Katzung Pharmacology Review 10e 100 Q Exam#1

Question 98: A 30-year-old patient in the intensive care unit is to receive a β-agonist drug. Typical responses to β-receptor blockade include A Bradycardia B Decreased renin secretion C Decreased skeletal muscle tremor D Glycogen synthesis E Lipolysis

• adrenergic beta-antagonists Explanation: Beta antagonists typically increase PR interval. Renin secretion and tremor are decreased. Beta agonists increase lipolysis.

Question 77: Which of the following drugs often causes tachycardia and tremor when used in asthma? A Albuterol B Cromolyn sodium C Ipratropium D Montelukast E Prednisone

• albuterol Explanation: Skeletal muscle tremor is a common adverse effect of beta-adrenoceptor agonists such as albuterol when used in asthma. Even when administered via inhalation, this side effect as well as tachycardia can occur.

Question 35: A patient with an incurable cancer is suffering from pain that is gradually increasing in intensity and levorphanol (a strong μ-receptor agonist) is prescribed. With chronic use of the drug, tolerance is not likely to develop to constipation or to A Euphoria B Nausea and vomiting C Pupillary constriction D Sedation E Urinary retention

• opioids Explanation: Although miosis is characteristic of all opioids except meperidine, which has a muscarinic blocking action, little or no tolerance occurs. Pupillary constriction due to opioids can be blocked by atropine and by naloxone.

Question 55: A patient presents to the hematology clinic with a previously unknown clotting abnormality in which platelets aggregate extremely rapidly. Several relatives manifest the same abnormality. Laboratory investigation indicates that their platelets contain a very high eicosanoid concentration. The eicosanoid that stimulates platelet aggregation most strongly is A Leukotriene C4 B Prostacyclin C Prostaglandin E2 D Prostaglandin F2 E Thromboxane A2

• thromboxanes • thromboxane a2 Explanation: All of the choices listed are eicosanoids, but only thromboxane is associated with enhanced platelet aggregation. Thromboxane A2 is the pro-aggregation eicosanoid produced by platelets, whereas endothelial cells produce the prostaglandins that inhibit aggregation. Upon irreversible inhibition by aspirin, platelets (without a nucleus) cannot synthesize new COX enzyme to generate thromboxane A2, whereas the endothelial cell can replace the enzymes and continue to produce prostaglandins that prevent aggregation.

Question 64: In the treatment of hypothyroidism, thyroxine is preferred over liothyronine because thyroxine A Can be made more easily by recombinant DNA technology B Has a longer half-life C Has higher affinity for thyroid hormone receptors D Is faster acting E Is more likely to improve a patient's mood

• thyroxine Explanation: Thyroxine (T4) is preferred over liothyronine (T3) because it has a longer half-life. It is less expensive and has a slower onset of action. It is converted into T3 in the tissues; thus, the affinity for the receptor or the effects on the patient's mood will be the same.

Question 91: A wide range of receptor types and receptor mechanisms mediate the effects of endogenous signaling molecules and the drugs that mimic or block their effects. Which of the following drugs mediates its effects by binding to and activating an intracellular receptor that, when activated, acts as a transcription factor? A Albuterol B Captopril C Erythropoietin D Morphine E Prednisone

- Prednisone correct answer is (E). Explanation: Prednisone is a steroid and acts via binding the cytoplasmic steroid receptors, followed by a translocation of the receptor-ligand complex into the nucleus, altering gene transcription. All other agents listed in this question bind to membrane-bound extracellular receptors.

Question 63: The reason why clozapine causes less extrapyramidal dysfunction than haloperidol when used in schizophrenia is that in the CNS, clozapine A Activates GABA receptors B Blocks dopamine release C Has greater antagonism at muscarinic receptors D Has a low affinity for dopamine D2 receptors E Is an α-receptor agonist

- dozapine Explanation: Clozapine has greater muscarinic and alpha-blocking activity than haloperidol, but neither of these is the primary reason why the drug is less likely to cause extrapyramidal dysfunction. The main reason is that clozapine has very low affinity for the dopamine D2 receptor in the striatum..

Question 88: A physician was considering erythromycin for treatment of a 47-year-old man with an upper respiratory tract infection. However, the physician noted that the patient was taking simvastatin for treatment of hypercholesterolemia and realized that erythromycin, an inhibitor of cytochrome enzymes, would inhibit the metabolism of simvastatin. The physician opted for a different class of antibiotic to avoid exposing the patient to higher concentrations of simvastatin and a risk of dose-dependent toxicity. Which of the following is the primary dose-dependent toxicity of simvastatin? A Abdominal pain secondary to gallstone formation B Blurred vision secondary to optic neuritis C Elevated serum creatinine, possibly progressing to renal failure D Increased serum uric acid concentration and increased risk of gout E Muscle pain and weakness, possibly progressing to rhabdomyolysis

.- simvastatin Explanation: Rhabdomyolysis is a serious side effect that can occur with statins. Gallstones are a side effect of the fibrates; uric acid elevation is a side effect of niacin.

Question 10: A 29-year-old G1P1 (gravida-1, para-1) woman presents with infertility of 12 months' duration. Questioning reveals that the patient has had only 4 menstrual periods in the last year and that she sometimes notices breast nipple discharge. She has not been taking any prescription medications during the last year. A serum prolactin measurement reveals a concentration of 90 ng/mL (normal for a nonpregnant woman is <25 ng/mL). Based on these findings, which of the following drugs is most likely to help make this woman's ovulation more regular and restore her fertility? A Bromocriptine B Desmopressin C Leuprolide D Prochlorperazine E Spironolactone

• 2-bromoergocryptine mesylate Explanation: This patient has signs and symptoms of hyperprolactinemia, which is caused by prolactin-secreting pituitary adenomas. Dopamine D2 receptor agonists such as bromocriptine can be used to suppress the excessive prolactin secretion.

Question 65: A 40-year-old man had been consuming alcoholic beverages at lunch and in the evenings all his adult life. During the last 2 yr, his alcohol consumption had steadily increased, continuing throughout the day. In response to family pressures, he abruptly stopped drinking alcohol, and within a few hours he became increasingly anxious and agitated and showed symptoms of autonomic hyperexcitability. At this point, he was brought to the hospital. In the first week of this patient's recovery, he is at risk of a syndrome that is characterized by which of the following? A Ascites, mental confusion, and elevated serum transaminases B Headache, hypotension, and widespread petechiae C Hyperglycemia, acidosis, and stupor D Respiratory depression, miosis, and mental confusion E Tremor, delusions, and visual hallucinations

• alcohol withdrawal delirium Explanation: This patient is at risk for delirium tremens, which is characterized by tremors, delusions, and hallucinations.

Question 57: Which of the following is the drug of choice for the management of osteoporosis caused by high-dose use of glucocorticoids? A Alendronate B Anastrozole C Ethinyl estradiol D Omeprazole E Oxandrolone

• alendronate Explanation: "Dronates" inhibit bone resorption. Anastrozole is an aromatase inhibitor used for treatment of breast cancer. Ethinyl estradiol is an estrogen stimulating bone resorption. Omeprazole is a proton pump inhibitor. Oxandrolone is an androgen used when its anabolic action is needed (wasting due to illness: cancer, HIV, etc.)

Question 45: A 45-year-old man presents with pulmonary hypertension. Which of the following cause-treatment pairs is most relevant to this patient? A Angiotensin II-minoxidil B Atrial natriuretic peptide-losartan C Bradykinin-furosemide D Endothelin-ambrisentan E Substance P-capsaicin

• ambrisentan Explanation: Endothelin is the peptide most closely associated with pulmonary hypertension, and ambrisentan is an orally active ETA receptor antagonist.

Question 61: If an aerobic gram-negative rod causing bacteremia proves to be resistant to aminoglycosides, the mechanism of resistance is most likely due to A Changed pathway of bacterial folate synthesis B Decreased intracellular accumulation of the drug C Formation of drug-trapping thiol compounds D Inactivation by bacterial group transferases E Induced synthesis of beta-lactamases

• aminoglycosides Explanation: In gram-negative bacteria, the primary mechanism of resistance to aminoglycosides involves the plasmid-mediated formation of inactivating enzymes that acetylate, adenylate, or phosphorylate the drug molecule. Such enzymes are called group transferases.

