) Zidovudine

Acyclovir is eliminated in the urine by glomerular filtration and by active tubular secretion, which is inhibited by probenecid. Nephrotoxic effects, including hematuria and crystalluria, are enhanced in patients who are dehydrated or who have preexisting renal dysfunction. Adequate hydration is equally important in the case of indinavir because it causes nephrolithiasis. However, more than 80% of a dose of indinavir is eliminated via hepatic metabolism. Trifluridine is used topically to treat herpes keratoconjunctivitis. The answer is A.

Which of the following drugs slows conduction through the AV node and has a duration of action of 10-20 seconds? (A) Adenosine (B) Amiodarone (C) Diltiazem (D) Esmolol (E) Flecainide (F) Lidocaine (G) Mexiletine (H) Procainamide (I) Quinidine

Adenosine is a very short-acting parenteral agent often used for AV nodal arrhythmias. Diltiazem also slows AV conduction and aborts AV nodal arrhythmias but has a duration of hours, not seconds. (Beta blockers also slow AV conduction but have much smaller effects on calcium channels.) The answer is A.

A 3-year-old girl was referred to the genetic counselor by her pediatrician. She presents with short stature (height is 85 cm, -3 standard deviations) and appears to have loose skin on her neck. Cytogenetic testing reveals an XO karyotype. Which of the following drugs will allow her to achieve a higher adult height? (A) Adrenocorticotropin (ACTH) (B) Corticotropin-releasing hormone (CRH) (C) Growth hormone-releasing hormone (GHRH) (D) Gonadotropin-releasing hormone (GnRH) (E) Somatropin

Adrenocorticotropin (ACTH) is used diagnostically in suspected adrenal insufficiency. Corticotropin-releasing hormone (CRH) is used to distinguish Cushing's syndrome from ectopic ACTH secretion. GHRH is rarely used as treatment. Its main use is as a diagnostic tool. GnRH can be used to treat infertility. Somatropin, recombinant human GH, promotes growth in children with Turner syndrome (an XO genetic genotype) or chronic renal failure. It also helps combat the AIDS-associated wasting syndrome. The answer is E.

A patient was treated for a bacterial infection with a penicillin. Within a few minutes of the antibiotic injection, he developed severe bronchoconstriction, laryngeal edema, and hypotension. Because of the rapid administration of epinephrine, the patient survived. Unfortunately, a year later he was treated with an antipsychotic drug and developed agranulocytosis. Which type of immunologic process was triggered by the antipsychotic drug? (A) A type III drug reaction (B) A type IV drug reaction (C) Delayed-type hypersensitivity (D) Mediated by IgG or IgM antibodies (E) Stevens-Johnson syndrome

Agranulocytosis and systemic lupus erythematosus are autoimmune syndromes that can be drug-induced. They are type II reactions involving IgM and IgG antibodies that bind to circulating blood cells. The patient was probably treated with clozapine for his psychosis (see clozapine toxicity, Chapter 29). The answer is D.

A 23-year-old woman is using an albuterol inhaler for frequent acute episodes of asthma and complains of symptoms that she ascribes to the albuterol. Which of the following is not a recognized action of albuterol? (A) Diuretic effect (B) Positive inotropic effect (C) Skeletal muscle tremor (D) Smooth muscle relaxation (E) Tachycardia

Albuterol is a β2-selective receptor agonist, but in moderate to high doses it produces β 1 cardiac effects as well as β2 -mediated smooth and skeletal muscle effects. It does not cause diuresis. The answer is A.

A 50-year-old factory worker presents with cardio-respiratory symptoms and careful workup reveals idiopathic pulmonary hypertension. Which of the following binds endothelin receptors and is approved for use in pulmonary hypertension? (A) Aliskiren (B) Capsaicin (C) Conivaptan (D) Macitentan (E) Sacubitril

Aliskiren, a renin inhibitor, is used in primary hypertension. Capsaicin, the "hot" constituent of hot peppers, is the molecule responsible for release of substance P. Conivaptan, an AVP antagonist, is used in hyponatremia. Sacubitril, a neprilysin antagonist, is used in heart failure. Macitentan, an endothelin antagonist, is used in pulmonary hypertension. The answer is D.

Which drug is an antagonist at 5-HT 2receptors and widely used for the management of insomnia in depressed patients? (A) Estazolam (B) Flurazepam (C) Trazodone (D) Triazolam (E) Zolpidem

All of the drugs listed are effective hypnotic drugs, but only trazodone is an antagonist at 5-HT 2 receptors. Trazodone has wide use as a sleeping aid, especially in patients with symptoms of affective disorder. The answer is C.

Your 23-year-old female patient is pregnant and has gonorrhea. The medical history includes anaphylaxis following exposure to amoxicillin. The most appropriate drug to use is (A) Azithromycin (B) Cefixime (C) Ceftriaxone (D) Ciprofloxacin (E) Doxycycline

All of the listed drugs have been used for the treatment of gonorrhea. Cephalosporins should be avoided in patients with a history of severe hypersensitivity to penicillins, and fluoroquinolones (see Chapter 46) should be avoided in pregnancy. Tetracyclines including doxycycline have been used in the past for gonorrhea, but not as single doses, and they too should be avoided in pregnancy. The answer is A.

A 55-year-old man is admitted to the emergency department and is found to have an abnormal ECG. Overdose of an antiarrhythmic drug is considered. Which of the following drugs is correctly paired with its ECG effects? (A) Quinidine: Increased PR and decreased QT intervals (B) Flecainide: Increased QRS interval (C) Verapamil: Decreased PR interval (D) Lidocaine: Decreased QRS and PR interval (E) Metoprolol: Increased QRS duration

All the associations listed are incorrect except flecainide (see Table 14-1). Group 1C drugs block sodium channels but have little effect on K + and Ca 2+ channels. The answer is B.

A 36-year-old woman presents with symptoms of major depression that are unrelated to a general medical condition, bereavement, or substance abuse. She is not currently taking any prescription or over-the-counter medications. Drug treatment is to be initiated with sertraline. In your information to the patient, you would tell her that (A) Sertraline may take 2 weeks or more to become effective (B) It is preferable that she take the drug in the morning (C) Muscle cramps and twitches can occur (D) She should notify you if she anticipates using other prescription drugs (E) All of the above

All the statements are appropriate regarding the initiation of treatment with sertraline or any other SSRI in a depressed patient. The SSRIs have CNS-stimulating effects and may cause agitation, anxiety, "the jitters," and insomnia, especially early in treatment. Consequently, the evening is not the best time to take SSRI drugs. The answer is E.

A 52-year-old woman presented with intense pain, warmth, and redness in the first toe on her left foot. Examination of fluid withdrawn from the inflamed joint revealed crystals of uric acid. Over the next 7 mo, the patient had 2 more attacks of acute gout. Her serum concentration of uric acid was elevated. The decision was made to put her on chronic drug therapy to try to prevent subsequent attacks. Which of the following drugs could be used to decrease this woman's rate of production of uric acid? (A) Allopurinol (B) Aspirin (C) Colchicine (D) Hydroxychloroquine (E) Probenecid

Allopurinol is the only drug listed that decreases production of uric acid. Probenecid increases uric acid excretion. Colchicine and hydroxychloroquine do not affect uric acid metabolism. Aspirin actually slows renal secretion of uric acid and raises uric acid blood levels. It should not be used in gout. The answer is A.

The hospital pharmacy committee is preparing a formulary for staff use. Which of the following is a correct application of the drug mentioned? (A) Alosetron: for obstetric bleeding (B) Cetirizine: for hay fever (C) Ergonovine: for Alzheimer's disease (D) Ondansetron: for acute migraine headache (E) Ranitidine: for Parkinson's disease

Alosetron is indicated in irritable bowel syndrome. Ergonovine is used in uterine bleeding. Ondansetron is useful for chemotherapy-induced emesis. Cetirizine, a secondgeneration H 1 blocker, is used in the treatment of hay fever. The answer is B.

A 40-year-old woman has occasional acute attacks of intense anxiety with marked physical symptoms, including hyperventilation, tachycardia, and sweating. If she is diagnosed as suffering from a panic disorder, the most appropriate drug to use is (A) Alprazolam (B) Eszopiclone (C) Flurazepam (D) Propranolol (E) Ramelteon

Alprazolam and clonazepam (not listed) are the most effective of the benzodiazepines for the treatment of panic disorders. Eszopiclone and flumazenil are hypnotics. Propranolol is commonly used to attenuate excessive sympathomimetic activity in persons who suffer from performance anxiety ("stage fright"). The answer is A.

A 70-year-old retired businessman with a history of chronic heart failure has been taking digoxin and furosemide. He is now admitted with a history of vomiting, acute decompensated heart failure, and metabolic derangements. He has marked peripheral edema and metabolic alkalosis (pH, 7.50; pCO2 , 45; HCO3 , 36; Na + , 140). Which of the following drugs is most appropriate for the treatment of his edema? (A) Acetazolamide (B) Digoxin (C) Eplerenone (D) Hydrochlorothiazide (E) Tolvaptan

Although acetazolamide is rarely used in heart failure, carbonic anhydrase inhibitors are quite valuable in patients with edema and metabolic alkalosis. The high bicarbonate levels in these patients make them particularly susceptible to the action of carbonic anhydrase inhibitors. Digoxin is useful in chronic systolic failure but is not first-line therapy and may cause vomiting, with depletion of stomach acid and reduced serum chloride; increasing the digoxin dose might cause arrhythmias. Tolvaptan might be useful if the patient were hyponatremic. Hydrochlorothiazide and eplerenone are not adequate for firstline therapy of edema in acute heart failure. The answer is A.

A 16-year-old patient is in the emergency department receiving nasal oxygen. She has a heart rate of 125 bpm, a respiratory rate of 40 breaths/min, and a peak expiratory flow <50% of the predicted value. Wheezing and rales are audible without a stethoscope. Which of the following drugs can be used by nebulizer for a prompt direct bronchodilator effect in severe, acute asthma? (A) Albuterol (B) Ipratropium (C) Prednisone (D) Salmeterol (E) Theophylline

Although extremely important in severe chronic asthma and status asthmaticus, corticosteroids do not have a demonstrable direct bronchodilator action. Salmeterol has a slow onset of action and is not suitable for an acute asthmatic attack. Ipratropium has bronchodilator action but is not the drug of first choice. The answer is A.

A previously healthy 40-year-old woman begins to suffer from slowed mentation, lack of coordination, and brief writhing movements of her hands that are not rhythmic. In addition, she has delusions of being persecuted. The woman has no history of psychiatric or neurologic disorders but several relatives have had similar symptoms. Although further diagnostic assessment should be made, it is very likely that the most appropriate drug for treatment will be (A) Amantadine (B) Bromocriptine (C) Diazepam (D) Haloperidol (E) Levodopa

Although further diagnosis is desirable, choreoathetosis with decreased mental abilities and psychosis (paranoia) suggests that this patient has the symptoms of Huntington's disease. Drugs that are partly ameliorative include agents that deplete dopamine (eg, tetrabenazine) or that block dopamine receptors (eg, haloperidol). The answer is D.

A 45-year-old homeless man presents to the emergency department with fever, weight loss, and a productive cough. Chest x-ray shows right apical infiltrate and TB is suspected. He is started on empiric INH, rifampin, and pyrazinamide. The primary reason for the use of drug combinations in the treatment of this patient's TB is: (A) Delay or prevent the emergence of resistance (B) Ensure patient compliance with the drug regimen (C) Increase antibacterial activity synergistically (D) Provide prophylaxis against other bacterial infections (E) Reduce the incidence of adverse effects

Although it is sometimes possible to achieve synergistic effects against mycobacteria with drug combinations, the primary reason for their use is to delay the emergence of resistance. The answer is A.

Which statement about the pathophysiologic basis of schizophrenia is most accurate? (A) All clinically effective antipsychotic drugs have high affinity for dopamine D 2 receptors (B) Dopamine receptor-blocking drugs are used to alleviate psychotic symptoms in parkinsonism (C) Drug-induced psychosis can occur without activation of brain dopamine receptors (D) Serotonin receptors are present at lower than normal levels in the brains of untreated schizophrenics (E) The clinical potency of olanzapine correlates well with its dopamine receptor-blocking activity

Although most first generation antipsychotic drugs block D2 receptors, this action is not a requirement for antipsychotic action. Aripiprazole, clozapine, and most newer secondgeneration drugs have a very low affinity for such receptors, but a high affinity for serotonin 5-HT 2 receptors. There are no reports of decreased serotonin receptors in the brains of schizophrenics. The CNS effects of phencyclidine (PCP) closely parallel an acute schizophrenic episode, but PCP has no actions on brain dopamine receptors. Dopamine receptor blockers cause extrapyramidal dysfunction. The answer is C.

A 19-year-old woman complains of severe dysmenorrhea. A uterine stimulant derived from membrane lipid in the endometrium is (A) Angiotensin II (B) Oxytocin (C) Prostacyclin (PGI2 ) (D) Prostaglandin PGF2 α (E) Serotonin

Although serotonin and, in some species, histamine may cause uterine stimulation, these amines are not derived from membrane lipid. Similarly, oxytocin causes uterine contraction, but it is a peptide hormone released from the posterior pituitary. Prostacyclin relaxes the uterus (Table 18-1). The answer is D.

Which one of the following drugs is associated with clinically useful or physiologically important positive inotropic effect? (A) Captopril (B) Dobutamine (C) Enalapril (D) Losartan (E) Nesiritide

Although they are extremely useful in heart failure, ACE inhibitors (eg, captopril, enalapril), and angiotensin receptor blockers (ARBs, eg, losartan) have no positive inotropic effect on the heart. Nesiritide is a vasodilator with diuretic effects and renal toxicity. Dobutamine is a β1 -selective adrenoceptor agonist. The answer is B.

On your way to an examination, you experience the vulnerable feeling that an attack of diarrhea is imminent. If you stopped at a drugstore, which one of the following antidiarrheal drugs could you buy without a prescription even though it is related chemically to the strong opioid analgesic meperidine? (A) Aluminum hydroxide (B) Diphenoxylate (C) Loperamide (D) Magnesium hydroxide (E) Metoclopramide

Aluminum hydroxide is constipating but is not related chemically to meperidine; magnesium hydroxide is a strong laxative. The 2 antidiarrheal drugs that are structurally related to opioids are diphenoxylate and loperamide. Loperamide is available over-the-counter; diphenoxylate is mixed with atropine alkaloids, and the product (Lomotil, others) requires a prescription. The answer is C.

This transmitter is mostly located in diffuse neuronal systems in the CNS, with cell bodies particularly in the raphe nuclei. It appears to play a major role in the expression of mood states, and many antidepressant drugs are thought to increase its functional activity. (A) Acetylcholine (B) Dopamine (C) GABA (D) Glutamate (E) Serotonin

Amine transmitters thought to be involved in the control of mood states include norepinephrine and serotonin. Cell bodies of serotonergic neurons are found in the raphe nuclei. Many of the drugs used for the treatment of major depressive disorders (Chapter 30) act to increase serotonergic activity in the CNS. The answer is E.

Which of the following statements about the clinical uses of the aminoglycosides is accurate? (A) Effective in the treatment of infections caused by anaerobes such as Bacteroides fragilis (B) Gentamycin is used with ampicillin for synergistic effects in the treatment of enterococcal endocarditis (C) In the treatment of a hospital-acquired infection caused by Serratia marcescens, netilmicin is less effective than streptomycin (D) Often used as monotherapy in the empiric treatment of life-threatening bacterial infections (E) Aminoglycosides are well absorbed after oral administration

Aminoglycoside antibiotics act at the ribosomal level and their intracellular accumulation by bacteria is oxygen dependent. Anaerobic bacteria including B fragilis are innately resistant. Aminoglycosides are often used with a cell wall inhibitor. Due to their polar nature they are not absorbed from the GI tract after oral dosing. The answer is B.

A 34-year-old patient is febrile (39.5°C [103.1°F]), with a white blood cell count that has risen from 8500 to 20,000/mm*3. The ICU attending physician is concerned about a bloodstream infection and decides to treat with empiric combination therapy directed against Pseudomonas aeruginosa. The combination therapy includes tobramycin. Regarding the mechanism of action of aminoglycosides, the drugs (A) Are bacteriostatic (B) Bind to the 50S ribosomal subunit (C) Cause misreading of the code on the mRNA template (D) Inhibit peptidyl transferase (E) Stabilize polysomes

Aminoglycosides are bactericidal inhibitors of protein synthesis binding to specific components of the 30S ribosomal subunit. Their actions include block of the formation of the initiation complex, miscoding, and polysomal breakup. Peptidyl transferase is inhibited by chloramphenicol, not aminoglycosides. The answer is C.

When working in outlying areas, this 62-year-old rancher is away from his house for 12-14 h at a time. He has an arrhythmia that requires chronic therapy. Which of the following has the longest half-life of all antiarrhythmic drugs? (A) Adenosine (B) Amiodarone (C) Disopyramide (D) Esmolol (E) Flecainide (F) Lidocaine (G) Mexiletine (H) Procainamide (I) Quinidine (J) Verapamil

Amiodarone has the longest half-life of all the a mics (weeks). The answer is B.

Which of the following drugs may inhibit the hepatic micrsomal P450 responsible for warfarin metabolism? (A) Amiodarone (B) Ethanol (C) Phenobarbital (D) Procainamide (E) Rifampin

Amiodarone is an important antiarrhythmic drug and has a well-documented ability to inhibit the hepatic metabolism of many drugs. The answer is A.

62-year-old woman presents with complaints of fatigue, sluggishness, and weight gain. She needs to nap several times a day, which is unusual for her. She has been taking T 4 for the past 15 years without significant problems regarding her energy level. Her recent history is significant for diagnosis of arrhythmia, and she is currently taking an antiarrhythmic drug. What is the most likely cause of her current condition? (A) Amiodarone (B) Lidocaine (C) Procainamide (D) Sotalol (E) Verapamil

Amiodarone is an iodine-containing antiarrhythmic drug with complex effects on the thyroid gland and thyroid hormones. One of its actions is to inhibit peripheral conversion of T 4 to T3 . Note that propranolol also reduces conversion of T 4 to T3 . Procainamide (group 1a), lidocaine (group 1b), sotalol (group 3), and verapamil (group 4) are antiarrhythmics and have no effect on T 4 conversion. The answer is A.

A 54-year-old airline pilot is admitted to the emergency department with chest pain and a rapid heart rhythm. The ECG shows an inferior myocardial infarction and ventricular tachycardia. Amiodarone is ordered. Amiodarone (A) Decreases PR interval in normal sinus rhythm (B) Increases action potential duration (C) Increases contractility (D) Often causes liver function abnormalities (E) Reduces resting potential

Amiodarone typically decreases contractility only slightly; it prolongs the PR and QRS interval, as well as the QT interval and action potential duration; and it has no effect on the resting potential. Its major toxicity is pulmonary fibrosis, not liver toxicity. The answer is B.

Which of the following diuretics would be most useful in the acute treatment of a comatose patient with traumatic brain injury and cerebral edema? (A) Acetazolamide (B) Amiloride (C) Chlorthalidone (D) Furosemide (E) Mannitol

An osmotic agent is needed to remove water from the cells of the edematous brain and reduce intracranial pressure rapidly. The answer is E.

A 56-year-old man has hypertension and an enlarged prostate, which biopsy shows to be benign prostatic hyperplasia. He complains of urinary retention. Which of the following drugs would be the most appropriate initial therapy? (A) Albuterol (B) Atenolol (C) Metoprolol (D) Prazosin (E) Timolol

An α blocker is appropriate therapy in a man with both hypertension and benign prostatic hyperplasia because both conditions involve contraction of smooth muscle containing α receptors. Prazosin is the only α blocker in the list of choices. The answer is D.

While playing in the garden, a 7-year-old boy is stung by 3 bees. Because he has a previous history of bee sting allergy, he is brought to the emergency department by his mother who is very concerned about a possible anaphylactic reaction. Which of the following are probable signs of an anaphylactic reaction to bee stings? (A) Bronchodilation, tachycardia, hypertension, vomiting, diarrhea (B) Bronchospasm, tachycardia, hypotension, laryngeal edema (C) Diarrhea, bradycardia, vomiting (D) Laryngeal edema, bradycardia, hypotension, diarrhea (E) Miosis, tachycardia, vomiting, diarrhea

Anaphylaxis is caused by the release of several mediators. Leukotrienes and certain proteins are the most important of these. They cause severe bronchospasm and laryngeal edema and marked vasodilation with severe hypotension. Tachycardia is a common reflex response to the hypotension. Gastrointestinal disturbance is not as common nor as dangerous. The answer is B.

Which statement concerning nitrous oxide is most accurate? (A) A useful component of anesthesia protocols because it lacks cardiovascular depression (B) Anemia is a common adverse effect in patients exposed to nitrous oxide for periods longer than 2 h (C) It is the most potent of the inhaled anesthetics (D) There is a direct association between the use of nitrous oxide and malignant hyperthermia (E) Up to 50% of nitrous oxide is eliminated via hepatic metabolism

Anemia has not been reported in patients exposed to nitrous oxide anesthesia for periods as long as 6 h. Nitrous oxide is the least potent of the inhaled anesthetics, and the compound has not been implicated in malignant hyperthermia. More than 98% of the gas is eliminated via the lungs. The answer is A.

In a phase 2 clinical trial in hypertensive patients, an endogenous octapeptide vasoconstrictor was found to increase in the blood of patients treated with large doses of diuretics. Which of the following is the most likely endogenous peptide? (A) Angiotensin I (B) Angiotensin II (C) Atrial natriuretic peptide (D) Bradykinin (E) Calcitonin gene-related peptide (F) Endothelin (G) Neuropeptide Y (H) Substance P (I) Vasoactive intestinal peptide (VIP)

Angiotensin II, an octapeptide, increases when blood v ume decreases (a diuretic effect) because the compensatory response causes an increase in renin secretion. Its precursor, angiotensin I, would also increase, but it is a decapeptide. The answer is B.

A 2-year-old girl presented with lethargy, increased respiratory rate, and an elevated temperature that appeared to result from a drug poisoning. Laboratory testing revealed the following serum concentrations: glucose, 36 mg/dL; Na+ , 148 mEq/L; K+ , 5 mEq/L; Cl− , 111 mEq/L; HCO3 − , 12 mEq/L; BUN, 21 mg/dL; osmolality, 300 mOsm/L. The anion gap in this patient is (A) −60 mEq/L (B) −20 mEq/L (C) +5 mEq/L (D) +30 mEq/L (E) +304 mEq/L

Anion gap is calculated by subtracting measured serum anions (bicarbonate plus chloride) from cations (potassium plus sodium). Increases in anion gap above normal are due to the presence of unmeasured anions that accompany acidosis. The gap in this case is 30 mEq/L, a value that is well in excess of the normal gap (12-16 mEq/L). The answer is D.

A 27-year-old pregnant patient with a history of pyelonephritis has developed a severe upper respiratory tract infection that appears to be due to a bacterial pathogen. The woman is hospitalized, and an antibacterial agent is to be selected for treatment. Assuming that the physician is concerned about the effects of renal impairment on drug dosage in this patient, which drug would not require dosage modification in renal dysfunction? (A) Amoxicillin (B) Cefoperazone (C) Ciprofloxacin (D) Trimethoprim-sulfamethoxazole (E) Vancomycin

Antimicrobial drugs that are eliminated via hepatic metabolism or biliary excretion include erythromycin, cefoperazone, clindamycin, doxycycline, isoniazid, ketoconazole, and nafcillin. The answer is B.

A 65-year-old woman with impaired renal function and a necrotic ulcer in the sole of her right foot is admitted to the ward from the emergency department. She has longstanding type 2 diabetes mellitus and you wish to examine her retinas for possible vascular changes. Which of the following drugs is a good choice when pupillary dilation—but not cycloplegia—is desired? (A) Isoproterenol (B) Norepinephrine (C) Phenylephrine (D) Pilocarpine (E) Tropicamide

Antimuscarinics (eg, tropicamide) are mydriatic and c plegic; α-sympathomimetic agonists are only mydriatic. Isoproterenol has negligible effects on the eye. Norepinephrine penetrates the conjunctiva poorly and would produce intense vasoconstriction. Pilocarpine causes miosis. Phenylephrine is well absorbed from the conjunctival sac and produces useful mydriasis for 10-30 minutes. The answer is C.

Ms Brown, a 28-year-old accountant, has been treated for myasthenia gravis for several years. She reports to the emergency department complaining of recent onset of weakness of her hands, diplopia, and difficulty swallowing. She may be suffering from a change in response to her myasthenia therapy, that is, a cholinergic or a myasthenic crisis. Which of the following is the best drug for distinguishing between myasthenic crisis (insufficient therapy) and cholinergic crisis (excessive therapy)? (A) Atropine (B) Edrophonium (C) Physostigmine (D) Pralidoxime (E) Pyridostigmine

Any of the cholinesterase inhibitors (choices B, C, or E) would effectively correct myasthenic crisis. However, because cholinergic crisis (if that is what is causing the symptoms) would be worsened by a cholinomimetic, we choose the shortest-acting cholinesterase inhibitor, edrophonium. The answer is B.

A 51-year-old patient with parkinsonism is being maintained on levodopa-carbidopa with adjunctive use of low doses of tolcapone but continues to have off-periods of akinesia. A drug used to "rescue" the patient that provides temporary relief is (A) Apomorphine (B) Benztropine (C) Carbidopa (D) Pramipexole (E) Selegiline

Apomorphine, via subcutaneous injection, is used for temporary relief of off-periods of akinesia (rescue) in parkinsonian patients on dopaminergic drug therapy. Pretreatment with the antiemetic trimethobenzamide for 3 days is essential to prevent severe nausea. The answer is A.

Which of the following is an antagonist at NK 1receptors and is used to prevent or reduce chemotherapy-induced nausea and vomiting? (A) Angiotensin I (B) Aprepitant (C) Bosentan (D) Bradykinin (E) Brain natriuretic peptide (F) Enalapril (G) Ondansetron

Aprepitant and ondansetron are both used to reduce or p vent chemotherapy-induced nausea and vomiting. Ondansetron is an antagonist at 5-HT 3 receptors. The answer is B.

Which statement about antitubercular drugs is accurate? (A) Antimycobacterial actions of streptomycin involve inhibition of arabinosyltransferases (B) Cross-resistance of M tuberculosis to isoniazid and pyrazinamide is common (C) Ocular toxicity of ethambutol is prevented by thiamine (D) Pyrazinamide treatment should be discontinued immediately if hyperuricemia occurs (E) Resistance to ethambutol involves mutations in the emb gene

Arabinosyltransferase is inhibited by ethambutol (not s tomycin) and resistance involves alterations in the emb gene. Ocular adverse effects of ethambutol are dose-dependent and usually reversible when the drug is discontinued. Thiamine is not protective. There is minimal cross-resistance between pyrazinamide and other antimycobacterial drugs. Pyrazinamide uniformly causes hyperuricemia, but this is not a reason to halt therapy even though the drug may provoke gouty arthritis in susceptible persons. The answer is E.

The primary endogenous substrate for the enzyme nitric oxide synthase (NOS) is (A) Acetylcholine (B) Angiotensinogen (C) Arginine (D) Citrulline (E) Heme

Arginine is the substrate and citrulline and NO are the p ucts of NOS acting on arginine. The answer is C.

A 7-year-old child is brought to the emergency department in coma with cyanosis. Her mother states that the girl was given codeine with acetaminophen because of severe bruising after a fall. Shortly after the first dose, the child became unresponsive and "turned blue." Which of the following alleles might be responsible for this presentation? (A) CYP2D6*1x3 (B) CYP2C19*2 (C) CYP2C9*3 (D) DPYD*2A (E) UGT1A1*28

As noted in answer 4, SNPs in CYP2D6 may increase or decrease the efficacy and toxicity of codeine because the CYP2D6 enzyme is responsible for conversion of codeine to its active metabolite, morphine. CYP2D6*1xN and *2xN are gain-of-function alleles with increased copy number polymorphisms that result in more efficient conversion to morphine and increased risk of opioid-induced respiratory depression. The answer is A.

A 35-year-old woman with moderately severe arthritis has been treated with nonsteroidal anti-inflammatory drugs for 6 mo. Her arthritis symptoms have been well controlled. She now complains of heartburn and indigestion. A fecal blood test is positive. You give her a prescription for a drug to be taken along with the anti-inflammatory agent, but 2 d later she calls the office complaining that your last prescription has caused severe diarrhea and cramping that resembles her periods. Which of the following is most likely to be associated with increased gastrointestinal motility and uterine cramping? (A) Aspirin (B) Famotidine (C) Leukotriene LTB4 (D) Misoprostol (E) Zileuton

Aspirin and zileuton rarely cause diarrhea. LTB4 is a chemotactic factor. Famotidine is an H 2 blocker that does not cause diarrhea (Chapter 16). Misoprostol, a PGE 1 analog, increases gastrointestinal and uterine motility. It is sometimes used as part of an abortifacient. The answer is D.

Among NSAIDs, aspirin is unique because it (A) Irreversibly inhibits its target enzyme (B) Prevents episodes of gouty arthritis with long-term use (C) Reduces fever (D) Increases the risk of colon cancer (E) Selectively inhibits the COX-2 enzyme

Aspirin differs from other NSAIDs by irreversibly inhibiting cyclooxygenase. The answer is A.

A patient with a positive fecal blood test is referred to the gastroentrology clinic. He is apparently taking large amounts of an unidentified drug that inhibits platelet activity. Which of the following is taken orally and directly and reversibly inhibits platelet cyclooxygenase? (A) Alprostadil (B) Aspirin (C) Ibuprofen (D) Leukotriene LTC4 (E) Misoprostol (F) Prednisone (G) Prostacyclin (H) Zafirlukast (I) Zileuton

Aspirin is a direct but irreversible inhibitor of cyclooxygenase. NSAIDs other than aspirin (such as ibuprofen) are reversible inhibitors of COX. Corticosteroids reduce the synthesis of cyclooxygenase. The answer is C.

A 52-year-old woman presented with intense pain, warmth, and redness in the first toe on her left foot. Examination of fluid withdrawn from the inflamed joint revealed crystals of uric acid. In the treatment of this woman's acute attack of gout, a high dose of colchicine will reduce the pain and inflammation. However, many physicians prefer to treat acute gout with a corticosteroid or indomethacin because high doses of colchicine are likely to cause (A) Behavioral changes that include psychosis (B) High blood pressure (C) Rash (D) Severe diarrhea (E) Sudden gastrointestinal bleeding

At doses needed to treat acute gout, colchicine frequently causes significant diarrhea. Such gastrointestinal effects are less likely with the lower doses used in chronic gout. The answer is D.

Comparison of prazosin with atenolol shows that (A) Both decrease heart rate (B) Both increase cardiac output (C) Both increase renin secretion (D) Both increase sympathetic outflow from the CNS (E) Both produce orthostatic hypotension

Atenolol, but not prazosin, may decrease heart rate (choice A). Prazosin—but not atenolol—may increase cardiac output, a compensatory effect (choice B). Prazosin may increase renin output (a compensatory response), but β blockers inhibit its release by the kidney (choice C). By reducing blood pressure, both may increase central sympathetic outflow (a compensatory response). Beta blockers do not cause orthostatic hypotension. The answer is D.

Which of the following is an accepted therapeutic indication for the use of antimuscarinic drugs? (A) Atrial fibrillation (B) Botulinum poisoning (C) Chronic obstructive pulmonary disease (COPD) (D) Glaucoma (E) Postoperative urinary retention

Atrial fibrillation and other arrhythmias are not responsive to antimuscarinic agents. Botulinum poisoning is associated with parasympathetic blockade. Antimuscarinic drugs tend to cause urinary retention and may precipitate or exacerbate glaucoma. Bronchospasm is mediated in part by vagal outflow in many patients with COPD and in some with asthma. The answer is C.

Which one of the following can be blocked by atropine? (A) Decreased blood pressure caused by hexamethonium (B) Increased blood pressure caused by nicotine (C) Increased skeletal muscle strength caused by neostigmine (D) Tachycardia caused by exercise (E) Sweating caused by exercise

Atropine blocks muscarinic receptors and inhibits p pathomimetic effects. Nicotine can induce both parasympathomimetic and sympathomimetic effects by virtue of its ganglion-stimulating action. Hypertension and exercise-induced tachycardia reflect sympathetic discharge with norepinephrine release and therefore would not be blocked by atropine. Exerciseinduced sweating is another sympathomimetic response, but it is mediated by acetylcholine released from sympathetic nerve fibers at eccrine sweat glands. The answer is E.

In comparing the characteristics of thioridazine with other first generation antipsychotic drugs, which of the following statements is most accurate? (A) Most likely to cause extrapyramidal dysfunction (B) Least likely to cause urinary retention (C) Most likely to be safe in patients with history of cardiac arrhythmias (D) Most likely to cause ocular dysfunction (E) The safest antipsychotic drug in overdose

Atropine-like side effects are more prominent with thioridazine than with other phenothiazines, but the drug is less likely to cause extrapyramidal dysfunction. The drug has quinidine-like actions on the heart and, in overdose, may cause arrhythmias and cardiac conduction block with fatality. At high doses, thioridazine causes retinal deposits, which in advanced cases resemble retinitis pigmentosa. The patient may complain of browning of vision. The answer is D.

Which drug has resulted in severe hematotoxicity when administered to a patient being treated with azathioprine? (A) Allopurinol (B) Cholestyramine (C) Digoxin (D) Lithium (E) Theophylline

Azathioprine is converted to mercaptopurine, which is responsible for both its immunosuppressant action and its hematotoxicity. Allopurinol inhibits xanthine oxidase, the enzyme that metabolizes mercaptopurine. The answer is A.

A 24-year-old woman comes to a clinic with complaints of dry cough, headache, fever, and malaise, which have lasted 3 or 4 d. She appears to have some respiratory difficulty, and chest examination reveals rales but no other obvious signs of pulmonary involvement. However, extensive patchy infiltrates are seen on chest x-ray film. Gram stain of expectorated sputum fails to reveal any bacterial pathogens. The patient mentions that a colleague at work had similar symptoms to those she is experiencing. The patient has no history of serious medical problems. She takes loratadine for allergies and supplementary iron tablets, and she drinks at least 6 cups of caffeinated coffee per day. The physician makes an initial diagnosis of communityacquired pneumonia. A 5-d course of treatment for community-acquired pneumonia would be effective in this patient with little risk of drug interactions if the drug prescribed were (A) Azithromycin (B) Clindamycin (C) Doxycycline (D) Erythromycin (E) Vancomycin

Azithromycin has a half-life of more than 70 h, which allows for once-daily dosing and a 5-d course of treatment for community-acquired pneumonia. Unlike other macrolides, azithromycin does not inhibit cytochrome P450 enzymes involved in drug metabolism. The answer is A.

Which of the following endogenous molecules is elevated in heart failure and when given as a drug is a vasodilator with significant renal toxicity? (A) Angiotensin I (B) Angiotensin II (C) BNP (nesiritide) (D) Histamine (E) Vasoactive intestinal peptide

BNP is an atrial and brain peptide found in increased amounts in patients with heart failure. The commercial formulation (nesiritide) is approved for use in severe acute heart failure but has significant renal toxicity. The answer is C.

Regarding the spasmolytic drugs, which of the following statements is least accurate? (A) Baclofen acts on GABA receptors in the spinal cord to increase chloride ion conductance (B) Cyclobenzaprine decreases both oropharyngeal secretions and gut motility (C) Dantrolene has no significant effect on the release of calcium from sarcoplasmic reticulum in cardiac muscle (D) Diazepam causes slight sedation at doses commonly used to reduce muscle spasms (E) Intrathecal use of baclofen is effective in some refractory cases of muscle spasticity

Baclofen activates GABA Breceptors in the spinal cord. However, these receptors are coupled to K + channels (see Chapter 22). GABA A receptors in the CNS modulate chloride ion channels, an action facilitated by diazepam and other benzodiazepines. The answer is A.

A 30-year-old woman undergoes abdominal surgery. In spite of minimal tissue damage, complete ileus (absence of bowel motility) follows, and she complains of severe bloating. She also finds it difficult to urinate. Mild cholinomimetic stimulation with bethanechol or neostigmine is often effective in relieving these complications of surgery. Neostigmine and bethanechol in moderate doses have significantly different effects on which one of the following? (A) Gastric secretory cells (B) Vascular endothelium (C) Salivary glands (D) Sweat glands (E) Ureteral tone

Because neostigmine acts on the enzyme cholinesterase, which is present at all cholinergic synapses, this drug increases acetylcholine effects at nicotinic junctions as well as muscarinic ones. Bethanechol, on the other hand, is a direct-acting agent that is selective for muscarinic receptors regardless of whether the receptors are innervated or not. The muscarinic receptors on vascular endothelial cells are not innervated and respond only to direct-acting drugs. The answer is B.

Once-weekly administration of which of the following a biotics has prophylactic activity against bacteremia caused by M avium complex in AIDS patients? (A) Acedapsone (B) Azithromycin (C) Clarithromycin (D) Kanamycin (E) Rifabutin

Because of its long elimination half-life (3-4 d), weekly administration of azithromycin has proved to be equivalent to daily administration of clarithromycin when used for prophylaxis against M avium complex in AIDS patients. Acedapsone is a repository form of dapsone used in leprosy. The answer is B.

Mr Green is a 60-year-old man with atherosclerosis and poorly controlled hypertension of 170/110 mm Hg. He has been taking several antihypertensive drugs, including minoxidil. Minoxidil is a powerful arteriolar vasodilator that does not act on autonomic receptors. Which of the following effects will be observed if no other drugs are used? (A) Tachycardia and increased cardiac contractility (B) Tachycardia and decreased cardiac output (C) Decreased mean arterial pressure and decreased cardiac contractility (D) Decreased mean arterial pressure and increased salt and water excretion by the kidney (E) Bradycardia and decreased cardiac contractility

Because of the compensatory responses, a drug that directly decreases blood pressure through a decrease in peripheral vascular resistance will cause a reflex increase in sympathetic outflow, an increase in renin release, and a decrease in parasympathetic outflow. As a result, heart rate and cardiac force will increase. In addition, salt and water retention will occur. The answer is A.

A 13-year-old boy with type 1 diabetes is brought to the hospital complaining of dizziness. Laboratory findings include severe hyperglycemia, ketoacidosis, and a blood pH of 7.15. Which of the following is the most likely complication of insulin therapy in this patient? (A) Dilutional hyponatremia (B) Hypoglycemia (C) Increased bleeding tendency (D) Pancreatitis (E) Severe hypertension

Because of the risk of brain damage, the most important complication of insulin therapy is hypoglycemia. The other choices are not common effects of insulin. The answer is B.

A homeless middle-aged male patient presents in the emergency department in a state of intoxication. You note that he is behaviorally disinhibited and rowdy. He tells you that he has recently consumed about a pint of a red-colored liquid that his friends were using to "get high." He complains that his vision is blurred and that it is "like being in a snowstorm." His breath smells a bit like formaldehyde. He is acidotic. Consumption of which of the following is the most likely cause of this patient's intoxicated state? (A) Ethanol (B) Ethylene glycol (C) Isopropanol (D) Hexane (E) Methanol

Behavioral disinhibition is a feature of early intoxication from ethanol and most other alcohols but not the solvent, hexane. Ocular dysfunction, including horizontal nystagmus and diplopia, is also a common finding in poisoning with alcohols, but the complaint of "flickering white spots before the eyes" or "being in a snowstorm" is highly suggestive of methanol intoxication. In some cases, the odor of formaldehyde may be present on the breath. In this patient, blood methanol levels should be determined as soon as possible. The answer is E.

Methenamine salts are used as urinary antiseptics. The reason they lack systemic antibacterial action is that they are (A) Converted to formaldehyde only at low pH (B) Metabolized rapidly by hepatic drug-metabolizing enzymes (C) More than 98% bound to plasma proteins (D) Not absorbed into the systemic circulation after oral ingestion (E) Substrates for active tubular secretion

Below pH 5.5, methenamine releases formaldehyde, which is antibacterial. This pH is achieved in the urine but nowhere else in the body. Ascorbic acid is sometimes given with methenamine salts to ensure a low urinary pH. The answer is A.

A 43-year-old very overweight man complains of not sleeping well and feeling tired during the day. He says that his wife is the cause of the problem because she wakes him up several times during the night because of his loud snores. This appears to be a breathing-related sleep disorder, so you should probably write a prescription for (A) Clorazepate (B) Diazepam (C) Flurazepam (D) Pentobarbital (E) Weight loss

Benzodiazepines and barbiturates (and other sedative-hypnotics) are contraindicated in breathing-related sleep disorders because they further compromise ventilation. Obesity is a major cause of obstructive sleep apnea. The best prescription you can give this patient is to lose weight. The answer is E.

Which of the following best describes the mechanism of action of benzodiazepines? (A) Activate GABA B receptors in the spinal cord (B) Block glutamate receptors in hierarchical neuronal pathways in the brain (C) Increase frequency of opening of chloride ion channels coupled to GABA A receptors (D) Inhibit GABA transaminase to increase brain levels of GABA (E) Stimulate release of GABA from nerve endings in the brain

Benzodiazepines exert most of their CNS effects by increasing the inhibitory effects of GABA, interacting with components of the GABA A receptor-chloride ion channel macromolecular complex to increase the frequency of chloride ion channel opening. Benzodiazepines do not affect GABA metabolism or release, and they do not interact directly with the binding site for GABA. The answer is C.

Which statement concerning the proposed mechanisms of action of anticonvulsant drugs is most accurate? (A) Benzodiazepines facilitate glutamate-mediated inhibitory actions (B) Ethosuximide selectively blocks potassium ion (K+ ) channels in thalamic neurons (C) Phenobarbital produces a selective blockade of calcium ion (Ca2+ ) channels (D) Phenytoin prolongs the inactivated state of the Na+ channel (E) Zonisamide blocks voltage-gated K + channels

Benzodiazepines facilitate GABA-mediated inhibitory actions. Ethosuximide selectively blocks calcium channels in thalamic neurons. Phenobarbital produces multiple effects, mainly enhancement of GABA-chloride inhibitory activity. Zonisamide blocks voltage-gated Na + channels. Phenytoin selectively blocks the Na + channel and prolongs the inactivated state. The answer is D.

Which one of the following drugs causes vasodilation that can be blocked by atropine? (A) Benztropine (B) Bethanechol (C) Botulinum toxin (D) Cyclopentolate (E) Edrophonium (F) Neostigmine (G) Pralidoxime

Bethanechol (Chapter 7) causes vasodilation by directly activating muscarinic receptors on the endothelium of blood vessels. This effect can be blocked by atropine. Indirectly acting agents (AChE inhibitors) do not typically cause vasodilation because the endothelial receptors are not innervated and acetylcholine is not released at this site. Pralidoxime is a distracter in this answer list. The answer is B.

A 54-year-old obese patient with type 2 diabetes has a history of alcoholism. In this patient, metformin should either be avoided or used with extreme caution because the combination of metformin and ethanol increases the risk of which of the following? (A) A disulfiram-like reaction (B) Excessive weight gain (C) Hypoglycemia (D) Lactic acidosis (E) Serious hepatotoxicity

Biguanides, especially the older drug phenformin, have been associated with lactic acidosis. Thus, metformin should be avoided or used with extreme caution in patients with conditions that increase the risk of lactic acidosis, including acute ethanol ingestion. The answer is D.

You are planning to treat chronic major depression in a 35-year-old patient with recurrent suicidal thoughts. She has several comorbid conditions that require drug therapy, including rifampin for tuberculosis and amiodarone for arrhythmia. You are concerned about drug interactions caused by changes in drug metabolism in this patient. Drug metabolism in humans usually results in a product that is: (A) Less lipid soluble than the original drug (B) More likely to distribute intracellularly (C) More likely to be reabsorbed by kidney tubules (D) More lipid soluble than the original drug (E) Less water soluble than the original drug

Biotransformation usually results in a product that is less lipidsoluble. This facilitates elimination of drugs that would otherwise be reabsorbed from the renal tubule. The answer is A.

A patient with multiple myeloma was started on bortezomib after 2 rounds of other combination chemotherapy did not have any effect. What is the mechanism of action of bortezomib? (A) Cross-linking of double-stranded DNA (B) Inhibition of DNA-dependent RNA synthesis (C) Interference with the activity of topoisomerases I (D) Inhibition of the 26S proteasome (E) Selective inhibition of DNA polymerases

Bortezomib is an inhibitor of the proteasome structure, whose normal function is to break down ubiquitinated proteins. The answer is D.

A new 60-year-old patient presents to the medical clinic with hypertension and angina. He is 1.8 meters tall with a waist measurement of 1.1 m. Weight is 97 kg, blood pressure is 150/95, and pulse is 85. In considering adverse effects of possible drugs for these conditions, you note that an adverse effect that nitroglycerin and prazosin have in common is (A) Bradycardia (B) Impaired sexual function (C) Lupus erythematosus syndrome (D) Orthostatic hypotension (E) Weight gain

Both drugs cause venodilation and reduce venous return sufficiently to cause some degree of postural hypotension. Bradycardia, lupus, and urinary retention occur with neither of them, but prazosin has been used to relieve urinary retention in men with prostatic hyperplasia. While this patient has a high body mass index of 29.9, weight gain is not a risk with either drug. The answer is D.

