PDA Review questions-Block 1
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)
B) Clonidine Explanation: 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 via α2 effects. The answer is B.
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 PGF2α D) Prostacyclin E) Thromboxane
D) Prostacyclin Explanation: 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. PGF2α and thromboxane are vasoconstrictors. The answer is D.
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
D) Zafirlukast Explanation: 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.
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. If this child has signs of anaphylaxis, what is the treatment of choice? A) Diphenhydramine (an antihistamine) B) Ephedrine C) Epinephrine D) Isoproterenol E) Methylprednisolone (a corticosteroid)
C) Epinephrine Explanation: The treatment of anaphylaxis requires a powerful physiologic antagonist with the ability to cause rapid bronchodilation (β2 effect), and vasoconstriction (α effect). Epinephrine is the most effective agent with these properties and is considered the drug of choice if the diagnosis is definite. Antihistamines and corticosteroids are sometimes used as supplementary agents, but the prompt parenteral use of epinephrine is mandatory. The answer is C.
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
E) Varenicline Explanation: 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 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
A) Acetylcholine Explanation: 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 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
A) Albuterol Explanation: 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.
Which mechanism explains aspirin's inhibition of thromboxane synthesis? A) Blocks cyclooxygenase B) Blocks lipoxygenase C) Blocks phospholipase A2 D) Blocks PGE1 receptors E) Blocks PGI2 receptors
A) Blocks cyclooxygenase Explanation: Hydrocortisone and other corticosteroids inhibit phospholipase. 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.
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
A) Bradycardia induced by phenylephrine Explanation: 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 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
A) Diuretic effect Explanation: Albuterol is a β2-selective receptor agonist, but in moderate to high doses it produces β1 cardiac effects as well as β2-mediated smooth and skeletal muscle effects. It does not cause diuresis. The answer is A.
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
A) Tachycardia and increased cardiac contractility Explanation: 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.
Clinical studies have shown that adrenoceptor blockers have many useful effects in patients. However, a number of drug toxicities have been documented. Adverse effects that limit the use of adrenoceptor blockers include which one of the following? A) Bronchoconstriction (from α-blocking agents) B) Acute heart failure exacerbation (from β blockers) C) Impaired blood sugar response (with α blockers) D) Increased intraocular pressure (with β blockers) E) Sleep disturbances (from α-blocking drugs)
B) Acute heart failure exacerbation (from β blockers) Explanation: Although chronic heart failure is often treated with certain β blockers, acute heart failure can be precipitated by any β blocker. Choices A, C, and E reverse the correct pairing of receptor subtype (α versus β) with effect. Choice D reverses the direction of change of intraocular pressure. The answer is B.
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
B) Beclomethasone by aerosol Explanation: 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.
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
B) Bethanechol Explanation: Bethanechol 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 endogenous acetylcholine is not released at this site. Pralidoxime is a distracter in this answer list. The answer is B.
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. 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
B) Blockade of histamine receptors Explanation: 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.
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
B) Bronchospasm, tachycardia, hypotension, laryngeal edema Explanation: 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.
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
B) Cycloplegia Explanation: 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 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) IP3 (inositol 1,4,5-trisphosphate) E) NO (nitric oxide)
B) DAG (diacylglycerol) Explanation: Cholinomimetics cause smooth muscle contraction mainly through an action on M3 Gq-coupled receptors resulting in the release of intracellular calcium. This release is triggered by an increase in IP3 acting on IP3 receptors in the endoplasmic reticulum. The answer is D.
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 IP3 (inositol trisphosphate) in intestinal smooth muscle D) Increased potassium efflux from smooth muscle E) Increased sodium influx into the skeletal muscle end plate
B) Decreased DAG (diacylglycerol) in salivary gland tissue Explanation: Muscarinic M1 and M3 receptors mediate increases in IP3 and DAG in target tissues (intestine, salivary glands). M2 receptors (heart) mediate a decrease in cAMP and an increase in potassium permeability. Antimuscarinic agents block these effects. The answer is B.
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
B) Edrophonium Explanation: 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 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
B) Increased heart rate 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.
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)
B) Miosis (treatment of narrow angle glaucoma) Explanation: 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. Parasympathetic nerve stimulation and a slow infusion of bethanechol, 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.
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
B) Tachycardia 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 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
B) Vascular endothelium Explanation: 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 activates 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.
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
C) Chronic obstructive pulmonary disease (COPD) 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.
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
C) Diarrhea Explanation: Cholinesterase inhibition is typically associated with increased (never decreased) bowel activity. (Fortunately, many patients become tolerant to this effect.) 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)
C) HLA-B*57:01 (EM) Explanation: 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.
A patient with a positive fecal blood test is referred to the gastroenterology 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
C) Ibuprofen 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 patient presents at the emergency department with threatened anaphylaxis. Respiratory obstruction appears likely if she is not treated immediately. Her past medical history includes hypertension, for which she is receiving an adrenoceptor blocker. The emergency physician plans to use epinephrine to treat her anaphylactic reaction. Which of the following effects of epinephrine would be blocked by prazosin but not by metoprolol? A) Cardiac stimulation B) Increase of cAMP (cyclic adenosine monophosphate) in fat cells C) Mydriasis D) Relaxation of bronchial smooth muscle E) Relaxation of the uterus
C) Mydriasis Explanation: Mydriasis caused by contraction of the pupillary dilator radial smooth muscle is mediated by α receptors. All the other effects listed are mediated by β receptors. The answer is C.