Question 23: A 43-year-old woman was brought to a hospital emergency department by her brother. Visiting the halfway house in which she lived, he had found her to be lethargic, with slurred speech. The patient had a long history of treatment for depression, and the brother feared that she might have overdosed on 1 or more of her prescription drugs. Physical examination revealed hypotension, tachycardia, decreased bowel sounds, dilated pupils, hyperthermia, and mild parkinsonian symptoms. If this patient had taken a drug overdose, the most likely causative agent was A Amitriptyline B Celecoxib C Lithium D Ramelteon E Zaleplon

• amitriptyline Explanation: Adverse effects of the tricyclic antidepressant amitriptyline include sedation, hypotension, tachycardia, and symptoms of muscarinic blockade such as decreased bowel sounds and pupillary dilation. In severe overdose, watch for the "3 Cs"—coma, convulsions, and cardiotoxicity.

Question 5: An antifungal drug that binds to ergosterol forming "pores" that disrupt fungal membrane integrity is A Amphotericin B B Caspofungin C Fluconazole D Flucytosine E Terbinafine

• amphotericin b Explanation: The amphipathic character of amphotericin B following its interaction with ergosterol in fungal cell membranes leads to artificial "pores" that disrupt membrane integrity. Nystatin, another polyene, acts similarly but is too nephrotoxic for systemic use.

Question 40: Adverse effects of the opioid analgesics do not include A Diarrhea B Emesis C Increased intracranial pressure D Respiratory depression E Urinary retention

• analgesics, opioid Explanation: With the exception of diphenoxylate and loperamide, which are used for the treatment of diarrhea, constipation is considered an adverse effect of the opioid analgesics.

Question 25: Chemoprophylaxis for travelers to geographic regions where chloroquine-resistant Plasmodium falciparum is endemic is effectively provided by A Doxycycline B Malarone (atovaquone-proguanil) C Mefloquine D None of the drugs listed above E Any of the drugs listed above

• antimalarials Explanation: Doxycycline, atovaquone-proguanil (Malarone), and mefloquine are all prophylactic against chloroquine-resistant strains of P falciparum.

Question 26: A 20-year-old college student is brought to the emergency department after taking an overdose of a nonprescription drug. The patient is comatose. He has been hyperventilating and is now dehydrated with an elevated temperature. Serum analyses demonstrate that the patient has an anion gap metabolic acidosis. Toxic exposure to which of the following drugs is the most likely cause of these signs and symptoms? A Aspirin B Acetaminophen C Dextromethorphan D Diphenhydramine E Ethanol

• aspirin Explanation: An overdose of aspirin will cause anion gap metabolic acidosis, as described here. Ethanol can also cause anion gap acidosis as ethanol metabolism generates NADH, leading to conversion of pyruvate to lactate, but the condition is often mild even without treatment. Acetaminophen causes liver failure in overdose, whereasdextromethorphan, an opioid, will cause respiratory depression and not hyperventilation. Diphenhydramine, an antihistamine, causes sedation through its effect on central histamine receptors but does not generally cause acidosis.

Question 28: Mr. Q has been given an intravenous dose of isoproterenol and is now manifesting an undesirably strong heart rate response. Which of the following most effectively blocks the heart rate response to a moderate dose of isoproterenol in conscious patients? A Atropine B Atenolol C Phenoxybenzamine D Pancuronium E Propranolol

• atenolol Explanation: Isoproterenol causes tachycardia and facilitates arrhythmias through its β action. A β antagonist such as propranolol can prevent this action.

Question 80: The graph below shows a quantal dose-response graph of the results of a study of a new drug in patients with hypertension. The label on the Y-axis (vertical axis) should be View Full Size | Save Figure | Download Slide (.ppt) A Cumulative maximal efficacy of the experimental drug in the patients B Cumulative dose of the experimental drug in the patients C Percentage of patients with a specified response to the drug

• dose-response relationship, drug Explanation: Quantal dose-response curves plot the percentage of the subjects that show a specified response (Y axis) at each increment of dosage (X axis); see Chapter 2.

Question 56: A 54-year-old woman presented with angina of effort. Laboratory assessment of her serum revealed elevated total and LDL cholesterol. The patient was placed on atorvastatin. This drug lowers serum cholesterol by A Activating endothelial cell-associated lipoprotein lipase B Increasing the shunting of hepatic cholesterol into the biochemical pathway of bile acid synthesis C Indirectly increasing hepatic production of LDL receptors D Inhibiting the uptake of cholesterol in epithelial cells that line the small intestine E Stimulating hepatic fatty acid oxidation

• atorvastatin Explanation: The statins inhibit de novo cholesterol synthesis through inhibition of HMG-CoA reductase. This forces the liver to upregulate LDL receptors and replenish the cholesterol stores through uptake from the bloodstream. LPL is activated by fibrates. The resins lower cholesterol by shunting more cholesterol into the bile acid pathway. Ezetimibe inhibits uptake of cholesterol in the small intestine. Fibrates enhance fatty acid oxidation.

Question 3: A child with strabismus ("wandering eye") is to be treated pharmacologically for a prolonged period. Which of the following drugs is used by the topical route in ophthalmology and causes mydriasis and cycloplegia lasting more than 24 hrs? A Atropine B Echothiophate C Edrophonium D Pilocarpine E Timolol

• atropine Explanation: Atropine has a very long duration of action in the eye (>72 hr). By interfering with accommodation in the dominant eye, atropine can sometimes prevent amblyopia.Timolol has no significant effect on accommodation, whereas the other drugs listed cause miosis and cyclospasm.

Question 51: A 4-year-old child was brought to an emergency department after ingesting a product found in the home. Her symptoms included an elevated temperature; hot, dry skin; moderate tachycardia; and mydriasis. The most likely cause of these symptoms is A Acetaminophen overdose B Amphetamine-containing diet pills C Exposure to an organophosphate-containing insecticide D Ingestion of a medication containing atropine E Ingestion of phenylephrine-containing eye drops

• atropine Explanation: The patient has characteristic signs of antimuscarinic (also known as anticholinergic) toxicity, caused by drugs such as atropine. Children are especially susceptible to the hyperthermia caused by antimuscarinic drug overdose.

Question 32: A 62-year-old woman who presented with pain in her hips, knees, and several vertebrae was diagnosed with Paget's disease. She had been mostly immobile lately due to bone pain and presented with lethargy, fatigue, muscle weakness, anorexia, and constipation. Her serum calcium concentration was found to be 14 mg/dL (normal 9-10 mg/dL). In addition to the bisphosphonates, another drug that has proved useful in reducing bone pain and lowering serum calcium in female patients with Paget's disease is which of the following? A Calcitonin B Fluoride C Hydrochlorothiazide D Raloxifene E Teriparatide (recombinant form of PTH)

• calcitonin Explanation: Paget's is a condition of too much bone resorption leading to elevated serum calcium. Both the bisphosphonates ("dronates") and calcitonin will inhibit this. Calcitonin is the drug of choice for the acute lowering of serum calcium. Fluoride and raloxifene affect bone formation. PTH and HTZ increase serum calcium.

Question 52: A 66-year-old patient is diagnosed with hypertension and angina. A drug with benefits in both conditions is suggested. Which of the following drugs has both nonselective β-blocking and α1-selective blocking action? A Atenolol B Carvedilol C Nadolol D Pindolol E Timolol

• carvedilol Explanation: Carvedilol is the only β-blocker in the list that also has α-blocking action.

Question 20: Beta-lactamase production by strains of Haemophilus influenzae and N gonorrhoeae confers resistance against penicillin G. Which of the following drugs is most likely to be effective against resistant strains of these organisms? A Amoxicillin B Ceftriaxone C Clindamycin D Gentamicin E Vancomycin

• ceftriaxone Explanation: The third-generation cephalosporins ceftriaxone and cefotaxime (not listed) are currently the most active beta-lactam antibiotics against beta-lactamase-producing strains of H influenzae and Neisseria. However, some resistance has been reported recently.