Several children at a summer camp were hospitalized with symptoms thought to be due to ingestion of food containing botulinum toxin. Which one of the following signs or symptoms is consistent with the diagnosis of botulinum poisoning? (A) Bronchospasm (B) Cycloplegia (C) Diarrhea (D) Skeletal muscle spasms (E) Hyperventilation

Botulinum toxin impairs all types of cholinergic transmission, including transmission at ganglionic synapses and somatic motor nerve endings. Botulinum toxin prevents discharge of vesicular transmitter content from cholinergic nerve endings. All of the signs listed except cycloplegia indicate increased muscle contraction; cycloplegia (paralysis of accommodation) results in blurred near vision. The answer is B.

Which of the following is a vasodilator that increases in the blood or tissues of patients treated with captopril? (A) Angiotensin II (B) Bradykinin (C) Brain natriuretic peptide (D) Calcitonin gene-related peptide (E) Endothelin (F) Neuropeptide Y (G) Vasopressin (AVP)

Bradykinin increases because the enzyme inhibited by c topril, angiotensin converting enzyme, degrades kinins in addition to synthesizing angiotensin II (see Figure 11-3). The answer is B.

A 26-year-old woman presents with amenorrhea and galactorrhea. Her prolactin level is grossly elevated (200 ng/mL vs normal 20 ng/mL). Which of the following is most useful in the treatment of hyperprolactinemia? (A) Bromocriptine (B) Cimetidine (C) Ergotamine (D) Ketanserin (E) LSD (F) Ondansetron (G) Sumatriptan

Bromocriptine is an effective dopamine agonist in the CNS with the advantage of oral activity. The drug inhibits prolactin secretion by activating pituitary dopamine receptors. The answer is A.

A 27-year-old woman with amenorrhea, infertility, and galactorrhea was treated with a drug that successfully restored ovulation and menstruation. Before being given the drug, the woman was carefully questioned about previous mental health problems, which she did not have. She was advised to take the drug orally. Which of the following is most likely to be the drug that was used to treat this patient? (A) Bromocriptine (B) Desmopressin (C) Human gonadotropin hormone (D) Leuprolide (E) Octreotide

Bromocriptine, a dopamine receptor agonist, is used to treat the amenorrhea-galactorrhea syndrome, which is a consequence of hyperprolactinemia. Because of its central dopaminergic effects, the drug should not be used in patients with a history of schizophrenia or other forms of psychotic illness. The answer is A.

A 24-year-old stockbroker has developed a "nervous disposition." He is easily startled, worries about inconsequential matters, and sometimes complains of stomach cramps. At night he grinds his teeth in his sleep. There is no history of drug abuse. Diagnosed as suffering from generalized anxiety disorder, he is prescribed buspirone. The patient should be informed to anticipate (A) A need to continually increase drug dosage because of tolerance (B) A significant effect of the drug on memory (C) Additive CNS depression with alcoholic beverages (D) That the drug is likely to take a week or more to begin working (E) That if he stops taking the drug abruptly, he will experience withdrawal signs

Buspirone is a selective anxiolytic with pharmacologic c teristics different from those of sedative-hypnotics. Buspirone has minimal effects on cognition or memory; it is not additive with ethanol in terms of CNS depression; tolerance is minimal; and it has no dependence liability. Buspirone is not effective in acute anxiety because it has a slow onset of action (∼1 week). The answer is D.

A 45-year-old woman with small cell lung cancer has elected to participate in the trial of a new chemotherapeutic agent. It is given by constant intravenous infusion of 10 mg/h. Plasma concentrations (Cp ) are measured with the results shown in the following table. Time After Start of Infusion (h) Plasma Concentration (mg/L) ( 1, 0.7 ) ( 4, 3.0 ) ( 8, 3.6 ) ( 16, 3,84 ) ( 24, 0.4 ) What conclusion can be drawn from these data? (A) Clearance is 2.0 L/h (B) Doubling the rate of infusion would result in a plasma concentration of 16 mg/L at 40 h (C) Elimination follows zero-order kinetics (D) Half-life is 2 h (E) Volume of distribution is 30 L

By inspection of the data in the table, it is clear that the steady-state plasma concentration is approximately 4 mg/L. None of the measured concentrations is equal to one half of the steady state value; so the half-life is not immediately apparent. However, according to the constant infusion principle, 2 half-lives are required to reach 75% of the final concentration; 75% (3.0 mg/L) of the final steady-state concentration was reached at 4 h. If 4 h equals 2 half-lives, the half-life must be 2 h. Rearranging the equation for maintenance dosing (dosing rate = CL × Cp ), it can be determined that the clearance (CL) = dosing rate/plasma concentration (Cp ), or 2.5 L/h. The volume of distribution (Vd ) can be calculated from the half-life equation (t 1/2 = 0.693 × Vd /CL) and is equal to 7.2 L. This drug follows firstorder kinetics, as indicated by the progressive approach to the steady-state plasma concentration. The answer is D.

The pharmacokinetics of a new drug are under study in a phase 1 clinical trial. Which statement about the distribution of drugs to specific tissues is most correct? (A) Distribution to an organ is independent of blood flow (B) Distribution is independent of the solubility of the drug in that tissue (C) Distribution into a tissue depends on the unbound drug concentration gradient between blood and the tissue (D) Distribution is increased for drugs that are strongly bound to plasma proteins (E) Distribution has no effect on the half-life of the drug

C, This is a straightforward question of pharmacokinetic distribution concepts. From the list of determinants of drug distribution given on page 6, choice C is correct.

A 62-year-old woman with advanced colon cancer is treated with intravenous 5-fluorouracil. Within a few days, she develops severe diarrhea, and within a week, she shows severe neutropenia. Which of the following polymorphisms is most likely to be responsible? (A) CYP2D6*1x3 (B) CYP2C19*2 (C) CYP2C9*3 (D) DPYD*2A (E) UGT1A1*28

CYP2D6*1x3 is a gain-of-function allele enhanced by 3 copies ("x3" ) and is associated with increased effect and toxicity of codeine. CYP2C19*2 is a nonfunctional allele associated with reduced efficacy of clopidogrel. CYP2C9*3 with a reduced function allele of VCORC1 is associated with reduced warfarin clearance. UGT1A1*28 is a reduced function allele for uridine 5′-diphospho-(UDP) glucuronosyltransferase and enhances irinotecan toxicity. 5-Fluorouracil is cleared by dihydropyrimidine dehydrogenase (DPD). The DPYD*2A allele is nonfunctional. The answer is D.

A college student volunteers to have his genome decoded as part of a population-wide study of polymorphisms. He receives a call from the principal investigator informing him that his genome unexpectedly contains an important single nucleotide polymorphism. Which of the following polymorphisms is associated with risk of hemolysis and increased resistance to malaria? (A) CYP2D6*3 (B) CYP2D19*2 (C) TPMT*2 (D) UGT1A1*28 (E) G6PD-(A)-Canton

CYP2D6*3 is associated with reduced codeine efficacy. CYP2D19*2 results in reduced clopidogrel conversion to its active metabolite. TPMT*2 is associated with decreased clearance of 6-mercaptopurine and increased toxicity. UGT1A1*28 results in decreased clearance and increased toxicity of SN-38, the active metabolite of irinotecan. G6PD(A)-Canton is a reduced function allele of the glucose-6phosphate dehydrogenase gene that decreases intracellular stores of glutathione, increasing the risk of hemolysis but reducing susceptibility to malaria. The answer is E.

A 58-year-old postmenopausal woman was sent for dual-energy x-ray absorptiometry to evaluate the bone mineral density of her lumbar spine, femoral neck, and total hip. The test results revealed significantly low bone mineral density in all sites. The patient's condition was not sufficiently controlled with alendronate, so she began therapy with a nasal spray containing a protein that inhibits bone resorption. The drug contained in the nasal spray was which of the following? (A) Calcitonin (B) Calcitriol (C) Cinacalcet (D) Cortisol (E) Teriparatide

Calcitonin is a peptide hormone that prevents bone resorption. Salmon calcitonin is available as a nasal spray or a parenteral form for injection. The answer is A.

A 16-year-old girl has paroxysmal attacks of rapid heart rate with palpitations and shortness of breath. These episodes occasionally terminate spontaneously but often require a visit to the emergency department of the local hospital. Her ECG during these episodes reveals an AV nodal tachycardia. Which of the following drugs would be most suitable for prophylaxis of future episodes of acute AV nodal tachycardia? (A) Adenosine (B) Amiodarone (C) Flecainide (D) Propranolol (E) Verapamil

Calcium channel blockers are effective in both treating and preventing supraventricular AV nodal tachycardias. They are orally active and have a duration of action of several hours. Adenosine is very effective in most acute nodal tachycardias and is less toxic because of its extremely short duration of action. However, it is not useful for chronic prophylaxis because it must be given IV and has a very short duration of action. The answer is E.

Which of the following drugs is established to be both effective and safe to use in a pregnant patient suffering from bipolar disorder? (A) Carbamazepine (B) Fluphenazine (C) Lithium (D) Olanzapine (E) Valproic acid

Carbamazepine and valproic acid are effective in bipolar d order but are contraindicated in the pregnant patient because of possible teratogenic effects. Although the potential for dysmorphogenesis due to lithium is probably low, the most conservative approach would be to treat the patient with quetiapine or olanzapine. Fluphenazine has no proven efficacy in bipolar disorder. The answer is D.

A graduate student is planning to make a high-altitude climb in South America while on vacation. He will not have time to acclimate slowly to altitude. A drug that is useful in preventing high-altitude sickness is (A) Acetazolamide (B) Amiloride (C) Demeclocycline (D) Desmopressin (E) Ethacrynic acid

Carbonic anhydrase inhibitors are useful for the prevention of altitude sickness. The answer is A.

Which of the following chemicals is most likely to function as a neurotransmitter in hierarchical systems? (A) Glutamate (B) Met-enkephalin (C) Nitric oxide (D) Norepinephrine (E) Substance P

Catecholamines (dopamine, norepinephrine), peptides, and serotonin act as neurotransmitters in nonspecific or diffuse neuronal systems. Glutamate is the primary excitatory transmitter in hierarchical neuronal systems. These systems also contain numerous inhibitory neurons, which use GABA and glycine. Nitric oxide, though present in many brain regions, has a poorly understood role in CNS synaptic transmission. The answer is A.

A 31-year-old man has gonorrhea. He has no drug allergies, but a few years ago acute hemolysis followed use of an antimalarial drug. The physician is concerned that the patient has an accompanying urethritis caused by C trachomatis, although no cultures or enzyme tests have been performed. Which of the following drugs will be reliably effective against both gonococci and C trachomatis and safe to use in this patient? (A) Cefixime (B) Ciprofloxacin (C) Spectinomycin (D) Sulfamethoxazole-trimethoprim (E) None of the above

Cefixime in a single oral dose is effective in gonorrhea (Chapter 43), but it has no activity against organisms causing nongonococcal urethritis. Spectinomycin (Chapter 45) is active against most gonococci, but does not eradicate a urogenital chlamydial infection. Although ciprofloxacin might be effective in both gonorrhea and chlamydial urethritis, it is no longer recommended for treatment of gonorrhea in the United States, since resistance is now common. This patient could be treated by single oral doses of cefixime plus azithromycin (not listed). Sulfamethoxazole or TMP-SMZ would not be useful and may cause acute hemolysis in this patient. The answer is E.

A 54-year-old woman presented with signs and symptoms consistent with an early stage of rheumatoid arthritis. The decision was made to initiate NSAID therapy. Which of the following patient characteristics is the most compelling reason for avoiding celecoxib in the treatment of her arthritis? (A) History of alcohol abuse (B) History of gout (C) History of myocardial infarction (D) History of osteoporosis (E) History of peptic ulcer disease

Celecoxib is a COX-2-selective inhibitor. Although the COX-2 inhibitors have the advantage over nonselective NSAIDs of reduced gastrointestinal toxicity, clinical data suggest that they are more likely to cause arterial thrombotic events. A history of myocardial infarction would be a compelling reason to avoid a COX-2 inhibitor. The answer is C.

A 26-year-old woman was treated for a suspected chlamydial infection at a neighborhood clinic. She was given a prescription for oral doxycycline to be taken for 14 d. Three weeks later, she returned to the clinic with a mucopurulent cervicitis. On questioning she admitted not having the prescription filled. The best course of action at this point would be to (A) Delay drug treatment until the infecting organism is identified (B) Rewrite the original prescription for oral doxycycline (C) Treat her in the clinic with a single oral dose of azithromycin (D) Treat her in the clinic with an intravenous dose of amoxicillin (E) Write a prescription for oral erythromycin for 10 d

Cervicitis or urethritis is often caused by C trachomatis. Such infections may develop slowly because of the long incubation period of chlamydial infection. Treatment with oral doxycycline for 14 d (as originally prescribed) would have eradicated C trachomatis and most other organisms commonly associated with nongonococcal cervicitis or urethritis. Given the limited compliance of this patient, the best course of action would be the administration (in the clinic) of a single oral dose of azithromycin. The answer is C.

A 4-year-old child is brought to the hospital after ingesting pills that a parent had used for bacterial dysentery when traveling outside the United States. The child has been vomiting for more than 24 h and has had diarrhea with green stools. She is now lethargic with an ashen color. Other signs and symptoms include hypothermia, hypotension, and abdominal distention. The drug most likely to be the cause of this problem is (A) Ampicillin (B) Azithromycin (C) Chloramphenicol (D) Doxycycline (E) Erythromycin

Chloramphenicol is commonly used outside the United States for treatment of bacillary dysentery. The drug causes a dose-dependent (reversible) suppression of erythropoiesis. Although the gray baby syndrome was initially described in neonates, a similar syndrome has occurred with overdosage of chloramphenicol in older children and adults, especially those with hepatic dysfunction. The answer is C.

Parasympathetic nerve stimulation and a slow infusion of bethanechol will each (A) Cause ganglion cell depolarization (B) Cause skeletal muscle end plate depolarization (C) Cause vasodilation (D) Increase bronchial smooth muscle tone (E) Increase heart rate

Choice (E) is not correct because the vagus slows the heart. Parasympathetic nerve stimulation does not cause vasodilation (most vessels do not receive parasympathetic innervation), so choice (C) is incorrect. Ganglion cells and the end plate contain nicotinic receptors, which are not affected by bethanechol, a direct-acting muscarinic agonist. Efferent fibers in the vagus may cause bronchoconstriction. The answer is D.

Which of the following is the most dangerous effect of belladonna alkaloids in infants and toddlers? (A) Dehydration (B) Hallucinations (C) Hypertension (D) Hyperthermia (E) Intraventricular heart block

Choices B, D, and E are all possible effects of the atropine group. In infants, however, the most dangerous effect is hyperthermia. Deaths with body temperatures in excess of 42 °C have occurred after the use of atropine-containing eye drops in children. The answer is D.

A study was carried out in isolated intestinal smooth muscle preparations to determine the action of a new drug "novamine," which in separate studies bound to the same receptors as acetylcholine, an agonist. In the absence of other drugs, acetylcholine caused contraction of the muscle. Novamine alone caused relaxation of the preparation. In the presence of a low concentration of novamine, the EC 50 of acetylcholine was unchanged, but the E max was reduced. In the presence of a high concentration of novamine, extremely high concentrations of acetylcholine had no effect. Which of the following expressions best describes novamine? (A) A chemical antagonist (B) An irreversible antagonist (C) A partial agonist (D) A physiologic antagonist (E) A spare receptor agonist

Choices involving chemical or physiologic antagonism are incorrect because novamine is said to act at the same receptors as acetylcholine. When given alone, the novamine effect is opposite to that of acetylcholine; so choice C is incorrect. "Spare receptor agonist" is a nonsense distracter. The answer is B.

A 59-year-old female was referred to your clinic for evaluation of osteopenia. She was diagnosed with adult-onset cystic fibrosis (CF). She reported being treated with prednisone 2 times in the past for CF exacerbations. Since menopause at 52 years of age, she had been treated with raloxifene for osteoporosis prevention. She also was on daily calcium and vitamin D supplementation. Her bone mineral density test revealed a T score of -1.6 at the lumbar spine, -2.2 at the left femoral neck, and -1.6 at the total left hip. Which of the following drugs can be used to reduce the fracture risk by further stimulating bone formation in this patient? (A) Cholecalciferol (B) Ergocalciferol (C) Furosemide (D) Tamoxifen (E) Teriparatide

Cholecalciferol and ergocalciferol are precursors of vitamin D. Furosemide is a loop diuretic, which causes increased calcium excretion; tamoxifen is a selective estrogen receptor modulator (SERM) but is less selective for bone compared with raloxifene. Teriparatide increases bone formation and bone resorption; during the first 6 months, it causes a net gain in bone. Teriparatide should not be used longer than 2 years due to risk of osteosarcoma. The answer is E.

Mr Green has just been diagnosed with dysautonomia (chronic idiopathic autonomic insufficiency). You are considering different therapies for his disease. Pyridostigmine and neostigmine may cause which one of the following in this patient? (A) Bronchodilation (B) Cycloplegia (C) Diarrhea (D) Irreversible inhibition of acetylcholinesterase (E) Reduced gastric acid secretion

Cholinesterase inhibition is typically associated with increased (never decreased) bowel activity. (Fortunately, many patients become tolerant to this effect.) The answer is C.

Which of the following is the primary second-messenger process in the contraction of the ciliary muscle when focusing on near objects? (A) cAMP (cyclic adenosine monophosphate) (B) DAG (diacylglycerol) (C) Depolarizing influx of sodium ions via a channel (D) IP 3 (inositol 1,4,5-trisphosphate) (E) NO (nitric oxide)

Cholinomimetics cause smooth muscle contraction mainly through an action on M 3 Gq -coupled receptors resulting in the release of intracellular calcium. This release is triggered by an increase in IP 3 acting on IP 3 receptors in the endoplasmic reticulum. The answer is D.

A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL cholesterol, VLDL cholesterol, and triglycerides are normal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. Consumption of alcohol is associated with which of the following changes in serum lipid concentrations? (A) Decreased chylomicrons (B) Decreased HDL cholesterol (C) Decreased VLDL cholesterol (D) Increased LDL cholesterol (E) Increased triglyceride

Chronic ethanol ingestion can increase serum concentrations of VLDL and triglycerides. This is one of the factors that places patients with alcoholism at risk of pancreatitis. Chronic ethanol ingestion also has the possibly beneficial effect of raising, not decreasing, serum HDL concentrations. The answer is E.

A 19-year-old college student has well-controlled asthma but on reporting to the college health clinic, complains of a sore throat. On examination, he has typical signs of thrush, a fungal infection with Candida albicans. The asthma controller medication most likely to be associated with Candida infection is: (A) Albuterol by aerosol (B) Beclomethasone by aerosol (C) Ipratropium by inhaler (D) Prednisone by mouth (E) Theophylline in long-acting oral form

Chronic oral corticosteroids, eg, prednisone, have important toxicities (see Chapter 39). However, they are unlikely to cause oral fungal infection. In contrast, topical, inhaled steroids, eg, beclomethasone, are associated with this adverse effect because the inhalation route results in high concentrations in the oropharynx. The answer is B.

The regular ingestion of moderate or heavy amounts of alcohol predisposes to hepatic damage after overdose of acetaminophen because chronic ethanol ingestion (A) Blocks acetaminophen metabolism (B) Causes thiamine deficiency (C) Displaces acetaminophen from plasma proteins (D) Induces hepatic drug-metabolizing enzymes (E) Inhibits renal clearance of acetaminophen

Chronic use of ethanol induces CYP2E1, an isozyme that converts acetaminophen to a cytotoxic metabolite. This appears to be the cause of the increased susceptibility to acetaminophen-induced hepatotoxicity found in individuals who regularly ingest alcohol. The answer is D.

Couples who are attempting to conceive a child should avoid chronic use of which of the following? (A) Echinacea (B) Ephedra (C) Ginkgo (D) Ginseng (E) Melatonin

Chronic use of melatonin appears to suppress LH secretion in women and to decrease sperm quality in men. The answer is E.

A 63-year-old man is undergoing radiation treatment as an outpatient for metastatic bone cancer. His pain has been treated with a fixed combination of oxycodone plus acetaminophen taken orally. Despite increasing doses of the analgesic combination, the pain is getting worse. It is possible that this patient will have to increase the dose of the analgesic as his condition progresses as a result of developing tolerance. However, tolerance will not develop to a significant extent with respect to (A) Biliary smooth muscle (B) Emesis (C) Pupillary constriction (D) Sedation (E) Urinary retention

Chronic use of strong opioid analgesics leads to the development of tolerance to their analgesic, euphoric, and sedative actions. Tolerance also develops to their emetic effects and to effects on some smooth muscle, including the biliary and the urethral sphincter muscles. However, tolerance does not develop significantly to the constipating effects or the miotic actions of the opioid analgesics. The answer is C.

A significant number of patients started on ACE inhibitor therapy for hypertension are intolerant and must be switched to a different class of drug. What is the most common manifestation of this intolerance? (A) Angioedema (B) Glaucoma (C) Headache (D) Incessant cough (E) Ventricular arrhythmias

Chronic, intolerable cough is an important adverse effect of captopril and other ACE inhibitors. It may be associated with increased bradykinin levels because ARBs are not as frequently associated with cough. The ACE inhibitors are very commonly used in hypertensive diabetic patients because of their proven benefits in reducing diabetic renal damage. The ACE inhibitors are not associated with glaucoma; angioedema is not as common as cough; and headache and arrhythmias are rare. The answer is D.

A 67-year-old man with chronic kidney disease was found to have an elevated serum PTH concentration and a low serum concentration of 25-hydroxyvitamin D. He was successfully treated with ergocalciferol. Unfortunately, his kidney disease progressed so that he required dialysis and his serum PTH concentration became markedly elevated. In the treatment of patients like this with secondary hyperparathyroidism due to chronic kidney disease, cinacalcet is an alternative to vitamin D-based drugs. Cinacalcet lowers PTH by which of the following mechanisms? (A) Activating a steroid receptor that inhibits expression of the PTH gene (B) Activating the calcium-sensing receptor in parathyroid cells (C) Activating transporters in the GI tract that are involved in calcium absorption (D) Inducing the liver enzyme that converts vitamin D 3 to 25-hydroxyvitamin D3 (E) Inhibiting the farnesyl pyrophosphate synthase found in osteoclasts

Cinacalcet is a member of a novel class of drugs that activate the calcium-sensing receptor in parathyroid cells. When this receptor is activated by cinacalcet or free ionized calcium, it activates a signaling pathway that suppresses PTH synthesis and release. The answer is B.

Which statement about ciprofloxacin is accurate? (A) Antagonism occurs if used with dihydrofolate reductase inhibitors (B) Ciprofloxacin is active against MRSA strains of staphylococci (C) Most "first-time" urinary tract infections are resistant to ciprofloxacin (D) Organisms that commonly cause ear infections are highly resistant (E) Tendinitis may occur during treatment

Ciprofloxacin is commonly used for the treatment of urinary tract infections and is active against most strains of common causative agents of otitis media, including H influenzae and pneumococci. However, up to 50% of strains of MRSA are now resistant to ciprofloxacin. No clinical antagonism has been reported between fluoroquinolones and inhibitors of folic acid synthesis. Fluoroquinolones are not recommended for use in pregnancy or for children less than 10 years of age because they may damage growing cartilage. Tendonitis and tendon rupture are adverse effects of the fluoroquinolones. The answer is E.

Clarithromycin and erythromycin have very similar spectra of antimicrobial activity. The major advantage of clarithromycin is that it (A) Does not inhibit hepatic drug-metabolizing enzymes (B) Eradicates mycoplasmal infections in a single dose (C) Has greater activity against H pylori (D) Is active against methicillin-resistant strains of staphylococci (E) Is active against strains of streptococci that are resistant to erythromycin

Clarithromycin can be administered less frequently than erythromycin, but it is not effective in single doses against susceptible organisms. Organisms resistant to erythromycin, including pneumococci and methicillin-resistant staphylococci, are also resistant to other macrolides. Drug interactions have occurred with clarithromycin through its ability to inhibit cytochrome P450. Clarithromycin is more active than erythromycin against M avium complex, T gondii, and H pylori. The answer is C.

Which drug increases the hepatic metabolism of other drugs? (A) Clarithromycin (B) Erythromycin (C) Ketoconazole (D) Rifampin (E) Ritonavir

Clarithromycin, erythromycin, ketoconazole, and ritonavir inhibit the hepatic metabolism of various drugs. Rifampin, an inducer of liver microsomal drug-metabolizing enzymes can increase the metabolism of other drugs. The answer is D.

Which statement concerning the use of lithium in the treatment of bipolar affective disorder is most accurate? (A) Ingestion of foods with high salt content enhances the toxicity of lithium (B) Lithium usually alleviates the manic phase of bipolar disorder within 12 h (C) Lithium dosage may need to be decreased in patients taking thiazides (D) Since lithium does not cross the placental barrier, it is safe in pregnancy (E) The elimination rate of lithium is equivalent to that of creatinine

Clinical effects of lithium are slow in onset and may not be apparent before 1 or 2 weeks of daily treatment. High urinary levels of sodium inhibit renal tubular reabsorption of lithium, thus decreasing its plasma levels. Lithium clearance is decreased by distal tubule diuretics (eg, thiazides) because natriuresis stimulates a reflex increase in the proximal tubule reabsorption of both lithium and sodium. Any drug that can cross the blood-brain barrier can cross the placental barrier! Teratogenic risk is low, but use of lithium during pregnancy may contribute to low Apgar score in the neonate. The answer is C.

Which of the following drugs is most likely to be of value in obsessive-compulsive disorders? (A) Amitriptyline (B) Bupropion (C) Clomipramine (D) Trazodone (E) Venlafaxine

Clomipramine, a tricyclic agent, is a more selective inhibitor of 5-HT reuptake than other drugs in the tricyclic group. This activity appears to be important in the treatment of obsessive-compulsive disorder. However, the SSRIs have now become the drugs of choice for this disorder because they are safer in overdose than tricyclics. The answer is C.

Which drug used in the maintenance treatment of patients with tonic-clonic or partial seizure states increases the hepatic metabolism of many drugs including both phenytoin and warfarin? (A) Buspirone (B) Clonazepam (C) Eszopiclone (D) Phenobarbital (E) Triazolam

Clonazepam and phenobarbital are both used in seizure disorders. Chronic administration of phenobarbital (but not clonazepam) increases the activity of hepatic drug-metabolizing enzymes, including several cytochrome P450 isozymes. This can increase the rate of metabolism of drugs administered concomitantly, resulting in decreases in the intensity and duration of their effects. The answer is D.

A 55-year-old lawyer is brought to the emergency department 2 h after the onset of severe chest pain during a stressful meeting. He has a history of poorly controlled mild hypertension and elevated blood cholesterol but does not smoke. ECG changes (ST elevation) and cardiac enzymes confirm the diagnosis of myocardial infarction. The decision is made to attempt to open his occluded artery. If this patient undergoes a percutaneous coronary angiography procedure and placement of a stent in a coronary blood vessel, he will need to be on dual antiplatelet therapy, eg, aspirin and clopidogrel for at least a year. Which of the following most accurately describes the mechanism of action of clopidogrel? (A) Clopidogrel directly binds to the platelet ADP receptors (B) Clopidogrel irreversibly inhibits cyclooxygenase (C) Clopidogrel facilitates the action of antithrombin III (D) The active metabolite of clopidogrel binds to and inhibits the platelet ADP receptors (E) The active metabolite of clopidogrel binds to and inhibits the platelet glycoprotein IIb/IIIa receptors

Clopidogrel is a prodrug that is activated by CYP2C9 and CYP2C19. It irreversibly binds to the ADP receptor on the surface of platelets that serves as a key role in platelet aggregation. Aspirin and clopidogrel help prevent platelet-induced occlusion of coronary stents. The answer is D.

A 59-year-old man with acute coronary syndrome is admitted to the hospital for emergency percutaneous insertion of a coronary stent. Which of the following drugs might cause unexpected results based on the patient's CYP2C19 genotype? (A) Clopidogrel (B) Codeine (C) Prasugrel (D) Ticagrelor (E) Warfarin

Clopidogrel is a prodrug that must be metabolized to an active platelet-inhibiting metabolite by CYP2C19. Poor metabolizers achieve inadequate platelet inhibition, and EMs and UMs may have excess effect and bleed. Prasugrel and ticagrelor do not require P450 activation and are not subject to this risk. The answer is A.

A 10-year-old American girl presented to the emergency department with fever, chills, lethargy, and splenomegaly. She had recently returned from Nigeria, where she had spent 3 weeks with her grandparents. She had previously received all standard childhood immunizations but no prophylactic travel medications because her parents had returned to Nigeria several times previously without any medical problems. Laboratory examination reveals low hematocrit and platelet count and elevated creatinine. Blood smear reveals parasites in the erythrocytes and a diagnosis of falciparum malaria is made. This patient should immediately receive (A) Artemether plus lumefantrine (Coartem) (B) Artesunate (C) Pentamidine (D) Primaquine (E) Stibogluconate

Coartem is an oral combination drug not suitable for treatment of acute malaria. Artesunate is a parenteral artemisinin. Pentamidine is used for pneumocystis pneumonia. Primaquine is a drug of choice for eradication of P vivax. Stibogluconate is used for leishmaniasis. The answer is B.

You are on your way to take an examination and you suddenly get an attack of diarrhea. If you stop at a nearby drugstore for an over-the-counter opioid with antidiarrheal action, you will be asking for (A) Codeine (B) Dextromethorphan (C) Diphenoxylate (D) Loperamide (E) Nalbuphine

Codeine and nalbuphine could decrease gastrointestinal peristalsis, but not without marked side effects (and a prescription). Dextromethorphan is a cough suppressant. The other 2 drugs listed are opioids with antidiarrheal actions. Diphenoxylate is not available over the counter because it is a constituent of a proprietary combination that includes atropine sulfate (Lomotil). The answer is D.

Genetic polymorphisms in certain hepatic enzymes involved in drug metabolism are established to be responsible for variations in analgesic response to (A) Buprenorphine (B) Codeine (C) Fentanyl (D) Methadone (E) Tramadol

Codeine, hydrocodone, and oxycodone are metabolized by the cytochrome P450 isoform CYP2D6, and variations in analgesic response to these drugs have been attributed to genotypic polymorphisms in this isozyme. In the case of codeine, this may be especially important since the drug is demethylated by CYP2D6 to form the active metabolite, morphine (see Chapter 5). An ultra-rapid metabolizer of codeine given a normal dose may suffer symptoms of severe opioid overdose. The answer is B.

A patient with AIDS and a CD4 cell count of 100/µL has persistent fever and weight loss associated with invasive pulmonary disease due to M avium complex (MAC). Optimal management of this patient is to (A) Choose an antibiotic based on drug susceptibility of the cultured organism (B) Initiate a two-drug regimen of INH and pyrazinamide (C) Prescribe rifabutin because it prevents the development of MAC bacteremia (D) Start treatment with the combination of azithromycin, ethambutol, and rifabutin (E) Treat with trimethoprim-sulfamethoxazole

Combinations of antibiotics are essential for suppression of disease caused by M avium complex in the AIDS patient, and treatment should be started before culture results are available. Although rifabutin is prophylactic against MAC bacteremia when it is used as sole therapy in active disease, resistant strains of the organism emerge rapidly. MAC is much less susceptible than M tuberculosis to conventional antimycobacterial drugs. Currently, the optimum regimen consists of azithromycin (or clarithromycin) with ethambutol and rifabutin. The answer is D.

A hospitalized AIDS patient is receiving a roviral drugs but no antimicrobial prophylaxis. He develops sepsis with fever, suspected to be caused by a Gram-negative bacillus. A combination of drugs might be given to this patient to provide coverage against multiple organisms or to obtain a synergistic action. Examples of antimicrobial drug synergism established at the clinical level include the treatment of (A) Cryptococcal meningitis with amphotericin B and flucytosine (B) Coliform infections with sulfamethoxazole and trimethoprim (C) Enterococcal infections with rifampin and vancomycin (D) Pseudomonal infections with carbenicillin and gentamicin (E) All of the above

Combinations of antimicrobial drugs are not always synergistic and in some cases may even be antagonistic. However, all the choices listed are established examples of situations in which antimicrobial combinations have greater clinical efficacy than individual drugs. The answer is E.

With chronic use in seizure states, the adverse effects of this drug include coarsening of facial features, hirsutism, and gingival hyperplasia. (A) Carbamazepine (B) Ethosuximide (C) Phenytoin (D) Tiagabine (E) Zonisamide

Common adverse effects of phenytoin include nystagmus, diplopia, and ataxia. With chronic use, abnormalities of vitamin D metabolism, coarsening of facial features, gingival overgrowth, and hirsutism may also occur. A major adverse effect of carbamazepine, tiagabine, and zonisamide is CNS depression. The answer is C.

A hypertensive patient has been using nifedipine for some time without untoward effects. If he experiences a rapidly developing enhancement of the antihypertensive effect of the drug, it is most likely due to which of the following? (A) Concomitant use of antacids (B) Foods containing tyramine (C) Furanocoumarins in grapefruit juice (D) Induction of drug metabolism (E) Over-the-counter decongestants

Compounds in grapefruit juice can increase the rate and extent of bioavailability of several dihydropyridine calcium channel blockers, including felodipine and nifedipine. This interaction may be due to inhibition of the metabolism of the dihydropyridines by intestinal wall CYP3A4 or inhibition of the P-glycoprotein transporter in the same location. The answer is C.

In 2003, a study published in the Annals of Internal Medicine found that this botanical substance accounted for more than 60% of adverse events associated with dietary supplements used in the United States. The "herbal" in question, which is used to aid weight loss and promote sports performance, is which of the following? (A) Echinacea (B) Ephedra (C) Ginkgo (D) Ginseng (E) Saw palmetto

Concern about the risks of using products containing e dra during heavy workouts or in diet programs that stress the cardiovascular system has led to a ban on such nutritional supplements in the United States. The answer is B.

An emergency department patient with severe pain thought to be of gastrointestinal origin received 80 mg of meperidine. She subsequently developed a severe reaction characterized by tachycardia, hypertension, hyperpyrexia, and seizures. Questioning revealed that the patient had been taking a drug for a psychiatric condition. Which drug is most likely to be responsible for this untoward interaction with meperidine? (A) Alprazolam (B) Bupropion (C) Lithium (D) Phenelzine (E) Mirtazapine

Concomitant administration of meperidine and monoamine oxidase inhibitors such as isocarboxazid or phenelzine has resulted in life-threatening hyperpyrexic reactions that may culminate in seizures or coma. Such reactions have occurred even when the MAO inhibitor was administered more than a week after a patient had been treated with meperidine. Note that concomitant use of selective serotonin reuptake inhibitors and meperidine has resulted in the serotonin syndrome, another life-threatening drug interaction (see Chapter 16). The answer is D.

A 30-year-old male patient is on drug therapy for a psychiatric problem. He complains that he feels "flat" and that he gets confused at times. He has been gaining weight and has lost his sex drive. As he moves his hands, you notice a slight tremor. He tells you that since he has been on medication he is always thirsty and frequently has to urinate. The drug he is most likely to be taking is (A) Carbamazepine (B) Clozapine (C) Lithium (D) Risperidone (E) Valproic acid

Confusion, mood changes, decreased sexual interest, and weight gain are symptoms that may be unrelated to drug administration. On the other hand, psychiatric drugs are often responsible for such symptoms. Tremor and symptoms of nephrogenic diabetes insipidus are characteristic adverse effects of lithium that may occur at blood levels within the therapeutic range. The answer is C.

A 52-year-old postmenopausal patient has evidence of low bone mineral density. She and her physician are considering therapy with raloxifene or a combination of conjugated estrogens and medroxyprogesterone acetate. Which of the following patient characteristics is most likely to lead them to select raloxifene? (A) Previous hysterectomy (B) Recurrent vaginitis (C) Rheumatoid arthritis (D) Strong family history of breast cancer (E) Troublesome hot flushes

Conjugated estrogens and raloxifene both improve bone mineral density and protect against osteoporosis. The 2 advantages of raloxifene over full estrogen receptor agonists are that raloxifene has antagonist effects in breast tissue and lacks an agonistic effect in endometrium. If a patient's uterus was removed by surgery, the difference in the endometrial effect is moot. In patients with a strong family history of breast cancer, raloxifene may be a better choice than a full estrogen agonist because it will not further increase the woman's risk of breast cancer and may even lower her risk. The answer is D.

Which of the following chemicals does not satisfy the criteria for a neurotransmitter role in the CNS? (A) Acetylcholine (B) Cyclic AMP (C) Dopamine (D) Glycine (E) Substance P

Cyclic AMP (cAMP) is a mediator in many receptor mechanisms in the CNS, including those for acetylcholine (M2 ), and norepinephrine (β1 ). However, the characteristics of cAMP do not satisfy the criteria for a neurotransmitter role (see A. Criteria for Transmitter Status). The answer is B

Although sirolimus and cyclosporine have similar immunosuppressant effects, their toxicity profiles differ. Which of the following toxicities is more likely to be associated with sirolimus than with cyclosporine? (A) An anaphylactic reaction (B) Hypertension (C) Osteoporosis (D) Renal insufficiency (E) Thrombocytopenia

Cyclosporine and tacrolimus both are associated with renal toxicity and hypertension. In contrast, sirolimus appears to spare the kidney and instead is more likely to cause gastrointestinal disturbance, hypertriglyceridemia, and myelosuppression, especially in the form of thrombocytopenia. The answer is E.

HC is a 56-year-old man who underwent a successful lung transplant. Upon discharge he reviewed his drug regimen with the transplant team. It included cyclosporine. Which of the following most accurately describes the immunosuppressant action of cyclosporine? (A) Activation of NK cells (B) Blockade of tissue responses to inflammatory mediators (C) Increased catabolism of IgG antibodies (D) Inhibition of the gene transcription of interleukins (E) Interference with MHC II-peptide activation of T cells

Cyclosporine inhibits calcineurin, a serine phosphatase that is needed for activation of T-cell-specific transcription factors such as NF-AT. Gene transcription of IL-2, IL-3, and interferon-γ is inhibited. The answer is D.

A 23-year-old pregnant woman is referred by her obstetrician for evaluation of anemia. She is in her fourth month of pregnancy and has no history of anemia; her grandfather had pernicious anemia. Her hemoglobin is 10 g/dL (normal, 12-16 g/dL). If this woman has macrocytic anemia, an increased serum concentration of transferrin, and a normal serum concentration of vitamin B12 , the most likely cause of her anemia is deficiency of which of the following? (A) Cobalamin (B) Erythropoietin (C) Folic acid (D) Intrinsic factor (E) Iron

Deficiencies of folic acid or vitamin B12 are the most common causes of megaloblastic anemia. If a patient with this type of anemia has a normal serum vitamin B 12 concentration, folate deficiency is the most likely cause of the anemia. The answer is C.

The megaloblastic anemia that results from vitamin B12 deficiency is due to inadequate supplies of which of the following? (A) Cobalamin (B) dTMP (C) Folic acid (D) Homocysteine (E) N5 -methyltetrahydrofolate

Deficiency of vitamin B 12(cobalamin) leads to a deficiency in tetrahydrofolate and subsequently a deficiency of the dTMP required for DNA synthesis. Homocysteine and N5 -methyltetrahydrofolate accumulate. The answer is B.

A 21-year-old woman from Southeast Asia has been staying with family members in the United States for the last 3 mo and is looking after her sister's preschool children during the day. Because she has difficulty with the English language, her sister escorts her to the emergency department of a local hospital. She tells the staff that her sister has been feeling very tired for the last month, has a poor appetite, and has lost weight. The patient has been feeling somewhat better lately except for a cough that produces a greenish sputum, sometimes specked with blood. With the exception of rales in the left upper lobe, the physical examination is unremarkable and she does not seem to be acutely ill. Laboratory values show a white count of 12,000/µL and a hematocrit of 33%. Chest x-ray film reveals an infiltrate in the left upper lobe with a possible cavity. A Gram-stained smear of the sputum shows mixed flora with no dominance. An acidfast stain reveals many thin rods of pinkish hue. A preliminary diagnosis is made of pulmonary tuberculosis. Sputum is sent to the laboratory for culture. At this point, the most appropriate course of action is to (A) Hospitalize the patient and start treatmen

Despite the fact that this patient does not appear to be acutely ill, she would in most cases be treated with 4 drugs that have activity against M tuberculosis. This is because organisms infecting patients from Southeast Asia are commonly INH-resistant, and coverage must be provided with 3 other antituberculosis drugs in addition to isoniazid. This patient should be hospitalized for several reasons, including potential difficulties with compliance regarding the drug regimen and the fact that young children are in the home where she is living. The answer is A.

Which drug has spasmolytic activity and could also be used in the management of seizures caused by overdose of a local anesthetic? (A) Baclofen (B) Cyclobenzaprine (C) Diazepam (D) Gabapentin (E) Tizanidine

Diazepam is both an effective antiseizure drug and a spasmolytic. The spasmolytic action of diazepam is thought to be exerted partly in the spinal cord because it reduces spasm of skeletal muscle in patients with cord transection. Cyclobenzaprine is used for acute local spasm and has no antiseizure activity. The answer is C.

Diethylstilbestrol (DES) should never be used in pregnant women because it is associated with which of the following? (A) Deep vein thrombosis (B) Feminization of the external genitalia of male offspring (C) Infertility and development of vaginal cancer in female offspring (D) Miscarriages (E) Virilization of the external genitalia of female offspring

Diethylstilbestrol (DES) is a nonsteroidal estrogen agonist. Several decades ago, misguided use of the drug in pregnant women appears to have resulted in fetal damage that predisposed female offspring to infertility and a rare form of vaginal cancer. For this reason, the drug should be avoided in pregnant women. Other estrogenic drugs do not appear to have these effects. Although estrogens do increase the risk of deep vein thrombosis, this is not the reason why DES should be avoided. The answer is C.

Which of the following is the best-documented mechanism of beneficial action of cardiac glycosides? (A) A decrease in calcium uptake by the sarcoplasmic reticulum (B) An increase in a late transmembrane sodium current (C) A modification of the actin molecule (D) An increase in systolic cytoplasmic calcium levels (E) A block of cardiac β adrenoceptors

Digitalis does not decrease calcium uptake by the systemic reticulum or increase sodium current; it does not modify actin. Cardiac adrenoceptors are not affected. The most accurate description of digitalis's mechanism in this list is that it increases systolic cytoplasmic calcium by inhibiting Na + /K + transport by the ATPase sodium pump and indirectly altering Na+/Ca 2+exchange. The answer is D.

A 52-year-old man (weight 70 kg) is brought to the hospital emergency department in a confused and delirious state. He has had an elevated temperature for more than 24 h, during which time he had complained of a severe headache and had suffered from nausea and vomiting. Lumbar puncture reveals an elevated opening pressure, and cerebrospinal fluid findings include elevated protein, decreased glucose, and increased neutrophils. Gram stain of a smear of cerebrospinal fluid reveals Gram-positive diplococci, and a preliminary diagnosis is made of purulent meningitis. The microbiology report informs you that for approximately 15% of S pneumoniae isolates in the community, the minimal inhibitory concentration for penicillin G is 20 mcg/mL. If this patient had been 82 years old and the Gram stain of the smear of cerebrospinal fluid had revealed Gram-positive rods resembling diphtheroids, the antibiotic regimen for empiric treatment would include (A) Ampicillin (B) Cefoxitin (C) Ceftriaxone (D) Fosfomycin (E) Vancomycin

Diphtheroid-like Gram-positive rods in the cerebrospinal fluid smear of an elderly patient are indicative of L monocytogenes. Listeria infections are more common in neonates, elderly patients, and those who have been treated with immunosuppressive agents. Cephalosporins do not cover listeria. (The mnemonic for the hole in their spectrum is "LAME": listeria, atypicals, MRSA, and enterococcus.) Treatment consists of ampicillin with or without an aminoglycoside such as gentamicin. Trimethoprim-sulfamethoxazole can also be used (see Chapter 46). The answer is A.

A patient develops severe thrombocytopenia in response to treatment with unfractionated heparin and still requires parenteral anticoagulation. The patient is most likely to be treated with which of the following? (A) Abciximab (B) Bivalirudin (C) Tirofiban (D) Plasminogen (E) Vitamin K1

Direct thrombin inhibitors such as bivalirudin and argatroban provide parenteral anticoagulation similar to that achieved with heparin, but the direct thrombin inhibitors do not induce formation of antiplatelet antibodies. The answer is B.

In a patient suffering from pseudomembranous colitis due to C difficile with established hypersensitivity to metronidazole the most likely drug to be of clinical value is (A) Amoxicillin (B) Chloramphenicol (C) Doxycycline (D) Levofloxacin (E) Vancomycin

Disturbances of gut flora occur commonly during treatment with antibiotics, and pseudomembranous colitis has been associated with the use of many agents including ampicillin and clindamycin. Vancomycin can be used in treatment of pseudomembranous colitis in patients with established hypersensitivity to metronidazole. The answer is E.

A 62-year-old man with advanced prostate cancer is admitted to the emergency department with mental obtundation. An electrolyte panel shows a serum calcium of 16.5 (normal 8.5-10.5 mg/dL). Which of the following therapies would be most useful in the management of severe hypercalcemia? (A) Acetazolamide plus saline infusion (B) Furosemide plus saline infusion (C) Hydrochlorothiazide plus saline infusion (D) Mannitol plus saline infusion (E) Spironolactone plus saline infusion

Diuretic therapy of hypercalcemia requires a reduction in calcium reabsorption in the thick ascending limb, an effect of loop diuretics. However, a loop diuretic alone would reduce blood volume around the remaining calcium so that serum calcium would not decrease appropriately. Therefore, a saline infusion should accompany the loop diuretic. The answer is B.