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
C) Neostigmine Explanation: 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.
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 long-standing 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
C) Phenylephrine Explanation: Antimuscarinics (eg, tropicamide) are mydriatic and cycloplegic; 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.
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
C) Pupillary dilation (mydriasis) 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 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
D) Hyperthermia Explanation: 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.
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
D) Increase bronchial smooth muscle tone Explanation: 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.
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)
D) Increased pupillary constrictor tone (miosis) Explanation: Parasympathetic nerve discharge causes bronchial and intestinal 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.
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
D) Ipratropium Explanation: 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.
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
D) Leukotriene LTC4 Explanation: The leukotriene C and D series are major eicosanoid components of SRS-A. Leukotriene LTB4 is a chemotactic eicosanoid. The answer is D.
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
D) Leukotriene LTC4 Explanation: 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.
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
D) Lipoxygenase Phospholipase A2 converts 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.
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
D) Misoprostol Explanation: Aspirin and zileuton rarely cause diarrhea. LTB4 is a chemotactic factor. Famotidine is an H2 blocker that does not cause diarrhea (Chapter 16). Misoprostol, a PGE1 analog, increases gastrointestinal and uterine motility. It is sometimes used as part of an abortifacient. The answer is D.
Four new synthetic drugs (designated W, X, Y, and Z) are to be studied for their cardiovascular effects. They are given to 4 anesthetized animals while the heart rate is recorded. The first animal has received no pretreatment (control); the second has received an effective dose of hexamethonium; the third has received an effective dose of atropine; and the fourth has received an effective dose of phenoxybenzamine. The net changes induced by W, X, Y, and Z in the animals. Drug W increased heart rate in the control animal, the atropine-pretreated animal, and the phenoxybenzamine-pretreated animal. However, drug W had no effect on heart rate in the hexamethonium-pretreated animal. Drug W is probably a drug similar to A) Acetylcholine B) Edrophonium C) Isoproterenol D) Nicotine E) Norepinephrine
D) Nicotine Explanation: In developing a strategy for this type of question, consider first the actions of the known blocking drugs. Hexamethonium blocks reflexes as well as the direct action of nicotine. Atropine would block direct muscarinic effects of an unknown drug (if it had any) or reflex slowing of the heart mediated by the vagus. Phenoxybenzamine blocks only α-receptor-mediated processes. If the response produced in the nonpretreated animal is blocked or reversed by hexamethonium, it is probably a direct nicotinic effect or a reflex response to hypotension. In that case, consider all the receptors involved in mediating the reflex. Drug W causes tachycardia that is prevented by ganglion blockade. The only drug in the list of choices that causes hypotension and tachycardia that is not blocked by atropine is isoproterenol, and the tachycardia caused by isoproterenol is not blocked by ganglionic blockade. Thus, drug W must be nicotine or a drug similar to it. The answer is D.
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
D) Norepinephrine Explanation: "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 α2 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 β1 effects. 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
D) Postural hypotension Explanation: 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 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
D) Prazosin Explanation: 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.
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
D) Prostaglandin PGE1 Explanation: 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 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 PGF2α E) Serotonin
D) Prostaglandin PGF2α Explanation: 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.
Your 30-year-old patient has moderately severe new onset asthma, and you prescribe a highly selective β2 agonist inhaler to be used when needed. In considering the possible drug effects in this patient, you would note that β2 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
D) Skeletal muscle tremor Explanation: Tremor is a common β2 effect. Blood vessels in the skin have almost exclusively α (vasoconstrictor) receptors. Stimulation of renin release is a β1 effect. Beta2 agonists cause hyperglycemia and have little effect on cGMP. The answer is D.
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
E) Hypoglycemia in diabetes Explanation: 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.
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
E) If treated early, its toxicity may be partly reversed by pralidoxime Explanation: 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.
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
E) Montelukast Explanation: Zileuton blocks the synthesis of leukotrienes. Montelukast and zafirlukast block LTD4 receptors. 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 ganglion-blocked 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
E) Nicotine Explanation: 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.
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
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 β1 and β2 receptors so that direct-acting β agonists may have a greater than normal effect.)
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
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.
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
E) Sweating caused by exercise Explanation: Atropine blocks muscarinic receptors and inhibits parasympathomimetic 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. Exercise-induced sweating is another sympathomimetic response, but it is mediated by acetylcholine released from sympathetic nerve fibers at eccrine sweat glands. The answer is E.
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
E) Tachycardia Explanation: 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.
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
E)Hypoglycemia in diabetes Explanation: 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.
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
G) Pralidoxime Explanation: Pralidoxime has a very high affinity for the phosphorus atom in organophosphate insecticides. The answer is G.
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
G) Prednisone Explanation: 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.
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
H) Salmeterol Explanation: 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 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
H) Theophylline Explanation: 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.
