CVS

Question 1

A 32-year-old woman with hypertension wishes to become pregnant. Her physician informs her that she will have to switch to another antihypertensive drug. Which of the following drugs is absolutely contraindicated in pregnancy?

(A) Atenolol
(B) Losartan
(C) Methyldopa
(D) Nifedipine
(E) Propranolol

Answer 1

(B) Losartan

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

Question 2

A patient is admitted to the emergency department with severe tachycardia after a drug overdose. His family reports that he has been depressed about his hypertension. Which one of the following drugs increases the heart rate in a dose-dependent manner?

(A) Captopril
(B) Hydrochlorothiazide
(C) Losartan
(D) Minoxidil
(E) Verapamil

Answer 2

(D) Minoxidil

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

Question 3

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

Answer 3

(D) Decreases calcium influx into smooth muscle

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

Question 4

A 73-year-old man with a history of a recent change in his treatment for moderately severe hypertension is brought to the emergency department because of a fall at home. Which of the following drug groups is most likely to cause postural hypotension and thus an increased risk of falls?

(A) ACE inhibitors
(B) Alpha1-selective receptor blockers
(C) Arteriolar dilators
(D) Beta1-selective receptor blockers
(E) Nonselective β blockers

Answer 4

(B) Alpha1-selective receptor blockers

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

Question 5

A significant number of patients started on ACE inhibitor therapy for hypertension are intolerant and must be switched to a different class of drug. What is the most common manifestation of this intolerance?

(A) Angioedema
(B) Glaucoma
(C) Headache
(D) Incessant cough
(E) Ventricular arrhythmias

Answer 5

(D) Incessant cough

Chronic, intolerable cough is an important adverse effect of captopril and other ACE inhibitors. It may be reduced or prevented by prior administration of aspirin. These drugs are very commonly used in hypertensive diabetic patients because of their proven benefits in reducing diabetic renal damage. The ACE inhibitors are not associated with glaucoma; angioedema is not as common as cough; and headache and arrhythmias are rare. The answer is D.

Question 6

Which one of the following is a significant unwanted effect of the drug named?

(A) Constipation with verapamil
(B) Heart failure with hydralazine
(C) Hemolytic anemia with atenolol
(D) Hypokalemia with aliskiren
(E) Lupus-like syndrome with hydrochlorothiazide

Answer 6

(A) Constipation with verapamil

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

Question 7

Comparison of prazosin with atenolol shows that

(A) Both decrease heart rate
(B) Both increase cardiac output
(C) Both increase renin secretion
(D) Both increase sympathetic outflow from the CNS
(E) Both produce orthostatic hypotension

Answer 7

(D) Both** increase sympathetic outflow from the CNS**

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

Question 8

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

Answer 8

(C) Increased PR interval

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

Question 9

A 45-year-old man is brought to the emergency department with mental obtundation. He is found to have a blood pres sure of 220/160 and retinal hemorrhages. Which one of the following is used in severe hypertensive emergencies, is short-acting, acts on a G protein-coupled receptor, and must be given by intravenous infusion?

(A) Aliskiren
(B) Captopril
(C) Fenoldopam
(D) Hydralazine
(E) Losartan
(F) Metoprolol
(G) Nitroprusside
(H) Prazosin
(I) Propranolol

Answer 9

(C) Fenoldopam

Fenoldopam, nitroprusside, and propranolol are the drugs in the list that have been used in hypertensive emergencies. Fenoldopam and nitroprusside are used by infusion only, but nitroprusside releases nitric oxide, which acts on intracellular guanylyl cyclase. The answer is C

Question 10

Which of the following is very short-acting and acts by releasing nitric oxide?
(A) Atenolol
(B) Captopril
(C) Diltiazem
(D) Fenoldopam
(E) Hydrochlorothiazide
(F) Losartan
(G) Minoxidil
(H) Nitroprusside
(I) Prazosin

Answer 10

(H) Nitroprusside

The two agents in this list that act via a nitric oxide mecha
nism are hydralazine and nitroprusside (see Table 11–2). However, hydralazine has a duration of action of hours, whereas nitroprusside acts for seconds to minutes and must be given by intravenous infusion. The answer is H.