Question 62: An accepted clinical use of antimuscarinic drugs is for treatment of A Alzheimer's disease B Chronic obstructive pulmonary disease C Glaucoma D Hypertension E Prostatic hyperplasia

• chronic obstructive airway disease Explanation: Antimuscarinic drugs are contraindicated in Alzheimer's disease, glaucoma, and prostatic hyperplasia. They have no useful effect in hypertension. They can produce useful bronchodilation in COPD and appear to cause less cardiac toxicity than sympathomimetics.

Question 99: Which one of the following drugs is considered a first-line treatment for post-traumatic stress disorder? A Citalopram B Diazepam C Imipramine D Nefazodone E Selegiline

• citalopram Explanation: SSRIs are considered first-line treatment of PTSDs and can benefit a number of symptoms including anxious thoughts and hypervigilance. Psychotherapeutic interventions are usually required in addition to antidepressants.

Question 44: Phase 3 clinical trials typically involve A Collection of data regarding late-appearing toxicities from patients previously studied in phase 1 trials B Double-blind, closely monitored evaluation of the new drug in hundreds of patients with the target disease by specialists in academic centers C Evaluation of the new drug under conditions of actual use in 1000-5000 patients with the target disease D Measurement of the pharmacokinetics of the new drug in normal volunteers E Postmarketing surveillance of drug toxicities

• clinical trials Explanation: Phase 3 trials are carried out under the conditions of proposed use in (usually) several thousand patients.

Question 71: The selective serotonin reuptake inhibitors fluoxetine and paroxetine are potent inhibitors of hepatic CYP2D6 drug-metabolizing enzymes. This action may lead to changes in the intensity of the effects of A Benztropine B Codeine C Gentamicin D Lithium E Methotrexate

• codeine Explanation: Codeine, oxycodone, and hydrocodone are all metabolized by cytochrome CYP2D6, which can be inhibited by certain SSRIs including fluoxetine and paroxetine. This may lead to a decreased analgesic effects of codeine which is normally metabolized in part via CYP2D6 forming the more active compound morphine.

Question 43: Of the following drugs, which has established clinical uses that include attention deficit hyperkinetic disorder (ADHD), enuresis, and the management of chronic pain? A Bupropion B Citalopram C Imipramine D Risperidone E Sertraline

• imipramine Explanation: Enuresis is an established indication for tricyclic antidepressants including imipramine, and they are also used as backup drugs to methylphenidate in attention deficit disorder. Chronic pain states that may be unresponsive to conventional analgesics often respond to the tricyclics.

Question 85: A 45-year-old man who received an allogenic liver transplant received an immunosuppressive regimen containing prednisone, azathioprine, and cyclosporine. Which of the following most accurately describes the mechanism of anti-inflammatory activity of cyclosporine? A Activation of phospholipase A2 B Block of interleukin-2 receptors C Competitive inhibition of inosine monophosphate dehydrogenase D Inhibition of enzymes involved in purine metabolism E Inhibition of the cytoplasmic phosphatase calcineurin

• cyclosporine Explanation: Cyclosporine exerts its immunosuppressive effect by binding to the immunophilin cyclophilin and forming a complex with the cytosolic phosphatase calcineurin, which is necessary for activation of the T-cell nuclear factor of activated T-cell (NF-AT) transcription factor. As a result, cyclosporine inhibits the synthesis of interleukins such as IL-2 by activated T cells.

Question 34: A 45-year-old woman was suspected of having Cushing's syndrome. To confirm the diagnosis, the patient was given an oral medication late in the evening and had blood drawn the following morning for laboratory testing. The oral medication was which of the following? A Dexamethasone B Fludrocortisone C Glucose D Ketoconazole E Propylthiouracil

• dexamethasone Explanation: Cushing's syndrome is a consequence of too much steroid production and is most commonly due to an ACTH-secreting pituitary adenoma. Dexamethasone will suppress ACTH production and thus can be used diagnostically to separate pituitary Cushing's from those with ectopic ACTH-producing tumors. Fludrocortisone acts on mineralocorticoid receptors only. Glucose is already elevated as a consequence of the disease, and adding more will not be diagnostic. Ketoconazole will inhibit male hormone synthesis but will not provide differential diagnostic information. PTU (propylthiouracil) inhibits thyroid hormone signaling.

Question 39: A 40-year-old man had been consuming alcoholic beverages at lunch and in the evenings all his adult life. During the last 2 yr, his alcohol consumption had steadily increased, continuing throughout the day. In response to family pressures, he abruptly stopped drinking alcohol, and within a few hours he became increasingly anxious and agitated and showed symptoms of autonomic hyperexcitability. At this point, he was brought to the hospital. the symptoms increased in severity, with hyperreflexia progressing to seizures. He was given an intravenous injection of a drug that controlled the seizure activity and was then hospitalized. During the recovery period, the same agent was used in oral form with gradual dose tapering. The drug he received as an injection and then as an oral pill was which of the following? A Acamprosate B Amitriptyline C Diazepam

• diazepam Explanation: The patient appears to be suffering from the alcohol withdrawal syndrome, which is treated with a long-acting sedative-hypnotic such as diazepam. Diazepam is available in parenteral and oral formulations.

Question 29: A 65-year-old man with cardiomyopathy has recurrent congestive heart failure. Addition of digitalis to his regimen is being considered. The cellular cause of digitalis toxicity is A Intracellular calcium overload B Intracellular potassium overload C Increased parasympathetic activity D Increased adrenocorticosteroid levels E Impaired sympathetic activity

• digitalis glycosides Explanation: Cardiac glycosides act primarily by inhibiting Na+/K+-ATPase and thus increase intracellular Na+. This in turn reduces Ca2+ expulsion by the Na+-Ca2+ exchanger. Excess digitalis results in an excess of intracellular Ca2+.

Question 94: A 66-year-old woman is in the coronary care unit after an acute myocardial infarction. She has developed signs of pulmonary edema of rapidly increasing severity and several drugs have been suggested. Furosemide, dobutamine, and digoxin can each A Decrease conduction velocity in the atrioventricular node B Decrease venous return C Reduce pulmonary edema D Increase peripheral vascular resistance E Increase the amount of cAMP in cardiac muscle cells

• digoxin The correct answer is (C) Explanation: Digoxin decreases atrioventricular conduction. Furosemide does not increase vascular resistance. Of the agents listed, only dobutamine increases cAMP. All 3 drugs reduce pulmonary edema, albeit probably by different mechanisms.

Question 79: A 54-year-old contractor complains of anginal pain that occurs at rest. On examination, his blood pressure is 145/90 and his heart rate is 90. A treatment of angina that often decreases the heart rate and can prevent vasospastic angina attacks is A Diltiazem B Nifedipine C Nitroglycerin D Propranolol E Timolol

• diltiazem Explanation: Beta blockers usually decrease heart rate but are of no value in vasospastic angina. Nitrates usually increase heart rate. Calcium channel blockers such as diltiazem and verapamil decrease heart rate and are valuable in vasospastic angina, but nifedipine can increase heart rate.

Question 9: Which vasodilator acts on vascular smooth muscle to block calcium influx via L-type channels? A Diazoxide B Diltiazem C Hydralazine D Minoxidil E Nitroprusside

• diltiazem Explanation: Diltiazem, as well as nifedipine and verapamil, act as vasodilators by reducing calcium influx via L-type channels. Hydralazine and nitroprusside act through release of nitric oxide. Diazoxide and minoxidil facilitate potassium channel opening.

Question 81: In a study of new diuretics, an investigational drug was given daily for 8 d and urine output was analyzed. The following data were obtained. Which mechanism best explains the effects shown on the graph? A Carbonic anhydrase inhibition B Blockade of a Na+/K+/2Cl- transporter in the ascending limb of the loop of Henle C Blockade of a NaCl transporter in the distal convoluted tubule D Osmotic diuresis E Block of aldosterone in the cortical collecting tubule

• diuretics Explanation: The graph shows a self-limited diuresis, potassium wasting, and metabolic acidosis. This is most consistent with a carbonic anhydrase inhibitor like acetazolamide.