Abrupt withdrawal of antiseizure drugs can result in increases in seizure frequency and severity. Withdrawal is most easily accomplished if the patient is treated with (A) Carbamazepine (B) Clonazepam (C) Ethosuximide (D) Phenobarbital (E) Phenytoin

Dose tapering is an important principle in antiseizure drug withdrawal. As a rule, withdrawal from drugs used for absence seizures such as ethosuximide is easier than withdrawal from drugs used for partial and tonic-clonic seizures. Withdrawal is most difficult in patients who have been treated with barbiturates and benzodiazepines. The answer is C.

Which adverse effect occurs with the use of albendazole during intestinal nematode therapy? (A) Cholestatic jaundice (B) Corneal opacities (C) Hirsutism (D) Peripheral neuropathy (E) None of the above

Doses of albendazole required for intestinal nematode therapy are almost free of adverse effects even in the malnourished or debilitated patient. Gastrointestinal distress may occur in children with ascariasis who are heavily parasitized, together with a slight headache or dizziness. Avoid the drug in children younger than 2 years because of rare reports of seizures. The answer is E.

Two new synthetic drugs (X and Y) are to be studied for their cardiovascular effects. The drugs are given to three anesthetized animals while the blood pressure is recorded. The first animal has received no pretreatment (control), the second has received an effective dose of a long-acting ganglion blocker, and the third has received an effective dose of a long-acting muscarinic antagonist. Drug X caused a 50 mm Hg rise in mean blood pressure in the control animal, no blood pressure change in the ganglionblocked animal, and a 75 mm mean blood pressure rise in the atropine-pretreated animal. Drug X is probably a drug similar to (A) Acetylcholine (B) Atropine (C) Epinephrine (D) Hexamethonium (E) Nicotine

Drug X causes an increase in blood pressure that is blocked by a ganglion blocker but not by a muscarinic blocker. The pressor response is actually increased by pretreatment with atropine, a muscarinic blocker, suggesting that compensatory vagal discharge might have blunted the full response. This description fits a ganglion stimulant like nicotine but not epinephrine, since epinephrine's pressor effects are produced at α receptors, not in the ganglia. The answer is E.

A patient with AIDS has a CD4 count of 45/µL. He is being maintained on a 3-drug regimen of indinavir, didanosine, and zidovudine. For prophylaxis against opportunistic infections, he is also receiving cidofovir, fluconazole, rifabutin, and trimethoprim-sulfamethoxazole. The dose of indinavir in this patient may need to be increased above normal. This is because (A) Fluconazole slows gastric emptying (B) Ganciclovir increases the renal clearance of indinavir (C) Gastric absorption is inhibited by fluconazole (D) Rifabutin increases hepatic drug metabolism (E) Sulfamethoxazole increases indinavir plasma protein binding

Drug interactions can be severe in the immunocompromised patient because many of the drugs administered can influence the pharmacokinetic properties of other drugs. Rifabutin, like rifampin, acts as an inducer of several isoforms of hepatic cytochrome P450. This action can result in an increased clearance of other drugs, including indinavir. The answer is D.

A 73-year-old man with a history of a recent change in his treatment for moderately severe hypertension is brought to the emergency department because of a fall at home. Which of the following drug groups is most likely to cause postural hypotension and thus an increased risk of falls? (A) ACE inhibitors (B) Alpha1 -selective receptor blockers (C) Arteriolar dilators (D) Beta1 -selective receptor blockers (E) Calcium channel blockers

Drug-induced postural (orthostatic) hypotension is usually due to venous pooling or excessive diuresis and inadequate blood volume. Venous pooling is normally prevented by α-receptor activation in vascular smooth muscle; thus, orthostatic hypotension may be caused or exacerbated by α1 blockers, eg, prazosin. The answer is B.

Which of the following statements about animal testing of potential new therapeutic agents is most correct? (A) Extends at least 3 years to discover late toxicities (B) Requires at least 1 primate species (eg, rhesus monkey) (C) Requires the submission of histopathologic slides and specimens to the FDA for evaluation by government scientists (D) Has good predictability for drug allergy-type reactions (E) May be abbreviated in the case of some very toxic agents used in cancer

Drugs proposed for short-term use may not require long-term chronic testing. For some drugs, no primates are used; for other agents, only 1 species is used. The data from the tests, not the evidence itself, must be submitted to the FDA. Prediction of human drug allergy from animal testing is useful but not definitive (see answer 12). The answer is E.

In a phase 1 clinical trial, "Novexum," a new drug, was a istered intravenously to 25 volunteers, and blood samples were taken for several hours. Several inactive metabolites were found as well as declining concentrations of Novexum. A graph was prepared as shown below, with the Novexum plasma levels plotted on a logarithmic ordinate and time on a linear abscissa. It was concluded that the drug has first-order kinetics. From this graph, what is the best estimate of the elimination half-life of Novexum? (A) 0.5 h (B) 1 h (C) 3 h (D) 4 h (E) 7 h

Drugs with first-order kinetics have constant half-lives, and when the log of the concentration in a body compartment is plotted versus time, a straight line results. The half-life is defined as the time required for the concentration to decrease by 50%. As shown in the graph, the concentration of Novexum decreased from 16 units at 1 h to 8 units at 4 h and 4 units at 7 h; therefore, the half-life is 7 h minus 4 h or 3 h. The answer is C.

A 58-year-old woman with chronic hypertension and diabetes mellitus was recently admitted to the hospital for congestive heart failure and new onset atrial fibrillation. She is now seeing you after discharge and, though feeling better, is still in atrial fibrillation. An echocardiogram shows an ejection fraction of 40%; there are no valvular abnormalities. An ECG reveals only atrial fibrillation. You calculate her risk using the CHADS (2) system and the score indicates that she requires anticoagulation rather than antiplatelet therapy. She tells you that her main reason for not wanting oral a coagulation is that she does not want to come to clinic for frequent blood draws. You agree on an oral alternative and start her on apixaban. You counsel her extensively on the importance of taking the medication each day, as suddenly stopping can lead to (A) Anaphylaxis (B) Excess bleeding (C) Increase in INR (D) Stroke (E) Thrombocytopenia

Due to the shorter half-life of the oral factor X and thrombin inhibitors, the anticoagulant status of the patient changes rapidly. Sudden cessation of short-acting oral anticoagulants can lead to stroke. Excess bleeding is associated with taking any of the anticoagulants not with stopping them. An increase in INR reflects increased anticoagulation by warfarin. Thrombocytopenia is a risk associated with heparin. The answer is D.

A 36-year-old woman recently treated for leukemia is admitted to the hospital with malaise, chills, and high fever. A blood culture reveals the presence of Gram-negative bacilli. The initial diagnosis is bacteremia, and parenteral antibiotics are indicated. The records of the patient reveal that she had a severe urticarial rash, hypotension, and respiratory difficulty after oral penicillin V about 6 mo ago. The most appropriate drug regimen for empiric treatment is (A) Aztreonam (B) Ceftriaxone (C) Meropenem (D) Oxacillin (E) Ticarcillin plus clavulanic acid

Each of the drugs listed has activity against some Gramnegative bacilli. All penicillins should be avoided in patients with a history of allergic reactions to any individual penicillin drug. Cephalosporins should also be avoided in patients who have had anaphylaxis or other severe hypersensitivity reactions after use of a penicillin. There is partial cross-reactivity between penicillins and the carbapenems such as imipenem and meropenem, but no cross-reactivity between the penicillins and aztreonam. The answer is A.

All the following agents have been used in drug regimens for the treatment of breast carcinoma. Which one has specific activity in a subset of female breast cancers? (A) Cyclophosphamide (B) Doxorubicin (C) Fluoxymesterone (D) Methotrexate (E) Trastuzumab

Each of the drugs listed has been used in drug regimens for breast cancer, but only trastuzumab has specificity in its actions. The drug is a monoclonal antibody to a surface protein in breast cancer cells that overexpress the HER-2 protein. Consequently, trastuzumab has value in a specific subset of breast cancers. The answer is E.

A small child is brought to a hospital emergency department suffering from severe gastrointestinal distress and abdominal colic. If this patient has severe acute lead poisoning with signs and symptoms of encephalopathy, treatment should be instituted immediately with (A) Acetylcysteine (B) Deferoxamine (C) EDTA (D) Penicillamine (E) Succimer

Encephalopathy in severe lead poisoning is a medical e gency. Of the drugs listed, intravenous EDTA is the most effective chelating agent. Oral succimer is used in children with mild to moderate lead poisoning and may be initiated 4-5 d after the parenteral use of EDTA or dimercaprol in severe poisoning. The answer is C.

Botulinum toxin is a large protein molecule. Its action on cholinergic transmission depends on an intracellular action within nerve endings. Which one of the following processes is best suited for permeation of very large protein molecules into cells? (A) Aqueous diffusion (B) Endocytosis (C) First-pass effect (D) Lipid diffusion (E) Special carrier transport

Endocytosis is an important mechanism for transport of very large molecules across membranes. Aqueous diffusion is not involved in transport across the lipid barrier of cell membranes. Lipid diffusion and special carrier transport are common for smaller molecules. The first-pass effect has nothing to do with the mechanisms of permeation; rather, it denotes drug metabolism or excretion before absorption into the systemic circulation. The answer is B.

A 67-year-old woman presents with pain in her left thigh muscle. Duplex ultrasonography indicates the presence of deep vein thrombosis (DVT) in the affected limb. The decision was made to treat this woman with enoxaparin. Relative to unfractionated heparin, enoxaparin (A) Can be used without monitoring the patient's aPTT (B) Has a shorter duration of action (C) Is less likely to have a teratogenic effect (D) Is more likely to be given intravenously (E) Is more likely to cause thrombosis and thrombocytopenia

Enoxaparin is an LMW heparin. LMW heparins have a longer half-life than standard heparin and a more consistent relationship between dose and therapeutic effect. Enoxaparin is given subcutaneously, not intravenously. It is less, not more, likely to cause thrombosis and thrombocytopenia. Neither LMW heparins nor standard heparin are teratogenic. The aPTT is not useful for monitoring the effects of LMW heparins. The answer is A.

A vasoconstrictor added to a solution of lidocaine for a peripheral nerve block will (A) Decrease the risk of a seizure (B) Increase the duration of anesthetic action of the local anesthetic (C) Both A and B (D) Neither A nor B

Epinephrine increases the duration of a nerve block when it is administered with short- and medium-duration local anesthetics. As a result of the vasoconstriction that prolongs the duration of this block, less local anesthetic is required, so the risk of toxicity (eg, a seizure) is reduced. The answer is C.

A 40-year-old male CEO came to the emergency department with severe burning chest pain radiating into his neck. His electrocardiogram was normal and test for troponin was negative. A diagnosis of GERD was made and he was sent home with a prescription for a drug that inhibits stomach acid. Which of the following is a drug that irreversibly inhibits the H+ /K + ATPase in the parietal cells? (A) Cimetidine (B) Diphenoxylate (C) Esomeprazole (D) Metoclopramide (E) Sulfasalazine

Esomeprazole, the (S) isomer of omeprazole, is a prodrug converting spontaneously in the parietal cell canaliculus to a sulfonamide that irreversibly inactivates the proton pump. The answer is C.

A patient is brought to the emergency department having taken an overdose (unknown quantity) of a sustained-release preparation of theophylline by oral administration 2 h previously. He has marked gastrointestinal distress with vomiting, is agitated, and exhibits hyperreflexia and hypotension. The plasma level of theophylline measured immediately upon hospitalization was 80 mg/L. If the oral bioavailability of theophylline is 98%, the clearance is 50 mL/min, volume of distribution is 35 L, and the elimination half-life is 7.5 h, the amount ingested must have been at least (A) 0.3 g (B) 0.6 g (C) 1.6 g (D) 2.8 g (E) 8.0 g

Estimations of the quantity of a drug or toxin ingested may be of value in the management of the poisoned patient. Applying toxicokinetic principles, a rough estimate of ingested dose of theophylline could be made by multiplying the peak plasma level of the drug (80 mg/L) by its volume of distribution (35 L) to give a value of 2800 mg, or 2.8 g. Because only about one-fourth of a half-life has passed since ingestion, the amount eliminated since that time will be rather small. The answer is D.

A patient with heart failure has accidentally taken an overdose of digoxin. The blood concentration of the drug is 8 times the threshold for toxicity. Pharmacokinetic parameters for digoxin in this patient include a clearance of 7 L/h and an elimination half-life of 56 h. If no procedures are instituted to decontaminate this patient, the time taken to reach a safe level of digoxin will be approximately (A) 3.5 d (B) 7 d (C) 14 d (D) 28 d (E) 56 d

Estimations of the time period required for drug or toxin elimination may be of value in the management of the poisoned patient. If no procedures were used to hasten the elimination of digoxin in this patient, the time taken to reach a safe plasma level of the drug (12.5% of the measured level) is 3 half-lives, or approximately 7 d. The answer is B.

A 23-year-old woman desires a combined oral contraceptive for pregnancy protection. Which of the following patient factors would lead a health professional to recommend an alternative form of contraception? (A) Evidence of hirsutism (B) History of gastroesophageal reflux disease and is currently taking omeprazole (C) History of pelvic inflammatory disease (D) History of migraine headache that is well controlled by sumatriptan (E) She plans to use this contraceptive for about 1 year and will then attempt to become pregnant

Estrogen-containing hormonal contraceptives increase the risk of episodes of migraine headache. The answer is D.

A 54-year-old woman presented with signs and symptoms consistent with an early stage of rheumatoid arthritis. The decision was made to initiate NSAID therapy. Although the patient's disease was adequately controlled with an NSAID and methotrexate for some time, her symptoms began to worsen and radiologic studies of her hands indicated progressive destruction in the joints of several fingers. Treatment with another second-line agent for rheumatoid arthritis was considered. Which of the following is a parenterally administered DMARD whose mechanism of anti-inflammatory action is antagonism of tumor necrosis factor? (A) Cyclosporine (B) Etanercept (C) Penicillamine (D) Phenylbutazone (E) Sulfasalazine

Etanercept is a recombinant protein that binds to tumor necrosis factor and prevents its inflammatory effects. The answer is B

Which of the following drugs has higher first-pass metabolism in men than in women? (A) Cimetidine (B) Ethanol (C) Ketoconazole (D) Procainamide (E) Quinidine (F) Ritonavir (G) Succinylcholine (H) Verapamil

Ethanol is subject to metabolism in the stomach as well as in the liver. Independent of body weight and other factors, men have greater gastric ethanol metabolism and thus a lower ethanol bioavailability than women. The answer is B.

A 20-year-old woman suffers from absence seizures. Which of the following statements about her proposed drug management is least accurate? (A) Ethosuximide and valproic acid are preferred drugs (B) Gastrointestinal side effects are common with ethosuximide (C) If given valproic acid, patient should be examined every 2 or 3 months for deep tendon reflex activity (D) The use of valproic acid in pregnancy may cause congenital malformations (E) Weight gain is common in patients on valproic acid

Ethosuximide and valproic acid are preferred drugs in absence seizures because they cause minimal sedation. However, valproic acid causes gastrointestinal distress and weight gain and is potentially hepatotoxic. In addition, its use in pregnancy has been associated with teratogenicity (neural tube defects). Peripheral neuropathy, including diminished deep tendon reflexes in the lower extremities, occurs with the chronic use of phenytoin, not valproic acid. The answer is C.

Mr Jones has zero kidney function and is undergoing h dialysis 3 days per week while awaiting a kidney transplant. He takes metformin for type 2 diabetes mellitus and was previously stabilized (while his kidney function was adequate) at a dosage of 500 mg twice daily, given orally. The plasma concentration at this dosage with normal kidney function was found to be 1.4 mg/L. He has had 6 dialysis procedures and metformin toxicity is suspected. A blood sample now shows a metformin concentration of 4.2 mg/L. What was Mr Jones' clearance of metformin while his kidney function was normal? (A) 238 L/d (B) 29.8 L/h (C) 3 L/d (D) 238 L/h (E) 30 L/min

Examination questions often provide more information than is needed—to test the student's ability to classify and organize data. In question 1, the data provided for Mr Jones on dialysis is irrelevant, even though choice A, 238 L/d, is the correct clearance while on dialysis. By definition, clearance is calculated by dividing the rate of elimination by the plasma concentration: Rate in = rate out (elimination rate) at steady state (ss) CL = rate in/Cp(ss) 1000 mg/24 h / 1.4 mg/L= CL CL = 29.8 L/h The answer is B.

A 56-year-old woman with systemic lupus erythematosus had been maintained on a moderate daily dose of prednisone for 9 months. Her disease has finally gone into remission and she now wishes to gradually taper and then discontinue the prednisone. Gradual tapering of a glucocorticoid is required for recovery of which of the following? (A) Depressed release of insulin from pancreatic B cells (B) Hematopoiesis in the bone marrow (C) Normal osteoblast function (D) The control by vasopressin of water excretion (E) The hypothalamic-pituitary-adrenal system

Exogenous glucocorticoids act at the hypothalamus and pituitary to suppress the production of CRH and ACTH. As a result, adrenal production of endogenous corticosteroids is suppressed. On discontinuance, the recovery of normal hypothalamic-pituitary-adrenal function occurs slowly. Glucocorticoid doses must be tapered slowly, over several months, to prevent adrenal insufficiency. The answer is E.

Which drug has a biochemical effect that most closely resembles the proposed mechanism of action of the psychoactive constituent(s) of St. John's wort? (A) Alprazolam (B) Fluoxetine (C) Levodopa (D) Methylphenidate (E) Morphine

Extracts of the flowers of St. John's wort contain chemicals with possible antidepressant activity. In vitro studies have shown that these chemicals interfere with the neuronal reuptake of amine neurotransmitters in a fashion similar to the proposed mechanism of antidepressant actions of tricyclic antidepressants and SSRIs such as fluoxetine. The answer is B.

The clinical use of succinylcholine, especially in patients with diabetes, is associated with (A) Antagonism by pyridostigmine during the early phase of blockade (B) Aspiration of gastric contents (C) Decreased intragastric pressure (D) Histamine release in a genetically determined population (E) Metabolism at the neuromuscular junction by acetylcholinesterase

Fasciculations associated with succinylcholine may increase intragastric pressure with possible complications of regurgitation and aspiration of gastric contents. The complication is more likely in patients with delayed gastric emptying such as those with esophageal dysfunction or diabetes. Histamine release resulting from succinylcholine is not genetically determined. The answer is B.

A 21-year-old woman from Southeast Asia has been staying with family members in the United States for the last 3 mo and is looking after her sister's preschool children during the day. Because she has difficulty with the English language, her sister escorts her to the emergency department of a local hospital. She tells the staff that her sister has been feeling very tired for the last month, has a poor appetite, and has lost weight. The patient has been feeling somewhat better lately except for a cough that produces a greenish sputum, sometimes specked with blood. With the exception of rales in the left upper lobe, the physical examination is unremarkable and she does not seem to be acutely ill. Laboratory values show a white count of 12,000/µL and a hematocrit of 33%. Chest x-ray film reveals an infiltrate in the left upper lobe with a possible cavity. A Gram-stained smear of the sputum shows mixed flora with no dominance. An acidfast stain reveals many thin rods of pinkish hue. A preliminary diagnosis is made of pulmonary tuberculosis. Sputum is sent to the laboratory for culture. Which statement concerning the possible use of isoniazid (INH) in this patient is false? (A) Dyspnea, flu

Fast acetylators may require higher doses of the drug than others. Peripheral neuropathy caused by INH is due to pyridoxine deficiency. It is more common in the diabetic, malnourished, or AIDS patient and can be prevented by a daily dose of 25-50 mg of pyridoxine. INH can inhibit monoamine oxidase type A and has caused tyramine reactions. Hepatotoxicity is age-dependent, with an incidence of 0.3% in patients aged 21-35 years and greater than 2% in patients older than 50 years. The answer is B.

Which drug is a full agonist at opioid receptors with analgesic activity equivalent to morphine, a longer duration of action, and fewer withdrawal signs on abrupt discontinuance than morphine? (A) Fentanyl (B) Hydromorphone (C) Methadone (D) Nalbuphine (E) Oxycodone

Fentanyl, hydromorphone, and methadone are full agonists with analgesic efficacy similar to that of morphine. When given intravenously, fentanyl has a duration of action of just 60-90 min. Hydromorphone has poor oral bioavailability. Methadone has the greatest bioavailability of the drugs used orally, and its effects are more prolonged. Tolerance and physical dependence develop, and dissipate, more slowly with methadone than with morphine. These properties underlie the use of methadone for detoxification and maintenance programs. The answer is C.

In a patient who requires filgrastim (G-CSF) after being treated with anticancer drugs, the therapeutic objective is to prevent which of the following? (A) Allergic reactions (B) Cancer recurrence (C) Excessive bleeding (D) Hypoxia (E) Systemic infection

Filgrastim (G-CSF) stimulates the production and function of neutrophils, important cellular mediators of the innate immune system that serve as the first line of defense against infection. The answer is E.

Finasteride has efficacy in the prevention of male-pattern baldness by virtue of its ability to do which of the following? (A) Competitively antagonize androgen receptors (B) Decrease the release of gonadotropins (C) Increase the serum concentration of sex hormone-binding globulin (D) Inhibit the synthesis of testosterone (E) Reduce the production of dihydrotestosterone

Finasteride inhibits 5α-reductase, the enzyme that converts testosterone to DHT, the principal androgen in androgen- sensitive hair follicles. The answer is E.

Which of the following statements about beta-lactam antibiotics is most correct? (A) Cephalexin and other first-generation cephalosporins cross the blood-brain barrier (B) Ceftriaxone and nafcillin are both eliminated mainly via biliary secretion (C) Instability of penicillins in gastric acid does not limit their oral absorption (D) Renal tubular reabsorption of amoxicillin is inhibited by probenecid (E) Ticarcillin has limited activity against several Gramnegative rods

First- and second-generation cephalosporins are not effective in meningitis because they do not readily enter the cerebrospinal fluid. Instability of penicillins in gastric acid does limit their oral absorption, renal elimination of amoxicillin is inhibited by probenecid, and ticarcillin has activity against several Gram-negative rods. The answer is B.

Flumazenil will counteract the action of each of the following drugs except (A) Alprazolam (B) Buspirone (C) Diazepam (D) Eszopiclone (E) Zaleplon

Flumazenil binds to the chloride channel macromolecular complex and competes with the benzodiazepines, eszopiclone, zaleplon, and zolpidem. It does not reverse the action of barbiturates and has no effect on the antianxiety action of buspirone. The answer is B.

A 32-year-old woman underwent segmental mastectomy for a breast tumor of 3 cm diameter. Lymph node sampling revealed 2 involved nodes. Because chemotherapy is of established value in her situation, she underwent postoperative treatment with antineoplastic drugs. The regimen consisted of doxorubicin followed by cyclophosphamide/methotrexate/ fluorouracil. Adjunctive drugs included tamoxifen because the tumor cells were hormone receptor-positive. Which of the following best describes the mechanism of anticancer action of cellular metabolites of fluorouracil? (A) Cross-linking of double-stranded DNA (B) Inhibition of DNA-dependent RNA synthesis (C) Interference with the activity of topoisomerases I (D) Irreversible inhibition of thymidylate synthase (E) Selective inhibition of DNA polymerases

Fluorouracil (5-FU) undergoes metabolism to form 5-fluoro2′-deoxyuridine-5′-phosphate (5-dUMP). This metabolite forms a covalently bound ternary complex with thymidylate synthase and its coenzyme N-methylenetetrahydrofolate. The synthesis of thymine nucleotides is blocked, DNA synthesis is inhibited, and a "thymineless death" of cells results. The answer is D.

To be effective in breast cancer, tamoxifen must be converted to an active form by CYP2D6. Cases of inadequate treatment of breast cancer have occurred when tamoxifen was administered to patients who were being treated with (A) Amitriptyline (B) Bupropion (C) Fluoxetine (D) Mirtazapine (E) Phenelzine

Fluoxetine is an inhibitor of hepatic cytochrome P450s, especially CYP2D6, and to a lesser extent CYP3A4. Dosages of several drugs may need to be reduced if given concomitantly with fluoxetine. In the case of tamoxifen, however, its antineoplastic action is dependent on its conversion to an active metabolite by CYP2D6. The answer is C.

You are the only physician in a clinic that is cut off from the outside world by violent storms, flooding, and landslides. A 15-year-old girl is brought to the clinic with severe asthmatic wheezing. Because of the lack of other drugs, you decide to use intravenous theophylline for treatment. The pharmacokinetics of theophylline include the following average parameters: Vd 35 L; CL 48 mL/min; half-life 8 h. If an intravenous infusion of theophylline is started at a rate of 0.48 mg/min, how long would it take to reach 93.75% of the final steadystate concentration? (A) Approximately 48 min (B) Approximately 7.4 h (C) Approximately 8 h (D) Approximately 24 h (E) Approximately 32 h

For a drug with first-order kinetics, the approach of the drug plasma concentration to steady-state concentration during continuous infusion follows a stereotypical curve that rises rapidly at first and gradually reaches a plateau. It reaches 50% of steady state at 1 half-life, 75% at 2 halflives, 87.5% at 3, 93.75% at 4, and progressively halves the difference between its current level and 100% of steady state with each half-life. The answer is E, 32 h, or 4 half-lives.

A 24-year-old man was employed in the supply department of a company that manufactures semiconductors. After an accident at the plant, he presented with nausea and vomiting, headache, hypotension, and shivering. Laboratory analyses showed hemoglobinuria and a plasma free hemoglobin level greater than 1.4 g/dL. This young man was probably exposed to (A) Arsine (B) Inorganic arsenic (C) Mercury vapor (D) Methylmercury (E) Tetraethyl lead

From the signs and symptoms alone, a diagnosis of arsine gas poisoning cannot be made. However, clues to the cause of poisoning are often provided by a patient's occupation. The laboratory reports suggest marked hemolysis. Arsine gas binds to hemoglobin and decreases erythrocyte glutathione levels, causing membrane fragility and resulting hemolysis. The answer is A.

A young woman is brought to a hospital emergency department with intense abdominal pain of 2 days duration. The pain has spread to the right lower quadrant and is accompanied by nausea, vomiting, and fever. She arrives at the emergency department with a blood pressure of 85/45, pulse 120/min, and temperature 40°C. Her abdomen has a board-like rigidity with diffuse pain to palpation. Laboratory values include the following: WBC 20,000/µL and creatinine 1.5 mg/dL. After abdominal x-ray films are taken, a preliminary diagnosis of abdominal sepsis is made, possibly resulting from bowel perforation. After appropriate samples are sent to the laboratory for culture, the patient is hospitalized, and antimicrobial therapy is started with intravenous ampicillin and gentamicin. If the antibiotic regimen in this patient is modified to include metronidazole (A) Ampicillin should be excluded from the regimen (B) Coverage will be extended to methicillin-resistant staphylococci (C) Gentamicin should be excluded from the regimen (D) Metronidazole should not be administered intravenously (E) The patient should be monitored for candidiasis

Fungal superinfections, especially from Candida albicans, occur frequently during treatment with metronidazole. In most cases of abdominal sepsis, metronidazole would be given by slow intravenous infusion. Both ampicillin and gentamicin should be maintained until the infection is controlled, at which time surgery is indicated. Metronidazole has no activity against aerobes. The combination of ampicillin, gentamicin, and metronidazole does not provide coverage for methicillin-resistant staphylococci. The answer is E.

Which of the following drugs increases the plasma levels of endogenous BNP and also blocks angiotensin receptors? (A) Furosemide (B) Losartan (C) Nesiritide (D) Sacubitril (E) Spironolactone

Furosemide has no significant effect on peptide metabolism and does not block AT 1 receptors. Losartan blocks AT 1 receptors but has no effect on peptide metabolism. Nesiritide is a synthetic BNP and does not block AT 1 receptors. Spironolactone blocks the aldosterone receptor in the kidney. Only sacubitril/valsartan has the combined effect listed in the stem of this question. The answer is D.

Which of the following receptors shares the same potassium channel as the 5-HT 1A receptor? (A) Dopamine D 2 receptor (B) GABA B receptor (C) Mu opioid receptor (D) Muscarinic M 1 receptor (E) Substance P receptor

GABA Breceptors and 5-HT 1Areceptors share the same potassium ion channel, with a G protein involved in the coupling mechanism. The spasmolytic drug baclofen is an activator of GABA B receptors in the spinal cord. The anxiolytic drug buspirone may act as a partial agonist at brain 5-HT 1A receptors. The answer is B.

An increase of chloride conductance is the most important result of activation of (A) Acetylcholine M 1 receptors (B) Beta 1 adrenoceptors (C) 5-HT 3 receptors (D) GABA A receptors (E) Glutamate NMDA receptors

GABA is the most important inhibitory transmitter in the brain (glycine is also important in the spinal cord) and, via GABA A receptors, causes hyperpolarization mediated by increased chloride conductance. The answer is D.

A patient with AIDS has a CD4 count of 45/µL. He is being maintained on a 3-drug regimen of indinavir, didanosine, and zidovudine. For prophylaxis against opportunistic infections, he is also receiving cidofovir, fluconazole, rifabutin, and trimethoprim-sulfamethoxazole. The drug most likely to suppress herpetic infections and provide prophylaxis against CMV retinitis in this patient is (A) Fluconazole (B) Cidofovir (C) Indinavir (D) Rifabutin (E) Trimethoprim-sulfamethoxazole

Ganciclovir (not listed) has been the most commonly used drug for prevention and treatment of CMV infections in the immunocompromised patient. However, cidofovir is also very effective in CMV retinitis and has good activity against many strains of HSV, including those resistant to acyclovir. The answer is B.

A 40-year-old man with a history of major depression is admitted to the emergency department following a suicide attempt with a drug overdose. Which of the following signs or symptoms would be consistent with an overdose of a ganglion-blocking drug? (A) Increased blood pressure (B) Increased bowel sounds (C) Increased sweating (D) Miosis (E) Tachycardia

Ganglion blockade results in decreased blood pressure, bowel activity, and sweating. Because the parasympathetic system dominates the pupil and the sinoatrial node, ganglion block causes mydriasis and tachycardia. The answer is E.

Which of the following is a derivative of serotonin that may have value in managing symptoms of jet lag? (A) Ephedra (B) Garlic (C) Ginseng (D) Glucosamine (E) Melatonin

Garlic might get you a row of seats to yourself, but the compound that will help in jet lag is melatonin. The answer is E.

A 30-year-old male patient who is HIVpositive and symptomatic has a CD4 count of 250/µL and a viral RNA load of 15,000 copies/mL. His treatment involves a 3-drug antiviral regimen consisting of zidovudine, didanosine, and ritonavir. The patient is taking acyclovir for a herpes infection and ketoconazole for oral candidiasis. He now complains of anorexia, nausea and vomiting, and abdominal pain. His abdomen is tender in the epigastric area. Laboratory results reveal an amylase activity of 220 U/L, and a preliminary diagnosis is made of acute pancreatitis. If this patient has acute pancreatitis, the drug most likely to be responsible is (A) Acyclovir (B) Didanosine (C) Ketoconazole (D) Ritonavir (E) Zidovudine

Gastrointestinal problems occur with most antiviral drugs used in HIV-positive patients, and acute pancreatitis has been reported for several reverse transcriptase inhibitors. However, didanosine's most characteristic adverse effect is a dose-limiting acute pancreatitis. Other risk factors that are relative contraindications to didanosine are advanced AIDS, hypertriglyceridemia, and alcoholism. The answer is B.

Regarding the toxicity of aminoglycosides which statement is accurate? (A) Gentamicin and tobramycin are the least likely to cause renal damage (B) Ototoxicity due to amikacin and gentamicin includes vestibular dysfunction, which is often irreversible (C) Ototoxicity is reduced if loop diuretics are used to facilitate the renal excretion of aminoglycoside antibiotics (D) Reduced blood creatinine is an early sign of aminoglycoside nephrotoxicity (E) Skin reactions are very rare following topical use of neomycin

Gentamicin and tobramycin are the most nephrotoxic a glycosides. The incidence of nephrotoxic effects with gentamicin is 2 to 3 times greater than the incidence of ototoxicity. With traditional dosage regimens, the first indication of potential nephrotoxicity is an increase in trough serum levels of aminoglycosides, which is followed by an increase in blood creatinine. Although aminoglycoside ototoxicity usually involves irreversible effects on vestibular function, hearing loss can also occur. Ototoxicity is enhanced by loop diuretics. Skin reactions are common with topical use of neomycin. The answer is B.

After a backpacking trip in the mountains, a 24-year-old man develops diarrhea. He acknowledges drinking stream water without purification, and you suspect he is showing symptoms of giardiasis. Because you know that laboratory detection of cysts or trophozoites in the feces can be difficult, you decide to treat the patient empirically with (A) Chloroquine (B) Emetine (C) Pentamidine (D) Tinidazole (E) TMP-SMZ

Giardiasis is a common intestinal protozoan infection caused by Giardia lamblia. A large number of infections result from fecal contamination of food or water. Metronidazole is frequently used, but tinidazole is equally effective. The answer is D.

Which one of the following drugs promotes the release of endogenous insulin? (A) Acarbose (B) Canagliflozin (C) Glipizide (D) Metformin (E) Miglitol (F) Pioglitazone

Glipizide is a second-generation sulfonylurea that promotes insulin release by closing potassium channels in pancreatic B cells. The answer is C.

An 18-month-old boy presented in a semiconscious state with profound hypotension and bradycardia after ingesting a number of his grandmother's metoprolol tablets. In this case, the most appropriate antidote is (A) Atropine (B) Esmolol (C) Glucagon (D) Naloxone (E) Neostigmine

Glucagon (Chapter 41) stimulates heart rate and c tility through cardiac glucagon receptors that are coupled to adenylyl cyclase and the cAMP signaling pathway. This ability to increase cardiac cAMP without requiring access to β receptors makes it valuable for β-blocker overdose. The answer is C.

Which of the following patients is most likely to be treated with intravenous glucagon? (A) An 18-year-old woman who took an overdose of cocaine and now has a blood pressure of 190/110 mm Hg (B) A 27-year-old woman with severe diarrhea caused by a flare in her inflammatory bowel disease (C) A 57-year-old woman with type 2 diabetes who has not taken her glyburide for the last 3 d (D) A 62-year-old man with severe bradycardia and hypotension resulting from ingestion of an overdose of atenolol (E) A 74-year-old man with lactic acidosis as a complication of severe infection and shock

Glucagon acts through cardiac glucagon receptors to stimulate the rate and force of contraction of the heart. Because this bypasses cardiac β adrenoceptors, glucagon is useful in the treatment of β-blocker-induced cardiac depression. The answer is D.

Glucocorticoids have proved useful in the treatment of which of the following medical conditions? (A) Chemotherapy-induced vomiting (B) Essential hypertension (C) Hyperprolactinemia (D) Parkinson's disease (E) Type II diabetes

Glucocorticoids are used in combination with other antiemetics to prevent chemotherapy-induced nausea and vomiting, which are commonly associated with anticancer drugs. The answer is A.

A 50-year-old woman, a known asthmatic for the past 30 years, presented to the emergency department with a 2-d history of worsening breathlessness and cough. Chest auscultation revealed bilateral polyphonic inspiratory and expiratory wheeze. Supplemental oxygen, nebulized albuterol (salbutamol) (5 mg) and ipratropium (250 mcg), as well as intravenous methyl prednisolone (40 mg) were administered. Which of the following is a pharmacologic effect of exogenous glucocorticoids? (A) Increased muscle mass (B) Hypoglycemia (C) Inhibition of leukotriene synthesis (D) Improved wound healing (E) Increased excretion of salt and water

Glucocorticoids inhibit the production of both leukotrienes and prostaglandins via inhibition of phospholipase A2 . This is a key component of their anti-inflammatory action. The answer is C.

If ampicillin and piperacillin are used in combination in the treatment of infections resulting from Pseudomonas aeruginosa, antagonism may occur. The most likely explanation is that (A) Ampicillin is bacteriostatic (B) Ampicillin induces beta-lactamase production (C) Autolytic enzymes are inhibited by piperacillin (D) Piperacillin blocks the attachment of ampicillin to penicillin-binding proteins (E) The 2 drugs form an insoluble complex

Gram-negative rods such as Enterobacter and Pseudomonas aeruginosa have inducible beta-lactamases. Several betalactam antibiotics, including ampicillin, cefoxitin, and imipenem, are potent inducers of beta-lactamase production. When such inducers are used with a hydrolyzable penicillin (eg, piperacillin), antagonism may result. The answer is B.

Which drug is least likely to be effective in the treatment of esophageal candidiasis if it is used by the oral route? (A) Clotrimazole (B) Griseofulvin (C) Ketoconazole (D) Itraconazole (E) Nystatin

Griseofulvin has no activity against C albicans and is not effective in the treatment of systemic or superficial infections caused by such organisms. "Swish and swallow" formulations of clotrimazole and nystatin have been used commonly. Most of the azoles are effective in esophageal candidiasis. The answer is B.

A 20-year-old woman is taking over-the-counter diphenhydramine for severe hay fever. Which of the following adverse effects is she most likely to report? (A) Muscarinic increase in bladder tone (B) Nausea (C) Nervousness, anxiety (D) Sedation (E) Vertigo

H1 blockers do not activate muscarinic receptors, mediate vasoconstriction, or cause vertigo. Some relieve vertigo or motion sickness. They do not cause nervousness or anxiety. Diphenhydramine is a potent sedative with H1 - and M3-blocking actions. The answer is D.

A laboratory study of new H 2blockers is planned. Which of the following will result from blockade of H2 receptors? (A) Increased cAMP (cyclic adenosine monophosphate) in cardiac muscle (B) Decreased channel opening in enteric nerves (C) Decreased cAMP in gastric mucosa (D) Increased IP 3 (inositol trisphosphate) in platelets (E) Increased IP 3 in smooth muscle

H2 receptors are Gs-protein-coupled receptors, like β adrenoceptors. Blockade of this system will cause a decrease in cAMP in several tissues. The answer is C.

Your patient, a 45-year-old male, requires atorvastatin. He enjoys lifting weights and is worried about statin-induced muscle pain. He asks you if he can take anything to prevent that. You tell him there is an endogenous antioxidant available as a supplement that may help. Some clinical trials suggest that patients with statin-associated myopathy had reduced muscle pain after receiving this supplement. The supplement is which of the following? (A) Coenzyme Q10 (B) Glucosamine (C) Melatonin (D) Tyrosine (E) Vitamin E

HMG-CoA reductase, the enzyme required for coenzyme Q10 synthesis, is inhibited by statins (see Chapter 35). This inhibition may contribute to statin-associated myopathy. A small double-blind clinical trial found a significant reduction in muscle pain in patients with statin-associated myopathy who were treated with coenzyme Q10. The answer is A.

Mr Green, a 54-year-old banker, had a cardiac transplant 6 months ago. His current blood pressure is 120/70 mm Hg and heart rate is 100 bpm. Which of the following drugs would have the least effect on Mr Green's heart rate? (A) Albuterol (B) Epinephrine (C) Isoproterenol (D) Norepinephrine (E) Phenylephrine

Heart transplantation involves cutting of the autonomic nerves to the heart. As a result, autonomic nerve endings degenerate, and cardiac transmitter stores are absent for 2 years or longer after surgery. Therefore, indirect-acting sympathomimetics are ineffective in changing heart rate. All the drugs listed are direct-acting, and all but phenylephrine have significant effects on β receptors. Phenylephrine usually causes reflex bradycardia, which requires intact vagal innervation. The answer is E. (Note that denervation may result in upregulation of both β 1 and β 2 receptors so that direct-acting β agonists may have a greater than normal effect.)

Which of the following is an endogenous inhibitor/inactivator of nitric oxide? (A) Arginine (B) Angiotensinogen (C) Arachidonic acid (D) Hemoglobin (E) Thromboxane

Heme and hemoglobin inactivate NO. The answer is D.

Chemical warfare agents that had been manufactured in the 1950s were being stored at a military installation. Several civilian workers at the facility began to feel unwell, with symptoms that included dyspnea, abdominal cramps, and diarrhea. They also had copious nasal and tracheobronchial secretions. Which type of toxic compound is most likely to be the cause of these effects? (A) Aliphatic hydrocarbons (B) Botulinum toxins (C) Nitrogen mustards (D) Organophosphates (E) Rotenones

Highly potent organophosphate inhibitors of a esterase (eg, sarin, tabun) have been developed for chemical warfare purposes. Their storage represents a potential toxicologic hazard. It is important to recognize the signs and symptoms of excess acetylcholine (DUMBBELSS; see Chapter 7), which include those described. The answer is D.

Field workers exposed to a plant toxin develop painful fluidfilled blisters. Analysis of the blister fluid reveals high concentrations of a peptide. Which of the following is a peptide that causes increased capillary permeability and edema? (A) Angiotensin II (B) Bradykinin (C) Captopril (D) Histamine (E) Sacubitril

Histamine and bradykinin both cause a marked increase in capillary permeability that is often associated with edema, but histamine is not a peptide. The answer is B.

A 16-year-old patient is in the emergency d ment receiving nasal oxygen. She has a heart rate of 125 bpm, a respiratory rate of 40 breaths/min, and a peak expiratory flow <50% of the predicted value. Wheezing and rales are audible without a stethoscope. After successful treatment of the acute attack, the patient was referred to the outpatient clinic for follow-up treatment for asthma. Which of the following is not an established prophylactic strategy for asthma? (A) Avoidance of antigen exposure (B) Blockade of histamine receptors (C) Blockade of leukotriene receptors (D) IL-5 cytokine blockade (E) Inhibition of phospholipase A2

Histamine does not appear to play a significant role in asthma, and antihistaminic drugs, even in high doses, are of little or no value. Antigen avoidance is well established. Blockade of leukotriene receptors with montelukast or zafirlukast; inhibition of phospholipase with corticosteroids; and inhibition of cytokines are also useful. The answer is B.

PJ is a 5-year-old boy. At his checkup, the pediatrician notices cutaneous xanthomas and orders a lipid panel. Repeated measures confirm that the patient's serum cholesterol levels are high (936 mg/dL). Further testing confirms a diagnosis of homozygous familial hypercholesterolemia. Which of the following interventions will be least effective in this patient? (A) Atorvastatin (B) Ezetimibe (C) Lomitapide (D) Mipomersen (E) Niacin

Homozygous familial hypercholesterolemia is caused by mutations leading to dysfunctional LDL receptors incapable of taking up LDL from the bloodstream. Options B-E would have a cholesterol-lowering effect. Lomitapide and mipomersen are specifically indicated for patients with familial hypercholesterolemia. Reductase inhibitors such as atorvastatin rely on functional LDL receptors to achieve a LDL-lowering effect and thus will not work in patients with homozygous familial hypercholesterolemia. The answer is A.

A patient with AIDS has an extremely high viral RNA titer. While blood is being drawn from this patient, the syringe is accidentally dropped, contaminating the floor, which is made of porous material. The best way to deal with this is to (A) Clean the floor with a 10% solution of household bleach (B) Clean the floor with soap and water (C) Completely replace the contaminated part of the floor (D) Neutralize the spill with a solution of potassium permanganate (E) Seal the room and decontaminate with ethylene ox

Household bleach contains sodium hypochlorite. A 1:10 dilution of bleach is effective for disinfection of a direct blood spill on a porous surface. In addition to inactivating HIV, sodium hypochlorite solutions have disinfectant activity against other viruses, including hepatitis B virus. The answer is A.

Which one of the following is a significant unwanted effect of the drug named? (A) Constipation with verapamil (B) Heart failure with hydralazine (C) Hemolytic anemia with atenolol (D) Hypokalemia with aliskiren (E) Lupus-like syndrome with hydrochlorothiazide

Hydralazine (choice B) is sometimes used in heart failure. Beta blockers (choice C) are not associated with hematologic abnormalities, but methyldopa is. The thiazide diuretics (choice E) often cause mild hyperglycemia, hyperuricemia, and hyperlipidemia but not lupus; hydralazine is associated with a lupus-like syndrome. Aliskiren (choice D) and other inhibitors of the renin-angiotensin-aldosterone system may cause hyperkalemia, not hypokalemia. Verapamil (choice A) often causes constipation, probably by blocking L-type calcium channels in the colon. The answer is A.

Which mechanism explains aspirin's inhibition of thromboxane synthesis? (A) Blocks cyclooxygenase (B) Blocks lipoxygenase (C) Blocks phospholipase A2 (D) Blocks PGE 1 receptors (E) Blocks PGI 2 receptors

Hydrocortisone and other corticosteroids inhibit phosphlipase. Ibuprofen and indomethacin inhibit cyclooxygenase reversibly, whereas zileuton inhibits lipoxygenase. Because aspirin inhibits cyclooxygenase irreversibly, its action is more effective in platelets, which lack the ability to synthesize new enzyme, than in the endothelium. Aspirin does not block prostaglandin receptors. The answer is A.