Question 11

A 60-year-old man presents to his primary care physician with a complaint of severe chest pain when he walks uphill to his home in cold weather. The pain disappears when he rests. After evaluation and discussion of treatment options, a decision is made to treat him with nitroglycerin.

Which of the following is a common direct or reflex effect of nitroglycerin?

(A) Decreased heart rate
(B) Decreased venous capacitance
(C) Increased afterload
(D) Increased cardiac force
(E) Increased diastolic myocardial fiber tension

Answer 11

(D) Increased cardiac force

Nitroglycerin increases heart rate and venous capacitance and decreases afterload and diastolic fiber tension.

It increases cardiac contractile force because the decrease in blood pressure evokes a compensatory increase in sympathetic discharge.

The answer is D.

Question 12

A 60-year-old man presents to his primary care physician with a complaint of severe chest pain when he walks uphill to his home in cold weather. The pain disappears when he rests. After evaluation and discussion of treatment options, a decision is made to treat him with nitroglycerin.

In advising the patient about the adverse effects he may notice, you point out that nitroglycerin in moderate doses often produces certain symptoms. Which of the following effects might occur due to the mechanism listed?

(A) Constipation
(B) Dizziness due to reduced cardiac force of contraction
(C) Diuresis due to sympathetic discharge
(D) Headache due to meningeal vasodilation
(E) Hypertension due to reflex tachycardia

Answer 12

(D) Headache due to meningeal vasodilation

The nitrates relax many types of smooth muscle, but the effect on motility in the colon is insignificant. Nitroglycerin causes hypotension as a result of arterial and venous dilation. Dilation of arteries in the meninges has no effect on central nervous system function but does cause headache. The answer is D.

Question 13

A 60-year-old man presents to his primary care physician with a complaint of severe chest pain when he walks uphill to his home in cold weather. The pain disappears when he rests. After evaluation and discussion of treatment options, a decision is made to treat him with nitroglycerin.

One year later, the patient returns complaining that his nitroglycerin works well when he takes it for an acute attack but that he is now having more frequent attacks and would like something to prevent them. Useful drugs for the prophylaxis of angina of effort include

(A) Amyl nitrite
(B) Esmolol
(C) Sublingual isosorbide dinitrate
(D) Sublingual nitroglycerin
(E) Verapamil

Answer 13

(E) Verapamil

The calcium channel blockers and the β blockers are generally effective in reducing the number of attacks of angina of effort, and most have durations of 4–8 h. Oral and transdermal nitrates have similar or longer durations. Amyl nitrite and the sublingual nitrates have short durations of action (a few minutes to 30 min). Esmolol (an intravenous β blocker) must be given intravenously and also has a very short duration of action. These drugs are of no value in prophylaxis. The answer is E.

Question 14

A 60-year-old man presents to his primary care physician with a complaint of severe chest pain when he walks uphill to his home in cold weather. The pain disappears when he rests. After evaluation and discussion of treatment options, a decision is made to treat him with nitroglycerin.

If a β blocker were to be used for prophylaxis in this patient, what is the most probable mechanism of action in angina?

(A) Block of exercise-induced tachycardia
(B) Decreased end-diastolic ventricular volume
(C) Increased double product
(D) Increased cardiac force
(E) Decreased ventricular ejection time

Answer 14

(A) Block of exercise-induced tachycardia

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

Question 15

A new 60-year-old patient presents to the medical clinic with hypertension and angina. He is 1.8 meters tall with a waist measurement of 1.1 m. Weight is 97 kg. Blood pressure is 150/95 and pulse 85. In considering adverse effects of possible drugs for these conditions, you note that an adverse effect that nitroglycerin and prazosin have in common is

(A) Bradycardia
(B) Impaired sexual function
(C) Lupus erythematosus syndrome
(D) Orthostatic hypotension
(E) Weight gain

Answer 15

(D) Orthostatic hypotension

Both drugs cause venodilation and reduce venous return sufficiently to cause some degree of postural hypotension. Bradycardia, lupus, weight gain, and urinary retention occur with neither of them, but prazosin has been used to relieve urinary retention in men with prostatic hyperplasia. The answer is D.

Question 16

A man is admitted to the emergency department with a brownish cyanotic appearance, marked shortness of breath, and hypotension. Which of the following is most likely to cause methemoglobinemia?