Question 31: A neuronal cell body located in the substantia nigra has axonal projections to the striatum. The neurotransmitter that it releases, which exerts only inhibitory actions, is most likely to be A Acetylcholine B Dopamine C Glutamic acid D Norepinephrine E Serotonin

• dopamine Explanation: Dopamine exerts slow inhibitory actions at synapses in specific neural systems including the nigrostriatal projections via G protein-coupled activation of postsynaptic potassium channels or by inhibition of presynaptic calcium channels.

Question 38: This drug is prophylactic in meningococcal and staphylococcal carrier states. Although the drug eliminates a majority of meningococci from carriers, highly resistant strains may be selected out during treatment. A Ciprofloxacin B Clofazimine C Dapsone D Rifampin E Streptomycin

• rifampin Explanation: Resistance emerges rapidly when rifampin is used as a single agent in the treatment of bacterial infections. When used in the meningococcal carrier state, highly resistant strains may be selected out during treatment.

Question 69: A 17-year-old high school student presents with headache, fever, and cough of 2 days' duration. Sputum is scant and nonpurulent, and a Gram stain reveals many white cells but no organisms. Because this otherwise healthy patient appears to have a community-acquired pneumonia, you should initiate treatment with A Amoxicillin-clavulanate B Clindamycin C Doxycycline D Erythromycin E Quinupristin-dalfopristin

• doxycycline Explanation: With respect to microbial etiology, the most likely organisms in community-acquired pneumonia (CAP) are S pneumoniae, H influenzae, and M catarrhalis. Depending on resistance patterns in the community, it is possible to treat CAP with a single antibiotic, and doxycycline is one of the antibiotics commonly used.

Question 18: A 22-year-old woman presents with left lower quadrant abdominal pain and a purulent vaginal discharge that, on Gram stain, revealed gram-negative rods. A diagnosis is made of pelvic inflammatory disease possibly involving both N gonorrhoeae and C trachomatis.(A) drug or drug combination that provides adequate empiric coverage of the organisms involved in this infection is A Azithromycin B Ceftriaxone plus doxycycline C Metronidazole D Norfloxacin plus ampicillin E Trimethoprim-sulfamethoxazole

• doxycycline • ceftriaxone Explanation: Ceftriaxone (or cefixime) is a drug of choice for treatment of gonococcal infections, and chlamydial infections usually respond to a tetracycline. Though not listed,azithromycin as a single agent is considered a co-drug of choice for chlamydial infections and an alternative drug for gonococcal infections.

Question 53: A patient is admitted to a hospital emergency department 2 h after taking an overdose of diazepam. The plasma level of the drug at time of admission is 40 mg/L, and the apparent volume of distribution, half-life, and clearance of diazepam are 80 L, 40 h, and 35 L/day, respectively. The ingested dose was approximately A 1.3 g B 2.4 g C 3.2 g D 4.8 g E 6.4 g

• drug concentration Explanation: Two hours after an overdose of a drug with a 40-hr half-life, the plasma concentration will approximate that immediately after a loading dose. Using the loading dose equation (dose = Vd × Cp), we obtain dose = 80 L × 40 mg/L, or 3200 mg, or 3.2 g.

Question 92: Although it does not act at any histamine receptor and has no effect on histamine's metabolism, epinephrine reverses many effects of histamine. Epinephrine is a A Chemical antagonist of histamine B Competitive inhibitor of histamine C Metabolic inhibitor of histamine D Noncompetitive antagonist of histamine E Physiologic antagonist of histamine

• epinephrine .Explanation: A physiologic antagonist opposes the action of other drugs by acting at a different receptor; histamine acts at H1 and H2 in the periphery, while epinephrine opposes histamine by acting at α1 and β2 adrenoceptors.

Question 73: Which of the following drugs is a partial agonist and can cause vasoconstriction in the absence of other drugs? A Atropine B Ergotamine C Neostigmine D Phentolamine E Verapamil

• ergotamine Explanation: Ergotamine is a potent vasoconstrictor but is a partial agonist at α adrenoceptors; as such, it can cause epinephrine reversal.

Question 22: Which one of the following drugs is appropriate for treating a patient with moderate to severe rheumatoid arthritis but is not appropriate for treating a patient with moderate to severe osteoarthritis? A Acetaminophen B Etanercept C Ibuprofen D Interferon α E Fentanyl

• etanercept Explanation: Etanercept is not appropriate for osteoarthritis because it binds to and inactivates TNF-α. Thus, it will only be of use in inflammatory disorders that are mediated through TNF-α such as rheumatoid arthritis, juvenile-onset arthritis psoriasis, psoriatic arthritis, and ankylosing spondylitis.

Question 11: A 26-year-old woman comes to the outpatient clinic with a complaint of rapid heart rate and easy fatigability. Laboratory workup reveals low hemoglobin and microcytic red cell size. Which of the following is the most suitable therapy? A Ferrous sulfate B Folic acid C Iron dextran D Pyridoxine E Vitamin B12

• ferrous sulfate Explanation: The most common cause of microcytic anemia is iron deficiency, which can be treated in most patients with an oral iron supplement such as ferrous sulfate.

Question 70: A 70-year-old man has severe urinary hesitancy associated with benign prostatic hyperplasia. He has tried α blockers with little relief. His physician recommends a drug that blocks 5α-reductase in the prostate. Which of the following drugs did the physician most likely prescribe? A Finasteride B Flutamide C Ketoconazole D Leuprolide E Oxandrolone

• finasteride Explanation: Finasteride is a 5α-reductase inhibitor. Flutamide is an androgen receptor antagonist. Ketoconazole is a cytochrome P450 inhibitor (also used as an antifungal agent). Leuprolide is a GnRH agonist used in depot form for prostate carcinoma. Oxandrolone is an anabolic androgenic steroid.

Question 49: A cardiac Purkinje fiber was isolated from an animal heart and placed in a recording chamber. One of the Purkinje cells was impaled with a microelectrode, and action potentials were recorded while the preparation was stimulated at 1 stimulus per second. A representative control action potential is shown in red in the graph. After equilibration, oxygenation was reduced, and a drug was added to the perfusate while recording continued. A representative action potential obtained at the peak of drug action is shown as the superimposed action potential (blue). Identify the drug from the following list. A Adenosine B Amiodarone C Diltiazem D Flecainide

• flecainide Explanation: The action potential has a markedly slowed upstroke and unchanged duration. These effects are characteristic of group 1C drugs, including flecainide.

Question 60: After a very large overdose of diazepam a 2-year-old child is admitted to the hospital. Along with general supportive care, the administration of which of the following is most likely to be used to reverse the action of the benzodiazepine? A Acetylcysteine B Atropine C Flumazenil D Fomepizole E Naloxone

• flumazenil Explanation: Diazepam is a benzodiazepine sedative-hypnotic drug whose action can be competitively inhibited by flumazenil. Acetylcysteine is used for acetaminophen overdose. Atropine is used in organophosphate poisoning, fomepizole is used for methanol or ethylene glycol poisoning, and naloxone is used for opioid overdose.

Question 66: In a cancer cell, decreased ability to phosphorylate pyrimidines could result in resistance to the anticancer action of which of the following? A Cisplatin B Etoposide C Fluorouracil D Mercaptopurine E Methotrexate

• fluorouracil Explanation: The question asks about antimetabolites. The two options in this class are mercaptopurine and fluorouracil. Mercaptopurine is a purine affecting purine metabolism leaving FU, which is a suicide substrate for thymidylate synthase.