A 76-year-old retired postal worker with rheumatoid arthritis and chronic heart disease presents with a cardiac arrhythmia and is being considered for treatment with procainamide. She is already receiving an ACE inhibitor, digoxin, and hydrochlorothiazide for her cardiac condition. In deciding on a treatment regimen with procainamide for this patient, which of the following statements is most correct? (A) A probable drug interaction with digoxin suggests that digoxin blood levels should be obtained before and after starting procainamide. (B) Hyperkalemia should be avoided to reduce the likelihood of procainamide toxicity. (C) Procainamide cannot be used if the patient has asthma because it has a β-blocking effect. (D) Procainamide cannot be used if the patient has angina because it has a β-agonist effect. (E) Procainamide is not active by the oral route.

Hyperkalemia facilitates procainamide toxicity. Procainamide is active by the oral route and has a duration of action of 2-4 h (in the prompt-release form). Procainamide has no significant documented interaction with digoxin and no significant β-agonist or β-blocking action. The answer is B.

A 58-year-old woman with chronic hypertension and diabetes mellitus was recently admitted to the hospital for congestive heart failure and new onset atrial fibrillation. She is now seeing you after discharge and, though feeling better, is still in atrial fibrillation. An echocardiogram shows an ejection fraction of 40%; there are no valvular abnormalities. An ECG reveals only atrial fibrillation. You calculate her risk using the CHADS (2) system and the score indicates that she requires anticoagulation rather than antiplatelet therapy. She is excited about not having to come in for blood tests but wonders if there is a test, just in case the doctors need to know. Which of the following tests would provide accurate information about the coagulation status of a patient taking apixaban? (A) aPTT (B) Factor X test (C) INR (D) PT test

INR (measured as PT test) reflects changes due to warfarin and to some extent the thrombin inhibitors. Factor X inhibition is not reliably measured by the aPTT (used for unfractionated heparin) or PT test. The answer is B.

Which statement about "once-daily" dosing with aminoglycosides is accurate? (A) Dose adjustment is important in renal dysfunction (B) It is inconvenient for outpatient treatment (C) Extra nursing time is required for drug administration (D) Often more side effects than multiple (conventional) dosing regimens (E) It results in underdosing

In "once-daily dosing" with aminoglycosides, the selection of an appropriate dose is particularly critical in patients with renal insufficiency. The aminoglycosides are eliminated by the kidney in proportion to creatinine clearance. Knowledge of the degree of insufficiency, based on plasma creatinine (or BUN), is essential for estimation of the appropriate single daily dose of an aminoglycoside. The answer is A.

A 54-year-old man with advanced tuberculosis has developed signs of severe acute adrenal insufficiency. The patient should be treated immediately. Which of the following combinations is most rational? (A) Aldosterone and fludrocortisone (B) Cortisol and fludrocortisone (C) Dexamethasone and metyrapone (D) Fludrocortisone and metyrapone (E) Triamcinolone and dexamethasone

In acute adrenal insufficiency, there is loss of salt and water that is primarily due to reduced production of aldosterone. The loss of salt and water can lead to dehydration. A rational combination of drugs should include agents with complementary effects (ie, a glucocorticoid and a mineralocorticoid). The combination with these characteristics is cortisol and fludrocortisone. (Note that although fludrocortisone may have sufficient glucocorticoid activity for a patient with mild disease, a patient in severe acute adrenal insufficiency needs a full glucocorticoid such as cortisol.) The answer is B.

Haloperidol is not an appropriate drug for management of (A) Acute mania (B) Amenorrhea-galactorrhea syndrome (C) Phencyclidine intoxication (D) Schizoaffective disorders (E) Tourette syndrome

In addition to its use in schizophrenia and acute mania, haloperidol has been used in the management of intoxication due to phencyclidine (PCP) and in Tourette syndrome. Hyperprolactinemia and the amenorrhea-galactorrhea syndrome may occur as adverse effects during treatment with antipsychotic drugs, especially those like haloperidol that strongly antagonize dopamine receptors in the tuberoinfundibular tract. The answer is B.

A 68-year-old man with a history of chronic heart failure goes on vacation and abandons his low-salt diet. Three days later, he develops severe shortness of breath and is admitted to the local hospital emergency department with significant pulmonary edema. The first-line drug of choice in most cases of acute decompensation in patients with chronic heart failure is (A) Atenolol (B) Captopril (C) Carvedilol (D) Digoxin (E) Diltiazem (F) Dobutamine (G) Enalapril (H) Furosemide (I) Metoprolol (J) Spironolactone

In both acute and chronic failure and systolic (HFrEF) and diastolic heart failure (HFpEF), the initial treatment of choice is usually furosemide. The answer is H.

An 82-year-old woman, otherwise healthy for her age, has difficulty sleeping. Triazolam is prescribed for her at one half of the conventional adult dose. Which statement about the use of triazolam in this elderly patient is most accurate? (A) Ambulatory dysfunction is unlikely to occur in elderly patients taking one half of the conventional adult dose (B) Hypertension is a common adverse effect of benzodiazepines in elderly patients (C) Over-the-counter cold medications may antagonize the hypnotic effects of the drug (D) The patient may experience amnesia, especially if she also consumes alcoholic beverages (E) Triazolam does not cause rebound insomnia on abrupt discontinuance

In elderly patients taking benzodiazepines, hypotension is far more likely than an increase in blood pressure. Elderly patients are more prone to the CNS depressant effects of hypnotics; a dose reduction of 50% may still cause excessive sedation with possible ambulatory impairment. Additive CNS depression occurs commonly with drugs used in overthe-counter cold medications, especially antihistamines, and rebound insomnia can occur with abrupt discontinuance of benzodiazepines used as sleeping pills. Alcohol enhances psychomotor depression and the amnestic effects of the benzodiazepines. The answer is D.

A young woman complains of abdominal pain at the time of menstruation. Careful evaluation indicates the presence of significant endometrial deposits on the pelvic peritoneum. Which of the following is the most appropriate medical therapy for this patient? (A) Flutamide, orally (B) Medroxyprogesterone acetate by intramuscular injection (C) Norgestrel as an IUD (D) Oxandrolone by intramuscular injection (E) Raloxifene orally

In endometriosis, suppression of ovarian function and production of gonadal steroids are useful. Intramuscular injection of relatively large doses of medroxyprogesterone provides 3 months of an ovarian suppressive effect because of inhibition of pituitary production of gonadotropins. The answer is B.

Which helminthic infection does not respond to treatment with praziquantel? (A) Hydatid disease (B) Opisthorchiasis (C) Paragonimiasis (D) Pork tapeworm infection (E) Schistosomiasis

In hydatid disease, praziquantel has marginal efficacy because it does not affect the inner germinal membrane of Echinococcus granulosus present in hydatid cysts. The answer is A.

Men who use large doses of anabolic steroids are at increased risk of which of the following? (A) Anemia (B) Cholestatic jaundice and elevation of aspartate transaminase levels in the blood (C) Hirsutism (D) Hyperprolactinemia (E) Testicular enlargement

In men, large doses of anabolic steroids are associated with liver impairment, including cholestasis and elevation of serum concentrations of transaminases. The answer is B.

A 63-year-old man is undergoing radiation treatment as an outpatient for metastatic bone cancer. His pain has been treated with a fixed combination of oxycodone plus acetaminophen taken orally. Despite increasing doses of the analgesic combination, the pain is getting worse. The most appropriate oral medication for his increasing pain is (A) Buprenorphine (B) Codeine plus aspirin (C) Hydromorphone (D) Pentazocine (E) Tramadol

In most situations, pain associated with metastatic carcinoma ultimately necessitates the use of an opioid analgesic that is equivalent in strength to morphine, so hydromorphone, oxymorphone, or levorphanol would be indicated. Pentazocine or the combination of codeine plus salicylate would not be as effective as the original drug combination. Propoxyphene is even less active than codeine alone. Buprenorphine, a mixed agonist-antagonist, is not usually recommended for cancerassociated pain because it has a limited maximum analgesic effect ("ceiling") and because of possible dysphoric and psychotomimetic effects. The answer is C.

An 18-month-old boy dies from an accidental overdose of acetaminophen. Which of the following is the most likely cause of this patient's death? (A) Arrhythmia (B) Hemorrhagic stroke (C) Liver failure (D) Noncardiogenic pulmonary edema (E) Ventilatory failure

In overdose, acetaminophen causes fulminant liver failure as a result of its conversion by hepatic cytochrome P450 enzymes to a highly reactive metabolite. The answer is C.

A patient needs antibiotic treatment for native valve, culturepositive infective enterococcal endocarditis. His medical history includes a severe anaphylactic reaction to penicillin G during the last year. The best approach would be treatment with (A) Amoxicillin-clavulanate (B) Aztreonam (C) Ceftriaxone (D) Piperacillin (E) Vancomycin

In patients who have had a severe reaction to a penicillin, it is inadvisable to administer a cephalosporin or a carbapenem such as meropenem. Aztreonam has no significant activity against Gram-positive cocci, so the logical treatment in this case is vancomycin, often with an aminoglycoside (eg, gentamicin) for synergistic activity against enterococci. The answer is E.

A 67-year-old man with chronic kidney disease was found to have an elevated serum PTH concentration and a low serum concentration of 25-hydroxyvitamin D. He was successfully treated with ergocalciferol. Unfortunately, his kidney disease progressed so that he required dialysis and his serum PTH concentration became markedly elevated. Which of the following drugs is most likely to lower this patient's serum PTH concentration? (A) Calcitriol (B) Cholecalciferol (C) Furosemide (D) Gallium nitrate (E) Risedronate

In patients with chronic kidney disease that requires dialysis, the impaired production of active vitamin D metabolites compounded with elevated serum phosphate due to renal impairment leads to secondary hyperparathyroidism. Administration of the active vitamin D metabolite calcitriol acts directly on the parathyroid to inhibit PTH production. Cholecalciferol, a form of vitamin D, is not effective in patients with advanced renal disease who cannot form adequate amounts of active vitamin D metabolites. The answer is A.

A homeless middle-aged male patient presents in the emergency department in a state of intoxication. You note that he is behaviorally disinhibited and rowdy. He tells you that he has recently consumed about a pint of a red-colored liquid that his friends were using to "get high." He complains that his vision is blurred and that it is "like being in a snowstorm." His breath smells a bit like formaldehyde. He is acidotic. After assessing and stabilizing the patient's airway, respiration, and circulatory status, fomepizole was administered intravenously. Which of the following most accurately describes the therapeutic purpose of the fomepizole administration? (A) Accelerate the rate of elimination of the toxic liquid that he consumed (B) Combat acidosis (C) Inhibit the metabolic production of toxic metabolites (D) Prevent alcohol withdrawal seizures (E) Sedate the patient

In patients with suspected methanol intoxication, fomepizole is given intravenously to inhibit the ADH-catalyzed formation of toxic metabolites. The answer is C.

A 3-year-old girl presented with hirsutism, breast enlargment, and a height and bone age that was consistent with an age of 9. Diagnostic testing revealed precocious puberty. Which of the following is the most appropriate drug for treatment of this patient's precocious puberty? (A) Atosiban (B) Follitropin (C) Leuprolide (D) Octreotide (E) Pegvisomant

In precocious puberty, the hypothalamic-pituitary-gonadal axis becomes prematurely active for reasons that are not understood. Treatment involves suppressing gonadotropin secretion with continuous administration of a long-acting GnRH agonist such as leuprolide. The answer is C.

Bradykinesia has made drug treatment necessary in a 60-year-old male patient with Parkinson's disease, and therapy is to be initiated with levodopa. Regarding the anticipated actions of levodopa, the patient need not be informed that (A) Dizziness may occur, especially when standing (B) He should take the drug in divided doses to avoid nausea (C) Livedo reticularis is a possible side effect (D) The drug will probably improve his symptoms for a period of time but not indefinitely (E) Uncontrollable muscle jerks may occur

In prescribing levodopa, the patient should be informed about adverse effects, including gastrointestinal distress, postural hypotension, and dyskinesias. It is reasonable to advise the patient that therapeutic benefits cannot be expected to continue indefinitely. Livedo reticularis (a netlike rash) is an adverse effect of treatment with amantadine. The answer is C.

A 28-year-old man living on the East Coast was transferred by his employer to California for several months. On his return, he complains of having influenza-like symptoms with fever and a cough. He also has red, tender nodules on his shins. His physician suspects that these symptoms are due to coccidioidomycosis contracted during his stay in California. Which is the drug of choice if this patient is suffering from persistent lung lesions or disseminated disease caused by Coccidioides immitis? (A) Amphotericin B (B) Flucytosine (C) Itraconazole (D) Micafungin (E) Terbinafine

In progressive or disseminated forms of coccidioidomycosis, systemic antifungal drug treatment is needed. Until recently, amphotericin B was the recommended therapy, but fluconazole or itraconazole are now generally preferred. Note that the risk of dissemination is much greater in African Americans (10% incidence) and in pregnant women during the third trimester. The answer is C.

A 35-year-old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cholesterol, LDL cholesterol, and triglyceride are elevated. Her serum concentration of HDL cholesterol is somewhat reduced. Which of the following drugs is most likely to increase this patient's triglyceride and VLDL cholesterol concentrations when used as monotherapy? (A) Atorvastatin (B) Cholestyramine (C) Ezetimibe (D) Gemfibrozil (E) Niacin

In some patients with familial combined hyperlipidemia and elevated VLDL, the resins increase VLDL and triglyceride concentrations even though they also lower LDL cholesterol. The answer is B.

A 40-year-old man complains of periodic bouts of diarrhea with lower abdominal cramping and intermittent rectal bleeding. Seen in the clinic, he appears well nourished, with blood pressure in the normal range. Examination reveals moderate abdominal pain and tenderness. His current medications are limited to loperamide for his diarrhea. Sigmoidoscopy reveals mucosal edema, friability, and some pus. Laboratory findings include mild anemia and decreased serum albumin. Microbiologic examination via stool cultures and mucosal biopsies do not reveal any evidence for bacterial, amebic, or cytomegalovirus involvement. The most appropriate drug to use in this patient is (A) Ampicillin (B) Doxycycline (C) Norfloxacin (D) Sulfasalazine (E) Trimethoprim-sulfamethoxazole

In the absence of any evidence pointing toward a definite microbial cause for the colitis in this patient, a drug that decreases inflammation is indicated. Sulfasalazine has significant anti-inflammatory action, and its oral use results in symptomatic improvement in 50-75% of patients suffering from ulcerative colitis. The drug is also used for its antiinflammatory effects in rheumatoid arthritis. The answer is D.

A drug that can clear trypanosomes from the blood and lymph nodes and is active in the late CNS stages of African sleeping sickness is (A) Emetine (B) Melarsoprol (C) Nifurtimox (D) Pentamidine (E) Suramin

In the advanced stages of African sleeping sickness, melarsoprol is the drug of choice because, unlike pentamidine or suramin, it effectively enters the CNS. Nifurtimox is the most commonly used drug for Chagas' disease. The answer is B.

A 37-year-old woman with leukemia was undergoing chemotherapy with intravenous antineoplastic drugs. During treatment, she developed a systemic infection from an opportunistic pathogen. There was no erythema or edema at the catheter insertion site. A white vaginal discharge was observed. After appropriate specimens were obtained for culture, empiric antibiotic therapy was started with gentamicin, nafcillin, and ticarcillin intravenously. This regimen was maintained for 72 h, during which time the patient's condition did not improve significantly. Her throat was sore, and white plaques had appeared in her pharynx. On day 4, none of the cultures had shown any 408 bacterial growth, but both the blood and urine cultures grew out Candida albicans. Candida is a major cause of nosocomial bloodstream infection. The opportunistic fungal infection in this patient could have been prevented by administration of (A) Caspofungin (B) Flucytosine (C) Nystatin (D) Voriconazole (E) None of the above

In the case of opportunistic candidal infections in the immunocompromised patient, no prophylactic drugs have been shown to be clinically effective. Prophylaxis against other fungi may be effective in some instances, including suppression of cryptococcal meningitis in AIDS patients with fluconazole. However, prophylactic use of azoles may contribute to the development of fungal resistance. The answer is E.

An 81-year-old woman with type 2 diabetes presents to the emergency department in a coma and with tachypnea, tachycardia, hypotension, and severe lactic acidosis approximately 9 h after ingesting a number of her metformin tablets. Her serum glucose concentration is 148 mg/dL. Metformin is a base with a pK a of 12.4. The procedure that is most likely to improve her condition is (A) Administration of activated charcoal (B) Administration of glucagon (C) Administration of syrup of ipecac (D) Gastric lavage (E) Hemodialysis

In this woman with severe signs of poisoning due to the ingestion of metformin, hemodialysis can be used to accelerate the elimination of both metformin and lactic acid. Since most of the metformin has been absorbed by the time she presented (9 h after drug ingestion), efforts to decontaminate her gastrointestinal tract with activated charcoal, gastric lavage, or syrup of ipecac are unlikely to be beneficial. Furthermore, syrup of ipecac has fallen out of favor and should not be used in unconscious patients. Unlike other drugs used to treat type 2 diabetes, metformin in overdose is unlikely to cause hypoglycemia (see Chapter 41), and this patient's serum glucose is in the normal range so that glucagon administration is not required. The answer is E.

A 56-year-old woman presented to the emergency department with tachycardia, shortness of breath, and chest pain. She had had shortness of breath and diarrhea for the last 2 d and was sweating and anxious. A relative reported that the patient had run out of methimazole 2 weeks earlier. A TSH measurement revealed a value of <0.01 mIU/L (normal 0.4-4.0 mIU/L). The diagnosis of thyroid storm was made. Which of the following is a drug that is a useful adjuvant in the treatment of thyroid storm? (A) Amiodarone (B) Betamethasone (C) Epinephrine (D) Propranolol (E) Radioactive iodine

In thyroid storm, β blockers such as propranolol are useful in controlling the tachycardia and other cardiac abnormalities, and propranolol also inhibits peripheral conversion of T 4 to T3 . The answer is D.

Which of the following drugs is most suitable for management of essential tremor in a patient who has pulmonary disease? (A) Diazepam (B) Levodopa (C) Metoprolol (D) Propranolol (E) Terbutaline

Increased activation of β adrenoceptors has been implicated in essential tremor, and management commonly involves administration of propranolol. However, the more selective β 1 blocker metoprolol may be equally effective and is more suitable in a patient with pulmonary disease. The answer is C.

St. John's Wort, a popular botanical remedy, is a potent inducer of hepatic phase I CYP3A4 enzymes. Verapamil and phenytoin are both eliminated from the body by metabolism in the liver. Verapamil has a clearance of 1.5 L/min, approximately equal to liver blood flow, whereas phenytoin has a clearance of 0.1 L/min. Based on this fact, which of the following is most correct? (A) St. John's Wort will increase the half-life of phenytoin and verapamil (B) St. John's Wort will decrease the volume of distribution of CYP3A4 substrates (C) St. John's Wort will decrease the hepatic extraction of phenytoin (D) St. John's Wort will decrease the first-pass effect for verapamil (E) St. John's Wort will increase the clearance of phenytoin

Induction of phase I metabolizing enzymes will decrease the half-life of substrates of these enzymes. P450 enzyme induction has no effect on volume of distribution. Hepatic extraction, the first-pass effect, and clearance for CYP3A4 substrates will be increased by inducers. However, the extraction of verapamil is already equal to the hepatic blood flow, so further increase in metabolism will not increase clearance of this drug. The answer is E.

A newborn infant is diagnosed with transposition of the great vessels, wherein the aorta exits from the right ventricle and the pulmonary artery from the left ventricle. Which of the following drugs is likely to be used in preparation for surgical correction of this anomaly? (A) Aspirin (B) Leukotriene LTC4 (C) Prednisone (D) Prostaglandin PGE1 (E) Prostaglandin PGF2α

Infants with great vessel transposition pump venous blood to the aorta and oxygenated blood back to the lungs. Therefore, they require surgical correction as soon as they are strong enough to withstand the procedure. While awaiting surgery, they are dependent on a patent ductus arteriosus to allow some oxygenated blood to flow from the left ventricle via the pulmonary artery and ductus to the aorta. The ductus can be prevented from closing by infusing the vasodilator PGE1 . The answer is D.

A 36-year-old man presents with swollen, painful heels, nail changes, and left lower back pain that wakes him from sleep. The back pain gets better with exercise. He reports 1-2 h of morning stiffness. He has a history of psoriasis and psoriatic arthritis since age 12 years. You decide to change his current regimen of indomethacin to a biologic that targets TNF-α. Which of the following is a chimeric monoclonal antibody that binds to TNF-α and inhibits its action? (A) Etanercept (B) Infliximab (C) Sirolimus (D) Trastuzumab (E) Thalidomide

Infliximab is a chimeric monoclonal antibody that binds to TNF-α. Etanercept also binds to TNF-α, but it is a chimeric protein containing a portion of the human TNF-α receptor linked to the Fc region of a human IgG. Thalidomide is a small molecule that appears to inhibit production of TNF-α. Trastuzumab is a humanized monoclonal antibody against HER-2/neu. The answer is B.

A 37-year-old woman with leukemia was undergoing chemotherapy with intravenous antineoplastic drugs. During treatment, she developed a systemic infection from an opportunistic pathogen. There was no erythema or edema at the catheter insertion site. A white vaginal discharge was observed. After appropriate specimens were obtained for culture, empiric antibiotic therapy was started with gentamicin, nafcillin, and ticarcillin intravenously. This regimen was maintained for 72 h, during which time the patient's condition did not improve significantly. Her throat was sore, and white plaques had appeared in her pharynx. On day 4, none of the cultures had shown any 408 bacterial growth, but both the blood and urine cultures grew out Candida albicans. If amphotericin B is administered, the patient should be premedicated with (A) Diphenhydramine (B) Ibuprofen (C) Prednisone (D) Any or all of the above (E) None of the above

Infusion-related adverse effects of amphotericin B include chills and fevers (the "shake and bake" syndrome), muscle spasms, nausea, headache, and hypotension. Analgesicantipyretics, antihistamines, and glucocorticoids all have been shown to be helpful. The administration of a 1-mg test dose of amphotericin B is sometimes useful in predicting the severity of infusion-related toxicity. The answer is D.

Which of the following is an important effect of insulin? (A) Increased conversion of amino acids into glucose (B) Increased gluconeogenesis (C) Increased glucose transport into cells (D) Inhibition of lipoprotein lipase (E) Stimulation of glycogenolysis

Insulin lowers serum glucose concentration in part by driving glucose into cells, particularly into muscle cells. The answer is C.

A 24-year-old woman with type 1 diabetes wishes to try tight control of her diabetes to improve her long-term prognosis. Which of the following regimens is most appropriate? (A) Morning injections of mixed insulin lispro and insulin aspart (B) Evening injections of mixed regular insulin and insulin glargine (C) Morning and evening injections of regular insulin, supplemented by small amounts of NPH insulin at mealtimes (D) Morning injections of insulin glargine, supplemented by small amounts of insulin lispro at mealtimes (E) Morning injection of NPH insulin and evening injection of regular insulin

Insulin regimens for tight control usually take the form of establishing a basal level of insulin with a small amount of a long-acting preparation (eg, insulin glargine) and supplementing the insulin levels, when called for by food intake, with short-acting insulin lispro. Less tight control may be achieved with 2 injections of intermediate-acting insulin per day. Because intake of glucose is mainly during the day, longacting insulins are usually given in the morning, not at night. The answer is D.

Which of the following is an immune modulator that increases phagocytosis by macrophages in patients with chronic granulomatous disease? (A) Aldesleukin (B) Interferon-γ (C) Lymphocyte immune globulin (D) Prednisone (E) Trastuzumab

Interferon-γ is approved for use in chronic granulomatous disease, a condition that results from phagocyte deficiency. The agent markedly reduces the frequency of recurrent infections. The answer is B.

Recombinant interleukin-2 has proved useful in the treatment of which of the following diseases? (A) Graft-versus-host disease in patients with hematopoietic stem cell transplantation (B) Psoriasis (C) Renal cell carcinoma (D) Rheumatoid arthritis (E) Superficial bladder carcinoma

Interleukin-2 is a cytokine that stimulates T-cell p tion and activates Th1, NK, and lymphokine-activated killer (LAK) cells. It has shown efficacy in renal cell carcinoma and malignant melanoma, 2 cancers that respond poorly to conventional cytotoxic anticancer drugs. The answer is C.

Total intravenous anesthesia with fentanyl has been selected for a frail elderly woman about to undergo cardiac surgery. Which statement about this anesthesia protocol is most accurate? (A) Fentanyl's effects can be reversed with naloxone after the procedure (B) Marked relaxation of skeletal muscles is anticipated (C) Opioids such as fentanyl provide useful hypotensive effects (D) Patient awareness is rare during surgery, with minimal recall after recovery (E) The patient is likely to experience pain during surgery

Intravenous opioids (eg, fentanyl) are widely used in a sia for cardiac surgery because they provide full analgesia and cause less cardiac depression than inhaled anesthetic agents. The opioids are not cardiac stimulants, and fentanyl is more likely to cause skeletal muscle rigidity than relaxation. Disadvantages of this technique are patient recall (which can be decreased by concomitant use of a benzodiazepine) and the occurrence of hypertensive responses to surgical stimulation. The addition of vasodilators (eg, nitroprusside) or a β blocker (eg, esmolol) may be needed to prevent intraoperative hypertension. Opioid effects are readily reversed by naloxone. The answer is A.

A 65-year-old man with multinodular goiter is scheduled for a near-total thyroidectomy. Which of the following drugs will be administered for 10-14 d before surgery to reduce the vascularity of his thyroid gland? (A) Levothyroxine (B) Liothyronine (C) Lugol's solution (D) Prednisone (E) Radioactive iodine

Iodides inhibit the synthesis and release of thyroid hormone and decrease the size and vascularity of the hyperplastic gland. Lugol's solution contains a mixture of potassium iodide and iodine. The answer is C.

Mr Green is a 60-year-old former smoker with cardiac disease and severe chronic obstructive pulmonary disease (COPD) associated with frequent episodes of bronchospasm. Which of the following is a bronchodilator useful in COPD and least likely to cause cardiac arrhythmia? (A) Aminophylline (B) Cromolyn (C) Epinephrine (D) Ipratropium (E) Metaproterenol (F) Metoprolol (G) Prednisone (H) Salmeterol (I) Zafirlukast (J) Zileuton

Ipratropium or a similar antimuscarinic agent is the bronchodilator that is most likely to be useful in COPD without causing arrhythmias. The answer is D.

A 23-year-old pregnant woman is referred by her obstetrician for evaluation of anemia. She is in her fourth month of pregnancy and has no history of anemia; her grandfather had pernicious anemia. Her hemoglobin is 10 g/dL (normal, 12-16 g/dL). The laboratory data for your pregnant patient indicate that she does not have macrocytic anemia but rather microcytic anemia. Optimal treatment of normocytic or mild microcytic anemia associated with pregnancy uses which of the following? (A) A high-fiber diet (B) Erythropoietin injections (C) Ferrous sulfate tablets (D) Folic acid supplements (E) Hydroxocobalamin injections

Iron deficiency microcytic anemia is the anemia that is most commonly associated with pregnancy. In this condition, oral iron supplementation is indicated. The answer is C.

A 23-year-old man has a pheochromocytoma, blood pressure of 190/120 mm Hg, and hematocrit of 50%. Pulmonary function and renal function are normal. His catecholamines are elevated, and he has a well-defined abdominal tumor on MRI. He has been scheduled for surgery. Which one of the following agents should be avoided in the anesthesia protocol? (A) Desflurane (B) Fentanyl (C) Isoflurane (D) Midazolam (E) Sevoflurane

Isoflurane sensitizes the myocardium to catecholamines, as does halothane (not listed). Arrhythmias may occur in patients with cardiac disease who have high circulating levels of epinephrine and norepinephrine (eg, patients with pheochromocytoma). Other newer inhaled anesthetics are considerably less arrhythmogenic. The answer is C.

after a drug overdose. He is noted to have hypotension and severe bradycardia. He has been receiving therapy for hypertension and angina. Which of the following drugs in high doses causes bradycardia? A) Amlodipine (B) Isosorbide dinitrate (C) Nitroglycerin (D) Prazosin (E) Verapamil

Isosorbide dinitrate (like all the nitrates) and prazosin can cause reflex tachycardia. Amlodipine, a dihydropyridine calcium channel blocker, causes much more vasodilation than cardiac depression and may also cause reflex tachycardia. Verapamil typically slows heart rate and high doses may cause severe bradycardia. The answer is E.

A 24-year-old woman comes to a clinic with complaints of dry cough, headache, fever, and malaise, which have lasted 3 or 4 d. She appears to have some respiratory difficulty, and chest examination reveals rales but no other obvious signs of pulmonary involvement. However, extensive patchy infiltrates are seen on chest x-ray film. Gram stain of expectorated sputum fails to reveal any bacterial pathogens. The patient mentions that a colleague at work had similar symptoms to those she is experiencing. The patient has no history of serious medical problems. She takes loratadine for allergies and supplementary iron tablets, and she drinks at least 6 cups of caffeinated coffee per day. The physician makes an initial diagnosis of communityacquired pneumonia. Regarding the treatment of this patient, which of the following drugs is most suitable? (A) Ampicillin (B) Clindamycin (C) Doxycycline (D) Linezolid (E) Vancomycin

It is often difficult to establish a definite cause of communityacquired pneumonia (CAP). More than 80% of cases are caused by typical pathogens such as S pneumoniae, H influenzae, or M catarrhalis, and 15% are due to the nonzoonotic atypical pathogens such as Legionella species, Mycoplasma species, or C pneumoniae. Currently, monotherapy coverage of both typical and atypical pathogens in CAP is preferred to doubledrug therapy. Preferred initial therapy includes a macrolide, doxycycline, or a quinolone active against respiratory pathogens (Chapter 46). Ampicillin, clindamycin, and vancomycin have low activity against atypical pathogens in CAP. The answer is C.

Which drug enhances the actions of GABA in nematodes causing muscle paralysis? (A) Albendazole (B) Diethylcarbamazine (C) Ivermectin (D) Oxamniquine (E) Pyrantel pamoate

Ivermectin causes muscle paralysis in nematodes by actions on GABA receptors. Pyrantel pamoate blocks nicotinic receptors relaxing nematode muscles. Diethylcarbamazine also cause muscle relaxation but the mechanism is unknown. Dizziness (no driving for 24 h) is a common adverse effect of oxamniquine. The answer is C.

A missionary from the United States is sent to work in a geographic region of a Central American country where Onchocerca volvulus is endemic. Infections resulting from this tissue nematode (onchocerciasis) are a cause of "river blindness," because microfilariae migrate through subcutaneous tissues and concentrate in the eyes. Which drug should be used prophylactically to prevent onchocerciasis? (A) Albendazole (B) Diethylcarbamazine (C) Ivermectin (D) Oxamniquine (E) Pyrantel pamoate

Ivermectin prevents onchocerciasis and is the drug of choice in the individual and mass treatment of the disease. The only other drug listed with any activity against Onchocerca volvulus is diethylcarbamazine. Suramin (not listed) also has activity against onchocerciasis, but like diethylcarbamazine, it is less effective and more toxic than ivermectin. The answer is C.

If ketamine is used as the sole anesthetic in the attempted reduction of a dislocated shoulder joint, its actions will include (A) Analgesia (B) Bradycardia (C) Hypotension (D) Muscle rigidity (E) Respiratory depression

Ketamine is a cardiovascular stimulant, increasing heart rate and blood pressure. This results in part from central sympathetic stimulation and from inhibition of norepinephrine reuptake at sympathetic nerve endings. Analgesia and amnesia occur, with preservation of muscle tone and minimal depression of respiration. The answer is A.

A 46-year-old male patient has Cushing's syndrome due to an adrenal tumor. Which of the following drugs would be expected to reduce the signs and symptoms of this man's disease? (A) Betamethasone (B) Cortisol (C) Fludrocortisone (D) Ketoconazole (E) Triamcinolone

Ketoconazole inhibits many types of cytochrome P450 enzymes. It can be used to reduce the unregulated overproduction of corticosteroids by adrenal tumors. The answer is D.

Serious cardiac effects have occurred when this drug was taken by patients using the antihistamines astemizole or terfenadine (A) Amphotericin B (B) Griseofulvin (C) Ketoconazole (D) Terbinafine (E) Voriconazole

Ketoconazole was the first oral azole introduced into clinical use, but it has a greater propensity to inhibit human cytochrome P450 enzymes than other azoles and is no longer widely used in the United States. Cardiotoxicity may occur when ketoconazole is used by patients taking astemizole or terfenadine as a result of the ability of ketoconazole to inhibit their metabolism via hepatic cytochromes P450. The answer is C.

The main advantage of ketorolac over aspirin is that ketorolac (A) Can be combined more safely with an opioid such as codeine (B) Can be obtained as an over-the-counter agent (C) Does not prolong the bleeding time (D) Is available in a parenteral formulation that can be injected intramuscularly or intravenously (E) Is less likely to cause acute renal failure in patients with some preexisting degree of renal impairment

Ketorolac exerts typical NSAID effects. It prolongs the bleeding time and can impair renal function, especially in a patient with preexisting renal disease. Its primary use is as a parenteral agent for pain management, especially for treatment of postoperative patients. The answer is D.

Which of the following statements about interferon-α is false? (A) At the start of treatment, most patients experience flulike symptoms (B) Indications include treatment of genital warts (C) It is used in the management of hepatitis B and C (D) Lamivudine interferes with its activity against hepatitis B (E) Toxicity includes bone marrow suppression

Lamivudine is used in monotherapy of HBV infections and does not oppose the beneficial effects of interferon-α when both agents are used together in the treatment of hepatitis B. The answer is D.

Prilocaine is relatively contraindicated in patients with cardiovascular or pulmonary disease because the drug (A) Acts as an antagonist at β adrenoceptors in the heart and the lung (B) Causes decompensation through formation of methemoglobin (C) Inhibits cyclooxygenase in cardiac and pulmonary cells (D) Is a potent bronchoconstrictor (E) None of the above

Large doses of prilocaine may cause accumulation of o-toluidine, a metabolite that converts hemoglobin to methemoglobin. Patients may become cyanotic with blood "chocolate colored." High blood levels of methemoglobin have resulted in decompensation in patients who have cardiac or pulmonary diseases. The answer is B.

A new drug is under study in phase 1 trials. It is found that this molecule is avidly taken up by extravascular tissues so that the final total amount in the extravascular compartment at steady state is 100 times the amount remaining in the blood plasma. What is the probable volume of distribution in a hypothetical person with 8L of blood and 4L of plasma? (A) Insufficient data to calculate (B) 8 L (C) 14.14 L (D) 100 L (E) 404 L

Let Z be the amount in the blood plasma. If the amount in the rest of the body is 100 times greater, then the total amount in the body is 101Z. The concentration in the blood plasma (Cp ) is Z/4 L. According to the definition: Vd = amount in body/ Cp Vd =101Z/ Z/4L = 101 × 4 L = 404L The answer is E.

A 60-year-old man is found to have a prostate lump and an elevated prostate-specific antigen (PSA) blood test. Magnetic resonance imaging suggests several enlarged lymph nodes in the lower abdomen, and an x-ray reveals 2 radiolucent lesions in the bony pelvis. This patient is likely to be treated with which of the following drugs? (A) Anastrozole (B) Desogestrel (C) Leuprolide (D) Methyltestosterone (E) Oxandrolone

Leuprolide is a GnRH agonist used in the treatment of men with prostate cancer. Continuous use leads to downregulation of testosterone production. Initially, the agonist action increases testosterone, causing a tumor flare. To prevent this, flutamide, a competitive antagonist of the androgen receptor, is added until downregulation of testosterone is complete. The answer is C.

An important difference between leuprolide and ganirelix is that ganirelix (A) Can be administered as an oral formulation (B) Can be used alone to restore fertility to hypogonadal men and women (C) Immediately reduces gonadotropin secretion (D) Initially stimulates pituitary production of LH and FSH (E) Must be administered in a pulsatile fashion

Leuprolide is an agonist of GnRH receptors, whereas ganirelix is an antagonist. Although both drugs can be used to inhibit gonadotropin release, ganirelix does so immediately, whereas leuprolide does so only after about 1 wk of sustained activity. The answer is C.

Bradykinesia has made drug treatment necessary in a 60-year-old male patient with Parkinson's disease, and therapy is to be initiated with levodopa. The prescribing physician will (or should) know that levodopa (A) Causes fewer CNS side effects if given together with a drug that inhibits hepatic dopa decarboxylase (B) Fluctuates in its effectiveness with increasing frequency as treatment continues (C) Prevents extrapyramidal adverse effects of antipsychotic drugs (D) Protects against cancer in patients with melanoma (E) Has toxic effects, which include pulmonary infiltrates

Levodopa causes less peripheral toxicity but more CNS or behavioral side effects when its conversion to dopamine is inhibited outside the CNS. The drug is not effective in antagonizing the akinesia, rigidity, and tremor caused by treatment with antipsychotic agents. Levodopa is a precursor of melanin and may activate malignant melanoma. Use of levodopa is not associated with pulmonary dysfunction. The answer is B.

A 60-year-old woman comes to the emergency department with atypical chest pain. Her ECG reveals ventricular tachycardia with rare normal sinus beats, and ST-segment elevation. Troponin C levels are markedly increased, suggesting myocardial damage. A diagnosis of myocardial infarction is made, and the woman is admitted to the cardiac intensive care unit. Her arrhythmia will probably be treated initially with (A) Adenosine (B) Digoxin (C) Lidocaine (D) Quinidine (E) Verapamil

Lidocaine has limited applications as an antiarrhythmic drug, but emergency treatment of myocardial infarction arrhythmias is one of the most important. Procainamide or amiodarone are used as alternative drugs in this situation. Lidocaine is also useful in digoxin-induced arrhythmias. After recovery from the acute phase of a myocardial infarction, β blockers are used for 2 years or more to prevent sudden death arrhythmias. The answer is C.

Which of the following drugs is most likely to increase serum concentrations of conventional doses of methotrexate, a weak acid that is primarily cleared in the urine? (A) Acetaminophen (B) Allopurinol (C) Colchicine (D) Hydroxychloroquine (E) Probenecid

Like other weak acids, methotrexate depends on active tubular excretion in the proximal tubule for efficient elimination. Probenecid competes with methotrexate for binding to the proximal tubule transporter and thereby decreases the rate of clearance of methotrexate. The answer is E.

Regarding the clinical use of liposomal formulations of amphotericin B, which statement is accurate? (A) Amphotericin B affinity for these lipids is greater than affinity for ergosterol (B) Less expensive to use than conventional amphotericin B (C) More effective in fungal infections because they increase tissue uptake of amphotericin B (D) They decrease the nephrotoxicity of amphotericin B (E) They have a wider spectrum of antifungal activity than conventional formulations of amphotericin B

Liposomal formulations of amphotericin B result in decreased accumulation of the drug in tissues, including the kidney. As a result, nephrotoxicity is decreased. With some lipid formulations, infusion-related toxicity may also be reduced. Lipid formulations do not have a wider antifungal spectrum; their daily cost ranges from 10 to 40 times more than the conventional formulation of amphotericin B. The answer is D.

All of the following factors influence the action of local anesthetics except (A) Acetylcholinesterase activity in the region of the injection site (B) Blood flow through the tissue in which the injection is made (C) Dose of local anesthetic injected (D) The use of vasoconstrictors (E) Tissue pH

Local anesthetics are poor substrates for acetylcholinesterase, and the activity of this enzyme does not play a part in terminating the actions of local anesthetics. Ester-type local anesthetics are hydrolyzed by plasma (and tissue) pseudo- cholinesterases. Persons with genetically based defects in pseudocholinesterase activity are unusually sensitive to procaine and other esters. The answer is A.

Characteristic properties of local anesthetics include all of the following except (A) An increase in membrane refractory period (B) Blockade of voltage-dependent sodium channels (C) Effects on vascular tone (D) Preferential binding to resting channels (E) Slowing of axonal impulse conduction

Local anesthetics bind preferentially to sodium channels in the open and inactivated states. Recovery from drug-induced block is 10-1000 times slower than recovery of channels from normal inactivation. Resting channels have a lower affinity for local anesthetics. The answer is D.

A 58-year-old postmenopausal woman was sent for dual-energy x-ray absorptiometry to evaluate the bone mineral density of her lumbar spine, femoral neck, and total hip. The test results revealed significantly low bone mineral density in all sites. Chronic use of which of the following medications is most likely to have contributed to this woman's osteoporosis? (A) Lovastatin (B) Metformin (C) Prednisone (D) Propranolol (E) Thiazide diuretic

Long-term therapy with glucocorticoids such as prednisone is associated with a reduction in bone mineral density and an increased risk of fractures. The other drugs are not known to have significant effects on bone or serum calcium. The answer is C.

Which of the following is an important effect of chronic therapy with loop diuretics? (A) Decreased urinary excretion of calcium (B) Elevation of blood pressure (C) Elevation of pulmonary vascular pressure (D) Metabolic alkalosis (E) Teratogenic action in pregnancy

Loop diuretics increase urinary calcium excretion and decrease blood pressure (in hypertension) and pulmonary vascular pressure (in congestive heart failure). They have no recognized teratogenic action. They cause metabolic alkalosis (Table 15-1). Loop diuretics also cause ototoxicity. The answer is D.

A 32-year-old woman with hypertension wishes to become pregnant. Her physician informs her that she will have to switch to another antihypertensive drug. Which of the following drugs is absolutely contraindicated in pregnancy? (A) Atenolol (B) Losartan (C) Methyldopa (D) Nifedipine (E) Propranolol

Losartan Methyldopa is often recommended in pregnant patients because it has a good safety record. Calcium channel blockers (choice D) and β blockers (choices A and E) are not contraindicated. In contrast, ACE inhibitors and ARBs (choice B) have been shown to be teratogenic, causing severe renal abnormalities in the fetus. The answer is B.

Which statement concerning anesthetic MAC (minimum anesthetic concentration) value is most accurate? (A) Anesthetics with low MAC value have low potency (B) MAC values increase in elderly patients (C) MAC values give information about the slope of the dose-response curve (D) Methoxyflurane has an extremely low MAC value (E) Simultaneous use of opioid analgesics increases the MAC for inhaled anesthetics

MAC value is inversely related to potency; a low MAC means high potency. MAC gives no information about the slope of the dose-response curve. Use of opioid analgesics or other CNS depressants with inhaled anesthetics lowers the MAC value. As with most CNS depressants, the elderly patient is more sensitive, so MAC values are lower. Methoxyflurane has the lowest MAC value of the inhaled anesthetics. The answer is D.

Which statement about inhalants is most accurate? (A) Euphoria, numbness, and tingling sensations with visual and auditory disturbances occur in most persons who inhale organic nitrites (B) Methemoglobinemia is a common toxicologic problem after repetitive inhalation of industrial solvents (C) Nitrous oxide is the most commonly abused drug by medical personnel working in hospitals (D) Solvent inhalation is mainly a drug abuse problem in petroleum industry workers (E) The inhalation of isobutyl nitrite is likely to cause headache, hypotension, and flushing

Male preteens are most likely to "experiment" with solvent inhalation. This can result in central and peripheral neurotoxicity, liver and kidney damage, and pulmonary disease. Opioids, including fentanyl and meperidine, are the most widely abused by medical personnel working in hospitals. Industrial solvents rarely cause methemoglobinemia, but this (and headaches, flushing, and hypotension) occur after excessive use of nitrites. The answer is E.

A 20-year-old male patient scheduled for hernia surgery was anesthetized with halothane and nitrous oxide; tubocurarine was provided for skeletal muscle relaxation. The patient rapidly developed tachycardia and became hypertensive. Generalized skeletal muscle rigidity was accompanied by marked hyperthermia. Laboratory values revealed hyperkalemia and acidosis. This unusual complication of anesthesia is most likely to be caused by: (A) Acetylcholine release from somatic nerve endings at skeletal muscle (B) Activation of brain dopamine receptors by halothane (C) Antagonism of autonomic ganglia by tubocurarine (D) Calcium released within skeletal muscle (E) Toxic metabolites of nitrous oxide

Malignant hyperthermia is a rare but life-threatening reaction that may occur during general anesthesia with halogenated anesthetics and skeletal muscle relaxants, particularly succinylcholine and tubocurarine. Release of calcium from skeletal sarcoplasmic reticulum leads to muscle spasms, hyperthermia, and autonomic instability. Predisposing genetic factors include clinical myopathy associated with mutations in the gene loci for the skeletal muscle ryanodine receptor or L-type calcium receptors. Nitrous oxide is not metabolized! The answer is D.

A college student is brought to the emergency department by friends. The physician is informed that the student had taken a drug and then "went crazy." The patient is agitated and delirious. Several persons are required to hold him down. His skin is warm and sweaty, and his pupils are dilated. Bowel sounds are normal. Signs and symptoms include tachycardia, marked hypertension, hyperthermia, increased muscle tone, and both horizontal and vertical nystagmus. The management of this patient is likely to include (A) Administration of epinephrine (B) Alkalinization of the urine to increase drug elimination (C) Amitriptyline if psychosis ensues (D) Atropine to control hyperthermia (E) None of the above

Management of phencyclidine (PCP) overdose involves ventilatory support and control of seizures (with a benzodiazepine), hypertension, and hyperthermia. Antipsychotic drugs (eg, haloperidol) may also be useful for psychosis. None of the drugs listed are of value. Atropine may cause hyperthermia! Phencyclidine is a weak base, and its renal elimination may be accelerated by urinary acidification, not alkalinization! A large percentage of phencyclidine is secreted into the stomach, so removal of the drug may be hastened by activated charcoal or nasogastric suction. The answer is E.