(A) Amyl nitrite
(B) Isosorbide dinitrate
(C) Isosorbide mononitrate
(D) Nitroglycerin
(E) Sodium cyanide

Answer 16

(A) Amyl nitrite

Read carefully! Nitrites, not nitrates, cause methemoglobinemia in adults. Methemoglobinemia is delibrately induced in one of the treatments of cyanide poisoning. The answer is A.

Question 17

Another patient is admitted to the emergency department after a drug overdose. He is noted to have hypotension and severe bradycardia. He has been receiving therapy for hypertension and angina. Which of the following drugs in high doses causes bradycardia?

(A) Amlodipine
(B) Isosorbide dinitrate
(C) Nitroglycerin
(D) Prazosin
(E) Verapamil

Answer 17

(E) Verapamil

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

Question 18

A 45-year-old woman with hyperlipidemia and frequent migraine headaches develops angina of effort. Which of the following is relatively contraindicated because of her migraines?

(A) Amlodipine
(B) Diltiazem
(C) Metoprolol
(D) Nitroglycerin
(E) Verapamil

Answer 18

(D) Nitroglycerin

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

Question 19

When nitrates are used in combination with other drugs for the treatment of angina, which one of the following combinations results in additive effects on the variable specified?

(A) Beta blockers and nitrates on end-diastolic cardiac size
(B) Beta blockers and nitrates on heart rate
(C) Beta blockers and nitrates on venous tone
(D) Calcium channel blockers and β blockers on cardiac force
(E) Calcium channel blockers and nitrates on heart rate

Answer 19

(D) Calcium channel blockers and β blockers on cardiac force

The effects of β blockers (or calcium channel blockers) and nitrates on heart size, force, venous tone, and heart rate are opposite. The effects of β blockers and calcium channel blockers on the variables specified here are the same. The answer is D.

Question 20

Certain drugs can cause severe hypotension when combined with nitrates. Which of the following interacts with nitroglycerin by inhibiting the metabolism of cGMP?

(A) Atenolol
(B) Hydralazine
(C) Isosorbide mononitrate
(D) Nifedipine
(E) Ranolazine
(F) Sildenafil
(G) Terbutaline

Answer 20

(F) Sildenafil

Sildenafil inhibits phosphodiesterase 5, an enzyme that inactivates cGMP. The nitrates (via nitric oxide) increase the synthe
sis of cGMP. This combination is synergistic. The answer is F.

Question 21

A 73-year-old man with an inadequate response to other drugs is to receive digoxin for chronic heart failure. He is in normal sinus rhythm with a heart rate of 88 and blood pressure of 135/85 mm Hg.

Which of the following is the best documented mechanism of beneficial action of cardiac glycosides?

(A) A decrease in calcium uptake by the sarcoplasmic reticulum
(B) An increase in ATP synthesis
(C) A modification of the actin molecule
(D) An increase in systolic cytoplasmic calcium levels
(E) A block of cardiac β adrenoceptors

Answer 21

(D) An increase in systolic cytoplasmic calcium levels

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

Question 22

After your patient has been receiving digoxin for 3 wk, he presents to the emergency department with an arrhythmia. Which one of the following is most likely to contribute to the arrhythmogenic effect of digoxin?

(A) Increased parasympathetic discharge
(B) Increased intracellular calcium
(C) Decreased sympathetic discharge
(D) Decreased intracellular ATP
(E) Increased extracellular potassium

Answer 22

(B) Increased intracellular calcium

The effects of digitalis include increased vagal action on the heart (not arrhythmogenic) and increased intracellular calcium, including calcium overload, the most important cause of toxicity. Decreased sympathetic discharge and increased extracellular potassium and magnesium reduce digitalis arrhythmogenesis. The answer is B.

Question 23

A patient who has been taking digoxin for several years for atrial fibrillation and chronic heart failure is about to receive atropine for another condition. A common effect of digoxin (at therapeutic blood levels) that can be almost entirely blocked by atropine is

(A) Decreased appetite
(B) Headaches
(C) Increased atrial contractility
(D) Increased PR interval on ECG
(E) Tachycardia

Answer 23

(D) Increased PR interval on ECG

The parasympathomimetic effects of digitalis can be blocked by muscarinic blockers such as atropine. The only parasympathomimetic effect in the list provided is increased PR interval, a manifestation of slowed AV conduction. The answer is D.