Question 84: A 35-year-old woman who has never been pregnant suffers each month from pain, discomfort, and mood depression at the time of menses. She may benefit from the use of this selective inhibitor of the reuptake of serotonin in a form that can be taken once weekly. A Amoxapine B Bupropion C Fluoxetine D Mirtazapine E Tranylcypromine

• fluoxetine Explanation: Approximately 5% of women of child-bearing age experience symptoms during the late luteal phase of the menstrual cycle that are more serious than PMS. It is referred to as premenstrual dysphoric disorder (PMDD). SSRIs, including a long-acting form of fluoxetine given weekly, are approved for this indication.

Question 8: A patient is admitted to the emergency department for treatment of a drug overdose. The identity of the drug is unknown, but it is observed that when the urine pH is alkaline, the renal clearance of the drug is much greater than when the urine pH is acidic. The drug is probably a A Strong acid B Weak acid C Nonelectrolyte D Weak base E Strong base

• henderson-hasselbalch equation Explanation: According to the Henderson-Hasselbalch principle (Chapter 1), weak acids are less protonated (and more charged) in alkaline media, and weak bases are more protonated (and more charged) in acidic media. Since the clearance of the unknown drug is greater in alkaline urine, the drug must be a weak acid.

Question 87: Angioneurotic edema precipitated by exposure to an allergen can cause life-threatening laryngeal edema. A probable mediator of such reactions is A Angiotensin II B Epinephrine C Histamine D Norepinephrine E Serotonin

• histamine Explanation: Several autacoids may be involved in the edema of angioneurotic allergic reactions. Histamine and bradykinin are probable contributors.

Question 15: A 55-year-old man with a strong family history of cardiovascular disease has moderate hypertension and angina pectoris. Blood pressure is 160/109 mm Hg, and the ECG shows left ventricular hypertrophy. The rest of his physical examination and laboratory results are normal. His angina is precipitated by exercise. You have been asked to recommend a drug regimen for both conditions. The antihypertensive drug most likely to aggravate angina pectoris is A Captopril B Clonidine C Hydralazine D Methyldopa E Propranolol

• hydralazine Explanation: Angina pectoris can be precipitated by tachycardia; vasodilators such as hydralazine typically cause increased heart rate.

Question 59: The speed of induction of anesthesia with halogenated hydrocarbons (eg, halothane, isoflurane) is not affected by A Arteriovenous concentration gradient B Inspired gas partial pressure C Minimal alveolar anesthetic concentration D Pulmonary blood flow E Ventilation rate

• hydrocarbons, halogenated Explanation: All of the factors listed influence the rate of induction of the anesthetic state except the minimal alveolar anesthetic concentration. MAC reflects potency and is defined as the minimum alveolar anesthetic concentration that eliminates response to a standard painful stimulus in 50% of patients.

Question 68: A patient discharged from the hospital after a myocardial infarction had been receiving small doses of procainamide to suppress a ventricular tachycardia. One month later, his local physician prescribed high-dose hydrochlorothiazide therapy for ankle edema, which was ascribed to congestive heart failure. Three weeks after beginning thiazide therapy, the patient was readmitted to the hospital with a rapid multifocal ventricular tachycardia. The most probable cause of this arrhythmia is A Procainamide toxicity caused by inhibition of procainamide metabolism by the thiazide B Direct effects of hydrochlorothiazide on pacemaker cells of the heart C Direct effects of procainamide on pacemaker cells of the heart D Block of calcium current by the combination of procainamide plus thiazide E Reduction of serum potassium caused by the diuretic action of hydrochlorothiazide

• hydrochlorothiazide Explanation: Cardiac automaticity is enhanced by hypokalemia. Thiazides, loop diuretics, and even carbonic anhydrase inhibitors can reduce serum potassium levels because they present more sodium to the cortical collecting tubules, which attempt to compensate by wasting potassium in exchange for sodium.

Question 14: A 54-year-old woman with a recent history of deep vein thrombosis had been stable on warfarin therapy for the last 2 mos. However, her most recent prothrombin time (PT) test revealed a markedly reduced INR. When asked about changes in diet or medication during the last several weeks, the woman said that she had recently begun taking a dietary supplement recommended by a friend. Based on this information, the supplement is most likely to contain which of the following? A Ginkgo B Ginseng C Kava D Ma huang E St. John's wort

• hypericum perforatum / st. john's wort essence Explanation: Warfarin is metabolized by CYP3A4 (and CYP1A and CYP2C). The patient's INR is reduced; her plasma level of warfarin is subtherapeutic. This means the metabolism of warfarin is induced. St. John's wort is a potent inducer of CYP3A4. The other drugs do not appear to affect the CYP enzyme family.

Question 54: A 65-year-old man with cardiomyopathy has recurrent congestive heart failure. Addition of digitalis to his regimen is being considered. In a patient receiving digoxin for congestive heart failure, conditions that may facilitate the appearance of toxicity include A Hyperkalemia B Hypernatremia C Hypocalcemia D Hypomagnesemia E Hypophosphatemia

• hypomagnesemia Explanation: Digitalis toxicity is associated with hypokalemia and hypomagnesemia (and hypercalcemia). Hyperkalemia (choice A) is a trap for careless readers.

Question 19: A 55-year-old surgeon has developed symmetric early morning stiffness in her hands. She wishes to take a nonsteroidal anti-inflammatory drug to relieve these symptoms. Which drug is an NSAID that is appropriate for chronic therapy of her arthritis? A Colchicine B Hydroxychloroquine C Ibuprofen D Indomethacin E Sulfasalazine

• ibuprofen Explanation: Ibuprofen and indomethacin are the only NSAIDS listed here. Indomethacin is more potent and has more adverse effects compared with ibuprofen and is not the first NSAID of choice for milder symptoms. Colchicine exerts its anti-inflammatory effects by prevention of tubulin polymerization, and it is used predominantly in acute gout attacks. Hydroxychloroquine is an antimalarial with anti-inflammatory effects, and sulfasalazine inhibits the release of inflammatory cytokines (IL-1, IL-6, IL-12, and TNF-α).

Question 89: Which of the following is a tyrosine kinase enzyme inhibitor that is used to treat chronic myelogenous leukemia? A Anastrozole B Doxorubicin C Imatinib D Rituximab E Vincristine

• imatinib mesylate Explanation: Note that kinase inhibitors have names ending in "nib." Anastrozole is an aromatase inhibitor. Doxorubicin is an antitumor antibiotic. Imatinib (Gleevec) targets bcr-abl kinase. Rituximab is a monoclonal antibody against CD20. Vincristine is an alkaloid affecting microtubules.

Question 1: A 30-year-old hospitalized patient with AIDS has a CD4 cell count of 50/μL. He is being treated with a highly active antiretroviral therapy (HAART) regimen consisting of zidovudine (ZDV), lamivudine (3TC), and indinavir. Other drugs being administered to this patient include ganciclovir, clarithromycin, rifabutin, and trimethoprim-sulfamethoxazole. The drug in this patient's regimen that inhibits posttranslational modification of viral proteins is A Acyclovir B Indinavir C Lamivudine D Rifabutin E Zidovudine

• indinavir Explanation: Protease inhibitors such as indinavir act at the posttranslational step of HIV at which the viral enzyme cleaves precursor molecules to form the final structural proteins of the mature virion core.

Question 12: A 24-year-old man with a 7-year history of Crohn's disease was suffering from persistent diarrhea, abdominal pain, and signs of systemic inflammation that were poorly controlled by first-line agents. The patient's physician proposed treatment with an immunoglobin-based agent that inhibits tumor necrosis factor (TNF). Which of the following drugs fits this description? A Aldesleukin B Cyclosporine C Filgrastim D Infliximab E Interferon-γ

• infliximab Explanation: Infliximab is a humanized monoclonal antibody that binds to tumor necrosis factor-alpha (TNF-α). Anti-TNF-α antibody-based drugs (etanercept, adalimumab) are increasingly used to treat inflammatory disorders such as rheumatoid arthritis.