Which of the following drugs has a high affinity for 5-HT receptors in the brain, does not cause extrapyramidal dysfunction or hematotoxicity, but is reported to increase the risk of significant QT prolongation? (A) Clozapine (B) Haloperidol (C) Olanzapine (D) Valproic acid (E) Ziprasidone

Many of the newer antipsychotic drugs have a greater a ity for 5-HT 2 receptors than dopamine receptors. However, because clozapine is hematotoxic, the choice comes down to olanzapine and ziprasidone, both of which block 5-HT receptors. Of the currently available atypical antipsychotic drugs, ziprasidone carries the greatest risk of QT prolongation. The answer is E

Which statement about the development of new drugs is most correct? (A) Because they may cause anaphylaxis, proteins cannot be used as drugs (B) Most drugs fall between 100 and 1000 in molecular weight (C) Drugs for systemic action that are to be administered orally should be highly water soluble and insoluble in lipids (D) Water solubility is minimal in highly polarized (charged) drug molecules

Many peptide and protein drugs, eg, insulin, antibodies, are in use; if identical or sufficiently similar to the human molecules, anaphylaxis is uncommon. Most drugs do fall between 100 and 1000 in molecular weight. Drugs for systemic use should be at least minimally water soluble (so they do not precipitate in the intestine) and lipid soluble (so they can cross lipid barriers). Charged molecules attract a shell of water molecules, making them more water soluble. The answer is B.

A malnourished 12-year-old child who lives in a rural area of the southern United States presents with weakness, fever, cough, abdominal pain, and eosinophilia. His mother tells you that she has seen long, thin worms in the child's stools, sometimes with blood. A presumptive diagnosis of ascariasis is confirmed by the presence of the ova of A lumbricoides in the stools. However, microscopy reveals that the stools also contain the eggs of Necator americanus. The drug most likely to be effective in the treatment of this child is (A) Diethylcarbamazine (B) Ivermectin (C) Mebendazole (D) Niclosamide (E) Praziquantel

Mebendazole is effective against both nematodes causing infection in this child. Albendazole and pyrantel pamoate (not listed in this question) are also primary drugs for the treatment of combined infections due to hookworm and roundworm. The answer is C.

A 10-year-old American girl presented to the emergency department with fever, chills, lethargy, and splenomegaly. She had recently returned from Nigeria, where she had spent 3 weeks with her grandparents. She had previously received all standard childhood immunizations but no prophylactic travel medications because her parents had returned to Nigeria several times previously without any medical problems. Laboratory examination reveals low hematocrit and platelet count and elevated creatinine. Blood smear reveals parasites in the erythrocytes and a diagnosis of falciparum malaria is made. The patient should have received prophylaxis for the prevention of malaria; what prophylactic regimen would have been most appropriate? (A) Artesunate (B) Chloroquine (C) Mefloquine (D) Quinidine (E) Tetracycline

Mefloquine is a recommended drug for prophylaxis in regions of the world where chloroquine-resistant P falciparum is endemic. Quinidine is not indicated for prophylaxis. Doxycycline (not tetracycline) is an alternative drug for prophylaxis but must be given daily. The answer is C.

A 25-year-old college student went to student health care center for severe cramps, diarrhea, fever, and weight loss. She was diagnosed with Crohn's disease. Which drug is most likely to be useful in the treatment of her inflammatory bowel disease? (A) Diphenhydramine (B) Diphenoxylate (C) Mesalamine (D) Ondansetron (E) Ursodiol

Mesalamine is a form of 5-aminosalicylic acid that is active in the large intestine and thereby provides a local antiinflammatory effect that is useful in Crohn's disease, a form of inflammatory bowel disease. The answer is C.

The primary mechanism of resistance of Gram-positive organisms to macrolide antibiotics including erythromycin is (A) Changes in the 30S ribosomal subunit (B) Decreased drug permeability of the cytoplasmic membrane (C) Formation of drug-inactivating acetyltransferases (D) Formation of esterases that hydrolyze the lactone ring (E) Methylation of binding sites on the 50S ribosomal subunit

Methylase production and methylation of the receptor site are established mechanisms of resistance of Gram-positive organisms to macrolide antibiotics. Such enzymes may be inducible by macrolides or constitutive; in the latter case, cross-resistance occurs between macrolides and clindamycin. Increased expression of efflux pumps is also a mechanism of macrolide resistance. Esterase formation is a mechanism of macrolide resistance seen in coliforms. The answer is E.

A 55-year-old man presents with lower abdominal discomfort, flatulence, and occasional diarrhea. A diagnosis of intestinal amebiasis is made, and E histolytica is identified in his diarrheal stools. An oral drug is prescribed, which reduces his intestinal symptoms. Later he presents with severe dysentery, right upper quadrant pain, weight loss, fever, and an enlarged liver. Amebic liver abscess is diagnosed, and the patient is hospitalized. He has a recent history of drug treatment for a cardiac arrhythmia. The drug regimen most likely to be effective in treating severe extraintestinal disease in this patient is (A) Chloroquine (B) Diloxanide furoate plus iodoquinol (C) Emetine plus diloxanide furoate plus chloroquine (D) Pentamidine followed by mefloquine (E) Tinidazole plus diloxanide furoate

Metronidazole given for 10 d, or tinidazole for 5 d, plus a luminal agent is effective in most cases of hepatic abscess, and these regimens have the dual advantage of being both amebicidal and active against anaerobic bacteria. Though active in amebic hepatic abscess, treatment with emetine is contraindicated in patients with a history of cardiac disease. The answer is E.

Metronidazole is not effective in the treatment of (A) Amebiasis (B) Infections due to Bacteroides fragilis (C) Infections due to Pneumocystis jirovecii (D) Pseudomembranous colitis (E) Trichomoniasis

Metronidazole is the drug of first choice for all of the conditions listed except pneumocystosis. The answer is C.

A 55-year-old man presents with lower abdominal discomfort, flatulence, and occasional diarrhea. A diagnosis of intestinal amebiasis is made, and E histolytica is identified in his diarrheal stools. An oral drug is prescribed, which reduces his intestinal symptoms. Later he presents with severe dysentery, right upper quadrant pain, weight loss, fever, and an enlarged liver. Amebic liver abscess is diagnosed, and the patient is hospitalized. He has a recent history of drug treatment for a cardiac arrhythmia. The preferred treatment that he should have received for the initial symptoms (which were indicative of mild-to moderate disease) is (A) Diloxanide furoate (B) Iodoquinol (C) Metronidazole (D) Metronidazole plus diloxanide furoate (E) Paromomycin

Metronidazole plus a luminal amebicide is the treatment of choice in mild to moderate amebic colitis. Diloxanide furoate (or iodoquinol, or paromomycin) can be used as the sole agent in asymptomatic intestinal infection. The answer is D.

Which of the following is a drug that, in high doses, blocks the glucocorticoid receptor? (A) Aminoglutethimide (B) Beclomethasone (C) Ketoconazole (D) Mifepristone (E) Spironolactone

Mifepristone is a competitive antagonist of glucocorticoid and progesterone receptors. Ketoconazole and aminoglutethimide also antagonize corticosteroids; however, they act by inhibiting steroid hormone synthesis. The answer is D.

A teenager seeks postcoital contraception. Which of the f lowing preparations will be effective for this purpose? (A) Clomiphene (B) Tamoxifen (C) Diethylstilbestrol (DES) (D) Mifepristone

Mifepristone, an antagonist at progesterone and glucocorticoid receptors, has a luteolytic effect and is effective as a postcoital contraceptive. When combined with a prostaglandin, it is also an effective abortifacient. The answer is D.

A patient has accidentally ingested mushrooms identified as Amanita phalloides. Which herbal substance is claimed to protect against hepatic dysfunction? (A) Echinacea (B) Ginkgo (C) Melatonin (D) Milk thistle (E) Saw palmetto

Milk thistle contains compounds that may have cytoprotective actions against liver toxins, including those present in Amanita mushrooms. The answer is D.

A hospitalized AIDS patient is receiving a roviral drugs but no antimicrobial prophylaxis. He develops sepsis with fever, suspected to be caused by a Gram-negative bacillus. If amikacin is used in the treatment of this patient, monitoring of serum drug level may be advised because the drug (A) Does not penetrate into cerebrospinal fluid (B) Has a narrow therapeutic window (C) Is antagonized by beta-lactam antibiotics (D) Is hematotoxic (E) Is rapidly metabolized by the liver

Monitoring plasma aminoglycoside levels is important because amikacin and other aminoglycosides have a low therapeutic index; toxicity may occur when plasma levels are only 3-4 times higher than minimum inhibitory concentrations. Decreases in renal function may elevate the plasma levels of aminoglycosides to toxic levels within a few hours. Aminoglycosides undergo renal elimination and they are not hematotoxic. The answer is B.

A 72-kg patient with creatinine clearance of 80 mL/min has a Gram-negative infection. Amikacin is administered intramuscularly at a dose of 5 mg/kg every 8 h, and the patient begins to respond. After 2 d, creatinine clearance declines to 40 mL/min. Assuming that no information is available about amikacin plasma levels, what would be the most reasonable approach to management of the patient at this point? (A) Administer 5 mg/kg every 12 h (B) Decrease the dosage to daily total of 200 mg (C) Decrease the dosage to 180 mg every 8 h (D) Discontinue amikacin and switch to gentamicin (E) Maintain the patient on the present dosage and test auditory function

Monitoring plasma drug levels is important when a glycosides are used. In this case, the patient seems to be improving, so a decrease of the amikacin dose in proportion to decreased creatinine clearance is most appropriate. Because creatinine clearance is only one half of the starting value, a dose reduction should be made to one half of that given initially. The answer is C.

A child requires multiple minor surgical procedures involving the nasopharynx. Which drug has high surface local anesthetic activity and intrinsic vasoconstrictor actions that reduce bleeding in mucous membranes? (A) Bupivacaine (B) Cocaine (C) Lidocaine (D) Mepivacaine (E) Tetracaine

Most local anesthetics cause vasodilation. Cocaine is the only local anesthetic with intrinsic vasoconstrictor activity owing to its action to block the reuptake of norepinephrine released from sympathetic nerve endings (Chapter 9). Cocaine also has significant surface local anesthetic activity and is favored for head, neck, and pharyngeal surgery. The answer is B.

Risk factors for multidrug-resistant tuberculosis include (A) A history of treatment of tuberculosis without rifampin (B) Recent immigration from Asia and living in an area of over 4% isoniazid resistance (C) Recent immigration from Latin America (D) Residence in regions where isoniazid resistance is known to exceed 4% (E) All of the above

Multidrug-resistant tuberculosis (MDR-TB) is defined as resistance to 2 or more drugs. All the risk factors are relevant. In the case of resistance to both INH and rifampin, initial regimens still include both drugs, plus ethambutol, pyrazinamide, streptomycin (or other aminoglycoside), and a fluoroquinolone. Continuation therapy should include at least 3 drugs shown to be active in vitro against the infecting strain. The appropriate duration of therapy has not been established. The answer is E.

Which of the following is an expected effect of a therapeutic dose of an antimuscarinic drug? (A) Decreased cAMP (cyclic adenosine monophosphate) in cardiac muscle (B) Decreased DAG (diacylglycerol) in salivary gland tissue (C) Increased IP 3 (inositol trisphosphate) in intestinal smooth muscle (D) Increased potassium efflux from smooth muscle (E) Increased sodium influx into the skeletal muscle end plate

Muscarinic M 1and M 3receptors mediate increases in IP 3and DAG in target tissues (intestine, salivary glands). M 2 receptors (heart) mediate a decrease in cAMP and an increase in potassium permeability. Antimuscarinic agents block these effects. The answer is B.

Actions and clinical uses of muscarinic cholinoceptor agonists include which one of the following? (A) Bronchodilation (treatment of asthma) (B) Miosis (treatment of narrow angle glaucoma) (C) Decreased gastrointestinal motility (treatment of diarrhea) (D) Decreased neuromuscular transmission and relaxation of skeletal muscle (during surgical anesthesia) (E) Increased sweating (treatment of fever)

Muscarinic agonists cause accommodation and cyclospasm, the opposite of paralysis of accommodation (cycloplegia). Although not drugs of choice, in acute angle-closure glaucoma, this may result in a desirable increased outflow of aqueous and decreased intraocular pressure. As noted in question 6, these agents may cause bronchospasm but have no effect on neuromuscular transmission. They may cause diarrhea and must not be used in its treatment. Muscarinic agonists may also cause sweating, but drug-induced sweating is of no value in the treatment of fever. The answer is B.

A 24-year-old woman underwent kidney transplantation. A week later, she developed alloantibody-mediated acute rejection (acute humoral rejection [AHR]). She was successfully treated with tacrolimus and a second drug that targets both B and T lymphocytes. Which of the following is an immunosuppressant that suppresses both B and T lymphocytes via inhibition of de novo synthesis of purines? (A) Cyclophosphamide (B) Methotrexate (C) Mycophenolate mofetil (D) Prednisone (E) Tacrolimus

Mycophenolic acid, formed from mycophenolate mofetil, inhibits inosine monophosphate dehydrogenase, the rate-limiting enzyme in the de novo pathway of purine synthesis. This action suppresses both B- and T-lymphocyte activation. Mycophenolate mofetil is used in organ transplantation. The answer is C.

A 3-year-old child has been admitted to the emergency department having swallowed the contents of 2 bottles of a nasal decongestant. The active ingredient of the medication is phenylephrine, a potent, selective α-adrenoceptor agonist drug. Which of the following is a sign of α-receptor activation that may occur in this child? (A) Bronchodilation (B) Cardiac acceleration (tachycardia) (C) Pupillary dilation (mydriasis) (D) Renin release from the kidneys (E) Vasodilation of blood vessels

Mydriasis can be caused by contraction of the radial fibers of the iris; these smooth muscle cells have α receptors. All the other listed responses are mediated by β adrenoceptors (Table 6-3). The answer is C.

Which statement about the speed of onset of nerve blockade with local anesthetics is correct? (A) Faster in hypercalcemia (B) Faster in myelinated fibers (C) Faster in tissues that are infected (D) Slower in hyperkalemia (E) Slower in the periphery of a nerve bundle than in the center of a bundle

Myelinated nerve fibers are blocked by local anesthetics more readily than unmyelinated ones. The answer is B.

Which of the following is a recognized effect of nitric oxide (NO)? (A) Arrhythmia (B) Bronchoconstriction (C) Constipation (D) Inhibition of acute graft rejection (E) Pulmonary vasodilation

NO does not cause arrhythmias or constipation. It causes bronchodilation and may hasten graft rejection. NO does cause pulmonary vasodilation. The answer is E.

A 43-year-old woman with type 2 diabetes and hypertension visits your clinic. Her current blood pressure (measured 3 times) is not at target: 155/98 mm Hg, despite the fact that she is taking hydrochlorothiazide and captopril. The antihypertensive effects of captopril can be antagonized (reduced) by which of the following? (A) Angiotensin II receptor blockers (B) Loop diuretics (C) NSAIDs (D) Sulfonylurea hypoglycemics (E) Pioglitazone

NSAIDs interfere with the antihypertensive action of angiotensin-converting enzyme inhibitors; the other drugs listed enhance the blood pressure-lowering effects of captopril and other members of the "pril" drug family. Pioglitazone is a hypoglycemic drug used in patients with type 2 diabetes mellitus and has no significant effect on blood pressure. The answer is C.

Which statement about nalbuphine is most accurate? (A) Activates µ receptors (B) Does not cause respiratory depression (C) Is a nonsedating opioid (D) Pain-relieving action is not superior to that of codeine (E) Response to naloxone in overdose may be unreliable

Nalbuphine and butorphanol are κ agonists, with weak µ-receptor antagonist activity. They have analgesic efficacy superior to that of codeine, but not equivalent to that of strong µ-receptor agonists. Although these mixed agonistantagonist drugs are less likely to cause respiratory depression than strong µ activators, if depression does occur, reversal with opioid antagonists such as naloxone is unpredictable. Sedation is common. The answer is E.

The intense craving experienced by those who are trying to recover from chronic alcohol abuse can be ameliorated by a drug that is an (A) Agonist of α 1 adrenoceptors (B) Agonist of serotonin receptors (C) Antagonist of β 2 adrenoceptors (D) Antagonist of opioid receptors (E) Inhibitor of cyclooxygenase

Naltrexone, a competitive inhibitor of opioid receptors, decreases the craving for alcohol in patients who are recovering from alcoholism. The answer is D.

A 30-year-old man has been treated with several autonomic drugs for 4 weeks. He is now admitted to the emergency department showing signs of drug toxicity. Which of the following signs would distinguish between an overdose of a ganglion blocker versus a muscarinic blocker? (A) Cycloplegia (B) Dry skin in a warm environment (C) Miosis (D) Postural hypotension (E) Tachycardia

Neither ganglion blockers nor muscarinic blockers cause miosis; they cause mydriasis. Both classes of cholinoceptor blockers increase resting heart rate and cause cycloplegia, because these are determined largely by parasympathetic tone. Similarly, both can cause dry skin, since this requires cholinergic transmission. Postural hypotension, on the other hand, is a sign of sympathetic blockade, which would occur with ganglion blockers but not muscarinic blockers (Chapter 6). The answer is D

A contraindication to the use of gastric lavage for the removal of drugs from the stomach of a victim of poisoning is (A) An overdose of iron pills (B) An unconscious patient (C) Ingestion of a corrosive (D) Overdose with a sustained-release formulation

Neither gastric lavage nor syrup of ipecac should be used in patients who have ingested a corrosive because of the risk of esophageal damage. Gastric lavage can be used in a comatose patient if the airway has been protected with a cuffed endotracheal tube. The answer is C.

A patient with hypertension and angina is referred for treatment ment. Metoprolol and verapamil are among the drugs considered. Both metoprolol and verapamil are associated with which one of the following? (A) Diarrhea (B) Hypoglycemia (C) Increased PR interval (D) Tachycardia (E) Thyrotoxicosis

Neither β blockers nor calcium channel blockers cause diarrhea. Hypoglycemia is not a common effect of any of the antihypertensive drugs. Thyroid disorders are not associated with either drug group. However, calcium blockers, especially verapamil and diltiazem, and β blockers are associated with depression of calcium-dependent processes in the heart, for example, contractility, heart rate, and atrioventricular conduction. Therefore, bradycardia and increased PR interval may be expected. The dihydropyridines do not often cause cardiac depression, probably because they evoke increased sympathetic outflow as a result of their dominant vascular effects. The answer is C.

PB is a 28-year-old male who experienced a dull ache and a sensation of heaviness in the right testicle. On physical exam the right testis appeared to be enlarged. An orchidectomy was performed and chemotherapy started. Which of the following is a drug that is used in combination therapy for testicular carcinoma and is also associated with nephrotoxicity? (A) Bleomycin (B) Cisplatin (C) Etoposide (D) Leuprolide (E) Vinblastine

Nephrotoxicity is a characteristic toxicity of cisplatin. Renal toxicity can be reduced by slow intravenous infusion, maintenance of good hydration, and administration of mannitol to maximize urine flow. For testicular cancer, cisplatin is used in combination with etoposide and bleomycin. The answer is B.

An adult patient is being treated for acute leukemia with a combination of anticancer drugs that includes cyclophosphamide, mercaptopurine, methotrexate, vincristine, and prednisone. He is also using ondansetron for emesis, a chlorhexidine mouthwash to reduce mucositis, and laxatives. The patient complains of "pins and needle" sensations in the extremities and muscle weakness. He is not able to execute a deep knee bend or get up out of a chair without using his arm muscles. He is also very constipated. If these problems are related to the chemotherapy, which of the following is the most likely causative agent? (A) Cyclophosphamide (B) Mercaptopurine (C) Methotrexate (D) Prednisone (E) Vincristine

Neuropathy is a toxic side effect of vincristine. In its m est form, paresthesias occur, but it progresses to significant muscle weakness, initially in the quadriceps muscle group. Constipation is the most common symptom of autonomic neuropathy. The answer is E.

A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL cholesterol, VLDL cholesterol, and triglycerides are normal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. If the patient has a history of gout, which of the following drugs is most likely to exacerbate this condition? (A) Colestipol (B) Ezetimibe (C) Gemfibrozil (D) Niacin (E) Simvastatin

Niacin can exacerbate both hyperuricemia and glucose introlerance. The answer is D.

Which parasite is susceptible to niclosamide? (A) Ascaris lumbricoides (roundworm) (B) Echinococcus granulosus (hydatid disease) (C) Fasciola hepatica (sheep liver fluke) (D) Necator americanus (hookworm) (E) Taenia solium (pork tapeworm)

Niclosamide is not active against nematodes or flukes with the exception of the large intestinal fluke. It is a co-drug of choice (with praziquantel) to treat common tapeworm infections and is usually effective in a single dose. The drug is minimally absorbed from the gastrointestinal tract and causes few side effects. The answer is E.

One of the first neurotransmitter receptors to be identified in the CNS is located on the Renshaw cell in the spinal cord. Activation of+ this receptor results in excitation via an increase in cation (Na , K+ ) conductance independently of G-proteincoupled mechanisms. Which of the following compounds is most likely to activate this receptor? (A) Dopamine (B) Glycine (C) GABA (D) Nicotine (E) Serotonin

Nicotinic receptors on the Renshaw cell are activated by the release of ACh from motor neuron collaterals. This results in the release of glycine, which, via interaction with its receptors on the motor neuron, causes membrane hyperpolarization, an example of feedback inhibition. The receptors were so named because of their activation by nicotine. The answer is D.

Which one of the following is characteristic of nifedipine treatment in patients with essential hypertension? (A) Competitively blocks angiotensin II at its receptor (B) Decreases calcium efflux from skeletal muscle (C) Decreases renin concentration in the blood (D) Decreases calcium influx into smooth muscle (E) Increases calcium excretion in the urine

Nifedipine is a prototype L-type calcium channel blocker and lowers blood pressure by reducing calcium influx into vascular smooth muscle. It has no effect on angiotensin-converting enzyme. Calcium efflux from skeletal muscle cells does not involve the L-type Ca 2+ channel. The plasma renin level may increase as a result of the compensatory response to reduced blood pressure. Calcium channel blockers have negligible effects on urine calcium. The answer is D.

A 57-year-old woman presents to her primary care physician with a complaint of severe chest pain when she walks uphill in cold weather. The pain disappears when she rests. She has a 40-pack-year history of smoking but her plasma lipids are within the normal range. After evaluation and discussion of treatment options, a decision is made to treat her with nitroglycerin. Which of the following is a common direct or reflex effect of nitroglycerin? (A) Decreased heart rate (B) Decreased venous capacitance (C) Increased afterload (D) Increased cardiac force (E) Increased diastolic myocardial fiber tensions

Nitroglycerin increases heart rate and venous capacitance and decreases afterload and diastolic fiber tension. It increases cardiac contractile force because the decrease in blood pressure evokes a compensatory increase in sympathetic discharge. The answer is D.

Which one of the following is not a nitric oxide donor but causes it to be synthesized and released from endogenous precursors, resulting in vasodilation? (A) Acetylcholine (B) Arginine (C) Isosorbide mononitrate (D) Nitroglycerin (E) Nitroprusside

Nitroprusside and organic nitrites (eg, amyl nitrite) and nitrates (eg, nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate) contain NO groups that can be released as NO. Arginine is the normal source of endogenous NO. Acetylcholine, acting on M 3 receptors, stimulates the synthesis of NO from arginine. The answer is A.

An NO-containing molecule that releases nitric oxide in the blood is (A) Citrulline (B) Histamine (C) Isoproterenol (D) Nitroglycerin (E) Nitroprusside

Nitroprusside is the only molecule in this list that s ously releases NO in the bloodstream. The answer is E.

Regarding the clinical use of antidepressant drugs, which statement is most accurate? (A) Chronic use of serotonin-norepinephrine reuptake inhibitors (SNRIs) increases the activity of hepatic drugmetabolizing enzymes (B) In the treatment of major depressive disorders, citalopram is usually more effective than paroxetine (C) Tricyclics are highly effective in depressions with attendant anxiety, phobic features, and hypochondriasis (D) Weight gain often occurs during the first few months in patients taking SSRIs (E) When selecting an appropriate drug for treatment of depression, the history of patient response to specific drugs is a valuable guide

No antidepressant has been shown to increase hepatic drug metabolism. MAO inhibitors (not TCAs), though now used infrequently, are the drugs most likely to be effective in depression with attendant anxiety, phobic features, and hypochondriasis. SSRIs are usually associated with weight loss, at least during the first 6 months of treatment. There is no evidence that any SSRI is more effective than another, or more effective overall than a tricyclic drug, in treatment of major depressive disorder. The answer is E.

Which antiseptic promotes wound healing? (A) Cetylpyridinium chloride (B) Chlorhexidine (C) Hexachlorophene (D) Phenol (E) None of the above

No antiseptic in current use is able to promote wound healing, and most agents do the opposite. In general, cleansing of abrasions and superficial wounds with soap and water is just as effective as and less damaging than the application of topical antiseptics. Phenol is only used as a disinfectant of inanimate objects! The answer is E.

A 55-year-old man is seen in the clinic with hypertension of 150/95 mm Hg (millimeters of mercury). His personal medical history and physical examination are otherwise unremarkable but his family history is positive for early deaths due to cardiovascular disease. A decision is made to treat his hypertension, starting with a calcium channel blocker. Blocker A in a dose of 5 mg produces the same decrease in blood pressure as 500 mg of blocker B. Which of the following predictions is most accurate? (A) Blocker A will be more efficacious than blocker B (B) Blocker A will be about 100 times more potent than blocker B (C) Toxicity of blocker A will be less than that of blocker B (D) Blocker A will have a wider therapeutic window than blocker B (E) Blocker A will have a longer half-life than blocker B

No information is given regarding the maximal a sive response to either drug. Similarly, no information about half-life or toxicity is provided. The fact that a given response is achieved with a smaller dose of blocker A indicates only that A is more potent than B in the ratio of 500:5. The answer is B.

A 47-year-old man exhibited signs and symptoms of a megaly. Radiologic studies indicated the presence of a large pituitary tumor. Surgical treatment of the tumor was only partially effective in controlling his disease. At this point, which of the following drugs is most likely to be used as pharmacologic therapy? (A) Cosyntropin (B) Desmopressin (C) Leuprolide (D) Octreotide (E) Somatropin

Octreotide, a somatostatin analog, has some efficacy in reducing the excess GH production that causes acromegaly. The answer is D.

Which compound is the safest drug to use topically to treat scabies and pediculosis? (A) Benzoyl peroxide (B) Chlorhexidine (C) Lindane (D) Permethrin (E) Silver sulfadiazine

Of the agents listed, both lindane and permethrin are e tive scabicides and pediculicides. However, there is some concern about systemic absorption of lindane, which may cause neurotoxicity and hematotoxicity. Accidental ingestion of lindane in children has caused seizures. The answer is D.

A patient presents with pain and stiffness in his wrists and knees. The stiffness is worse first thing in the morning. A blood test confirms rheumatoid arthritis. You advise a short course of steroids. Which one of the following is the most potent anti-inflammatory steroid? (A) Cortisol (B) Dexamethasone (C) Fludrocortisone (D) Prednisone (E) Triamcinolone

Of the drugs listed, cortisol has the lowest and dexamethasone the highest anti-inflammatory activity. The answer is B.

A 72-year-old woman has long-standing heart failure. Which one of the following drugs has been shown to reduce mortality in chronic heart failure? (A) Atenolol (B) Digoxin (C) Furosemide (D) Nitroprusside (E) Spironolactone

Of the drugs listed, only spironolactone has been shown to reduce mortality in this highly lethal disease. Digoxin, furosemide, and nitroprusside are used in the management of symptoms. The answer is E.

A 2-year-old girl presented with lethargy, increased respiratory rate, and an elevated temperature that appeared to result from a drug poisoning. Laboratory testing revealed the following serum concentrations: glucose, 36 mg/dL; Na+ , 148 mEq/L; K+ , 5 mEq/L; Cl− , 111 mEq/L; HCO3 − , 12 mEq/L; BUN, 21 mg/dL; osmolality, 300 mOsm/L. The patient's signs, symptoms, and laboratory values are most consistent with an overdose of (A) Acetaminophen (B) Aspirin (C) Ethylene glycol (D) Lead (E) Phencyclidine

Of the drugs listed, the 2 that are likely to cause an anion gap are aspirin and ethylene glycol. However, if the child had ingested ethylene glycol, she would be expected to exhibit a significant osmolal gap. The anion gap, lethargy, tachypnea, and hyperthermia all are consistent with aspirin poisoning. The answer is B.

The most important effect of inadvertent intravenous a istration of a large dose of lidocaine is (A) Bronchoconstriction (B) Methemoglobinemia (C) Renal failure (D) Seizures (E) Tachycardia

Of the effects listed, the most important in local anesthetic overdose (of both amide and ester types) concern the CNS. Such effects can include sedation or restlessness, nystagmus, coma, respiratory depression, and seizures. Intravenous diazepam is commonly used for seizures caused by local anesthetics. Methemoglobinemia is caused by a prilocaine metabolite. The answer is D.

Which statement concerning the adverse effects of antipsychotic drugs is most accurate? (A) Acute dystonic reactions occur commonly with olanzapine (B) Akathisias due to antipsychotic drugs are managed by increasing the drug dose (C) Blurring of vision and urinary retention are common adverse effects of haloperidol (D) Retinal pigmentation is a dose-dependent toxic effect of thioridazine (E) The late-occurring choreoathetoid movements caused by conventional antipsychotic drugs may be alleviated by atropine

Olanzapine has minimal dopamine receptor-blocking action and is unlikely to cause acute dystonias. Muscarinic blockers such as atropine exacerbate tardive dyskinesias. Akathisias (uncontrollable restlessness) resulting from antipsychotic drugs may be relieved by a reduction in dosage. Retinal pigmentation may occur from treatment with thioridazine. The answer is D.

A recently widowed 76-year-old woman was treated with a benzodiazepine for several weeks after the death of her husband, but she did not like the daytime sedation it caused even at low dosage. Living independently, she has no major medical problems but appears rather infirm for her age and has poor eyesight. Because her depressive symptoms are not abating, you decide on a trial of an antidepressant medication. Which of the following drugs would be the most appropriate choice for this patient? (A) Amitriptyline (B) Citalopram (C) Mirtazapine (D) Phenelzine (E) Trazodone

Older patients are more likely to be sensitive to antideoressant drugs that cause sedation, atropine-like adverse effects, or postural hypotension. Tricyclics and MAO inhibitors cause many autonomic side effects; mirtazapine and trazodone are highly sedating. Citalopram (or another SSRI) is often the best choice in such patients. The answer is B.

A 37-year-old woman with infertility due to obstructed falllopian tubes was undergoing ovulation induction in preparation for in vitro fertilization. After 10 d of treatment with leuprolide, the next step in the procedure is most likely to involve 10-14 d of treatment with which of the following? (A) Bromocriptine (B) Follitropin (C) Gonadorelin (D) hCG (E) Pergolide

Once the patient's endogenous gonadotropin production has been inhibited through continuous administration of the GnRH agonist leuprolide, the next step in ovulation induction is the administration of a drug with FSH activity to stimulate follicle maturation. Follitropin is recombinant FSH. The only other drug listed that is used in ovulation induction is hCG, but this is an LH analog. The answer is B.

A 40-year-old patient with breast cancer is about to undergo cancer chemotherapy with a highly emetogenic (nausea- and vomiting-causing) drug combination. The antiemetic drug most likely to be included in her regimen is (A) Bromocriptine (B) Cetirizine (C) Cimetidine (D) Ketanserin (E) Ondansetron

Ondansetron and other 5-HT 3antagonists have significant antiemetic effects. Diphenhydramine and prednisone are also used for this purpose. The answer is E.

A 34-year-old woman with ulcerative colitis has required long-term treatment with pharmacologic doses of a glucocorticoid agonist. Which of the following is a toxic effect associated with long-term glucocorticoid treatment? (A) A lupus-like syndrome (B) Adrenal gland neoplasm (C) Hepatotoxicity (D) Osteoporosis (E) Precocious puberty in children

One of the adverse metabolic effects of long-term g corticoid therapy is a net loss of bone, which can result in osteoporosis. The answer is D.

A patient underwent a surgical procedure of 2 h. Anesthesia was provided by isoflurane, supplemented by intravenous midazolam and a nondepolarizing muscle relaxant. At the end of the procedure, a low dose of atropine was administered followed by pyridostigmine. A muscarinic receptor antagonist would probably not be needed when a cholinesterase inhibitor was given for reversal of the skeletal muscle relaxant actions of a nondepolarizing drug if the NM blocking agent used was (A) Cisatracurium (B) Mivacurium (C) Pancuronium (D) Tubocurarine (E) Vecuronium

One of the distinctive characteristics of pancuronium is that it can block muscarinic receptors, especially those in the heart. It has sometimes caused tachycardia and hypertension and may cause dysrhythmias in predisposed individuals. The answer is C.

This drug is used in the management of insomnia and facilitates the inhibitory actions of GABA, but it lacks anticonvulsant or muscle-relaxing properties and has minimal effect on REM sleep. Its actions are antagonized by flumazenil. (A) Buspirone (B) Chlordiazepoxide (C) Eszopiclone (D) Ramelteon (E) Phenobarbital

Only two of the drugs listed are used for insomnia, eszopiclone and ramelteon. Eszopiclone, zaleplon, and zolpidem are related hypnotics that, though structurally different from benzodiazepines, appear to have a similar mechanism of action. However, unlike benzodiazepines, these drugs are not used in seizures or in muscle spasticity states. Compared with benzodiazepines, the newer hypnotics are less likely to alter sleep patterns. Ramelteon activates melatonin receptors in the suprachiasmatic nuclei; flumazenil does not reverse its effects. Buspirone is not a hypnotic! The answer is C.

After undergoing surgery for breast cancer, a 53-year-old woman is scheduled to receive 4 cycles of cancer chemotherapy. The cycles are to be administered every 3-5 weeks. Her first cycle was complicated by severe chemotherapy-induced thrombocytopenia. During the second cycle of chemotherapy, it would be appropriate to consider treating this patient with which of the following? (A) Darbepoetin alpha (B) Filgrastim (G-CSF) (C) Iron dextran (D) Oprelvekin (IL-11) (E) Vitamin B12

Oprelvekin (IL-11) stimulates platelet production and decreases the number of platelet transfusions required by patients undergoing bone marrow suppression therapy for cancer. The answer is D.

A 13-year-old boy with type 1 diabetes is brought to the hospital complaining of dizziness. Laboratory findings include severe hyperglycemia, ketoacidosis, and a blood pH of 7.15. Which of the following agents should be administered to achieve rapid control of the severe ketoacidosis in this diabetic boy? (A) Glyburide (B) Insulin glargine (C) NPH insulin suspension (D) Regular insulin (E) Tolbutamide

Oral antidiabetic agents (listed in Table 41-1) are inappropriate in this patient because he has insulin-dependent diabetes. He needs a rapid-acting insulin preparation that can be given intravenously (see Figure 41-1). The answer is D.

A 58-year-old postmenopausal woman was sent for dual-energy x-ray absorptiometry to evaluate the bone mineral density of her lumbar spine, femoral neck, and total hip. The test results revealed significantly low bone mineral density in all sites. If this patient began oral therapy with alendronate, she would be advised to drink large quantities of water with the tablets and remain in an upright position for at least 30 min and until eating the first meal of the day. These instructions would be given to decrease the risk of which of the following? (A) Cholelithiasis (B) Diarrhea (C) Constipation (D) Erosive esophagitis (E) Pernicious anemia

Oral bisphosphonates such as alendronate can irritate the esophagus and stomach. The risk of this toxicity is reduced by drinking water and by remaining in an upright position for 30 min after taking the medication. The answer is D.

A farm worker was accidentally in the field during the aerial spraying with parathion. He was brought to the emergency department. Which of the following will be used in the treatment of this patient? (A) Antiseizure drugs (B) Atropine and pralidoxime (C) Hemodialysis (D) Hyperbaric oxygen (E) Measures to reduce pulmonary edema

Organophosphate poisoning is treated with the muscarinic receptor antagonist atropine and pralidoxime, which regenerates cholinesterase. The answer is B.

A patient under treatment for a major depressive disorder is brought to the emergency department after ingesting 30 times the normal daily therapeutic dose of imipramine. Which of the following would be least useful? (A) Administer bicarbonate and potassium chloride (to correct acidosis and hypokalemia) (B) Administer lidocaine (to control cardiac arrhythmias) (C) Initiate hemodialysis (to hasten drug elimination) (D) Maintain heart rhythm by electrical pacing (E) Use intravenous diazepam to control seizures

Overdose with imipramine or any other tricyclic a pressant drug is a medical emergency. The "3 Cs"—coma, convulsions, and cardiac problems—are the most common causes of death. Widening of the QRS complex on the ECG is a major diagnostic feature of cardiac toxicity. Arrhythmias resulting from cardiac toxicity require the use of drugs with the least effect on cardiac conductivity (eg, lidocaine). Hemodialysis does not increase the rate of elimination of tricyclic antidepressants in overdose. The answer is C.

A young man is brought to the emergency department suffering from an intravenous overdose of cocaine. His signs and symptoms are not likely to include (A) Agitation (B) Bradycardia (C) Hyperthermia (D) Myocardial infarct (E) Seizures

Overdoses with amphetamines or cocaine have many signs and symptoms in common. However, the ability of cocaine to block the reuptake of norepinephrine at sympathetic nerve terminals results in greater cardiotoxicity. Tachycardia is the rule, with the possibility of an arrhythmia, infarct, or stroke. The answer is B.

A student studying medicine at a Caribbean university develops intestinal bilharziasis and oxamniquine is prescribed. Which statement about the proposed drug therapy is accurate? (A) Hospitalization is recommended if the patient has a history of seizure disorders (B) Oxamniquine is not effective in the late stages of the disease (C) Oxamniquine is safe to use in pregnancy (D) The drug is an antagonist at GABA receptors in trematodes (E) The drug is very effective in tapeworm infections

Oxamniquine may cause seizures, especially in persons with a history of convulsive disorders. Such persons should be hospitalized or treated with praziquantel. Oxamniquine is effective in all stages of disease caused by S mansoni, including advanced hepatosplenomegaly, and it has been used extensively for mass treatment. The drug is not effective in other schistosomal diseases, and it is contraindicated in pregnancy. The answer is A.

A 29-year-old woman in her 41st week of gestation had been in labor for 12 h. Although her uterine contractions had been strong and regular initially, they had diminished in force during the past hour. Which of the following agents would be used to facilitate this woman's labor and delivery? (A) Dopamine (B) Leuprolide (C) Oxytocin (D) Prolactin (E) Vasopressin

Oxytocin is an effective stimulant of uterine contraction that is routinely used to augment labor. The answer is C.

Which of the following drugs is most useful for the treatment of hypercalcemia in Paget's disease? (A) Fluoride (B) Hydrochlorothiazide (C) Pamidronate (D) Raloxifene (E) Teriparatide

Paget's disease is characterized by excessive bone resorption, poorly organized bone formation, and hypercalcemia. Bisphosphonates and calcitonin are first-line treatments. Pamidronate is a powerful bisphosphonate used parenterally to treat hypercalcemia. The answer is C.

An employee of a company engaged in clearing vegetation from county roadsides accidentally ingested a small quantity of an herbicidal solution that contained paraquat. Within 2 h, he was admitted to the emergency department of a nearby hospital. Which of the following best describes his probable signs and symptoms in the emergency department? (A) Diarrhea, vomiting, sweating, and profound skeletal muscle weakness (B) Dizziness, nausea, agitation, and hyperreflexia (C) Dyspnea, pulmonary dysfunction, and elevated body temperature (D) Gastrointestinal irritation with hematemesis and bloody stools (E) Hypotension, tachycardia, and respiratory impairment

Paraquat is highly corrosive to the gastrointestinal tract. Oral ingestion of the herbicide leads to marked gastrointestinal irritation, hematemesis, and usually blood in the stools. Signs of pulmonary impairment do not appear for several days and are usually progressive, resulting in severe pulmonary fibrosis and, often, death. The answer is D.

Full activation of the parasympathetic nerves is likely to produce which of the following effects? (A) Bronchodilation (B) Decreased intestinal motility (C) Increased thermoregulatory sweating (D) Increased pupillary constrictor tone (miosis) (E) Increased heart rate (tachycardia)

Parasympathetic nerve discharge causes bronchial and i nal smooth muscle contraction and bradycardia. Thermoregulatory (eccrine) sweat glands are innervated by sympathetic cholinergic fibers, not parasympathetic. The pupillary constrictor muscle is under parasympathetic cholinergic control. The answer is D.

Which of the following in its parenteral form is life-saving in severe status asthmaticus and acts, at least in part, by inhibiting phospholipase A2 ? (A) Aminophylline (B) Cromolyn (C) Epinephrine (D) Ipratropium (E) Metaproterenol (F) Metoprolol (G) Prednisone (H) Salmeterol (I) Zafirlukast (J) Zileuton

Parenteral corticosteroids such as prednisolone (the active metabolite of prednisone) are lifesaving in status asthmaticus. They probably act by reducing production of leukotrienes (see Chapter 18). The answer is G.

A 60-year-old patient complains of paresthesias and occasional nausea associated with one of the drugs she is taking. She is found to have hyperchloremic metabolic acidosis. She is probably taking (A) Acetazolamide for glaucoma (B) Amiloride for edema associated with aldosteronism (C) Furosemide for severe hypertension and heart failure (D) Hydrochlorothiazide for hypertension (E) Mannitol for cerebral edema

Paresthesias and gastrointestinal distress are common adverse effects of acetazolamide, especially when it is taken chronically, as in glaucoma. The observation that the patient has metabolic acidosis also suggests the use of a carbonic anhydrase inhibitor like acetazolamide. The answer is A.

A 67-year-old man with chronic kidney disease was found to have an elevated serum PTH concentration and a low serum concentration of 25-hydroxyvitamin D. He was successfully treated with ergocalciferol. Unfortunately, his kidney disease progressed so that he required dialysis and his serum PTH concentration became markedly elevated. Although the drug therapy was effective at lowering serum PTH concentrations, the patient experienced several episodes of hypercalcemia. He was switched to a vitamin D analog that suppresses PTH with less risk of hypercalcemia. Which drug was the patient switched to? (A) Calcitriol (B) Cholecalciferol (C) Furosemide (D) Paricalcitol (E) Risedronate

Paricalcitol is an analog of 1,25-dihydroxyvitamin D 3( citriol) that lowers serum PTH at doses that rarely precipitate hypercalcemia. The molecular basis of this selective action is poorly understood but is of value in the management of hyperparathyroidism and psoriasis. The answer is D.

When initiating T 4therapy for an elderly patient with long-standing hypothyroidism, it is important to begin with small doses to avoid which of the following? (A) A flare-up of exophthalmos (B) Acute renal failure (C) Hemolysis (D) Overstimulation of the heart (E) Seizures

Patients with longstanding hypothyroidism, especially those who are elderly, are highly sensitive to the stimulatory effects of T 4 on cardiac function. Administration of regular doses can cause overstimulation of the heart and cardiac collapse. The answer is D.

JT is a 14-year-old patient who is diagnosed with otitis media, requiring amoxicillin. The primary mechanism of antibacterial action of amoxicillin involves inhibition of (A) Beta-lactamases (B) Cell membrane synthesis (C) N-acetylmuramic acid synthesis (D) Peptidoglycan cross-linking (E) Transglycosylation

Penicillins (and cephalosporins) bind to PBPs acting at the transpeptidation stage of cell wall synthesis (the final step) to inhibit peptidoglycan cross-linking. The beta-lactam antibiotics also activate autolysins, which break down the bacterial cell wall. Synthesis of N-acetylmuramic acid is inhibited by fosfomycin. Vancomycin inhibits transglycolase, preventing elongation of peptidoglycan chains. The answer is D.

Characteristics of phase I depolarizing neuromuscular blockade due to succinylcholine include (A) Easy reversibility with nicotinic receptor antagonists (B) Marked muscarinic blockade (C) Muscle fasciculations only in the later stages of block (D) Reversibility by acetylcholinesterase (AChE) inhibitors (E) Sustained tension during a period of tetanic stimulation

Phase I depolarizing blockade caused by succinylcholine is not associated with antagonism at muscarinic receptors, nor is it reversible with cholinesterase inhibitors. Muscle fasciculations occur at the start of the action of succinylcholine. The answer is E.

Trifluoperazine was prescribed for a young male patient diagnosed as suffering from schizophrenia. He complains about the side effects of his medication. Which of the following is not likely to be one of his complaints? (A) Constipation (B) Decreased libido (C) Excessive salivation (D) Postural hypotensio

Phenothiazines such as trifluoperazine cause sedation and are antagonists at muscarinic and α adrenoceptors. Postural hypotension, blurring of vision, and dry mouth are common autonomic adverse effects, as is constipation. Effects on the male libido may result from increased prolactin or from increased peripheral conversion of androgens to estrogens. The answer is C.

When given to a patient, phentolamine blocks which one of the following? (A) Bradycardia induced by phenylephrine (B) Bronchodilation induced by epinephrine (C) Increased cardiac contractile force induced by norepinephrine (D) Miosis induced by acetylcholine (E) Vasodilation induced by isoproterenol

Phenylephrine, an α agonist, increases blood pressure and causes bradycardia through the baroreceptor reflex. Blockade of this drug's α-mediated vasoconstrictor effect prevents the bradycardia. The answer is A.

A 7-year-old boy underwent successful chemotherapy and cranial radiation for treatment of acute lymphocytic leukemia. One month after the completion of therapy, the patient presented with excessive thirst and urination plus hypernatremia. Laboratory testing revealed pituitary diabetes insipidus. To correct these problems, this patient is likely to be treated with which of the following? (A) Corticotropin (B) Desmopressin (C) hCG (D) Menotropins (E) Thyrotropin

Pituitary diabetes insipidus results from deficiency in vasopressin. It is treated with desmopressin, a peptide agonist of vasopressin V2 receptors. The answer is B.

A 52-year-old man (weight 70 kg) is brought to the hospital emergency department in a confused and delirious state. He has had an elevated temperature for more than 24 h, during which time he had complained of a severe headache and had suffered from nausea and vomiting. Lumbar puncture reveals an elevated opening pressure, and cerebrospinal fluid findings include elevated protein, decreased glucose, and increased neutrophils. Gram stain of a smear of cerebrospinal fluid reveals Gram-positive diplococci, and a preliminary diagnosis is made of purulent meningitis. The microbiology report informs you that for approximately 15% of S pneumoniae isolates in the community, the minimal inhibitory concentration for penicillin G is 20 mcg/mL. Treatment of this patient should be initiated immediately with intravenous administration of (A) Amoxicillin (B) Cephalexin (C) Ceftriaxone plus vancomycin (D) Nafcillin (E) Piperacillin

Pneumococcal isolates with a minimal inhibitory concentration for penicillin G of greater than 2 mcg/mL are highly resistant. Such strains are not killed by the concentrations of penicillin G or ampicillin that can be achieved in the cerebrospinal fluid. Nafcillin has minimal activity against penicillin-resistant pneumococci and piperacillin is mainly used for infections caused by Gram-negative rods. Cefotaxime and ceftriaxone are the most active cephalosporins against penicillin-resistant pneumococci, and the addition of vancomycin is recommended in the case of highly resistant strains. The answer is C.

A 52-year-old man (weight 70 kg) is brought to the hospital emergency department in a confused and delirious state. He has had an elevated temperature for more than 24 h, during which time he had complained of a severe headache and had suffered from nausea and vomiting. Lumbar puncture reveals an elevated opening pressure, and cerebrospinal fluid findings include elevated protein, decreased glucose, and increased neutrophils. Gram stain of a smear of cerebrospinal fluid reveals Gram-positive diplococci, and a preliminary diagnosis is made of purulent meningitis. The microbiology report informs you that for approximately 15% of S pneumoniae isolates in the community, the minimal inhibitory concentration for penicillin G is 20 mcg/mL. Resistance of pneumococci to penicillin G is due to (A) Alterations in porin structure (B) Beta-lactamase production (C) Changes in chemical structure of target penicillinbinding proteins (D) Changes in the d-Ala-d-Ala building block of peptidoglycan precursor (E) Decreased intracellular accumulation of penicillin G

Pneumococcal resistance to penicillins is due to changes in the chemical structures of the target penicillin-binding proteins located in the bacterial cytoplasmic membrane. A similar mechanism underlies the resistance of staphylococci to methicillin (MRSA strains). A structural alteration in the d-Ala-d-Ala component of the pentapeptide side chains of peptidoglycans is the basis for a mechanism of resistance to vancomycin. The answer is C.

A 38-year-old man is being treated for HIV-induced acquired immunodeficiency syndrome (AIDS). When abacavir therapy is begun, he develops a severe skin rash. Which of the following pharmacogenomic diagnoses might explain this skin rash? (A) CYP2D6*3 (PM) (B) CYP3A5*3 (PM) (C) HLA-B*57:01 (EM) (D) SLCO1B1*5 (PM)

Poor metabolizers of the CYP2D6*3 genotype are prone to reduced efficacy of codeine. Poor metabolizers of the CYP3A5*3 type show reduced tacrolimus clearance. Simvastatin toxicity (myopathy) is enhanced in SLCO1B1 poor metabolizers. Enhanced metabolizers of the HLA-B*57:01 type are prone to abacavir rashes and flucloxacillin liver damage. The answer is C.

Which one of the following drugs has a very high affinity for the phosphorus atom in parathion and is often used to treat life-threatening insecticide toxicity? (A) Atropine (B) Benztropine (C) Bethanechol (D) Botulinum (E) Cyclopentolate (F) Neostigmine (G) Pralidoxime

Pralidoxime has a very high affinity for the phosphorus atom in organophosphate insecticides. The answer is G.

Which statement about pramipexole is most accurate? (A) Effectiveness in Parkinson's disease requires its metabolic conversion to an active metabolite (B) It should not be administered to patients taking antimuscarinic drugs (C) Pramipexole causes less mental disturbances than levodopa (D) The drug selectively activates the dopamine D 3 receptor subtype (E) Warfarin may enhance the actions of pramipexole

Pramipexole is a dopamine D 3receptor activator and does not require bioactivation. It is excreted in unchanged form. Confusion, delusions, and hallucinations occur more frequently with dopamine receptor activators than with levodopa. The use of dopaminergic agents in combination with antimuscarinic drugs is common in the treatment of parkinsonism. Warfarin may enhance the action of ropinirole, another dopamine receptor agonist. The answer is D.

With respect to pramipexole, which of the following is most accurate? (A) Activates brain dopamine D 3 receptors (B) Effective as monotherapy in mild parkinsonism (C) May cause postural hypotension (D) Not an ergot derivative (E) All of the above

Pramipexole is a non-ergot agonist at dopamine receptors and has greater selectivity for D 3 receptors in the striatum. Pramipexole (or the D 2 receptor agonist ropinirole) is often chosen for monotherapy of mild parkinsonism, and these drugs sometimes have value in patients who have become refractory to levodopa. Adverse effects of these drugs include dyskinesias, postural hypotension, and somnolence. The answer is E.

A 22-year-old man from South Korea has recently moved to Minnesota. He has symptoms of clonorchiasis (anorexia, upper abdominal pain, eosinophilia), presumably contracted in his homeland where the Oriental liver fluke is endemic. He also has symptoms of diphyllobothriasis (abdominal discomfort, diarrhea, megaloblastic anemia), probably caused by consumption of raw fish from lakes near the Canadian border. Which drug is most likely to be effective in the treatment of both clonorchiasis and diphyllobothriasis in this patient? (A) Albendazole (B) Ivermectin (C) Niclosamide (D) Praziquantel (E) Pyrantel pamoate

Praziquantel is a primary drug for treatment of infections caused by the Oriental liver fluke and by the fish tapeworm. Both types of infection are transmitted mainly via the consumption of raw fish. Niclosamide is also a primary drug for fish tapeworm infections, but it is not active against Clonorchis sinensis. Albendazole is not effective in fish tapeworm infections, but it is useful in the pork tapeworm larval stage (cysticercosis). Pyrantel pamoate is not active against cestodes or trematodes. The answer is D.

Graded and quantal dose-response curves are being used for evaluation of a new analgesic drug in the animal laboratory and in clinical trials. Which of the following statements best describes graded dose-response curves? (A) More precisely quantitated than quantal dose-response curves (B) Obtainable from isolated tissue preparations but not from the study of intact subjects (C) Used to determine the maximal efficacy of the drug (D) Used to determine the therapeutic index of the drug (E) Used to determine the variation in sensitivity of subjects to the drug

Precise quantitation is possible with both types of doseresponse curves. Quantal dose-response curves show the frequency of occurrence of a specified response, which may be therapeutically effective (ED) or toxic (TD). Thus, quantal studies are used to determine the therapeutic index and the variation in sensitivity to the drug in the population studied. Graded (not quantal) dose-response curves are used to determine maximal efficacy (maximal response). The answer is C.

A young man is brought to the emergency department in an anxious and agitated state. He informs the attending physician that he uses "street drugs" and that he gave himself an intravenous "fix" approximately 12 h ago. After an initial period of contentment and relaxation, he now has chills and muscle aches and has also been vomiting. His symptoms include hyperventilation and hyperthermia. The attending physician notes that his pupil size is larger than normal. Which drug will be most effective in alleviating the symptoms experienced by this patient? (A) Buprenorphine (B) Codeine (C) Methadone (D) Naltrexone (E) Tramadol

Prevention of signs and symptoms of withdrawal after chronic use of a strong opiate like heroin requires replacement with another strong opioid analgesic drug. Methadone is most commonly used, but other strong µ-receptor agonists would also be effective. Acetaminophen and codeine will not be effective. Beneficial effects of diazepam are restricted to relief of anxiety and agitation. The antagonist drug naltrexone may exacerbate withdrawal symptoms. The answer is C.

A 10-year-old American girl presented to the emergency department with fever, chills, lethargy, and splenomegaly. She had recently returned from Nigeria, where she had spent 3 weeks with her grandparents. She had previously received all standard childhood immunizations but no prophylactic travel medications because her parents had returned to Nigeria several times previously without any medical problems. Laboratory examination reveals low hematocrit and platelet count and elevated creatinine. Blood smear reveals parasites in the erythrocytes and a diagnosis of falciparum malaria is made. If the girl recovers from the acute falciparum attack but a month later develops P vivax malaria, what drug or drugs should be given to eradicate schizonts and latent hypnozoites in the liver? (A) Artesunate (B) Dapsone (C) Halofantrine (D) Primaquine (E) Quinine

Primaquine is the only antimalarial drug that reliably acts on tissue schizonts in liver cells. Quinine is a highly effective blood schizonticide against all 4 species of human malaria parasites, but it is not active against liver stages. Starting about day 4 after an acute attack, primaquine should be given daily for 2 weeks. The answer is D.

Which statement about antiprotozoal drugs is most accurate? (A) Chloroquine is an inhibitor of plasmodial dihydrofolate reductase (B) Mefloquine destroys secondary exoerythrocytic schizonts (C) Primaquine is a blood schizonticide and does not affect secondary tissue schizonts (D) Proguanil complexes with double-stranded DNA, blocking replication (E) Trimethoprim-sulfamethoxazole is the drug of choice for Pneumocystis jirovecii pneumonia

Proguanil (not chloroquine) is an inhibitor of dihydrofolate reductase. Primaquine (not mefloquine) is the drug that destroys secondary exoerythrocytic schizonts. TMP-SMZ is the drug of choice for Pneumocystis jirovecii pneumonia. The answer is E.

Which of the following drugs is the most effective in the emergency management of malignant hyperthermia? (A) Atropine (B) Dantrolene (C) Haloperidol (D) Succinylcholine (E) Vecuronium

Prompt treatment is essential in malignant hyperthermia to control body temperature, correct acidosis, and prevent calcium release. Dantrolene interacts with the RyR1 channel to block the release of activator calcium from the sarcoplasmic reticulum, which prevents the tension-generating interaction of actin with myosin. The answer is B.

Which statement concerning the effects of anesthetic agents is most accurate? (A) Bronchiolar smooth muscle contraction occurs during halothane anesthesia (B) Chest muscle rigidity often follows the administration of fentanyl (C) Mild, generalized muscle twitching occurs at high doses of isoflurane (D) Severe nausea and vomiting has been reported after the use of propofol (E) The use of thiopental preceding inhalation anesthetics may prolong postanesthesia recovery

Propofol has an antiemetic effect. Halothane and other inhaled anesthetics have been used in the management of status asthmaticus; they do not cause bronchoconstriction. Enflurane, not isoflurane, is associated with muscle twitching. Opioids such as fentanyl may cause truncal rigidity. Thiopental has a rapid redistribution and recovery from anesthesia is not prolonged. The answer is B.

Postoperative vomiting is uncommon with this intravenous agent, and patients are often able to ambulate sooner than those who receive other anesthetics. (A) Enflurane (B) Etomidate (C) Midazolam (D) Propofol (E) Thiopental

Propofol is used extensively in anesthesia protocols, including those for day surgery. The favorable properties of the drug include an antiemetic effect and recovery more rapid than that after use of other intravenous drugs. Propofol does not cause cumulative effects, possibly because of its short half-life (2-8 min) in the body. The drug is also used for prolonged sedation in critical care settings. The answer is D.

If a β blocker were to be used for prophylaxis in this patient, what is the most probable mechanism of action in angina? (A) Block of exercise-induced tachycardia (B) Decreased end-diastolic ventricular volume (C) Increased double product (D) Increased cardiac force (E) Decreased ventricular ejection time

Propranolol blocks tachycardia but has none of the other effects listed. Only revascularization increases double product; drugs that decrease cardiac work increase exercise time by decreasing double product. The answer is A.

A 25-year-old woman presents with insomnia and fears she may have "something wrong with her heart." She describes "her heart jumping out of her chest." She feels healthy otherwise and reports she has lots of energy. Lab tests confirm hyperthyroidism. Which of the following is a drug that produces a permanent reduction in thyroid activity? (A) 131 I (B) Methimazole (C) Propylthiouracil (D) Thiocyanate (SCN- ) (E) Thyroglobulin

Propylthiouracil and, to a much lesser extent, methimazole inhibit peripheral conversion of T 4 to T3 . Thyroglobulin is not a drug. Radioactive iodine is the only medical therapy that produces a permanent reduction of thyroid activity. Anions such as thiocyanate (SCN - ) and perchlorate (ClO 4 - ) block the uptake of iodide by the thyroid gland through competitive inhibition of the iodide transporter. Their effectiveness is unpredictable and ClO 4 - can cause aplastic anemia, so these drugs are rarely used. The answer is A.

A 57-year-old man has severe pulmonary hypertension and right ventricular hypertrophy. Which of the following agents causes vasodilation and may be useful in pulmonary hypertension? (A) Acetylcholine (B) Bradykinin (C) Prostaglandin PGF2 α (D) Prostacyclin (E) Thromboxane

Prostacyclin (PGI2) is a very potent vasodilator. Acetylcholine and bradykinin cause generalized vasodilation and many other undesirable effects; they are not useful in pulmonary or systemic hypertension. PGF 2 α and thromboxane are vasoconstrictors. The answer is D.

Infections caused by Gram-negative bacilli have occurred when this cationic surfactant has been used as a skin antiseptic. (A) Acetic acid (B) Benzalkonium chloride (C) Lindane (D) Hexachlorophene (E) Thimerosal

Pseudomonas and other Gram-negative bacteria have caused infections after the use of cationic surfactants such as benzalkonium and cetylpyridinium chlorides, partly because they form a film on the skin under which microorganisms can survive. In addition, some Gram-negative bacilli are able to grow in solutions containing benzalkonium salts. Bacterial growth may also occur in solutions of povidone-iodine. The answer is B.

Which statement about hallucinogens is most accurate? (A) Dilated pupils and tachycardia are characteristic effects of scopolamine (B) LSD is unique among hallucinogens in that animals will self-administer it (C) Mescaline and psilocybin exert their CNS actions through dopaminergic systems in the brain (D) Phencyclidine is a known teratogen (E) Withdrawal signs characteristic of dependence occur with abrupt discontinuance of ketamine

Psilocybin, mescaline, and LSD have similar central (via s tonergic systems) and peripheral (sympathomimetic) effects, but no actions on dopaminergic receptors in the CNS. None of the hallucinogenic drugs have been shown to have teratogenic potential. Unlike most hallucinogens, PCP (not LSD) acts as a positive reinforcer of self-administration in animals. Emergence reactions can occur after use of ketamine, but they are not signs of withdrawal. Scopolamine blocks muscarinic receptors. The answer is A.

Which statement about pyrantel pamoate is accurate? (A) Acts as an antagonist at GABA receptors (B) Equivalent in efficacy to niclosamide in the treatment of tapeworm infections (C) Eradicates adult worms in the colon but not the eggs (D) Hepatotoxicity is dose-limiting (E) Synergistic with praziquantel in cestode infections

Pyrantel pamoate, an agonist at nicotinic receptors, is equivalent to albendazole and mebendazole in the treatment of common nematode infections. It acts on adult worms in the colon, but not on eggs. The drug causes only mild gastrointestinal side effects and is not hepatotoxic. It is not effective in the treatment of infections caused by cestodes or flukes. The answer is C.

Concerning quinupristin-dalfopristin, which statement is accurate? (A) Active in treatment of infections caused by E faecalis (B) An effective drug in treatment of multidrug-resistant streptococcal infections (C) Bacteriostatic (D) Hepatotoxicity has led to FDA drug alerts (E) Increase the activity of hepatic drug-metabolizing enzymes

Quinupristin-dalfopristin is bactericidal against many drugresistant Gram-positive cocci, including multidrug-resistant streptococci, MRSA, and vancomycin-resistant enterococci. The streptogramins have activity against E faecium (not E faecalis). The drugs are potent inhibitors of CYP3A4 and interfere with the metabolism of many other drugs. The streptogramins are not hepatotoxic. The answer is B.

A 24-year-old woman was found to have mild hyperthyroidism due to Graves' disease. She appears to be in good health otherwise. Though rare, a serious toxicity associated with the thioamides is which of the following? (A) Agranulocytosis (B) Lupus erythematosus-like syndrome (C) Myopathy (D) Torsades de pointes arrhythmia (E) Thrombotic thrombocytopenic purpura (TTP)

Rarely, the thioamides cause severe adverse reactions that include agranulocytosis, vasculitis, hepatic damage, and hypoprothrombinemia. The answer is A.

A 25-year-old man is admitted to the emergency d ment with a brownish cyanotic appearance, marked shortness of breath, and hypotension. He has needle marks in both arms. Which of the following is most likely to cause methemoglobinemia? (A) Amyl nitrite (B) Isosorbide dinitrate (C) Isosorbide mononitrate (D) Nitroglycerin (E) Sodium cyanide

Read carefully! Nitrites, not nitrates, cause methemoglobinemia in adults. Methemoglobinemia is deliberately induced in one of the treatments of cyanide poisoning. Amyl nitrite and isobutyl nitrite, obtained as street drugs, have been heavily used as sex-enhancers. The answer is A.

Which drug used in management of seizure disorders is most likely to elevate the plasma concentration of other drugs administered concomitantly? (A) Carbamazepine (B) Clonazepam (C) Phenobarbital (D) Phenytoin (E) Valproic acid

Read the question carefully. Several of these agents ( azepine, phenobarbital, and phenytoin) induce drug metabolizing enzymes and reduce the plasma concentration of other drugs. Valproic acid, an inhibitor of drug metabolism, can increase the plasma levels of many drugs, including those used in seizure disorders such as carbamazepine, lamotrigine, phenobarbital, and phenytoin. Benzodiazepines (including clonazepam and diazepam) as well as gabapentin and vigabatrin have no major effects on the metabolism of other drugs. The answer is E.

Which statement about the clinical use of sulfonamides is correct? (A) Cannot be used topically for treatment of chlamydial infections of the eye (B) Effective as sole agents in the treatment of prostatitis (C) Effective in Rocky Mountain spotted fever (D) In some bacterial strains resistance occurs via reduced PABA formation (E) Reduced intracellular uptake is a mechanism of sulfonamide resistance in some bacterial strains

Reduced uptake of sulfonamides is one way organisms can become resistant. All of the other statements about sulfonamide antimicrobial drugs are incorrect. The answer is E.

An obese 40-year-old man (BMI 31) is being seen in the cardio-pulmonary clinic for pulmonary hypertension and a cardiac murmur. He took fenfluramine for several years in an attempt to reduce his weight. The mechanism by which fenfluramine affected appetite is: (A) 5-HT 2 agonist action (B) Amphetamine-mimetic action (C) Anti-opioid/antidepressant action (D) Glucagon-like peptide (GLP) agonist action (E) Intestinal lipase inhibition

Refer to Table 16-3. Fenfluramine, a 5-HT 2cagonist, is now banned because it caused pulmonary hypertension and cardiac valve malfunction. Phentermine has an amphetamine-like action. Naltrexone is a long-acting opioid antagonist; bupropion is an antidepressant. Liraglutide is a GLP-1 agonist. Orlistat is an inhibitor of intestinal lipase. The answer is A.

A 45-year-old male stomach cancer patient underwent tumor removal surgery. After surgery, he developed megaloblastic anemia. His anemia is caused by a deficiency of X and can be treated with Y. (A) X = intrinsic factor; Y = folic acid (B) X = intrinsic factor; Y = vitamin B12 (C) X = extrinsic factor; Y = parenteral iron (D) X = extrinsic factor; Y = sargramostim

Resection of the stomach does lead to loss of intrinsic factor and the patient will be deficient in vitamin B12 . Prevention or treatment of iron deficiency anemia (microcytic cell size) is the only indication for iron administration. Sargramostim is a GM-CSF and is used to stimulate the production of neutrophils and other myeloid and megakaryocyte progenitors. The answer is B.

Which statement about the actions of antimicrobial agents is false? (A) Metronidazole has activity against C difficile (B) Neonatal gonococcal ophthalmia can be prevented by silver nitrate (C) Polymyxins act as cationic detergents to disrupt bacterial cell membranes (D) Resistance to nitrofurans emerges rapidly, and there is cross-resistance with sulfonamides (E) Salicylic acid has useful antidermatophytic activity when applied locally

Resistance emerges very slowly when nitrofurantoin is used as a urinary antiseptic. There is no cross-resistance between the drug and other drugs used in the treatment of bacterial infections of the urinary tract. The answer is D.

Plasmodial resistance to chloroquine is due to (A) Change in receptor structure (B) Decreased accumulation of the drug in the food vacuole (C) Increased activity of DNA repair mechanisms (D) Increased synthesis of dihydrofolate reductase (E) Induction of drug-inactivating enzymes

Resistance to chloroquine in P falciparum can result from decreased accumulation of the drug in the food vacuole caused by the activity of a transporter system encoded by the pfcrt gene. The answer is B.

A crop duster pilot has been accidentally exposed to a high concentration of a highly toxic agricultural organophosphate insecticide. If untreated, the cause of death from such exposure would probably be (A) Cardiac arrhythmia (B) Gastrointestinal bleeding (C) Heart failure (D) Hypotension (E) Respiratory failure

Respiratory failure, from neuromuscular paralysis or CNS depression, is the most important cause of acute deaths in cholinesterase inhibitor toxicity. The answer is E.

A 58-year-old woman with lung cancer has abnormally low serum osmolality and hyponatremia. A drug that increases the formation of dilute urine and is used to treat SIADH is (A) Acetazolamide (B) Amiloride (C) Desmopressin (D) Ethacrynic acid (E) Furosemide (F) Hydrochlorothiazide (G) Mannitol (H) Spironolactone (I) Triamterene (J) Tolvaptan

Retention of water with hyponatremia and inability to form dilute urine in the fully hydrated condition is characteristic of SIADH. Antagonists of ADH are needed to treat this condition. The answer is J, tolvaptan.

A 55-year-old lawyer is brought to the emergency department 2 h after the onset of severe chest pain during a stressful meeting. He has a history of poorly controlled mild hypertension and elevated blood cholesterol but does not smoke. ECG changes (ST elevation) and cardiac enzymes confirm the diagnosis of myocardial infarction. The decision is made to attempt to open his occluded artery. Which of the following drugs accelerates the conversion of plasminogen to plasmin? (A) Aminocaproic acid (B) Heparin (C) Argatroban (D) Reteplase (E) Warfarin

Reteplase is the only thrombolytic drug listed. Heparin and warfarin are anticoagulants. Argatroban is a direct inhibitor of thrombin, and aminocaproic acid is an inhibitor, not an activator, of the conversion of plasminogen to plasmin. The answer is D.

A 30-year-old woman has one living child, age 6 years. Her child and her husband are Rh positive and she is Rh o (D) and D u negative. She is now in her ninth month of pregnancy and is in the labor room having frequent contractions. Her Rh antibody test taken earlier in the pregnancy was negative. What immunotherapy is appropriate for this patient? (A) Cyclosporine (B) Cyclophosphamide (C) Methotrexate (D) Rho (D) immune globulin (E) Tacrolimus

Rho(D) immune globulin contains antibodies against Rho(D) antigens. If an injection of Rho (D) antibody is administered to the Rh-negative mother within 24-72 h after the birth of an Rh-positive infant, the mother's own antibody response to the foreign Rho (D)-positive cells is suppressed because the infant's red cells are cleared from circulation before the mother can generate a B-cell response against Rho (D). Therefore, she has no memory B cells that can activate upon subsequent pregnancies with an Rho (D)-positive fetus. The answer is D.

Which of the following factors is likely to increase the duration of action of a drug that is metabolized by CYP3A4 in the liver? (A) Chronic administration of rifampin during therapy with the drug in question (B) Chronic therapy with amiodarone (C) Displacement from tissue-binding sites by another drug (D) Increased cardiac output (E) Chronic administration of carbamazepine

Rifampin and carbamazepine can induce drug-metabolizing enzymes and thereby may reduce the duration of drug action. Displacement of drug from tissue may transiently increase the intensity of the effect but decreases the volume of distribution. Amiodarone is recognized as an inhibitor of P450 and may decrease clearance of drugs metabolized by CYP2C9, CYP2D6, and CYP3A4. The answer is B.

On her release from the hospital, the patient is advised not to rely solely on oral contraceptives to prevent pregnancy because they may be less effective while she is being maintained on antimycobacterial drugs. The agent most likely to interfere with the action of oral contraceptives is (A) Amikacin (B) Ethambutol (C) Isoniazid (D) Pyrazinamide (E) Rifampin

Rifampin induces the formation of several microsomal drugmetabolizing enzymes, including cytochrome P450 isoforms. This action increases the rate of elimination of a number of drugs, including anticoagulants, ketoconazole, methadone, and steroids that are present in oral contraceptives. The pharmacologic activity of these drugs can be reduced markedly in patients taking rifampin. The answer is E.

AJ is a 45-year-old homeless man participating in a drug rehabilitation program that supplies daily methadone. AJ reports that he needs more methadone to avoid withdrawal, since he started treatment for his tuberculosis. Which of the following drugs might have caused this scenario? (A) Ciprofloxacin (B) Cyclosporine (C) Erythromycin (D) Rifampin (E) Tetracycline

Rifampin is an effective inducer of hepatic P450 isozymes. Cyclosporine and tetracycline have no significant effects on drug metabolism. Ciprofloxacin and erythromycin are inhibitors of drug metabolism. The answer is D.

Which of the following agents, when used in combination with other anti-HIV drugs, permits dose reductions? (A) Cimetidine (B) Efavirenz (C) Ketoconazole (D) Procainamide (E) Quinidine (F) Ritonavir (G) Succinylcholine (H) Verapamil

Ritonavir inhibits hepatic drug metabolism, and its use at low doses in combination regimens has permitted dose reductions of other HIV protease inhibitors (eg, indinavir). The answer is F.

Which of the following is a unique property of SERMs? (A) Act as agonists in some tissues and antagonists in other tissues (B) Activate a unique plasma membrane-bound receptor (C) Have both estrogenic and progestational agonist activity (D) Inhibit the aromatase enzyme required for estrogen synthesis (E) Produce estrogenic effects without binding to estrogen receptors

SERMs such as tamoxifen and raloxifene exhibit tissuespecific estrogenic and antiestrogenic effects. The answer is A.

A 16-year-old girl comes to the emergency department suffering from the effects of an aspirin overdose. Which of the following syndromes is this patient most likely to exhibit as a result of this drug overdose? (A) Bone marrow suppression and possibly aplastic anemia (B) Fever, hepatic dysfunction, and encephalopathy (C) Hyperthermia, metabolic acidosis, and coma (D) Rapid, fulminant hepatic failure (E) Rash, interstitial nephritis, and acute renal failure

Salicylate intoxication is associated with metabolic acidosis, dehydration, and hyperthermia. If these problems are not corrected, coma and death ensue. The answer is C.

Which of the following has a slow onset but long duration of action and is always used in combination with a corticosteroid by inhalation? (A) Aminophylline (B) Cromolyn (C) Epinephrine (D) Ipratropium (E) Metaproterenol (F) Metoprolol (G) Prednisone/prednisolone (H) Salmeterol (I) Zafirlukast (J) Zileuton

Salmeterol is a β2-selective agonist that has a slow onset and long duration of action. Used alone, it increases asthma mortality, but in combination with inhaled corticosteroids prophylactic use improves asthma control. The answer is H.

A 67-year-old male reports difficulty starting a urine stream and feeling an urge to urinate again soon after urinating. Examination confirms benign prostatic hyperplasia (BPH). He prefers not to take prescription medications. Which of the following is an alternative medicine that is commonly used to treat the urinary symptoms associated with BPH? (A) Echinacea (B) Ephedra (C) Ginseng (D) Milk thistle (E) Saw palmetto

Saw palmetto, a complex extract from the berries of Serenoa repens or Sabal serrulata, is widely purported to improve the symptoms of BPH. The answer is E.

A 48-year-old patient is scheduled for a vaginal hysterectomy. An antimicrobial drug will be used for prophylaxis against postoperative infection. It is proposed that cefazolin, a first-generation cephalosporin, be given intravenously at the normal therapeutic dose immediately before surgery and continued until the patient is released from the hospital. If the patient had been scheduled for elective colonic surgery, optimal prophylaxis against infection would be achieved by mechanical bowel preparation and the use of (A) Intravenous cefoxitin (B) Intravenous third-generation cephalosporin (C) Oral amoxicillin (D) Oral ciprofloxacin (E) Oral erythromycin and neomycin

Second-generation cephalosporins, including cefoxitin and cefotetan, are more active than cefazolin against bowel anaerobes such as Bacteroides fragilis and are sometimes used for prophylaxis in "dirty" surgical procedures. However, for elective bowel surgery, most authorities favor the oral use of neomycin together with a poorly absorbed formulation of erythromycin, in conjunction with mechanical bowel preparation. In cases of bowel perforation, the use of a second- or third-generation cephalosporin is more appropriate. The answer is E.

Inflammation is a complex tissue reaction that includes the release of cytokines, leukotrienes, prostaglandins, and peptides. Leukotrienes involved in inflammatory processes are typically produced from arachidonic acid by which of the following enzymes? (A) Cyclooxygenase-1 (B) Cyclooxygenase-2 (C) Glutathione-S-transferase (D) Lipoxygenase (E) Phospholipase A2

See Figure 18-1. Phospholipase A 2converts membrane phospholipid to arachidonic acid. Cyclooxygenases convert arachidonic acid to prostaglandins. COX-1 products appear to be important in normal physiologic processes. Lipoxygenase is the enzyme responsible for the production of leukotrienes from arachidonic acid in inflammatory cells. The answer is D.

Your 37-year-old patient has been diagnosed with a rare metastatic carcinoid tumor. This neoplasm is releasing serotonin, bradykinin, and several unknown peptides. The effects of serotonin in this patient are most likely to include (A) Constipation (B) Episodes of bronchospasm (C) Hypersecretion of gastric acid (D) Hypotension (E) Urinary retention

Serotonin causes bronchospasm, but the other effects listed are not observed. Carcinoid is associated with diarrhea and hypertension. The answer is B.

A 34-year-old woman has irritable bowel syndrome with diarrhea that is not responsive to conventional therapies. Despite the small risk of severe constipation and ischemic colitis, the patient decides to begin therapy with alosetron. Alosetron has which of the following receptor actions? (A) 5-HT 3 receptor antagonist (B) 5-HT 4 receptor agonist (C) D 2 receptor antagonist (D) NK 1 receptor antagonist (E) Muscarinic receptor antagonist

Serotonin plays a major regulatory role in the enteric nervous system, and the potent 5-HT 3 receptor antagonist alosetron has shown efficacy in treating women with IBS that is accompanied by diarrhea. The answer is A.

A 27-year-old pregnant patient with a h tory of pyelonephritis has developed a severe upper respiratory tract infection that appears to be due to a bacterial pathogen. The woman is hospitalized, and an antibacterial agent is to be selected for treatment. Which antibacterial agent appears to be the safest to use in the pregnant patient? (A) Amikacin (B) Azithromycin (C) Ciprofloxacin (D) Erythromycin (E) Tetracycline

Several groups of antimicrobial drugs are best avoided in pregnancy if at all possible, including aminoglycosides, sulfonamides, and tetracyclines. The macrolide azithromycin appears to be safe, but studies in animals have shown that clarithromycin is potentially embryotoxic. The answer is B.

Which of the following has been shown to prolong life in patients with chronic congestive failure in spite of having a negative inotropic effect on cardiac contractility? (A) Carvedilol (B) Digoxin (C) Dobutamine (D) Enalapril (E) Furosemide

Several β blockers, including carvedilol, have been shown to prolong life in heart failure patients even though these drugs may have a negative inotropic action on the heart. Their benefits presumably result from some other β-mediated effect, and at least one other β blocker has failed to show a mortality benefit. The answer is A.

Certain drugs can cause severe hypotension when combined with nitrates. Which of the following interacts with nitroglycerin by inhibiting the metabolism of cGMP? (A) Atenolol (B) Hydralazine (C) Isosorbide mononitrate (D) Nifedipine (E) Ranolazine (F) Sildenafil (G) Terbutaline

Sildenafil inhibits phosphodiesterase 5, an enzyme that inactivates cGMP. The nitrates (via nitric oxide) increase the synthesis of cGMP. This combination is synergistic. The answer is F.

Which drug is most likely to cause hyperkalemia leading to cardiac arrest in patients with spinal cord injuries? (A) Baclofen (B) Dantrolene (C) Pancuronium (D) Succinylcholine (E) Vecuronium

Skeletal muscle depolarization by succinylcholine releases potassium from the cells, and the ensuing hyperkalemia can be life-threatening in terms of cardiac arrest. Patients most susceptible include those with extensive burns, spinal cord injuries, neurologic dysfunction, or intra-abdominal infection. The answer is D.

The light brownish color of smog often apparent in a major metropolitan area on a hot summer day is mainly due to (A) Carbon monoxide (B) Hydrocarbons (C) Ozone (D) Nitrogen dioxide (E) Sulfur dioxide

Smog color is derived in part from suspended particulate matter. When smog is light brown, the color derives from nitrogen oxides. All of the other air pollutants listed are colorless. The answer is D.

A young couple (25-year-old male, 23-year-old female) wants to start a family. They have not conceived after 1 year of unprotected intercourse. Infertility evaluation revealed no abnormalities in the female partner and low sperm count in the male. Which of the following is a drug that is purified from the urine of postmenopausal women and is used to promote spermatogenesis in infertile men? (A) Desmopressin (B) Gonadorelin (C) Goserelin (D) Somatropin (E) Urofollitropin

Spermatogenesis in males requires the action of FSH and LH. Urofollitropin, which is purified from the urine of postmenopausal women, is used clinically to provide FSH activity. The answer is E.

A 21-year-old woman from Southeast Asia has been staying with family members in the United States for the last 3 mo and is looking after her sister's preschool children during the day. Because she has difficulty with the English language, her sister escorts her to the emergency department of a local hospital. She tells the staff that her sister has been feeling very tired for the last month, has a poor appetite, and has lost weight. The patient has been feeling somewhat better lately except for a cough that produces a greenish sputum, sometimes specked with blood. With the exception of rales in the left upper lobe, the physical examination is unremarkable and she does not seem to be acutely ill. Laboratory values show a white count of 12,000/µL and a hematocrit of 33%. Chest x-ray film reveals an infiltrate in the left upper lobe with a possible cavity. A Gram-stained smear of the sputum shows mixed flora with no dominance. An acidfast stain reveals many thin rods of pinkish hue. A preliminary diagnosis is made of pulmonary tuberculosis. Sputum is sent to the laboratory for culture. Which drug regimen should be initiated in this patient when treatment is started? (A) Amikacin, isoniazid

Sputum cultures will not be available for several weeks, and no information is available regarding drug susceptibility of the organism at this stage. For optimum coverage, the initial regimen should include INH, rifampin, pyrazinamide, and ethambutol. INH-resistant organisms are usually sensitive to both rifampin and pyrazinamide. Streptomycin is usually reserved for use in severe forms of tuberculosis or for infections known to be resistant to first-line drugs. Likewise, amikacin and ciprofloxacin are possible agents for treatment of multidrug-resistant strains of M tuberculosis. Cycloserine, PAS, and rifabutin are alternative second-line drugs that may be used in cases of failed response to more conventional agents. The answer is C.

Rejection of heart transplants has occurred in patients being treated with standard doses of cyclosporine when they also used which of the following dietary supplements? (A) Echinacea (B) Ginkgo (C) Milk thistle (D) St. John's wort (E) Saw palmetto

St. John's wort induces the formation of hepatic enzymes that metabolize cyclosporine, and its use can decrease the effectiveness of the immunosuppressant drug in organ and tissue transplantation. The answer is D.

In a laboratory study of several peptides, one is found that decreases peripheral resistance but constricts veins. Which of the following causes arteriolar vasodilation and venoconstriction? (A) Atrial natriuretic peptide (ANP) (B) Bradykinin (C) Endothelin-1 (D) Substance P (E) Vasoactive intestinal peptide

Substance P is a potent arterial vasodilator and venoconstrictor. The answer is D.

A 60-year-old financial consultant presents with severe pain in a neuronal dermatome region of her chest. This area was previously affected by a herpes zoster rash. Which of the following might be of benefit in controlling this postherpetic pain? (A) Aliskiren (B) Aprepitant (C) Bosentan (D) Capsaicin (E) Captopril (F) Losartan (G) Macitentan

Substance P is an important pain-mediating neurotransmitter peptide and appears to be involved in post-herpetic pain as well as arthritic pain. Capsaicin can be used topically to deplete substance P stores from sensory nerves. The answer is D.

Sugammadex is a drug that reverses the action of rocuronium and certain other skeletal muscle-relaxing agents (nondepolarizing neuromuscular blocking agents). It appears to interact directly with the rocuronium molecule and not at all with the rocuronium receptor. Which of the following terms best describes sugammadex? (A) Chemical antagonist (B) Noncompetitive antagonist (C) Partial agonist (D) Pharmacologic antagonist (E) Physiologic antagonist

Sugammadex interacts directly with rocuronium and not with the rocuronium receptor; therefore, it is a chemical antagonist. The answer is A.

Which drug is effective in the treatment of nocardiosis and, in combination with pyrimethamine, is prophylactic against Pneumocystis jirovecii infections in AIDS patients? (A) Amoxicillin (B) Erythromycin (C) Levofloxacin (D) Sulfadiazine (E) Trimethopr

Sulfadiazine and TMP-SMZ are drugs of choice in nocardiosis. In combination with pyrimethamine (an effective dihydrofolate reductase inhibitor in protozoa), sulfadiazine is effective in toxoplasmosis and is prophylactic against pneumocystis pneumonia in the AIDS patient. However, TMP-SMZ is more commonly used for the latter purpose. The answer is D.

Which statement about phenytoin is most accurate? (A) Displaces sulfonamides from plasma proteins (B) Drug of choice in myoclonic seizures (C) Half-life is increased if used with phenobarbital (D) Isoniazid (INH) decreases steady-state blood levels of phenytoin (E) Toxic effects may occur with only small increments in dose

Sulfonamides can displace phenytoin from its binding sites, increasing the free fraction of the drug in the plasma. Induction of liver drug-metabolizing enzymes by phenobarbital results in a decreased half-life of phenytoin, and isoniazid increases plasma levels of phenytoin by inhibiting its metabolism. Because of the dose-dependent elimination kinetics of phenytoin, some toxicity may occur with only small increments in dose. The answer is E.

A 28-year-old office worker suffers from intense migraine headaches. Which of the following is a serotonin 5-HT1D/1B agonist useful for aborting an acute migraine headache? (A) Bromocriptine (C) Ephedrine (D) Ketanserin (E) Loratadine (F) Ondansetron (G) Sumatriptan

Sumatriptan, an agonist at 5-HT 1D/1Breceptors, is indicated for prevention or treatment of migraine and cluster headaches. Ergotamine (not on the list) is also effective for acute migraine but is produced by the fungus Claviceps purpurea. The answer is G.

A 30-year-old male patient who is HIVpositive and symptomatic has a CD4 count of 250/µL and a viral RNA load of 15,000 copies/mL. His treatment involves a 3-drug antiviral regimen consisting of zidovudine, didanosine, and ritonavir. The patient is taking acyclovir for a herpes infection and ketoconazole for oral candidiasis. He now complains of anorexia, nausea and vomiting, and abdominal pain. His abdomen is tender in the epigastric area. Laboratory results reveal an amylase activity of 220 U/L, and a preliminary diagnosis is made of acute pancreatitis. In the further treatment of this patient, the drug causing the pancreatitis should be withdrawn and replaced by (A) Atazanavir (B) Cidofovir (C) Foscarnet (D) Lamivudine (E) Ribavirin

Symptomatic AIDS patients should be treated with a HAART regimen regardless of a relatively high CD4 count or a relatively low HIV RNA load. Because didanosine must be discontinued, lamivudine would be a good NRTI replacement. Use of a second protease inhibitor (eg, atazanavir) with a single reverse transcriptase inhibitor could be as effective as regimens that include 2 reverse transcriptase inhibitors, although there may be an increased possibility of drug interactions. Atazanavir use is associated with electrocardiographic PR-interval prolongation, which may be exacerbated by other causative agents such as the calcium channel blocker verapamil which an older patient might be taking for angina. The answer is D.

Which statement about abuse of the opioid analgesics is false? (A) Lacrimation, rhinorrhea, yawning, and sweating are early signs of withdrawal from opioid analgesics (B) In withdrawal from opioids, clonidine may be useful in reducing symptoms caused by sympathetic overactivity (C) Methadone alleviates most of the symptoms of heroin withdrawal (D) Most patients experiencing withdrawal from heroin are free of the symptoms of abstinence in 6-8 d (E) Naloxone may precipitate a severe withdrawal state in abusers of opioid analgesics with symptoms starting in less than 15-30 min

Symptoms of opioid withdrawal usually begin within 6-8 h, and the acute course may last 6-8 d. However, a secondary phase of heroin withdrawal, characterized by bradycardia, hypotension, hypothermia, and mydriasis, may last 26-30 weeks. Methadone is commonly used in detoxification of the heroin addict because it is a strong agonist, has high oral bioavailability, and has a relatively long half-life. The answer is D.

A 27-year old compulsive drug user injected a drug he thought was methamphetamine, but he has not developed any signs of methamphetamine action. He has been admitted to the emergency department and antimuscarinic drug overdose is suspected. Probable signs of atropine overdose include which one of the following? (A) Gastrointestinal smooth muscle cramping (B) Increased heart rate (C) Increased gastric secretion (D) Pupillary constriction (E) Urinary frequency

Tachycardia is a characteristic atropine overdose effect. Bradycardia is sometimes observed after small doses. None of the other choices are typical of atropine or methamphetamine overdose. The answer is B.

A 50-year-old woman with a positive mammogram undergoes lumpectomy and a small carcinoma is removed. Biochemical analysis of the cancer reveals the presence of estrogen and progesterone receptors. After this procedure, she will probably receive which of the following drugs? (A) Danazol (B) Flutamide (C) Leuprolide (D) Mifepristone (E) Tamoxifen

Tamoxifen has proved useful in adjunctive therapy of breast cancer; the drug decreases the rate of recurrence of cancer. The answer is E.

Tetracyclines are the drugs of choice for Rocky Mountain spotted fever and Lyme disease. The mechanism of antibacterial action of tetracycline involves (A) Antagonism of bacterial translocase activity (B) Binding to a component of the 50S ribosomal subunit (C) Inhibition of DNA-dependent RNA polymerase (D) Interference with binding of aminoacyl-tRNA to bacterial ribosomes (E) Selective inhibition of ribosomal peptidyl transferases

Tetracyclines inhibit bacterial protein synthesis by interfering with the binding of aminoacyl-tRNA molecules to bacterial ribosomes. Peptidyl transferase is inhibited by chloramphenicol. The answer is D.

JR, a 35-year-old farm worker, is admitted to the emergency department suffering from insecticide poisoning. Parathion has which one of the following characteristics? (A) It is inactivated by conversion to paraoxon (B) It is less toxic to humans than malathion (C) It is more persistent in the environment than DDT (D) It is poorly absorbed through skin and lungs (E) If treated early, its toxicity may be partly reversed by pralidoxime

The "-thion" organophosphates (those containing the P=S bond) are activated, not inactivated, by conversion to "-oxon" (P=O) derivatives. They are less stable than halogenated hydrocarbon insecticides of the DDT type; therefore, they are less persistent in the environment. Parathion is more toxic than malathion. It is very lipid-soluble and rapidly absorbed through the lungs and skin. Pralidoxime has very high affinity for the phosphorus atom and is a chemical antagonist of organophosphates. The answer is E.

A young woman employed as a dental laboratory technician complains of conjunctivitis, skin irritation, and hair loss. On examination, she has perforation of the nasal septum and a "milk and roses" complexion. These signs and symptoms are most likely due to (A) Acute mercury poisoning (B) Chronic inorganic arsenic poisoning (C) Chronic mercury poisoning (D) Excessive use of supplementary iron tablets (E) Lead poisoning

The "milk and roses" complexion, which results from v dilation and anemia, is a characteristic of chronic inorganic arsenic poisoning, whereas patients with lead poisoning often have a gray pallor. Other signs and symptoms of arsenic poisoning include gastrointestinal distress, hyperpigmentation, and white lines on the nails. We hope you were not led astray by her employment. The answer is B.

Which of the following drugs is routinely added to calcium supplements and milk for the purpose of preventing rickets in children and osteomalacia in adults? (A) Cholecalciferol (B) Calcitriol (C) Gallium nitrate (D) Sevelamer (E) Plicamycin

The 2 forms of vitamin D—cholecalciferol and ergocalciferol—are commonly added to calcium supplements and dairy products. Calcitriol, the active 1,25-dihydroxyvitamin D3 metabolite, would prevent vitamin D deficiency and is available as an oral formulation. However, because it is not subject to the complex mechanisms that regulate endogenous production of active vitamin D metabolites, it is not suitable for widespread use. The answer is A.