Question 95: The graph below shows the serum insulin level that results from a 2-injection regimen given to a child with type 1 diabetes. Assume that both injections (indicated by arrows along the time line) contain the same medication(s). The drug or drug combination that is most likely to generate the levels of insulin depicted in the figure is View Full Size | Save Figure | Download Slide (.ppt) A 100% Regular insulin B 100% Lispro insulin C 70% NPH insulin plus 30% regular insulin D 100% NPH insulin E 100% Insulin glargine

• insulin Explanation: In order to replicate the physiological situation with a baseline and mealtime peaks, one needs to combine insulin preparations with different durations of action. Review duration of action of different insulin formulations in Figure 41-1. FIGURE 41-1 View Full Size | Save Figure | Download Slide (.ppt) Extent and duration of action of various types of insulin as indicated by the glucose infusion rates (mg/kg/min) required to maintain a constant glucose concentration. The durations of action shown are typical of an average dose of 0.2-0.3 U/kg; the duration of regular and NPH insulin increases considerably when dosage is increased. (Reproduced, with permission, from Katzung BG, editor:(B)asic & Clinical Pharmacology, 12th ed. McGraw-Hill, 2012: Fig. 41-5.)

Question 86: A patient has been taking aspirin for rheumatoid arthritis for 8 yrs. Exacerbations are becoming worse, and she asks the physician about drugs that might stop the progression of the disease. Which of the following is a disease-modifying antirheumatic drug (DMARD)? A Colchicine B Epoprostenol C Leflunomide D Naproxen E Zafirlukast

• leflunomide Explanation: Colchicine is used predominantly in acute gout attacks and exerts its anti-inflammatory effects by prevention of tubulin polymerization. Epoprostenol is a prostacyclin (PGI2), and it is used in the treatment of pulmonary hypertension. Naproxen is an NSAID with a relatively long half-life, and zafirlukast is a LT4 receptor antagonist used in the treatment of asthma.

Question 30: Relative to ciprofloxacin, levofloxacin has improved activity against A Bacteroides fragilis B Escherichia coli C Haemophilus influenzae D Mycoplasma pneumoniae E Streptococcus pneumoniae

• levofloxacin Explanation: In the case described below, though not listed, levofloxacin is also used both as a single drug and in drug combinations in CAP, precisely because the drug has much greater activity than ciprofloxacin against likely organisms, especially the pneumococcus. (A 17-year-old high school student presents with headache, fever, and cough of 2 days' duration. Sputum is scant and nonpurulent, and a Gram stain reveals many white cells but no organisms. Because this otherwise healthy patient appears to have a community-acquired pneumonia, you should initiate treatment with doxycycline.)

Question 42: A 24-year-old woman is to be treated with levofloxacin for a urinary tract infection. A contraindication to the use of the antibiotic in this patient is a history of A Deep vein thrombosis B Glucose-6-phosphate dehydrogenase (G6PD) deficiency C Gout D Q-T prolongation E Use at the present time of a combined hormonal contraceptive

• levofloxacin Explanation: Patients with a history of cardiac irregularities should avoid certain fluoroquinolones including levofloxacin and moxifloxacin since they are known to cause QT prolongation.

Question 76: A young woman seeks advice because she had unprotected sexual intercourse 12 hr earlier. Based on her menstrual cycle, she believes that conception is possible. Which drug should she use as a postcoital contraceptive? A Clomiphene B Diethylstilbestrol plus raloxifene C Flutamide D Letrozole plus finasteride E Levonorgestrel

• levonorgestrel Explanation: Levonorgestrel is a progestin. Progestins used within 72 hr are effective as emergency contraception either alone or in combination with estrogens. "Progestin-only" emergency contraceptives have fewer side effects than those containing estrogens.

Question 33: A patient taking medications for a psychiatric disorder develops a tremor, thyroid enlargement, edema, and acneiform eruptions on the face. The drug he is taking is most likely to be A Carbamazepine B Haloperidol C Lamotrigine D Lithium E Sertraline

• lithium Explanation: Edema and thyroid enlargement are common adverse effects of lithium, although the latter does not usually involve hypothyroidism. Neurologic side effects of lithiuminclude tremor, ataxia, and aphasia.

Question 2: A 46-year-old man has hypertension of 155/95. His cardiac and kidney function is normal. Losartan has been suggested as therapy. This drug provides an antihypertensive effect by which of the following effects? A Accelerating the rate of enzymatic inactivation of amine neurotransmitters in the CNS B Activating α2-adrenoceptors located in the presynaptic membranes of CNS neurons that regulate peripheral SANS activity C Blocking the transport of amine neurotransmitters from the cytoplasm to the inside of synaptic transmitter storage vesicles D Inhibiting the uptake of amine neurotransmitters from the extracellular fluid into the cytoplasm in the presynaptic nerve terminus E Interfering with the combination of angiotensin II with its receptor

• losartan Explanation: Losartan is a member of the angiotensin receptor-blocking group. It is a competitive antagonist of angiotensin II at its receptor.

Question 100: A 55-year-old woman with type 2 diabetes was going to be started on metformin. Before initiating therapy, it is important to confirm that the patient has normal renal function because patients with unrecognized renal insufficiency who take normal doses of metformin are at increased risk of which of the following? A Hypoglycemia B Interstitial nephritis C Lactic acidosis D Liver failure E Torsades de pointes cardiac arrhythmia

• metformin Explanation: Metformin carries a black box warning for lactic acidosis. Note that metformin is a "euglycemic agent" (ie, it does not cause hypoglycemia).

Question 78: A 39-year-old woman with recurrent sinusitis has been treated with different antibiotics on several occasions. During the course of one such treatment, she developed a severe diarrhea and was hospitalized. Sigmoidoscopy revealed colitis, and pseudomembranes were confirmed histologically. Which of the following drugs, administered orally, is most likely to be effective in the treatment of colitis caused by Clostridium difficile? A Ampicillin B Cefazolin C Metronidazole D Tetracycline E Trimethoprim-sulfamethoxazole

• metronidazole Explanation: The anaerobic bacterium Clostridium difficile is a cause of life-threatening pseudomembranous colitis. The primary drugs used in management of such infections are vancomycin (not listed) or metronidazole.

Question 17: A 44-year-old patient suffering from an alcohol-use disorder enters a residential treatment program that emphasizes group therapy and also uses pharmacologic agents adjunctively. The patient is given a drug that decreases the craving for alcohol. Because the drug will not cause adverse effects if the patient consumes alcoholic beverages, it can be identified as which of the following? A Bupropion B Disulfiram C Olanzapine D Naltrexone E Sertraline

• naltrexone Explanation: Naloxone, a nonselective opioid receptor antagonist, is used by individuals recovering from alcohol-use disorders.

Question 47: While on vacation, a 35-year-old man with a 10-year history of myasthenia gravis loses his supply of medications. He is now admitted to the emergency department complaining of diplopia, dysarthria, and difficulty swallowing. The most appropriate drug from the following list for reversing myasthenic crisis in this patient is A Calcium B Neostigmine C Pralidoxime D Succinylcholine E Vecuronium

• neostigmine Explanation: The appropriate treatment for myasthenic crisis is an indirect-acting cholinomimetic, the same medication used for chronic therapy of this condition. Neostigmine is the only cholinesterase inhibitor in the list of choices.

Question 13: Hypothetical investigational drugs as blockers of the membrane transporters (reuptake systems) for 3 CNS neurotransmitters. | Print Blocking Actions on CNS Transporters for Drug Dopamine Serotonin Norepinephrine UCSF 1 +++ None None UCSF 2 +++ ++++ ++ UCSF 3 None ++ ++ UCSF 4 None +++ ++ UCSF 5 + + None Key: Number of + signs denotes intensity of blocking actions Which drug is likely to be effective in the treatment of major depressive disorders but may also cause marked adverse effects, including thought disorders, delusions, hallucinations, and paranoia? A UCSF 1 B UCSF 2 C UCSF 3 D UCSF 4 E UCSF 5

• neurotransmitters Explanation: Enhancement of the actions of norepinephrine and/or serotonin via inhibition of reuptake transporters is characteristic of many antidepressants including the tricyclics and the SSRIs. However, inhibition of the reuptake of dopamine leading to enhancement of its CNS effects has been equated with thought disorders, delusions, hallucinations, and paranoia.