A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL cholesterol, VLDL cholesterol, and triglycerides are normal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. After being counseled about lifestyle and dietary changes, the patient was started on atorvastatin. During his treatment with atorvastatin, it is important to routinely monitor serum concentrations of which of the following? (A) Blood urea nitrogen (B) Alanine and aspartate aminotransferase (C) Platelets (D) Red blood cells (E) Uric acid

The 2 primary adverse effects of the HMG-CoA reductase inhibitors are hepatotoxicity and myopathy. Patients taking these drugs should have liver function tests performed before starting therapy, and at regular intervals as needed during therapy. Serum concentrations of alanine and aspartate aminotransferase are used as markers of hepatocellular toxicity. The answer is B.

A patient is receiving highly emetogenic chemotherapy for metastatic carcinoma. To prevent chemotherapy-induced nausea and vomiting, she is likely to be treated with which of the following? (A) Levodopa (B) Methotrexate (C) Misoprostol (D) Ondansetron (E) Sucralfate

The 5-HT3 receptor antagonists are highly effective at preventing chemotherapy-induced nausea and vomiting, which can be a dose-limiting toxicity of anticancer drugs. The answer is D.

The Ames test is frequently carried out before clinical trials are begun. The Ames test is a method that detects (A) Carcinogenesis in primates (B) Carcinogenesis in rodents (C) Mutagenesis in bacteria (D) Teratogenesis in any mammalian species (E) Teratogenesis in primates

The Ames test is carried out in Salmonella and detects mutations in the bacterial DNA. Because mutagenic potential is associated with carcinogenic risk for many chemicals, a positive Ames test is often used to suggest that a particular agent may be a carcinogen. However, the test itself only detects mutations. The answer is C.

A 35-year-old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cholesterol, LDL cholesterol, and triglyceride are elevated. Her serum concentration of HDL cholesterol is somewhat reduced. If this patient is pregnant, which of the following drugs should be avoided because of a risk of harming the fetus? (A) Cholestyramine (B) Ezetimibe (C) Fenofibrate (D) Niacin (E) Pravastatin

The HMG-CoA reductase inhibitors are contraindicated in pregnancy because of the risk of teratogenic effects. The answer is E.

A cancer cell that is resistant to the effects of both vincristine and methotrexate probably has developed the resistance as a result of which of the following mechanisms? (A) Changes in the properties of a target enzyme (B) Decreased activity of an activating enzyme (C) Increased expression of a P-glycoprotein transporter (D) Increased production of drug-trapping molecules (E) Increase in proteins that are involved in DNA repair

The P-glycoprotein family of transporters moves foreign molecules out of cells. Cancer cells acquire resistance to multiple drugs that act through different mechanisms by increasing the expressions of genes encoding these transporters. The answer is C.

The PPAR-γ receptor that is activated by thiazolidinediones increases tissue sensitivity to insulin by which of the following mechanisms? (A) Activating adenylyl cyclase and increasing the intracellular concentration of cAMP (B) Inactivating a cellular inhibitor of the GLUT2 glucose transporter (C) Inhibiting acid glucosidase, a key enzyme in glycogen breakdown pathways (D) Regulating transcription of genes involved in glucose utilization (E) Stimulating the activity of a tyrosine kinase that phosphorylates the insulin receptor

The PPAR-γ receptor belongs to a family of nuclear receptors. When activated, these receptors translocate to the nucleus, where they regulate the transcription of genes encoding proteins involved in the metabolism of carbohydrate and lipids. The answer is D.

A 34-year-old man who was prescribed citalopram for depression has decided he wants to stop taking the drug. When questioned, he said that it was affecting his sexual performance. You ascertain that he is also trying to overcome his dependency on tobacco products. If you decide to reinstitute drug therapy in this patient, the best choice would be (A) Amitriptyline (B) Bupropion (C) Fluoxetine (D) Imipramine (E) Venlafaxine

The SSRIs (eg, fluoxetine) and venlafaxine (an SNRI) can cause sexual dysfunction with decreased libido, erectile dysfunction, and anorgasmia. TCAs may also decrease libido or prevent ejaculation. Bupropion is the least likely antidepressant to affect sexual performance. The drug is also purportedly useful in withdrawal from nicotine dependence, which could be helpful in this patient. The answer is B.

SSRIs are much less effective than tricyclic antidepressants in the management of (A) Bulimia (B) Chronic neuropathic pain (C) Generalized anxiety disorder (D) Obsessive-compulsive disorder (E) Premenstrual dysphoric disorder

The SSRIs are not effective in chronic pain of neuropathic origin. All the other uses of SSRIs are approved indications with clinical effectiveness equivalent or superior to that of tricyclic drugs. In addition to treatment of chronic pain states and depression the tricyclics are also used to treat enuresis and attention deficit hyperactivity disorder. The answer is B.

The active metabolites of vitamin D act through a nuclear receptor to produce which of the following effects? (A) Decrease the absorption of calcium from bone (B) Increase PTH formation (C) Increase renal production of erythropoietin (D) Increase the absorption of calcium from the gastrointestinal tract (E) Lower the serum phosphate concentration

The active metabolites of vitamin D increase serum calcium and phosphate by promoting calcium and phosphate uptake from the gastrointestinal tract, increasing bone resorption, and decreasing renal excretion of both electrolytes. They inhibit, rather than stimulate, PTH formation. The answer is D.

Which of the following is a popular supplement whose purported efficacy in osteoarthritis is believed to be due to its role as a precursor to the glycosaminoglycans that form joint cartilage? (A) Coenzyme Q10 (B) Dehydroepiandrosterone (DHEA) (C) Glucosamine (D) Nicotinic acid (E) Melatonin

The amino sugar glucosamine, a building block for g cosaminoglycans, has become popular among people with osteoarthritis of the knee. The answer is C.

Which of the following statements about new drug development is most correct? (A) If the need is great, drugs that test positive for teratogenicity, mutagenicity, or carcinogenicity can be tested in humans but the IND must specify safety measures to be taken (B) Food supplements and herbal (botanical) remedies must be shown to be effective for the target condition before marketing is approved by the FDA (C) All new drugs must be studied in at least 1 primate species before NDA submission (D) Orphan drugs are drugs that are no longer produced by the original manufacturer (E) Phase 4 (surveillance) is the most rigidly regulated phase of clinical drug trials

The answer is A. Food supplements and botanicals are much more loosely regulated than conventional drugs; they are not required to be shown effective before marketing. Primates are not required in any phase of new drug testing, although they are sometimes used. (Note the trigger word "all" in choice (C); answers claiming "all..." are almost always wrong.) Orphan drugs are those for which the anticipated patient population is smaller than 200,000 patients in the United States. Phase 4 surveillance is the most loosely regulated phase of clinical trials. Many drugs in current clinical use test positive for teratogenicity, mutagenicity, or carcinogenicity. Such drugs are usually labeled with warnings about these toxicities and, in the case of teratogenicity, are labeled as contraindicated in pregnancy.

The pK aof lidocaine is 7.7. In infected tissue, which can be acidic, for example, at pH 6.7, the percentage of the drug in the nonionized form will be (A) 1% (B) 10% (C) 50% (D) 90% (E) 99%

The answer is B Because the drug is a weak base, it is more ionized ( ated) at pH values lower than its pKa . Because the pH given is 1 log unit lower (more acid) than the pKa , the ratio of ionized to nonionized drug will be approximately 90:10. The answer is B. (Recall from Chapter 1 that at a pH equal to pKa , the ratio is 1:1; at 1 log unit difference, the ratio is approximately 90:10; at 2 log units difference, 99:1; and so on.)

Two cholesterol-lowering drugs, X and Y, were studied in a large group of patients, and the percentages of the group showing a specific therapeutic effect (35% reduction in lowdensity lipoprotein [LDL] cholesterol) were determined. The results are shown in the following table. ( ترتيب الاعداد حسب الجمل، مثال👇) Drug Dose (mg): 5 Percent Responding to Drug X: 1 Percent Responding to Drug Y: 10 5,1,10 10,5,20 20,10,50 50,50,70 100,70,90 200,90,100 Which of the following statements about these results is correct? (A) drug X is safer than drug Y (B) drug Y is more effective than drug X (C) The 2 drugs act on the same receptors (D) Drug X is less potent than drug Y (E) The therapeutic index of drug Y is 10

The answer is D. No information is presented regarding the safety of these drugs. Similarly, no information on efficacy (maximal effect) is presented; this requires graded dose-response curves. Although both drugs are said to be producing a therapeutic effect, no information on their receptor mechanisms is given. Since no data on toxicity are available, the therapeutic index cannot be determined. The answer is D because the ED 50 of drug Y (20 mg/d) is less than that of drug X (50 mg/d).

Which statement is accurate regarding the antibacterial action of the aminoglycoside amikacin? (A) Antibacterial activity is often reduced by the presence of an inhibitor of cell wall synthesis (B) Antibacterial action is not concentration-dependent (C) Antibacterial action is time-dependent (D) Efficacy is directly proportional to the duration of time that the plasma level is greater than the minimal inhibitory concentration (E) The drug continues to exert antibacterial effects even after plasma levels decrease below detectable levels

The antibacterial action of aminoglycosides is concentration dependent rather than time dependent. The activity of amikacin continues to increase as its plasma level rises above the minimal inhibitory concentration (MIC). When the plasma level falls below the MIC, aminoglycosides continue to exert antibacterial effects for several hours, exerting a postantibiotic effect. Inhibitors of bacterial cell wall synthesis often exert synergistic effects with aminoglycosides, possibly by increasing the intracellular accumulation of the aminoglycoside. The answer is E.

A 37-year-old woman with leukemia was undergoing chemotherapy with intravenous antineoplastic drugs. During treatment, she developed a systemic infection from an opportunistic pathogen. There was no erythema or edema at the catheter insertion site. A white vaginal discharge was observed. After appropriate specimens were obtained for culture, empiric antibiotic therapy was started with gentamicin, nafcillin, and ticarcillin intravenously. This regimen was maintained for 72 h, during which time the patient's condition did not improve significantly. Her throat was sore, and white plaques had appeared in her pharynx. On day 4, none of the cultures had shown any bacterial growth, but both the blood and urine cultures grew out Candida albicans. At this point, the best course of action is to (A) Continue current antibiotics and start griseofulvin (B) Continue current antibiotics and start amphotericin B (C) Stop current antibiotics and start itraconazole (D) Stop current antibiotics and start amphotericin B (E) Stop current antibiotics and start terbinafine

The antibiotic regimen should be stopped immediately, since the condition of the patient did not improve after 3 d of such treatment, the cultures were negative for bacteria, and the clinical picture suggested that the patient had a fungal infection. This was subsequently confirmed by blood culture. The answer is D.

A 24-year-old woman was found to have mild hyperthyroidism due to Graves' disease. She appears to be in good health otherwise. In Graves' disease, the cause of the hyperthyroidism is the production of an antibody that does which of the following? (A) Activates the pituitary thyrotropin-releasing hormone (TRH) receptor and stimulates TSH release (B) Activates the thyroid gland TSH receptor and stimulates thyroid hormone synthesis and release (C) Activates thyroid hormone receptors in peripheral tissues (D) Binds to thyroid gland thyroglobulin and accelerates its proteolysis and the release of its supply of T 4 and T3 (E) Binds to thyroid-binding globulin (TBG) and displaces bound T 4 and T3

The antibodies produced in Graves' disease activate thyroid gland TSH receptors. Their effects mimic those of TSH. The answer is B.

A 23-year-old man with Hodgkin's lymphoma was treated unsuccessfully with the MOPP regimen (mechlorethamine, vincristine, prednisone, procarbazine). He subsequently underwent a successful course of therapy with the ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine). During the second course of drug treatment (ABVD r men), this patient developed dyspnea, a nonproductive cough, and intermittent fever. Chest x-ray film revealed pulmonary infiltration. If these problems are due to the anticancer drugs to which he has been exposed, which of the following is the most likely causative agent? (A) Bleomycin (B) Dacarbazine (C) Doxorubicin (D) Prednisone (E) Vinblastine

The anticancer drug most commonly associated with p nary toxicity is bleomycin. The answer is A.

A compound that is toxic to bone marrow cells in the early stages of development and that may also be leukemogenic is (A) Benzene (B) Carbon monoxide (C) Glyphosate (D) DDT (E) Pyrethrum

The aromatic hydrocarbon benzene is used as a solvent in industry. Long-term exposure is associated with increased risk of leukemia. The answer is A.

A freshman student (weight 70 kg) attends a college party where he rapidly consumes a quantity of an alcoholic beverage that results in a blood level of 500 mg/dL. Assuming that this young man has not had an opportunity to develop tolerance to ethanol, his present condition is best characterized as (A) Able to walk, but not in a straight line (B) Alert and competent to drive a car (C) Comatose and near death (D) Sedated with increased reaction times (E) Slightly inebriated

The blood level of ethanol achieved in this individual is extremely high, probably associated with coma, and likely to result in death due to respiratory arrest in a person who lacks tolerance to ethanol. The answer is C.

This neurotransmitter, found in diffuse systems, can exert both excitatory and inhibitory actions. Multiple receptor subtypes and a transporter have been identified, some of which are targets for drugs that are used in major depressive disorder and attention deficit hyperactivity disorder. (A) Acetylcholine (B) Beta-endorphin (C) Glycine (D) Glutamate (E) Norepinephrine

The brief description might apply to several CNS n mitters, including serotonin and possibly dopamine (neither of which is listed). Cell bodies of noradrenergic neurons located in the pons and brain stem project to all levels of the CNS. Most of the subclasses of adrenoceptors that occur in peripheral tissues are present in the CNS. Tricyclic antidepressants target norepinephrine as well as serotonin reuptake transporters; amphetamine and its analogs are used in ADHD. The answer is E.

A 57-year-old woman presents to her primary care physician with a complaint of severe chest pain when she walks uphill in cold weather. The pain disappears when she rests. She has a 40-pack-year history of smoking but her plasma lipids are within the normal range. After evaluation and discussion of treatment options, a decision is made to treat her with nitroglycerin. One year later, the patient returns complaining that her nitroglycerin works well when she takes it for an acute attack but that she is now having more frequent attacks and would like something to prevent them. Useful drugs for the prophylaxis of angina of effort include (A) Amyl nitrite (B) Esmolol (C) Sublingual isosorbide dinitrate (D) Sublingual nitroglycerin (E) Verapamil

The calcium channel blockers and the β blockers are generally effective in reducing the number of attacks of angina of effort, and most have durations of 4-8 h. Oral and transdermal nitrates have similar or longer durations. Amyl nitrite and the sublingual nitrates have short durations of action (a few minutes to 30 min). Esmolol (an intravenous β blocker) must be given intravenously and also has a very short duration of action. Thus, nitrites, sublingual nitrates, and esmolol are of no value in prophylaxis. The answer is E.

A 70-year-old woman is admitted to the emergency department because of a "fainting spell" at home. She appears to have suffered no trauma from her fall, but her blood pressure is 120/60 when lying down and 60/20 when she sits up. Neurologic examination and an ECG are within normal limits when she is lying down. Questioning reveals that she has recently started taking "water pills" (diuretics) for a heart condition. Which of the following drugs is the most likely cause of her fainting spell? (A) Acetazolamide (B) Amiloride (C) Furosemide (D) Hydrochlorothiazide (E) Spironolactone

The case history suggests that the syncope (fainting) is associated with diuretic use. Complications of diuretics that can result in syncope include both postural hypotension (which this patient exhibits) due to excessive reduction of blood volume and arrhythmias due to excessive potassium loss. Potassium wasting is more common with thiazides (because of their long duration of action), but these drugs rarely cause reduction of blood volume sufficient to result in orthostatic hypotension. The answer is C, furosemide.

A 23-year-old man with Hodgkin's lymphoma was treated unsuccessfully with the MOPP regimen (mechlorethamine, vincristine, prednisone, procarbazine). He subsequently underwent a successful course of therapy with the ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine). Which of the following classes of anticancer drugs used in the treatment of this patient is cell cycle specific (CCS) and used in both the MOPP and ABVD regimens? (A) Alkylating agents (B) Antibiotics (C) Antimetabolites (D) Glucocorticoids (E) Plant alkaloids

The cell cycle-specific drugs used in standard treatment protocols for Hodgkin's lymphoma are bleomycin and the vinca alkaloids. Vinblastine is used in the ABVD regimen, and vincristine (Oncovin) is used in the MOPP regimen. The answer is E.

A 14-year-old patient has experienced severe headache and double vision for a month. His temperature is 38.6°C (101.5°F). His CSF culture was positive for cryptococcal antigen. Which of the following drugs would be appropriate to treat this patient systemically (not intrathecally)? (A) Amphotericin B (B) Fluconazole (C) Itraconazole (D) Ketoconazole (E) Nystatin

The classes of antifungal drugs that have activity against Cryptococcus are the polyenes (amphotericin B formulations), the azoles, and flucytosine. Fluconazole is the best-absorbed member of the azole group and the only one that readily penetrates into cerebrospinal fluid. Amphotericin would work if it were delivered intrathecally. The answer is B.

In addition to cyclosporine HC received two other drugs. Can you identify the second drug? It suppresses cellular immunity, inhibits prostaglandin and leukotriene synthesis, and increases the catabolism of IgG antibodies. (A) Cyclophosphamide (B) Etanercept (C) Infliximab (D) Mycophenolate mofetil (E) Prednisone

The corticosteroid prednisone is used extensively as an immunosuppressant in autoimmune diseases and organ transplantation. Glucocorticoids have multiple actions, including those described. The answer is E.

Myalgias are a common postoperative complaint of patients who receive large doses of succinylcholine, possibly the result of muscle fasciculations caused by depolarization. Which drug administered in the operating room can be used to prevent postoperative pain caused by succinylcholine? (A) Atracurium (B) Baclofen (C) Dantrolene (D) Diazepam (E) Lidocaine

The depolarizing action of succinylcholine at the skeletal muscle end plate can be antagonized by small doses of nondepolarizing blockers. To prevent skeletal muscle fasciculations and the resulting postoperative pain caused by succinylcholine, a small nonparalyzing dose of a nondepolarizing drug (eg, atracurium) is sometimes given immediately before succinylcholine. The answer is A.

The "dominant lethal" test involves the treatment of a male adult animal with a chemical before mating; the pregnant female is later examined for fetal death and abnormalities. The dominant lethal test therefore is a test of (A) Teratogenicity (B) Mutagenicity (C) Carcinogenicity (D) Sperm viability

The description of the test indicates that a chromosomal change (passed from father to fetus) is the toxicity detected. This is a mutation. The answer is B.

A 76-year-old man is seen in a hospital emergency department complaining of pain in and behind the right ear. Physical examination shows edema of the external otic canal with purulent exudate and weakness of the muscles on the right side of the face. The patient informs the physician that he is a diabetic. Gram stain of the exudate from the ear shows many polymorphonucleocytes and Gram-negative rods, and samples are sent to the microbiology laboratory for culture and drug susceptibility testing. A preliminary diagnosis is made of external otitis. At this point, which of the following is most appropriate? (A) Amikacin should be injected intramuscularly and the patient should be sent home (B) Analgesics should be prescribed, but antibiotics should be withheld pending microbiological results (C) Oral cefaclor should be prescribed together with analgesics, and the patient should be sent home (D) The patient should be hospitalized and treatment started with imipenem-cilastatin (E) The patient should be hospitalized and treatment started with gentamicin plus ticarcillin

The diabetic patient with external otitis is at special risk because of the danger of spread to the middle ear and possibly the meninges, so hospitalization is advisable, especially in the elderly. Likely pathogens include E coli and Pseudomonas aeruginosa, and coverage must be provided for these and possibly other Gram-negative rods. The combination of an aminoglycoside plus a wider-spectrum penicillin is most suitable in this case and is synergistic against many pseudomonas strains. Imipenem-cilastatin is also possible, but resistant strains of P aeruginosa have emerged during treatment. Cefaclor lacks antipseudomonal activity. The answer is E.

If phenelzine is administered to a patient taking fluoxetine, which of the following is most likely to occur? (A) A decrease in the plasma levels of fluoxetine (B) Antagonism of the antidepressant action of fluoxetine (C) Agitation, muscle rigidity, hyperthermia, seizures (D) Decreased metabolism of fluoxetine (E) Priapism

The drug interaction between the inhibitors of monoamine oxidase used for depression and the drugs that selectively block serotonin reuptake (SSRIs) is called the serotonin syndrome. In the case of phenelzine and fluoxetine, the interaction has resulted in a fatal outcome. Key interventions include control of hyperthermia and seizures. The answer is C.

A 74-year-old retired mechanic is admitted with a myocardial infarction and a severe acute cardiac arrhythmia. You decide to give lidocaine to correct the arrhythmia. A continuous intravenous infusion of lidocaine, 1.92 mg/min, is started at 8 AM. The average pharmacokinetic parameters of lidocaine are: Vd 77 L; clearance 640 mL/min; half-life 1.4 h. What is the expected steady-state plasma concentration? (A) 40 mg/L (B) 3.0 mg/L (C) 0.025 mg/L (D) 7.2 mg/L (E) 3.46 mg/L

The drug is being administered continuously and the steadystate concentration (Cp(ss) ) for a continuously administered drug is given by the equation in question 1. Thus, Dosage = Plasma level ss × Clearance 1.92 mg/min = Cp ( ss) × CL Rearranging: 1.92 mg/min /CL= Cp(ss) Cp(ss) = 1.92 mg/min / 640 mL/min Cp(ss) = 0.003 mg/mL or 3 mg/L The answer is B.

A 20-year-old male patient scheduled for hernia surgery was anesthetized with halothane and nitrous oxide; tubocurarine was provided for skeletal muscle relaxation. The patient rapidly developed tachycardia and became hypertensive. Generalized skeletal muscle rigidity was accompanied by marked hyperthermia. Laboratory values revealed hyperkalemia and acidosis. The patient should be treated immediately with (A) Atropine (B) Baclofen (C) Dantrolene (D) Edrophonium (E) Flumazenil

The drug of choice in malignant hyperthermia is dantrolene, which prevents release of calcium from the sarcoplasmic reticulum of skeletal muscle cells. Appropriate measures must be taken to lower body temperature, control hypertension, and restore acid-base and electrolyte balance. The answer is C.

A 5-year-old child was vomiting and was brought to the emergency department with sinus arrest and a ventricular rate of 35 bpm. An empty bottle of his uncle's digoxin was found where he was playing. Which of the following is the drug of choice in treating a severe overdose of digoxin? (A) Digoxin antibodies (B) Lidocaine infusion (C) Magnesium infusion (D) Phenytoin by mouth (E) Potassium by mouth

The drug of choice in severe, massive overdose with any cardiac glycoside is digoxin antibody, Digibind. The other drugs listed are used in moderate overdosage associated with increased automaticity. The answer is A.

A group of volunteers are involved in a phase 1 clinical trial of a new autonomic drug. When administered by intravenous bolus, the blood pressure increases. When given orally for 1 week, the blood pressure decreases. Which of the following standard agents does the new drug most resemble? (A) Atropine (B) Clonidine (C) Phentolamine (an α blocker) (D) Phenylephrine (E) Propranolol (a β blocker)

The dual blood pressure effects of the drug suggest that initially it is causing a direct α-agonist vasoconstrictor effect, but when given for a week, it is accumulating in a blood pressure-controlling center, eg, the CNS, and reducing sympathetic outflow. The answer is B.

After your patient has been receiving digoxin for 3 weeks, he presents to the emergency department with an arrhythmia. Which one of the following is most likely to contribute to the arrhythmogenic effect of digoxin? (A) Increased parasympathetic discharge (B) Increased intracellular calcium (C) Decreased sympathetic discharge (D) Decreased intracellular ATP (E) Increased extracellular potassium

The effects of digitalis include increased vagal action on the heart (not arrhythmogenic) and increased intracellular calcium, including calcium overload, the most important cause of toxicity. Decreased sympathetic discharge and increased extracellular potassium and magnesium reduce digitalis arrhythmogenesis. The answer is B.

When nitrates are used in combination with other drugs for the treatment of angina, which one of the following combinations results in additive effects on the variable specified? (A) Beta blockers and nitrates on end-diastolic cardiac size (B) Beta blockers and nitrates on heart rate (C) Beta blockers and nitrates on venous tone (D) Calcium channel blockers and β blockers on cardiac force (E) Calcium channel blockers and nitrates on heart rate

The effects of β blockers and nitrates on heart size, force, venous tone, and heart rate are opposite. The effects of β blockers and calcium channel blockers on heart size, force, and rate are the same. The answer is D.

A 67-year-old woman presents with pain in her left thigh muscle. Duplex ultrasonography indicates the presence of deep vein thrombosis (DVT) in the affected limb. During the next week, the patient was started on warfarin and her enoxaparin was discontinued. Two months later, she returned after a severe nosebleed. Laboratory analysis revealed an INR (international normalized ratio) of 7.0 (INR value in such a warfarin-treated patient should be 2.0-3.0). To prevent severe hemorrhage, the warfarin should be discontinued and this patient should be treated immediately with which of the following? (A) Aminocaproic acid (B) Desmopressin (C) Factor VIII (D) Protamine (E) Vitamin K1

The elevated INR indicates excessive anticoagulation with a high risk of hemorrhage. Warfarin should be discontinued and vitamin K 1 administered to accelerate formation of vitamin K-dependent factors. The answer is E.

A patient with liver dysfunction is scheduled for a surgical procedure. Lorazepam or oxazepam can be used for preanesthetic sedation in this patient without special concern regarding excessive CNS depression because these drugs are (A) Actively secreted in the renal proximal tubule (B) Conjugated extrahepatically (C) Eliminated via the lungs (D) Reversible by administration of naloxone (E) Selective anxiolytics like buspirone

The elimination of most benzodiazepines involves their metabolism by liver enzymes, including cytochrome P450 isozymes. In a patient with liver dysfunction, lorazepam and oxazepam, which are metabolized extrahepatically, are less likely to cause excessive CNS depression. Benzodiazepines are not eliminated via the kidneys or lungs. Flumazenil is used to reverse excessive CNS depression caused by benzodiazepines. The answer is B.

Which statement concerning the pharmacokinetics of anti-seizure drugs is most accurate? (A) Administration of phenytoin to patients in methadone maintenance programs has led to symptoms of opioid overdose, including respiratory depression (B) To reduce gastrointestinal toxicity, ethosuximide is usually taken twice a day (C) At high doses, phenytoin elimination follows first-order kinetics (D) Gabapentin has a very long half-life and is usually given every other day (E) Treatment with vigabatrin reduces the effectiveness of oral contraceptives (F) Valproic acid may increase the activity of hepatic ALA synthase and the synthesis of porphyrins

The enzyme-inducing activity of phenytoin and carbamazepine has led to symptoms of opioid withdrawal, presumably because of an increase in the rate of metabolism of opioids. Monitoring of plasma concentration of phenytoin may be critical in establishing an effective dosage because of nonlinear zero-order elimination kinetics at high doses. Valproic acid has no effect on porphyrin synthesis. Vigabatrin does not affect the metabolism of oral contraceptives. Gabapentin has a relatively short half-life (5-8 hours) and is given twice or three times daily. Twice-daily dosage of ethosuximide reduces the severity of adverse gastrointestinal effects. The answer is B.

The pharmacokinetic process or property that distinguishes the elimination of ethanol and high doses of phenytoin and aspirin from the elimination of most other drugs is called (A) Distribution (B) Excretion (C) First-pass effect (D) First-order elimination (E) Zero-order elimination

The excretion of most drugs follows first-order kinetics. However, ethanol and, in higher doses, aspirin and phenytoin follow zero-order kinetics; that is, their elimination rates are constant regardless of blood concentration. The answer is E.

A 3-year-old child is admitted to the emergency department after taking a drug from her parents' medicine cabinet and swallowing multiple tablets. The signs suggest that the drug is a cholinomimetic with little or no vascular effect, little or no CNS effect, and a duration of action of about 2-4 h. Which of the following is the most likely cause of these effects? (A) Acetylcholine (B) Bethanechol (C) Neostigmine (D) Physostigmine (E) Pilocarpine

The fact that the drug has no vascular effect suggests that it is an indirect-acting agent. Neostigmine is the prototypical indirect-acting cholinomimetic; it is a quaternary (charged) substance with poor lipid solubility and little or no CNS action; its duration of action is about 2-4 h. Physostigmine is similar but has good lipid solubility and significant CNS effects. The answer is C.

You have a vial containing 10 mL of a 2% solution of lidocaine. How much lidocaine is present in 1 mL? (A) 2 mg (B) 5 mg (C) 10 mg (D) 20 mg (E) 50 mg

The fact that you have 10 mL of the solution of lidocaine is irrelevant. A 2% solution of any drug contains 2 g/100 mL. The amount of lidocaine in 1 mL of a 2% solution is thus 0.02 g, or 20 mg. The answer is D.

Which of the following would probably not be included in an optimal phase 3 clinical trial of a new analgesic drug for mild pain? (A) A negative control (placebo) (B) A positive control (current standard analgesic therapy) (C) Double-blind protocol (in which neither the patient nor immediate observers of the patient know which agent is active) (D) A group of 1000-5000 subjects with a clinical condition requiring analgesia (E) Prior submission of an NDA (new drug application) to the FDA

The first 4 items (A-D) are correct; they would be included. An NDA cannot be acted upon until the first 3 phases of clinical trials have been completed. (The IND must be approved before clinical trials can be conducted.) The answer is E.

A patient with parkinsonism is being treated with levodopa. He suffers from irregular, involuntary muscle jerks that affect the proximal muscles of the limbs. Which of the following statements about these symptoms is most accurate? (A) Coadministration of muscarinic blockers prevents the occurrence of dyskinesias during treatment with levodopa (B) Drugs that activate dopamine receptors can exacerbate dyskinesias in a patient taking levodopa (C) Dyskinesias are less likely to occur if levodopa is administered with carbidopa (D) Symptoms are likely to be alleviated by continued treatment with levodopa (E) The symptoms are usually reduced if the dose of levodopa is increased

The form and severity of dyskinesias resulting from levodopa may vary widely in individual patients. Dyskinesias occur in up to 80% of patients receiving levodopa for long periods. With continued treatment, dyskinesias may develop at a dose of levodopa that was previously well tolerated. Muscarinic receptor blockers do not prevent their occurrence. They occur more commonly in patients treated with levodopa in combination with carbidopa or with other dopamine receptor agonists. The answer is B.

Which compound enhances immune function in vitro and is used to decrease the symptoms of the common cold? (A) Echinacea (B) Ginkgo (C) Garlic (D) Melatonin (E) Milk thistle

The freshly pressed juice of the aerial parts of Echinacea purpurea is purported to reduce the symptoms of the common cold and the time of recovery if ingested within 24 h of onset. The answer is A.

The inducible isoform of nitric oxide synthase (iNOS, isoform 2) is found primarily in which of the following? (A) Adipose tissue (B) Eosinophils (C) Macrophages (D) Platelets (E) Vascular endothelial cells

The inducible form of NOS is associated with inflammation, and the enzyme is found in highest concentration in macrophages, cells that are particularly involved in inflammation. The answer is C.

A 24-year-old woman comes to a clinic with complaints of dry cough, headache, fever, and malaise, which have lasted 3 or 4 d. She appears to have some respiratory difficulty, and chest examination reveals rales but no other obvious signs of pulmonary involvement. However, extensive patchy infiltrates are seen on chest x-ray film. Gram stain of expectorated sputum fails to reveal any bacterial pathogens. The patient mentions that a colleague at work had similar symptoms to those she is experiencing. The patient has no history of serious medical problems. She takes loratadine for allergies and supplementary iron tablets, and she drinks at least 6 cups of caffeinated coffee per day. The physician makes an initial diagnosis of communityacquired pneumonia. If this patient were to be treated with erythromycin, she should (A) Avoid exposure to sunlight (B) Avoid taking supplementary iron tablets (C) Decrease her intake of caffeinated beverages (D) Have her plasma urea nitrogen or creatinine checked before treatment (E) Temporarily stop taking loratadine

The inhibition of liver cytochrome P450 by erythromycin has led to serious drug interactions. Although erythromycin does not inhibit loratadine metabolism, it does inhibit the CYP1A2 form of cytochrome P450, which metabolizes methylxanthines. Consequently, cardiac and/or CNS toxicity may occur with excessive ingestion of caffeine. Unlike the tetracyclines, the oral absorption of erythromycin is not affected by cations and the drug does not cause photosensitivity. Because erythromycin undergoes biliary excretion, there is little reason to assess renal function before treatment. The answer is C.

Which of the following drugs is most likely to cause hypoglycemia when used as monotherapy in the treatment of type 2 diabetes? (A) Acarbose (B) Canagliflozin (C) Glyburide (D) Metformin (E) Miglitol (F) Rosiglitazone

The insulin secretagogues, including the sulfonylurea glyburide, can cause hypoglycemia as a result of their ability to increase serum insulin levels. The biguanides, thiazolidinediones, α-glucosidase inhibitors, and canagliflozin are euglycemics that are unlikely to cause hypoglycemia when used alone. The answer is C.

A new drug was given by subcutaneous injection to 25 n mal subjects in a phase 1 clinical trial. The cardiovascular effects are summarized in the table below. Systolic BP (mm Hg) Control 116 Peak drug effect 156 Diastolic BP (mm Hg) Control 76 Peak drug effect 96 Cardiac output (L/min) Control 5.0 Peak drug effect 7.7 Heart rate (beats/min) Control 71.2 Peak drug effect 94.3 Which of the following drugs does the new experimental agent most resemble? (A) Atropine (B) Epinephrine (C) Isoproterenol (D) Phenylephrine (E) Physostigmine

The investigational agent caused a marked increase in systolic and diastolic pressures and a moderate increase in pulse pressure (from 40 to 60 mm Hg). These changes suggest a strong alpha effect on vessels and an increase in stroke volume, a β-agonist action in the heart. A dominant α action might be expected to cause a reflex bradycardia, but heart rate actually increased significantly, reflecting a large β response. Note that the stroke volume also increased (cardiac output divided by heart rate—from 70.2 to 81.7 mL), suggesting increased contractility, another β response. The drug behaves most like a mixed α and β agonist, eg, epinephrine. The answer is B.

Which of the following is most likely to be required by a 5-year-old boy with chronic renal insufficiency? (A) Cyanocobalamin (B) Deferoxamine (C) Erythropoietin (D) Filgrastim (G-CSF) (E) Oprelvekin (IL-11)

The kidney produces erythropoietin; patients with chronic renal insufficiency often require exogenous erythropoietin to avoid chronic anemia. The answer is C.

Which of the following is a component of slow-reacting substance of anaphylaxis (SRS-A)? (A) Alprostadil (B) Aspirin (C) Leukotriene LTB4 (D) Leukotriene LTC4 (E) Misoprostol (F) Prednisone (G) Prostacyclin (H) Zafirlukast (I) Zileuton

The leukotriene C and D series are major eicosanoid c ponents of SRS-A. Leukotriene LTB 4 is a chemotactic eicosanoid. The answer is D.

An adult patient (weight 80 kg) has bacteremia suspected to be due to a Gram-negative rod. Tobramycin is to be administered using a once-daily dosing regimen, and the loading dose must be calculated to achieve a peak plasma level of 20 mg/L. Assume that the patient has normal renal function. Pharmacokinetic parameters of tobramycin in this patient are as follows: V d = 30 L; t 1/2 = 3 h; CL = 80 mL/min. What loading dose should be given? (A) 100 mg (B) 200 mg (C) 400 mg (D) 600 mg (E) 800 mg

The loading dose of any drug is calculated by multiplying the desired plasma concentration (mg/L) by the volume of distribution (L). The answer is D.

A 45-year-old man with a duodenal ulcer was treated with a combination of drugs intended to heal the mucosal damage and to eradicate Helicobacter pylori. Which of the following antibacterial drugs is used commonly to eradicate intestinal H pylori? (A) Cefazolin (B) Ciprofloxacin (C) Clarithromycin (D) Clindamycin (E) Vancomycin

The macrolide antibiotic clarithromycin is commonly used in antibiotic regimens designed to treat duodenal ulcers caused by H pylori. The other antibiotics that are used include amoxicillin, tetracycline, and metronidazole. Bismuth also has an antibacterial action. The answer is C.

A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL cholesterol, VLDL cholesterol, and triglycerides are normal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. Six months after beginning atorvastatin, the patient's total and LDL cholesterol concentrations remained above normal, and he continued to have anginal attacks despite good adherence to his antianginal medications. His physician decided to add ezetimibe. Which of the following is the most accurate description of ezetimibe's mechanism of an action? (A) Decreased lipid synthesis in adipose tissue (B) Decreased secretion of VLDL by the liver (C) Decreased gastrointestinal absorption of cholesterol (D) Increased endocytosis of HDL by the liver (E) Increased lipid hydrolysis by lipoprotein lipase

The major recognized effect of ezetimibe is inhibition of absorption of cholesterol in the intestine. The answer is C.

Concerning the proposed mechanisms of action of a pressant drugs, which statement is most accurate? (A) Bupropion inhibits NE reuptake into nerve endings in the CNS (B) Chronic treatment with tricyclic antidepressants leads to downregulation of adrenoceptors in the CNS (C) Decreased levels of NE and 5-HT in cerebrospinal fluid is a characteristic of depressed patients before drug therapy (D) Nefazodone activates 5-HT receptors in the CNS (E) Selegiline selectively decreases the metabolism of serotonin

The mechanism of action of bupropion is unknown, but the drug does not inhibit either NE or 5-HT transporters. Levels of NE and 5-HT metabolites in the cerebrospinal fluid of depressed patients before drug treatment are not higher than normal. Selegiline is a selective inhibitor of MAO-B, the enzyme form that metabolizes dopamine (see Chapter 28). Nefazodone is a highly selective antagonist at the 5-HT2 receptor subtype. Downregulation of adrenoceptors appears to be a common feature of chronic treatment of depression with tricyclic drugs such as amitriptyline. The answer is B.

The mechanism of antiseizure activity of carbamazepine is (A) Block of sodium ion channels (B) Block of calcium ion channels (C) Facilitation of GABA actions on chloride ion channels (D) Glutamate receptor antagonism (E) Inhibition of GABA transaminase

The mechanism of action of carbamazepine is similar to that of phenytoin, blocking sodium ion channels. Ethosuximide blocks calcium channels; benzodiazepines and barbiturates facilitate the inhibitory actions of GABA; topiramate may block glutamate receptors; and vigabatrin inhibits GABA metabolism. The answer is A.

The cytochrome P450-dependent microsomal ethanol oxidizing system (MEOS) pathway of ethanol metabolism is most likely to be maximally activated under the condition of low concentrations of (A) Acetaldehyde (B) Ethanol (C) NAD+ (D) NADPH (E) Oxygen

The microsomal ethanol-oxidizing system (MEOS) c utes most to ethanol metabolism at relatively high blood alcohol concentrations (>100 mg/dL), when the alcohol dehydrogenase pathway is saturated due to depletion of NAD . So, the MEOS system contributes most when the NAD + + concentration is low. NADPH and oxygen are cofactors for MEOS reactions. The concentration of acetaldehyde does not appear to affect the rate of either the ADH or the MEOS reactions. The answer is C.

Which adverse effect is most common with sulfonamides? (A) Fanconi's aminoaciduria syndrome (B) Hematuria (C) Kernicterus in the newborn (D) Neurologic dysfunction (E) Skin rash

The most common adverse effect of the sulfonamides is a skin rash caused by hypersensitivity. Neurologic dysfunction and hematuria occur less frequently. Sulfonamides are usually avoided in the third trimester of pregnancy or in neonates, so kernicterus is rare. Fanconi's syndrome is associated with the use of outdated tetracyclines. The answer is E.

A 55-year-old lawyer is brought to the emergency department 2 h after the onset of severe chest pain during a stressful meeting. He has a history of poorly controlled mild hypertension and elevated blood cholesterol but does not smoke. ECG changes (ST elevation) and cardiac enzymes confirm the diagnosis of myocardial infarction. The decision is made to attempt to open his occluded artery. If a fibrinolytic drug is used for treatment of this man's acute myocardial infarction, which of the following adverse drug effects is most likely to occur? (A) Acute renal failure (B) Development of antiplatelet antibodies (C) Encephalitis secondary to liver dysfunction (D) Hemorrhagic stroke (E) Neutropenia

The most common serious adverse effect of the fibrinolytics is bleeding, especially in the cerebral circulation. The fibrinolytics do not usually have serious effects on the renal, hepatic, or hematologic systems. Unlike heparin, they do not induce antiplatelet antibodies. The answer is D.

A 76-year-old retired postal worker with rheumatoid arthritis and chronic heart disease presents with a cardiac arrhythmia and is being considered for treatment with procainamide. She is already receiving an ACE inhibitor, digoxin, and hydrochlorothiazide for her cardiac condition. If this patient should take an overdose and manifest severe acute procainamide toxicity with markedly prolonged QRS, which of the following should be given immediately? (A) A calcium chelator such as EDTA (B) Adenosine (C) Nitroprusside (D) Potassium chloride (E) Sodium lactate

The most effective therapy for procainamide (and quinidine) toxicity appears to be concentrated sodium lactate. This drug may (1) increase sodium current by increasing the sodium ion gradient and (2) reduce drug-receptor binding by alkalinizing the tissue. The answer is E.

The combination of ethanol and disulfiram results in nausea and hypotension as a result of the accumulation of (A) Acetaldehyde (B) Acetate (C) Methanol (D) NADH (E) Pyruvate

The nausea, hypotension, and ill feeling that result from drinking ethanol while also taking disulfiram stems from acetaldehyde accumulation. Disulfiram inhibits acetaldehyde dehydrogenase, the enzyme that converts acetaldehyde to acetate. The answer is A.

A 57-year-old woman presents to her primary care physician with a complaint of severe chest pain when she walks uphill in cold weather. The pain disappears when she rests. She has a 40-pack-year history of smoking but her plasma lipids are within the normal range. After evaluation and discussion of treatment options, a decision is made to treat her with nitroglycerin. In advising the patient about the adverse effects she may notice, you point out that nitroglycerin in moderate doses often produces certain symptoms. Which of the following effects might occur due to the mechanism listed? (A) Constipation due to reduced colonic activity (B) Dizziness due to reduced cardiac force of contraction (C) Diuresis due to sympathetic discharge (D) Headache due to meningeal vasodilation (E) Hypertension due to reflex tachycardia

The nitrates relax many types of smooth muscle, but the effect on motility in the colon is insignificant. Nitroglycerin causes hypotension as a result of arterial and venous dilation. Dilation of arteries in the meninges has no effect on central nervous system function but does cause headache. The answer is D.

Concerning the drugs used in parkinsonism, which statement is most accurate? (A) Dopamine receptor agonists should never be used in Parkinson's disease before a trial of levodopa (B) Levodopa causes mydriasis and may precipitate an acute attack of glaucoma (C) Selegiline is a selective inhibitor of COMT (D) The primary benefit of antimuscarinic drugs in parkinsonism is their ability to relieve bradykinesia (E) Therapeutic effects of amantadine continue for several years

The non-ergot dopamine agonists (pramipexole, ropinirole) are sometimes used prior to levodopa in mild parkinsonism. The mydriatic action of levodopa may increase intraocular pressure; the drug should be used cautiously in patients with open-angle glaucoma and is contraindicated in those with angle-closure glaucoma. Antimuscarinic drugs may improve the tremor and rigidity of parkinsonism but have little effect on bradykinesia. Selegiline is a selective inhibitor of MAO type B. Amantadine is effective for only a few weeks. The answer is B.

Which drug does not activate opioid receptors, has been proposed as a maintenance drug in treatment programs for opioid addicts, and with a single oral dose, will block the effects of injected heroin for up to 48 h? (A) Fentanyl (B) Nalbuphine (C) Naloxone (D) Naltrexone (E) Propoxyphene

The opioid antagonist naltrexone has a much longer half-life than naloxone, and its effects may last 2 d. A high degree of client compliance would be required for naltrexone to be of value in opioid dependence treatment programs. The same reservation is applicable to the use of naltrexone in alcoholism. The answer is D.

A 2-year-old girl presented with lethargy, increased respiratory rate, and an elevated temperature that appeared to result from a drug poisoning. Laboratory testing revealed the following serum concentrations: glucose, 36 mg/dL; Na+ , 148 mEq/L; K+ , 5 mEq/L; Cl− , 111 mEq/L; HCO3 − , 12 mEq/L; BUN, 21 mg/dL; osmolality, 300 mOsm/L. The osmolal gap in this patient is (A) −40 mOsm/L (B) −5 mOsm/L (C) +15 mOsm/L (D) +60 mOsm/L (E) +305 mOsm/L

The osmolar gap is the difference between the measured serum osmolality and the osmolality calculated from the serum sodium, glucose, and BUN concentrations according to the equation above for calculating the osmolal gap. In this case, the measured osmolality is 300 mOsm/L, whereas the calculated osmolality is 305 mOsm/L; the difference is −5 mOsm/L. The answer is B.