Question 21: A 45-year-old man with a duodenal ulcer and laboratory evidence of Helicobacter pylori infection was treated with omeprazole, clarithromycin, and amoxicillin. Which of the following is the most accurate description of the mechanism of omeprazole's therapeutic action? A Activation of prostaglandin E receptors B Formation of protective coating over the ulcer bed C Inhibition of bacterial protein synthesis D Inhibition of H2 histamine receptors E Irreversible inactivation of an H+/K+(A)TPase

• omeprazole Explanation: Omeprazole, a proton pump inhibitor, very effectively reduces gastric acid secretion by being converted to an active metabolite that irreversibly inhibits the parietal cell H+/K+(A)TPase that is responsible for acid secretion. Misoprostol activates prostaglandin E receptors. Sucralfate forms a protective coating over an ulcer bed, andcimetidine inhibits H2 histamine receptors.

Question 27: A 65-year-old woman with endometrial cancer came to an outpatient cancer treatment center for her first cycle of platinum-based chemotherapy. To prevent chemotherapy-induced nausea and vomiting, this patient is likely to be given which of the following? A Famotidine B Leucovorin C Mesalamine D Ondansetron E Sumatriptan

• ondansetron Explanation: Ondansetron, a serotonin 5-HT3 receptor antagonist, is a highly effective antiemetic. Famotidine is a H2 receptor antagonist used for acid-peptic disease. Leucovorin is a form of tetrahydrofolate that can be used to reverse the effects of the anticancer drug methotrexate. Mesalamine is a form of 5-aminosalicylic acid (5-ASA) used for inflammatory bowel disease, and sumatriptan is a serotonin 5-HT1D/1B agonist used for migraine headache.

Question 41: A 30-year-old hospitalized patient with AIDS has a CD4 cell count of 50/μL. He is being treated with a highly active antiretroviral therapy (HAART) regimen consisting of zidovudine (ZDV), lamivudine (3TC), and indinavir. Other drugs being administered to this patient include ganciclovir, clarithromycin, rifabutin, and trimethoprim-sulfamethoxazole. None of the drugs being administered to this patient are useful for prevention or treatment of opportunistic infections caused by A Candida albicans B Cytomegalovirus C Mycobacterium avium-intracellulare D Pneumocystis jiroveci E Toxoplasma gondii

• opportunistic infections The correct answer is (A). Explanation: Prophylactic drugs used in this AIDS patient provide coverage against most opportunistic infections, including cytomegalovirus (ganciclovir), but there is no coverage against fungal infections commonly due to Candida albicans.

Question 58: A 20-year-old college student is brought to the emergency department after taking an overdose of a nonprescription drug. The patient is comatose. He has been hyperventilating and is now dehydrated with an elevated temperature. Serum analyses demonstrate that the patient has an anion gap metabolic acidosis. In the management of this patient, it would be most appropriate to A Administer acetylcysteine B Administer fomepizole C Administer glucagon D Alkalinize the urine E Induce vomiting with syrup of ipecac

• overdose Explanation: Aspirin is a weak acid with a pKa of 3.5. Urinary alkalinization to a pH of 7.5 or above by administration of sodium bicarbonate will enhance urinary excretion of aspirinand other salicylates. Urinary alkalinization traps the charged, polar form of the salicylates in the renal tubule fluid. Hemodialysis is also very effective at removing salicylates.

Question 97: A semiconscious patient in the intensive care unit is being artificially ventilated. Random spontaneous respiratory movements are rendering the mechanical ventilation ineffective. A useful drug to reduce the patient's ineffective spontaneous respiratory activity is A Baclofen B Dantrolene C Pancuronium D Neostigmine E Succinylcholine

• pancuronium Explanation: A drug that antagonizes nicotinic receptors at skeletal neuromuscular junctions (pancuronium) is required to inhibit spontaneous respiratory movements. Succinylcholineis not appropriate partly because it may initially stimulate N-receptors and also because its duration of action is very short.

Question 48: In a laboratory demonstration of the interactions of drugs, an anesthetized dog is given several agents intravenously. Intravenous administration of norepinephrine in a subject already receiving an effective dose of atropine often A Decreases blood sugar B Decreases total peripheral resistance C Increases heart rate D Increases skin temperature E Reduces pupil size

• parasympathetic nervous system Explanation: Atropine blocks vagal and other parasympathetic pathways. Norepinephrine causes vasoconstriction and increased blood pressure. The increase in blood pressure usually evokes a reflex bradycardia that is mediated by the vagus nerve. When vagal slowing is blocked, the beta-agonist action of norepinephrine is unmasked, resulting in tachycardia.

Question 74: An anesthetized subject was given an intravenous bolus dose of a drug (Drug 1) while the systolic and diastolic blood pressures (blue) and the heart rate were recorded, as shown on the left side of the graph below. While the recorder was stopped, Drug 2 was given (center). Drug 1 was then administered again, as shown on the right side of the graph. Identify Drug 2 from the following list H Norepinephrine I Phentolamine J Phenylephrine K Terbutaline

• phentolamine Explanation: As noted in the answer to the previous question, the agonist drug (drug 1) is probably a strong α-agonist sympathomimetic. Drug 2 markedly reduces the pressor action of drug 1 (compatible with α blockade) and also suppresses the change in heart rate. If drug 1 was norepinephrine, its β-agonist effect on heart rate would have been unmasked. Thus, drug 2 is a simple α blocker.

Question 36: An anesthetized subject was given an intravenous bolus dose of a drug (Drug 1) while the systolic and diastolic blood pressures (blue) and the heart rate were recorded, as shown on the left side of the graph below. While the recorder was stopped, Drug 2 was given (center). Drug 1 was then administered again, as shown on the right side of the graph. Identify Drug 1 from the following list J Phenylephrine K Terbutaline

• phenylephrine Explanation: This question and the following one require a combined knowledge of agonist and antagonist actions. Note that systolic and diastolic blood pressures are increased, but heart rate is decreased. This is compatible with a strong α-agonist drug such as norepinephrine (choice H) or phenylephrine (choice J). The final choice must be withheld until the actions of drug 2 are evaluated. Following drug 2, there is no change in heart rate, suggesting that the bradycardia seen previously was a reflex response to the pressor effect. Thus, drug 1 lacks β-agonist effect; it is a "pure" α agonist.

Question 82: The pharmacokinetic characteristics of several hydantoin derivatives, each with anticonvulsant activity equivalent to that of phenytoin, were examined in phase 1 clinical trials. The rationale was to identify a drug with more desirable kinetic properties than those of phenytoin. | Print Drug Oral Bioavailability (%) Plasma Protein Binding (%) Elimination Kinetics Cytochrome P450 Induction ABC 10 90 First order ++ DEF 90 50 First order ++ GHI 50 98 Zero order None JKL 85 10 First order None MNO 95 10 First order ++ Based on the data shown in the table above, which drug has the optimum pharmacokinetic properties for oral use in the management of patients with seizure disorders? JKL 85 10 First order None

• phenytoin Explanation: Compared with phenytoin, favorable characteristics of a new anticonvulsant would include good oral bioavailability, minimal plasma protein binding, first-order elimination kinetics, and no induction (or inhibition) of cytochromes P450.

Question 93: A 28-year-old man was diagnosed with Hodgkin's lymphoma, and chemotherapy with multiple anticancer drugs was initiated. Which of the following agents is an agonist of a hormone receptor and is used in the treatment of Hodgkin's lymphoma? A Dacarbazine B Doxorubicin C Prednisone D Procarbazine E Vinblastine

• prednisone Explanation: Hodgkin's lymphoma is a cancer of lymph tissue found in the lymph nodes, spleen, liver, bone marrow, and other sites. It responds well to prednisone. Prednisone acts via binding the cytoplasmic steroid receptors followed by a translocation of the receptor-ligand complex into the nucleus, binding to DNA, and altering gene transcription. All other agents listed in this question are cytotoxic agents.