A patient who has been taking digoxin for several years for atrial fibrillation and chronic heart failure is about to receive atropine for another condition. A common effect of digoxin (at therapeutic blood levels) that can be almost entirely blocked by atropine is (A) Decreased appetite (B) Headaches (C) Increased atrial contractility (D) Increased PR interval on ECG (E) Tachycardia

The parasympathomimetic effects of digitalis can be blocked by muscarinic blockers such as atropine. The only parasympathomimetic effect in the list provided is increased PR interval, a manifestation of slowed AV conduction. The answer is D.

A new halogenated gas anesthetic has a blood:gas partition coefficient of 0.5 and a MAC value of 1%. Which prediction about this agent is most accurate? (Refer to Table 25-1 for comparison of agents.) (A) Equilibrium between arterial and venous gas tension will be achieved very slowly (B) It will be metabolized by the liver to release fluoride ions (C) It will be more soluble in the blood than isoflurane (D) Speed of onset will be similar to that of nitrous oxide (E) The new agent will be more potent than halothane

The partition coefficient of an inhaled anesthetic is a determinant of its kinetic characteristics. Agents with low blood:gas solubility have a fast onset of action and a short duration of recovery. The new agent described here resembles nitrous oxide but is more potent, as indicated by its low MAC value. Not all halogenated anesthetics undergo significant hepatic metabolism or release fluoride ions. The answer is D.

A patient was treated for a bacterial infection with a penicillin. Within a few minutes of the antibiotic injection, he developed severe bronchoconstriction, laryngeal edema, and hypotension. Because of the rapid administration of epinephrine, the patient survived. Unfortunately, a year later he was treated with an antipsychotic drug and developed agranulocytosis. Which type of immunologic process was triggered by the penicillin injection? (A) An autoimmune syndrome (B) A cell-mediated reaction (C) A type II drug allergy (D) Mediated by IgE (E) Serum sickness

The patient experienced an anaphylactic response to the penicillin. This is a type I (immediate) drug reaction, mediated by IgE antibodies. The answer is D.

A compound or group of compounds that damages the skin and whose use in manufacturing has largely been eliminated because of extensive persistence in the environment and bioaccumulation is (A) Aromatic hydrocarbons such as benzene (B) Dichlorvos (C) Phenoxyacetic acids such as 2,4-dichlorophenoxyacetic acid (D) Polychlorinated biphenyls (PCBs) (E) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

The polychlorinated biphenyls (PCBs) are dermatotoxic drugs that persist in the environment and accumulate in living organisms. PCBs have been banned from manufacture in the United States since 1979. However, many electrical transformers still retain traces of them. The answer is D.

Interactions between this drug and cell membrane components can result in the formation of pores lined by hydrophilic groups present in the drug molecule. (A) Caspofungin (B) Flucytosine (C) Griseofulvin (D) Nystatin (E) Terbinafine

The polyene antifungal drugs amphotericin B and nystatin are amphipathic molecules that can interact with ergosterol in fungal cell membranes to form artificial pores. In these structures, the lipophilic groups on the drug molecule are arranged on the outside of the pore, and the hydrophilic regions are located on the inside. The fungicidal action of the polyenes derives from this interaction, which results in leakage of intracellular constituents. The answer is D.

A 65-year-old woman has returned from a vacation abroad suffering from traveler's diarrhea, and her problem has not responded to antidiarrheal drugs. A pathogenic Gram-negative bacillus is suspected. Which drug is most likely to be effective in the treatment of this patient? (A) Ampicillin (B) Ofloxacin (C) Sulfadiazine (D) Trimethoprim (E) Vancomycin

The second-generation fluoroquinolones are very effective in diarrhea caused by bacterial Gram-negative pathogens, including E coli, Shigella, and Salmonella. None of the other drugs listed would be appropriate. Many coliforms are now resistant to amoxicillin and ampicillin. Although trimethoprim is available as a single drug, resistance emerges rapidly during treatment unless it is used for urinary tract infections, in which high concentrations can be achieved. Vancomycin has no activity against Gram-negative bacilli. The answer is B.

A patient is brought to the emergency department having taken an overdose (unknown quantity) of a sustained-release preparation of theophylline by oral administration 2 h previously. He has marked gastrointestinal distress with vomiting, is agitated, and exhibits hyperreflexia and hypotension. A short-acting antidote that can reduce this patient's tachycardia is (A) Acetylcysteine (B) Deferoxamine (C) Esmolol (D) Fomepizole (E) Pralidoxime

The short-acting β blocker esmolol helps reverse the t cardia and possibly the vasodilation associated with an overdose of theophylline. The answer is C.

A young man is brought to the emergency department in an anxious and agitated state. He informs the attending physician that he uses "street drugs" and that he gave himself an intravenous "fix" approximately 12 h ago. After an initial period of contentment and relaxation, he now has chills and muscle aches and has also been vomiting. His symptoms include hyperventilation and hyperthermia. The attending physician notes that his pupil size is larger than normal. What is the most likely cause of these signs and symptoms? (A) The patient had injected dextroamphetamine (B) The patient has hepatitis B (C) The patient has overdosed with an opioid (D) The signs and symptoms are those of the opioid abstinence syndrome (E) These are early signs of toxicity due to contaminants in "street heroin"

The signs and symptoms are those of withdrawal in a patient physically dependent on an opioid agonist, especially morphine or heroin. They usually start within 6-10 h after the last dose; their intensity depends on the degree of physical dependence, and peak effects usually occur at 36-48 h. Mydriasis is a prominent feature of the abstinence syndrome; other symptoms include rhinorrhea, lacrimation, piloerection, muscle jerks, and yawning. An overdose of dextroamphetamine would not produce an initial feeling of contentment and relaxation. The answer is D.

A college student is brought to the emergency department by friends. The physician is informed that the student had taken a drug and then "went crazy." The patient is agitated and delirious. Several persons are required to hold him down. His skin is warm and sweaty, and his pupils are dilated. Bowel sounds are normal. Signs and symptoms include tachycardia, marked hypertension, hyperthermia, increased muscle tone, and both horizontal and vertical nystagmus. The most likely cause of these signs and symptoms is intoxication from (A) Hashish (B) LSD (C) Mescaline (D) Methamphetamine (E) Phencyclidine

The signs and symptoms point to PCP intoxication. The presence of both horizontal and vertical nystagmus is pathognomonic. The answer is E.

You are planning to treat chronic major depression in a 35-year-old patient with recurrent suicidal thoughts. She has several comorbid conditions that require drug therapy, including rifampin for tuberculosis and amiodarone for arrhythmia. You are concerned about drug interactions caused by changes in drug metabolism in this patient. If therapy with multiple drugs causes induction of drug metabolism in your depressed patient, it will (A) Be associated with increased smooth endoplasmic reticulum (B) Be associated with increased rough endoplasmic reticulum (C) Be associated with decreased enzymes in the soluble cytoplasmic fraction (D) Require 3-4 months to reach completion (E) Be irreversible

The smooth endoplasmic reticulum, which contains the mixed-function oxidase drug-metabolizing enzymes, is selectively increased by inducers. The answer is A.

A 23-year-old woman is admitted to the emergency department with difficulty breathing. Examination reveals significant laryngeal edema. Past medical history indicates that she suffers from recurrent episodes of angioneurotic edema with release of histamine and other mediators. Which of the following drugs is the most effective physiologic antagonist of histamine in smooth muscle? (A) Epinephrine (B) Loratadine (C) Ondansetron (D) Ranitidine (E) Sumatriptan

The smooth muscle effects of histamine are mediated mainly by H 1 receptors. Loratadine is a pharmacologic antagonist of histamine at these receptors. Ondansetron is a 5-HT 3 antagonist used to prevent postsurgical and chemotherapy-induced vomiting. Sumatriptan is a 5-HT 1D/1B agonist. Ranitidine is a pharmacologic histamine antagonist that blocks the H2 receptor in the stomach and the heart, not H 1 receptors in smooth muscle. Epinephrine has a physiologic antagonist action that reverses histamine's effects on smooth muscle. The answer is A.

After undergoing surgery for breast cancer, a 53-year-old woman is scheduled to receive 4 cycles of cancer chemotherapy. The cycles are to be administered every 3-5 weeks. Her first cycle was complicated by severe chemotherapy-induced thrombocytopenia. Twenty months after finishing her chemotherapy, the woman had a relapse of breast cancer. The cancer was now unresponsive to standard doses of chemotherapy. The decision was made to treat the patient with high-dose chemotherapy followed by autologous stem cell transplantation. Which of the following drugs is most likely to be used to mobilize the peripheral blood stem cells needed for the patient's autologous stem cell transplantation? (A) Erythropoietin (B) Filgrastim (G-CSF) (C) Folic acid (D) Intrinsic factor (E) Oprelvekin (interleukin-11)

The success of transplantation with peripheral blood stem cells depends on infusion of adequate numbers of hematopoietic stem cells. Administration of G-CSF to the donor (in the case of autologous transplantation, the patient who also will be the recipient of the transplantation) greatly increases the number of hematopoietic stem cells harvested from the donor's blood. The answer is B.

A nonindigenous person who develops onchocerciasis in an endemic region and receives drug treatment is likely to experience a severe reaction. Symptoms include headache, weakness, rash, muscle aches, hypotension, and peripheral edema. Which statement concerning this reaction is accurate? (A) Extensive fluid replacement is essential (B) Symptoms are more intense in indigenous adults than nonindigenous adults (C) The reaction is due to treatment with suramin (D) The reaction is due to killing of microfilariae (E) The symptoms are characteristic of treatment with diethylcarbamazine

The symptoms described are those of the so-called Mazzotti reaction. They are due to the killing by ivermectin of microfilariae, and their intensity correlates with skin microfilaria load and is not a drug toxicity. The reaction occurs more frequently and with greater severity in nonindigenous persons than in the indigenous inhabitants of endemic areas. The answer is D.

A 50-year-old man has a history of frequent episodes of renal colic with calcium-containing renal stones. A careful workup indicates that he has a defect in proximal tubular calcium reabsorption, which results in high concentrations of calcium salts in the tubular urine. The most useful diuretic agent in the treatment of recurrent calcium stones is (A) Chlorthalidone (B) Diazoxide (C) Ethacrynic acid (D) Mannitol (E) Spironolactone

The thiazides are useful in the prevention of calcium stones because these drugs reduce tubular calcium concentration, probably by increasing passive proximal tubular and distal convoluted tubule reabsorption of calcium. In contrast, the loop agents (choice C) facilitate calcium excretion. Diazoxide is a thiazide-like vasodilator drug but has no diuretic action; in fact, it may cause sodium retention. It is used in hypertension and insulinoma (see Chapter 11). The answer is A.

A 27-year-old woman underwent near total thyroidectomy. She was started on levothyroxine. What hormone is produced in the peripheral tissues when levothyroxine is administered? (A) Methimazole (B) T3 (C) T4 (D) TSH (E) FSH

The thioamides (methimazole and propylthiouracil) act in thyroid cells to prevent conversion of tyrosine residues in thyroglobulin to MIT or DIT. Levothyroxine (T4 ) is converted into T 3 in the periphery. FSH is follicle-stimulating hormone. The answer is B.

A 24-year-old woman was found to have mild hyperthyroidism due to Graves' disease. She appears to be in good health otherwise. The decision is made to begin treatment with methimazole. Methimazole reduces serum concentration of T 3 primarily by which of the following mechanisms? (A) Accelerating the peripheral metabolism of T3 (B) Inhibiting the proteolysis of thyroid-binding globulin (C) Inhibiting the secretion of TSH (D) Inhibiting the uptake of iodide by cells in the thyroid (E) Preventing the addition of iodine to tyrosine residues on thyroglobulin

The thioamides (methimazole and propylthiouracil) act in thyroid cells to prevent conversion of tyrosine residues in thyroglobulin to MIT or DIT. The answer is E.

A young engineer involved in the smelting process of cobalt and gold presented with severe GI discomfort, rice water stools, and a sweet garlicky breath. Acute inorganic arsenic poisoning was diagnosed. Which of the following drugs should be included in the management of this patient? (A) Deferoxamine (B) Dimercaprol (C) EDTA (D) Penicillamine (E) Succimer

The treatment of choice in acute arsenic poisoning is i muscular dimercaprol. Although succimer is less toxic, it is only available in an oral formulation, and its absorption may be impaired by the severe gastroenteritis that occurs in acute arsenic poisoning. The answer is B.

In an accidental needlestick, an unknown quantity of blood from an AIDS patient is injected into a resident physician. The most recent laboratory report on the AIDS patient shows a CD4 count of 20/µL and a viral RNA load of greater than 10 7 copies/mL. The most appropriate course of action regarding treatment of the resident is to (A) Determine whether HIV transmission has occurred by monitoring the patient's blood (B) Treat with a single high dose of zidovudine (C) Treat with full doses of zidovudine for 4 weeks (D) Treat with single doses of zidovudine and indinavir (E) Treat with zidovudine plus lamivudine plus ritonavir for 4 weeks

The viral RNA titer in the blood from the AIDS patient in this case is very high, and this needlestick must be considered as a high-risk situation. Although full doses of zidovudine for 4 weeks have been shown to have prophylactic value, in high-risk situations combination regimens are favored. Optimal prophylaxis in this case might best be provided by the combination of zidovudine with lamivudine (basic regimen), plus the addition of protease inhibitors (expanded regimen). The answer is E.

Ms Smith, a 65-year-old woman with pneumonia, was given tobramycin, 150 mg, intravenously. After 20 minutes, the plasma concentration was measured and was found to be 3 mg/L. Assuming no elimination of the drug in 20 minutes, what is the apparent volume of distribution of tobramycin in Ms Smith? (A) 3 L/min (B) 3 L (C) 50 L (D) 7 L (E) 0.1 mg/min

The volume of distribution (Vd) is the apparent volume into which the loading dose is distributed. It is calculated by dividing the dose by the resulting plasma concentration, Cp : Vd = loading dose/Cp Vd =150 mg/ 3 mg/L V d = 50 L The answer is C.

Your 75-year-old patient with multiple comorbidities is to receive a β-blocking drug. For which of the following conditions are β-blocking drugs NOT indicated? (A) Acute arrhythmias during surgery (B) Atherosclerotic angina pectoris (angina of effort) (C) Chronic heart failure (D) Hypertension (E) Hypoglycemia in diabetes

The β blockers have several important cardiovascular indications, including acute arrhythmias, angina, chronic (but not acute) heart failure, and hypertension. In addition they are useful in glaucoma, hyperthyroidism, tremor, and possibly, COPD. However, they mask the signs of hypoglycemia and are potentially hazardous in diabetic patients. The answer is E.

One effect that theophylline, nitroglycerin, isoproterenol, and histamine have in common is (A) Direct stimulation of cardiac contractile force (B) Tachycardia (C) Bronchodilation (D) Postural hypotension (E) Throbbing headache

Theophylline does not ordinarily cause headache or postural hypotension. Nitroglycerin does not cause direct cardiac stimulation but does evoke a compensatory sympathetic reflex. Histamine does not cause bronchodilation. The answer is B.

A 22-year-old man is brought to the emergency department after suffering seizures resulting from an overdose of a drug he has been taking. His friends state that he took the drug orally and sometimes had insomnia after taking it. Which of the following is a direct bronchodilator that is most often used in asthma by the oral route and is capable of causing insomnia and seizures? (A) Cromolyn (B) Epinephrine (C) Ipratropium (D) Metaproterenol (E) Metoprolol (F) Prednisone (G) Salmeterol (H) Theophylline (I) Zileuton

Theophylline is a bronchodilator that is active by the oral route. It causes insomnia in therapeutic doses and seizures in overdosage. The answer is H.

A 42-year-old homemaker suffers from anxiety with phobic symptoms and occasional panic attacks. She uses over-the-counter antihistamines for allergic rhinitis and claims that ethanol use is "just 1 or 2 glasses of wine with dinner." Alprazolam, a benzodiazepine, is prescribed, and the patient is maintained on the drug for 3 years, with several dose increments over that time period. Her family notices that she does not seem to be improving and that her speech is often slurred in the evenings. She is finally hospitalized with severe withdrawal signs on one weekend while attempting to end her dependence on drugs. Which statement about the use of alprazolam is most accurate? (A) Abrupt discontinuance of alprazolam after 4 weeks of treatment may elicit withdrawal signs (B) Additive CNS depression occurs with ethanol (C) Most benzodiazepines are Schedule IV-controlled drugs (D) Tolerance can occur with chronic use of any benzodiazepine (E) All of the above statements are accurate

Therapeutic doses of benzodiazepines may lead to dependence with withdrawal symptoms including anxiety and agitation observable on abrupt discontinuance after a few weeks of treatment. Like most sedative-hypnotics, benzodiazepines are schedule-controlled, exhibiting dependence liability and the development of tolerance. Additive depression occurs with ethanol and many other CNS drugs. The answer is E.

Beta adrenoceptors in the heart regulate cardiac rate and contractile strength. Several studies have indicated that in humans and experimental animals, about 90% of β adrenoceptors in the heart are spare receptors. Which of the following statements about spare receptors is most correct? (A) Spare receptors, in the absence of drug, are sequestered in the cytoplasm (B) Spare receptors may be detected by finding that the drug-receptor interaction lasts longer than the intracellular effect (C) Spare receptors influence the maximal efficacy of the drug-receptor system (D) Spare receptors activate the effector machinery of the cell without the need for a drug (E) Spare receptors may be detected by finding that the EC 50 is smaller than the K d for the agonist

There is no difference in location between "spare" and other receptors. Spare receptors may be defined as those that are not needed for binding drug to achieve the maximal effect. Spare receptors influence the sensitivity of the system to an agonist because the statistical probability of a drug-receptor interaction increases with the total number of receptors. They do not alter the maximal efficacy. If they do not bind an agonist molecule, spare receptors do not activate an effector molecule. EC 50 less than K d is an indication of the presence of spare receptors. The answer is E.

A 55-year-old patient currently receiving a drug for a psychiatric condition is to be started on diuretic therapy for mild heart failure. Consideration should be given to the fact that thiazides are known to reduce the excretion of which of the following? (A) Diazepam (B) Fluoxetine (C) Imipramine (D) Lithium (E) Trifluoperazine

Thiazides reduce the clearance of lithium by about 25%. They do not alter the clearance of the other agents listed. The answer is D.

A 9-year-old child is having learning difficulties at school. He has brief lapses of awareness with eyelid fluttering that occur every 5-10 min. Electroencephalogram (EEG) studies reveal brief 3-Hz spike and wave discharges appearing synchronously in all leads. Which drug would be effective in this child without the disadvantages of excessive sedation or tolerance development? (A) Clonazepam (B) Diazepam (C) Ethosuximide (D) Gabapentin (E) Phenobarbital

This child suffers from absence seizures, and 2 of the drugs listed are effective in this seizure disorder. Clonazepam is effective but exerts troublesome CNS-depressant effects, and tolerance develops with chronic use. Ethosuximide is not excessively sedating, and tolerance does not develop to its antiseizure activity. Valproic acid (not listed) is also used in absence seizures. The answer is C.

A 3-year-old boy with failure to thrive and metabolic d bances was found to have an inactivating mutation in the gene that encodes the growth hormone receptor. Which of the following drugs is most likely to improve his metabolic function and promote his growth? (A) Atosiban (B) Bromocriptine (C) Mecasermin (D) Octreotide (E) Somatropin

This child's condition is due to the inability of GH to s late the production of insulin-like growth factors, the ultimate mediators of GH effects. Mecasermin, a combination of recombinant IGF-1 and the binding protein that protects IGF-1 from immediate destruction, will help correct the IGF deficiency. Because of the inactive GH receptors, somatropin will not be effective. The answer is C.

A patient suffering from a depressive disorder is being treated with imipramine. If he uses diphenhydramine for allergic rhinitis, a drug interaction is likely to occur because (A) Both drugs block muscarinic receptors (B) Both drugs block reuptake of norepinephrine released from sympathetic nerve endings (C) Diphenhydramine inhibits imipramine metabolism (D) Imipramine inhibits the metabolism of diphenhydramine (E) The drugs compete with each other for renal elimination

This is a good example of an additive drug interaction r ing from 2 drugs acting on the same type of receptor. Most tricyclic antidepressants, phenothiazines, and older antihistaminic drugs (those available without prescription) are blockers of muscarinic receptors. Used concomitantly, any pair of these agents will demonstrate a predictable increase in atropine-like adverse effects. The answer is A.

A 45-year-old moderately obese man has been drinking heavily for 72 h. This level of drinking is much higher than his regular habit of drinking 1 alcoholic drink per day. His only significant medical problem is mild hypertension, which is adequately controlled by metoprolol. With this history, this man is at significant risk for (A) Bacterial pneumonia (B) Cardiac arrhythmia (C) Hyperthermia (D) Tonic-clonic seizures (E) Wernicke-Korsakoff syndrome

This man's regular rate of alcohol consumption is not high enough to put him at risk of long-term consequences such as Wernicke-Korsakoff syndrome, increased susceptibility to bacterial pneumonia, or alcohol withdrawal seizures. This pattern of "binge drinking" does put him at increased risk of cardiac arrhythmia. The answer is B.

A 42-year-old man with a history of alcoholism is brought to the emergency department in a confused and delirious state. He has truncal ataxia and ophthalmoplegia. The most appropriate immediate course of action is to administer diazepam plus (A) Chlordiazepoxide (B) Disulfiram (C) Folic acid (D) Glucosamine (E) Thiamine

This patient has symptoms of Wernicke's encephalopathy, including delirium, gait disturbances, and paralysis of the external eye muscles. The condition results from thiamine deficiency but is rarely seen in the absence of alcoholism. The diazepam is administered to prevent the alcohol withdrawal syndrome. Glucosamine is primarily used for pain associated with arthritis. The answer is E.

A 55-year-old patient with a prosthetic heart valve is to undergo a periodontal procedure involving scaling and root planing. Several years ago, the patient had a severe allergic reaction to procaine penicillin G. Regarding prophylaxis against bacterial endocarditis, which one of the following drugs taken orally is most appropriate? (A) Amoxicillin 10 min before the procedure (B) Clindamycin 1 h before the procedure (C) Erythromycin 1 h before the procedure and 4 h after the procedure (D) Vancomycin 15 min before the procedure (E) No prophylaxis is needed because this patient is in the negligible risk category

This patient is in the high-risk category for bacterial e carditis and should receive prophylactic antibiotics before many dental procedures. The American Heart Association recommends that clindamycin be used in patients allergic to penicillins. Oral erythromycin is not recommended because it is no more effective than clindamycin and causes more gastrointestinal adverse effects. Intravenous vancomycin (not oral), sometimes with gentamicin, is recommended for prophylaxis in high-risk penicillin-allergic patients undergoing genitourinary and lower gastrointestinal surgical procedures. Complete cross-allergenicity must be assumed between individual penicillins. The answer is B.

A 42-year-old homemaker suffers from anxiety with phobic symptoms and occasional panic attacks. She uses over-the-counter antihistamines for allergic rhinitis and claims that ethanol use is "just 1 or 2 glasses of wine with dinner." Alprazolam, a benzodiazepine, is prescribed, and the patient is maintained on the drug for 3 years, with several dose increments over that time period. Her family notices that she does not seem to be improving and that her speech is often slurred in the evenings. She is finally hospitalized with severe withdrawal signs on one weekend while attempting to end her dependence on drugs. The main reason for hospitalization of this patient was to be able to effectively control (A) Cardiac arrhythmias (B) Delirium (C) Hepatic dysfunction (D) Seizures (E) None of the above

This patient is probably withdrawing from dependence on both alprazolam and alcohol use. In addition to the symptoms described previously, abrupt withdrawal from sedativehypnotic dependence may include hyperreflexia progressing to seizures, with ensuing coma and possibly death. The risk of a seizure is increased if the patient abruptly withdraws from ethanol use at the same time. Depending on severity of symptoms, initial management may require parenteral diazepam or lorazepam, with the latter drug often favored in hepatic dysfunction. The answer is D.

A 36-year-old woman with a history of poorly controlled thyrotoxicosis has recurrent episodes of tachycardia with severe shortness of breath. During elective surgery to remove her thyroid, she develops a heart rate of 200 with a slightly decreased blood pressure. Which of the following drugs would be most suitable? (A) Amiodarone (B) Disopyramide (C) Esmolol (D) Quinidine (E) Verapamil

This patient is suffering from a typical perisurgical a mia, exacerbated by her thyroid disorder. Beta blockers are the most effective agents in acute thyrotoxic arrhythmias. While β blockers are used to decrease blood pressure in hypertension, this patient's lowered blood pressure is probably due to the arrhythmia and will normalize when the tachycardia is converted to normal sinus rhythm. Esmolol is a parenteral, rapid-acting β blocker (see Chapter 10). The answer is C.

A young man suffers from a seizure disorder characterized by tonic rigidity of the extremities followed in 15-30 s of tremor progressing to massive jerking of the body. This clonic phase lasts for 1 or 2 min, leaving the patient in a stuporous state. Of the following drugs, which is most suitable for long-term management of this patient? (A) Clonazepam (B) Ethosuximide (C) Felbamate (D) Phenytoin (E) Pregabalin

This patient is suffering from generalized tonic-clonic seizures. For many years, the drugs of choice in this seizure disorder have been carbamazepine or phenytoin or valproic acid. However, many newer drugs are also effective, including gabapentin, lamotrigine, levetiracetam, topiramate, and zonisamide. Clonazepam and ethosuximide are not effective in this type of seizure disorder. Pregabalin is approved for use only in partial seizures. The answer is D.

A 33-year-old man was seen in a clinic with a complaint of dysuria and urethral discharge of yellow pus. He had a painless clean-based ulcer on the penis and nontender enlargement of the regional lymph nodes. Gram stain of the urethral exudate showed Gram-negative diplococci within polymorphonucleocytes. The patient informed the clinic staff that he was unemployed and had not eaten a meal for 2 d. Immunofluorescent microscopic examination of fluid expressed from the penile chancre of this patient revealed treponemes. Because he appears to be infected with Treponema pallidum, the best course of action would be to (A) Administer a single oral dose of fosfomycin (B) Give no other antibiotics because drug treatment of gonorrhea provides coverage for incubating syphilis (C) Inject intramuscular benzathine penicillin G (D) Treat with oral tetracycline for 7 d (E) Treat with vancomycin

This patient with gonorrhea also has primary syphilis. The penile chancre, the enlarged nontender lymph nodes, and the microscopic identification of treponemes in fluid expressed from the lesion are essentials of diagnosis. Although a single dose of ceftriaxone may cure incubating syphilis, it cannot be relied on for treating primary syphilis. The most appropriate course of action in this patient is to administer a single intramuscular injection of 2.4 million units of benzathine penicillin G. For penicillin-allergic patients, oral doxycycline or tetracycline for 15 d (not 7 d) is effective in most cases (see Chapter 44). However, lack of compliance may be a problem with oral therapy. Fosfomycin and vancomycin have no significant activity against spirochetes. The answer is C.

Gentamicin, an aminoglycoside antibiotic, is sometimes given as a single large intravenous bolus dose of once a day to achieve a highly active peak plasma concentration. Gentamicin's volume of distribution is about 20 L in a 70 kg patient and, in your patient, the half-life is 4 h. If your patient is given an IV bolus dose of 360 mg, what will the trough concentration of gentamicin be 24 hours later just before the next intravenous bolus? (A) 18 mg/L (B) 4.5 mg/L (C) 1.13 mg/L (D) 0.56 mg/L (E) 0. 28 mg/L

This problem requires, first, the calculation of the initial peak plasma concentration, and then the decline in concentration as the drug is eliminated by 50% in each half-life. The peak concentration = dose/Vd , or 360 mg/20 L or 18 mg/L. The trough concentration will be measured 24 hours or 6 halflives later. After 1 half-life C p will be 9; after 2, 4.5; after 3, 2.25; after 4 half-lives, 1.125 mg/L; after 5, 0.56; and after 6 half-lives, 0.28 mg/L. The answer is E.

A 2-year-old child was brought to the emergency department 1 h after ingestion of tablets he had managed to obtain from a bottle on top of the refrigerator. His symptoms included marked gastrointestinal distress, vomiting (with hematemesis), and epigastric pain. Metabolic acidosis and leukocytosis were also present. This patient is most likely to have ingested tablets containing (A) Acetaminophen (B) Aspirin (C) Diphenhydramine (D) Iron (E) Vitamin C

This question emphasizes that the ingestion of iron tablets is a relatively common cause of accidental poisoning in young children. The signs and symptoms described usually occur in the first 6 h after ingestion. In a child whose body weight is 22 lb, the ingestion of 600 mg can cause severe, perhaps lethal, toxicity. The answer is D.

A 23-year-old pregnant woman with alcoholism presented to the emergency department in the early stages of labor. She had consumed large amounts of alcohol throughout her pregnancy. This patient's infant is at high risk of a syndrome that includes (A) Ambiguous genitalia in a male fetus and normal genitalia in a female fetus (B) Failure of closure of the atrial septum or ventricular septum result in death due to respiratory arrest in a person who lacks tolerance to ethanol. The answer is C. (C) Limb or digit malformation (D) Mental retardation and craniofacial abnormalities (E) Underdevelopment of the lungs

This woman's infant is at risk for fetal alcohol syndrome, a syndrome associated with mental retardation, abnormalities of the head and face, and growth deficiency. This syndrome is a leading cause of mental retardation. The answer is D.

A 27-year-old nursing mother is diagnosed as suffering from genital herpes. She has a history of this viral infection. Previously, she responded to a drug used topically. Apart from her current problem, she is in good health. Which drug to be used orally is most likely to be prescribed at this time? (A) Amantadine (B) Foscarnet (C) Ritonavir (D) Trifluridine (E) Valacyclovir

Three of the drugs listed (foscarnet, trifluridine, valacyclovir) are active against strains of herpes simplex virus. Foscarnet is not used in genital infections (HSV-2) because clinical efficacy has not been established, it has poor oral bioavailability and the drug causes many toxic effects. Trifluridine is used topically but only for herpes keratoconjunctivitis (HSV-1). Valacyclovir is converted to acyclovir by first-pass metabolism in the intestine and liver. The answer is E.

Oral formulations of this drug should not be used in a pregnant AIDS patient because they contain propylene glycol. One of the characteristic adverse effects of the drug is hyperpigmentation on the palms of the hands and soles of the feet, especially in African-American patients. (A) Amprenavir (B) Emtricitabine (C) Efavirenz (D) Fosamprenavir (E) Zalcitabine

Three of the drugs listed should be avoided, or used with extreme caution, in the pregnant patient. Oral forms of amprenavir and emtricitabine both contain propylene glycol, a potentially toxic compound. Efavirenz has caused fetal abnormalities in pregnant monkeys. However, one of the distinctive adverse effects of emtricitabine is hyperpigmentation. The answer is B.

Which drug is most often associated with hypotension and is related to clonidine? (A) Baclofen (B) Pancuronium (C) Succinylcholine (D) Tizanidine (E) Vecuronium

Tizanidine causes hypotension via α2-adrenoceptor activation, like its congener clonidine. Hypotension may occur with tubocurarine (not listed) due partly to histamine release and to ganglionic blockade. The answer is D.

Which of the following drugs is taken during the first part of a meal for the purpose of delaying the absorption of dietary carbohydrates? (A) Acarbose (B) Exenatide (C) Glipizide (D) Pioglitazone (E) Repaglinide

To be absorbed, carbohydrates must be converted into monosaccharides by the action of α-glucosidase enzymes in the gastrointestinal tract. Acarbose inhibits α-glucosidase and, when present during digestion, delays the uptake of carbohydrates. The answer is A.

A hospitalized AIDS patient is receiving a roviral drugs but no antimicrobial prophylaxis. He develops sepsis with fever, suspected to be caused by a Gram-negative bacillus. Antimicrobial treatment of this severely immune-depressed patient should not be initiated before (A) Antipyretic drugs have been given to reduce body temperature (B) Infecting organism(s) have been identified by the microbiology laboratory (C) Results of a Gram stain are available (D) Results of antibacterial susceptibility tests are available (E) Specimens have been taken for laboratory tests and examination

To delay therapy until laboratory results are available is inappropriate in serious bacterial infections, but specimens for possible microbial identification must be obtained before drugs are administered. The answer is E.

This drug has characteristics almost identical to those of gentamicin but has much weaker activity in combination with penicillin against enterococci. (A) Amikacin (B) Erythromycin (C) Netilmicin (D) Spectinomycin (E) Tobramycin

Tobramycin is almost identical to gentamicin in both its pharmacodynamic and pharmacokinetic properties. However, for reasons that are unclear, it is much less active than either gentamicin or streptomycin when used in combination with a penicillin in the treatment of enterococcal endocarditis. The answer is E.

Tolcapone may be of value in patients being treated with levodopa-carbidopa because it (A) Activates COMT (B) Decreases the formation of 3-O-methyldopa (C) Inhibits monoamine oxidase type A (D) Inhibits neuronal reuptake of dopamine (E) Releases dopamine from nerve endings

Tolcapone and entacapone are inhibitors of COMT used adjunctively in patients treated with levodopa-carbidopa. The drugs decrease the formation of 3-O-methyldopa (3-OMD) from levodopa. This improves patient response by increasing levodopa levels and by decreasing competition between 3-OMD and levodopa for active transport into the brain by l-amino acid carrier mechanism. The answer is B.

Reports of cardiac arrhythmias caused by unusually high blood levels of 2 antihistamines, terfenadine, and astemizole, led to their removal from the market. Which of the following best explains these effects? (A) Concomitant treatment with rifampin (B) Use of these drugs by chronic alcoholics (C) Use of these drugs by chronic smokers (D) Treatment of these patients with ketoconazole, an azole antifungal agent

Treatment with rifampin and chronic alcohol or tobacco use are associated with increased drug metabolism and lower, not higher, blood levels. Ketoconazole, itraconazole, erythromycin, and some substances in grapefruit juice slow the metabolism of certain older non-sedating antihistamines (Chapter 16). The answer is D.

A 33-year-old man was seen in a clinic with a complaint of dysuria and urethral discharge of yellow pus. He had a painless clean-based ulcer on the penis and nontender enlargement of the regional lymph nodes. Gram stain of the urethral exudate showed Gram-negative diplococci within polymorphonucleocytes. The patient informed the clinic staff that he was unemployed and had not eaten a meal for 2 d. The most appropriate treatment of gonorrhea in this patient is (A) A single intramuscular dose of ceftriaxone (B) Amoxicillin orally for 7 d (C) Procaine penicillin G intramuscularly as a single dose plus oral probenecid (D) Meropenem orally for 7 d (E) Vancomycin intramuscularly as a single dose

Treatments of choice for gonorrhea include a single dose of ceftriaxone (intramuscularly). Because of the high incidence of beta-lactamase-producing gonococci, the use of penicillin G or amoxicillin is no longer appropriate for gonorrhea. Similarly, many strains of gonococci are resistant to tetracyclines. Alternative drugs (not listed) for gonorrhea include cefixime, azithromycin (see Chapter 44) or spectinomycin (see Chapter 45). The answer is A.

Your 30-year-old patient has moderately severe new onset asthma, and you prescribe a highly selective β 2 agonist inhaler to be used when needed. In considering the possible drug effects in this patient, you would note that β 2 stimulants frequently cause (A) Direct stimulation of renin release (B) Hypoglycemia (C) Itching due to increased cGMP (cyclic guanine monophosphate) in mast cells (D) Skeletal muscle tremor (E) Vasodilation in the skin

Tremor is a common β 2effect. Blood vessels in the skin have almost exclusively α (vasoconstrictor) receptors. Stimulation of renin release is a β 1 effect. Beta 2 agonists cause hyperglycemia and have little effect on cGMP. The answer is D.

A 24-year-old female was rushed to the emergency department after she was found in her room hypotensive, with seizures. In the emergency department, the electrocardiogram confirmed ventricular arrhythmias. An overdose of which of the following drugs is the most likely cause of her symptoms? (A) Acetaminophen (B) Amitriptyline (C) Diazepam (D) Ethylene glycol (E) Morphine

Tricyclic antidepressants such as amitriptyline are extremely toxic in overdose because of their effects in the CNS and cardiovascular system. In addition to hypotension, seizures, and cardiac arrhythmias, the tricyclics have strong antimuscarinic effects. The answer is B.

Supplementary folinic acid may prevent anemia in folatedeficient persons who use this drug; it is a weak base achieving tissue levels similar to those in plasma. (A) Ciprofloxacin (B) Levofloxacin (C) Linezolid (D) Sulfamethoxazole (E) Trimethoprim

Trimethoprim is the only weak base listed (fluoroquinolones and sulfonamides are acidic compounds), and its high lipid solubility at blood pH allows penetration of the drug into prostatic and vaginal fluid to reach levels similar to those in plasma. Leukopenia and thrombocytopenia may occur in folate deficiency when the drug is used alone or in combination with sulfamethoxazole. Fluoroquinolones and linezolid do not exacerbate symptoms of folic acid deficiency. The answer is E.

Trimethoprim-sulfamethoxazole is established to be effective against which of the following opportunistic infections in the AIDS patient? (A) Cryptococcal meningitis (B) Herpes simplex (C) Oral candidiasis (D) Toxoplasmosis (E) Tuberculosis

Trimethoprim-sulfamethoxazole is not effective in the treament of infections caused by viruses, fungi, or mycobacteria. However, the drug combination is active against certain protozoans, including Toxoplasma, and can be used for both prevention and treatment of toxoplasmosis in the severely immunocompromised AIDS patient. The answer is D.

Which sign or symptom is most likely to occur with marijuana? (A) Bradycardia (B) Conjunctival reddening (C) Hypertension (D) Increased psychomotor performance (E) Mydriasis

Two of the most characteristic signs of marijuana use are increased pulse rate and reddening of the conjunctiva. Decreases in blood pressure and in psychomotor performance occur. Pupil size is not changed by marijuana. The answer is B.

A 22-year-old man with gonorrhea is to be treated with cefixime and will need another drug to provide coverage for possible urethritis caused by C trachomatis. Which of the following drugs is least likely to be effective in nongonococcal urethritis? (A) Azithromycin (B) Ciprofloxacin (C) Erythromycin (D) Nitrofurantoin (E) Tetracycline

Urinary tract infections resulting from C trachomatis are likely to respond to all of the drugs listed except nitrofurantoin. However, nitrofurantoin is effective against many bacterial urinary tract pathogens with the exception of Pseudomonas aeruginosa and strains of Proteus. The answer is D.

Which statement about vancomycin is accurate? (A) Active against methicillin-resistant staphylococci (B) Bacteriostatic (C) Binds to PBPs (D) Inhibits transpeptidation (E) Oral bioavailability

Vancomycin is a bactericidal glycoprotein. It inhibits cell wall synthesis but does not bind to PBPs and is not susceptible to beta-lactamases. Vancomycin is not absorbed after oral administration and is used by this route in the treatment of colitis caused by C difficile and staphylococci. It undergoes renal elimination and inhibits transglycosylation. Vancomycin is commonly considered the drug of first choice for parenteral use against methicillin-resistant staphylococci. The answer is A.

Which of the following is a direct-acting cholinomimetic that is lipid-soluble and is used to facilitate smoking cessation? (A) Acetylcholine (B) Bethanechol (C) Neostigmine (D) Physostigmine (E) Varenicline

Varenicline is a lipid-soluble partial agonist at nicotinic receptors and is used to reduce craving for tobacco in smokers. The answer is E.

Which of the following drugs is an established inhibitor of P-glycoprotein (P-gp) drug transporters? (A) Cimetidine (B) Ethanol (C) Ketoconazole (D) Procainamide (E) Quinidine (F) Ritonavir (G) Succinylcholine (H) Verapamil

Verapamil is an inhibitor of P-glycoprotein drug transporters and has been used to enhance the cytotoxic actions of methotrexate in cancer chemotherapy. The answer is H.

Which one of the following is the primary neurotransmitter agent normally released in the sinoatrial node of the heart in response to a blood pressure increase? (A) Acetylcholine (B) Dopamine (C) Epinephrine (D) Glutamate (E) Norepinephrine

When blood pressure increases, the parasympathetic system is activated and heart rate decreases. Acetylcholine is the transmitter at parasympathetic nerve endings innervating the sinus node (nerve endings of the vagus nerve). The answer is A.

A 17-year-old patient complains that he develops wheezing and severe shortness of breath whenever he takes aspirin for headache. Increased levels of which of the following may be responsible, in part, for some cases of aspirin hypersensitivity? (A) Alprostadil (B) Hydrocortisone (C) Ibuprofen (D) Leukotriene LTC4 (E) Misoprostol (F) PGE2 (G) Prostacyclin (H) Thromboxane (I) Zileuton

When cyclooxygenase is blocked, leukotrienes may be produced in increased amounts by diversion of prostaglandin precursors into the lipoxygenase pathway (Figure 18-1). In patients with aspirin hypersensitivity, this might precipitate the bronchoconstriction often observed in this condition. The answer is D.

Which of the following cytochrome isoforms is responsible for metabolizing the largest number of drugs? (A) CYP1A2 (B) CYP2C9 (C) CYP2C19 (D) CYP2D6 (E) CYP3A4

While CYP2D6 is responsible for metabolizing approximately 25% of drugs, CYP3A4 is involved in almost 50% of such reactions. The answer is E.

A 48-year-old patient is scheduled for a vaginal hysterectomy. An antimicrobial drug will be used for prophylaxis against postoperative infection. It is proposed that cefazolin, a first-generation cephalosporin, be given intravenously at the normal therapeutic dose immediately before surgery and continued until the patient is released from the hospital. Which statement about the proposed drug management of this patient is not accurate? (A) Antibiotic treatment throughout hospitalization will prevent nosocomial infections (B) Likely pathogens include anaerobes, enteric Gramnegative bacteria, and group B streptococci (C) Prophylaxis with antimicrobial drugs has efficacy in this type of surgical procedure (D) This drug will not be effective against anaerobes (E) Without prophylaxis, the infection rate following this procedure exceeds 5% under optimal conditions

With few exceptions, the prophylactic use of antibiotics in surgery should not extend beyond the duration of the procedure. After routine surgical procedures, the risk of opportunistic infection (from disturbances in microbial flora) increases in a hospitalized patient if prophylaxis is prolonged; there is also more likelihood of drug toxicity. Cefazolin (or cefoxitin) constitutes the drug(s) of choice for prophylaxis in most hysterectomy procedures. The answer is A.

Which statement concerning the barbiturates is most accurate? (A) Abstinence syndromes are more severe during withdrawal from phenobarbital than from secobarbital (B) Alkalinization of the urine accelerates the elimination of phenobarbital (C) Barbiturates may increase the half-lives of drugs metabolized by the liver (D) Compared with barbiturates, the benzodiazepines exhibit a steeper dose-response relationship (E) Respiratory depression caused by barbiturate overdosage can be reversed by flumazenil

Withdrawal symptoms from use of the shorter-acting barbiturate secobarbital are more severe than with phenobarbital. The dose-response curve for benzodiazepines is flatter than that for barbiturates. Induction of liver drug-metabolizing enzymes occurs with barbiturates and may lead to decreases in half-life of other drugs. Flumazenil is an antagonist at BZ receptors and is used to reverse CNS depressant effects of benzodiazepines. As a weak acid (pK a 7), phenobarbital will be more ionized (nonprotonated) in the urine at alkaline pH and less reabsorbed in the renal tubule. The answer is B.

Which of the following is a leukotriene receptor blocker? (A) Alprostadil (B) Aspirin (C) Ibuprofen (D) Leukotriene LTC4 (E) Montelukast (F) Prednisone (G) Prostacyclin (H) Zileuton

Zileuton blocks the synthesis of leukotrienes. Montelukast and zafirlukast block LTD 4receptors. The answer is E.

Oral medications are popular for the treatment of asthma in children because young children may have difficulty with the proper use of aerosol inhalers. Which of the following is an orally active inhibitor of leukotriene receptors? (A) Albuterol (B) Aminophylline (C) Ipratropium (D) Zafirlukast (E) Zileuton

Zileuton is an inhibitor of the lipoxygenase enzyme involved in the synthesis of leukotrienes. Montelukast and zafirlukast are leukotriene antagonists at the leukotriene receptor. The answer is D.

Which of the following is a sign or symptom that would be expected to occur in the event of chronic overdose with exogenous T4 ? (A) Bradycardia (B) Dry, puffy skin (C) Large tongue and drooping of the eyelids (D) Lethargy, sleepiness (E) Weight loss

hyperthyroidism, the metabolic rate increases, and even though there is increased appetite, weight loss often occurs. The other choices are symptoms seen in hypothyroidism. The answer is E.

Which statement about the fluoroquinolones is accurate? (A) Antacids increase their oral bioavailability (B) Contraindicated in patients with hepatic dysfunction (C) Fluoroquinolones are drugs of choice in a 6-year-old child with a urinary tract infection (D) Gonococcal resistance to fluoroquinolones may involve changes in DNA gyrase (E) Modification of moxifloxacin dosage is required in patients when creatinine clearance is less than 50 mL/min

ntacids can decrease oral bioavailability of fluoroquinolones. Neither hepatic nor renal dysfunction is a contraindication to the use of fluoroquinolones. Most fluoroquinolones undergo renal elimination and dosage should be modified with creatinine clearance <50 mL/min. Moxifloxacin elimination occurs mainly via the liver. The fluoroquinolones should not be used to treat uncomplicated first-time urinary tract infections in children because of possible effects on cartilage development. Uncomplicated urinary tract infections in children are usually due to a strain of E coli that is sensitive to many other drugs, including beta-lactam antibiotics. The answer is D.