Question 83: A patient is to undergo surgery, and a short-acting anesthetic with a fast onset will be used. Recovery, unhampered by postoperative nausea, will be rapid because the clearance of the drug is greater than hepatic blood flow. The drug to be used is A Enflurane B Halothane C Midazolam D Phenobarbital E Propofol

• propofol The correct answer is (E). Explanation: The onset of anesthesia with propofol is more rapid than intravenous barbiturates. Its clearance is greater than hepatic blood flow, which suggests extrahepatic elimination. The drug has antiemetic actions, and recovery is not delayed after prolonged infusion.

Question 96: A 20-year-old foreign exchange student attending college in California is to be treated for pulmonary tuberculosis. Because drug resistance is anticipated, the proposed antibiotic regimen includes ethambutol, isoniazid (with supplementary vitamin B6), pyrazinamide, and rifampin. Provided that his disease responds well to the drug regimen and that the microbiology laboratory results show sensitivity to the drugs, it would be appropriate after 2 mo to A Change his drug regimen to prophylaxis with isoniazid B Discontinue pyrazinamide C Establish baseline ocular function D Monitor amylase activity E Stop the supplementary vitamin B6

• pyrazinamide Explanation: A 4-drug initial regimen would be appropriate in this case, and if the laboratory reports show sensitivity to the drugs, it would be appropriate to discontinuepyrazinamide, maintaining the 3-drug regimen that includes both isoniazid and rifampin. Pyrazinamide has a high incidence of adverse effects including polyarthralgia as well as hepatic dysfunction, porphyria, and photosensitivity reactions.

Question 72: Most drug receptors are A Small molecules with a molecular weight between 100 and 1000 B Lipids arranged in a bilayer configuration C Proteins located on cell membranes or in the cytosol D DNA molecules E RNA molecules

• receptors, drug Explanation: As described in Chapter 1, receptors are usually regulatory molecules or enzymes; proteins constitute the vast majority of regulatory and enzyme molecules.

Question 6: Diners at a popular seafood restaurant became ill after consuming clams and mussels. Consultation with the local coastal authorities revealed that the area from which the seafood had been harvested had recently had a major "red tide." The consumption of shellfish harvested during a red tide (resulting from a large population of a dinoflagellate species) is not recommended because of contamination with saxitoxin, a drug that resembles tetrodotoxin. These toxins cause which of the following effects? A Clonic-tonic seizures B Malignant hypertension C Nerve transmission blockade D Renal failure E Ventricular torsades de pointes arrhythmias

• saxitoxin Explanation: Dinoflagellates secrete saxitoxin, a blocker of voltage-gated Na+ channels in nerves. Exposure to this toxin results in block of transmission initially in sensory nerves (causing numbness and tingling) but may extend to block of motor nerves with paralysis of voluntary muscle, including the diaphragm.

Question 16: Drugs that selectively inhibit D2 dopamine receptors in the CNS have efficacy in the treatment of schizophrenia. Efficacy in the treatment of schizophrenia is also seen with drugs that block A α-Adrenoceptors or D1 dopamine receptors B D4 dopamine receptors or 5-HT2A serotonin receptors C GABAA receptors or 5-HT3 serotonin receptors D H1 histamine receptors or β-adrenoceptors E β-Adrenoceptors or NMDA receptors

• schizophrenia Explanation: Although all effective antipsychotic drugs block D2 receptors, some are more potent inhibitors of D4 dopamine receptors (eg, clozapine) or 5-HT2A serotonin receptors (eg, olanzapine).

Question 4: A 46-year-old man consults you regarding his sexual performance issues. A drug that is used in the treatment of male erectile dysfunction and inhibits a phosphodiesterase is A Finasteride B Fluoxetine C Mifepristone D Sildenafil (Viagra) E Timolol

• sildenafil Explanation: Inhibitors of phosphodiesterase, isoform 5, are useful in enhancing erection. Note: Because the mechanism involves increased cGMP in vascular smooth muscle, these drugs also potentiate the hypotensive action of nitrates.

Question 46: In anesthesia protocols that include succinylcholine, which of the following is a premonitory sign of malignant hyperthermia? A Acidosis B Bradycardia C Hypotension D Transient hypothermia E Trismus

• succinylcholine Explanation: Trismus, or masseter hypertonia, that results from the use of succinylcholine during induction of anesthesia is a rare and dangerous phenomenon. It presents to the anesthesio-logist the immediate problem of airway management but it also must be recognized by the physician as a harbinger of malignant hyperthermia.

Question 24: Which of the following effects are characteristic of methylxanthine drugs such as theophylline? A Activation of adenosine receptors B Blockade of the enzyme phosphodiesterase C Decrease in the amount of cAMP in mast cells D Inhibition of cardiac β receptors E Sedation

• theophylline Explanation: The methylxanthines block phosphodiesterase and increase the concentration of cAMP. They may also block adenosine receptors.

Question 37: Which of the following is an anticlotting drug that binds to and inhibits the platelet glycoprotein IIb/IIIa protein? A Aspirin B Clopidogrel C Enoxaparin D Fondaparinux E Tirofiban

• tirofiban Explanation: Aspirin exerts its antiplatelet effect through irreversible inhibition of COX-1 and COX-2. Clopidogrel is a prodrug, and its metabolite irreversibly binds ADP receptors.Enoxaparin is LMW heparin and acts through antithrombin III. Fondaparinux is a small portion of LMW heparin with similar actions. Tirofiban is the only IIb/IIIa protein ligand in the list of options.

Question 90: The primary clinical application of the 5-HT2 receptor antagonist trazodone is the treatment of A Bipolar disorder B Chronic pain C Insomnia D Major depressive disorder E Premenstrual dysphoric disorder

• trazodone Explanation: Nefazodone and trazodone are 5-HT2 receptor antagonists with both anxiolytic and antidepressant actions. In addition, at a relatively low dose, trazodone is a widely used and effective hypnotic with minimal dependence liability compared with most of the sedative-hypnotic drugs used in sleep disorders.

Question 67: In the management of patients with AIDS, trimethoprim-sulfamethoxazole is commonly used to prevent infection resulting from A Campylobacter jejuni B Mycobacterium avium-intracellulare C Neisseria gonorrhea D Pneumocystis jiroveci E Treponema pallidum

• trimethoprim-sulfamethoxazole combination Explanation: One double-strength tablet of sulfamethoxazole-trimethoprim three times weekly is prophylactic against P jiroveci infection in AIDS patients but may cause rash, fever, and leukopenia.

Question 75: A 50-year-old man has macrocytic anemia and early signs of neurologic abnormality. Which of the following drugs will probably be required in this case? A Erythropoietin B Filgrastim C Folic acid D Iron dextran E Vitamin B12

• vitamin b 12 Explanation: The most common cause of macrocytic anemia is deficiency of folic acid or vitamin B12. The additional finding of neurologic abnormality suggests vitamin B12deficiency, which is treated with vitamin B12 replacement.

Question 50: A patient in the coronary care unit has received warfarin for 2 wk. As a result of this therapy, the patient will exhibit which of the following? A Reduced plasma prothrombin (factor II) activity B Reduced plasma factor VIII activity C Reduced plasma plasminogen activity D Increased tissue plasminogen activator activity E Increased platelet adenosine stores

• warfarin Explanation: Warfarin inhibits vitamin K-dependent gamma-carboxylation of the clotting factors X, IX, VII, and II (mnemonic "1972"). Warfarin acts through inhibition of vitamin K epoxide reductase in the liver. It does not interact with plasminogen or platelets.

Question 7: The mechanism of action of the hypnotic drug zolpidem is A Activation of GABAB receptors B Antagonism of glycine receptors in the spinal cord C Blockade of the action of glutamic acid D Increased GABA-mediated chloride ion conductance E Inhibition of GABA aminotransferase

• zolpidem The correct answer is (D) Explanation: Though not benzodiazepines, zolpidem, zaleplon, and eszopiclone exert their hypnotic effects via interaction with benzodiazepine receptors in the CNS, leading to an increase in GABA-mediated chloride ion conductance.