Question 24

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

(A) Digoxin
(B) Furosemide
(C) Minoxidil
(D) Propranolol
(E) Spironolactone

Answer 24

(B) Furosemide

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

Question 25

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

Answer 25

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

Question 26

Which row in the following table correctly shows the major effects of full therapeutic doses of digoxin on the AV node and the ECG?

Answer 26

Digitalis increases the AV node refractory period—a parasympa thomimetic action. Its effects on the ventricles include shortened action potential and QT interval, and a change in repolarization with flattening or inversion of the T wave. The answer is B.

Question 27

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

Answer 27

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

Question 28

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

Answer 28

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

Question 29

Which of the following has been shown to prolong life in patients with chronic congestive failure in spite of having a negative inotropic effect on cardiac contractility? (A) Carvedilol (B) Digoxin (C) Dobutamine (D) Enalapril (E) Furosemide

Answer 29

(A) Carvedilol Several β blockers, including carvedilol, have been shown to prolong life in heart failure patients even though these drugs have a negative inotropic action on the heart. Their benefits presumably result from some other effect, and at least one β blocker has failed to show a mortality benefit. The answer is A.

Question 30

A 5-year-old child was vomiting and was brought to the emergency department with sinus arrest and a ventricular rate of 35 bpm. An empty bottle of his uncle’s digoxin was found where he was playing. Which of the following is the drug of choice in treating a severe overdose of digoxin? (A) Digoxin antibodies (B) Lidocaine infusion (C) Magnesium infusion (D) Phenytoin by mouth (E) Potassium by mouth

Answer 30

(A) Digoxin antibodies The drug of choice in severe, massive overdose with any cardiac glycoside is digoxin antibody, Digibind. The other drugs listed are used in moderate overdosage associated with increased automaticity. The answer is A.

Question 31

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

Answer 31

(B) Hyperkalemia should be avoided to reduce the likelihood of procainamide toxicity

Question 32

76-year-old patient with rheumatoid arthritis and chronic heart disease is being considered for treatment with procainamide. She is already receiving digoxin, hydrochlorothiazide, and potassium supplements for her cardiac condition. If this patient should take an overdose and manifest severe acute procainamide toxicity with markedly prolonged QRS, which of the following should be given immediately? (A) A calcium chelator such as EDTA (B) Digitalis (C) Nitroprusside (D) Potassium chloride (E) Sodium lactate

Answer 32

(E) Sodium lactate

Question 33

A 57-year-old man is admitted to the emergency depart- ment with chest pain and a fast irregular heart rhythm. The ECG shows an inferior myocardial infarction and ventricular tachycardia. Lidocaine is ordered. When used as an antiarrhythmic drug, lidocaine typically (A) Increases action potential duration (B) Increases contractility (C) Increases PR interval (D) Reduces abnormal automaticity (E) Reduces resting potential

Answer 33

(D) Reduces abnormal automaticity

Question 34

A 36-year-old woman with a history of poorly controlled thy- rotoxicosis has recurrent episodes of tachycardia with severe shortness of breath. When she is admitted to the emergency department with one of these episodes, which of the following drugs would be most suitable? (A) Amiodarone (B) Disopyramide (C) Esmolol (D) Quinidine (E) Verapamil

Answer 34

(C) Esmolol

Question 35

A 16-year-old girl has paroxysmal attacks of rapid heart rate with palpitations and shortness of breath. These episodes occasionally terminate spontaneously but often require a visit to the emergency department of the local hospital. Her ECG during these episodes reveals an **AV nodal tachycardia.** The antiarrhythmic of choice in most cases of acute AV nodal tachycardia is (A) Adenosine (B) Amiodarone (C) Flecainide (D) Propranolol (E) Verapamil

Answer 35

(A) Adenosine

Question 36

A55-year old man is admitted to the emergency department and is found to have an abnormal ECG. Overdose of an anti- arrhythmic drug is considered. Which of the following drugs is correctly paired with its ECG effects? (A) Quinidine: Increased PR and decreased QT intervals (B) Flecainide: Increased PR, QRS, and QT intervals (C) Verapamil: Increased PR interval (D) Lidocaine: Decreased QRS and PR interval (E) Metoprolol: Increased QRS duration

Answer 36

(C) Verapamil: Increased PR interval

Question 37

A 60-year-old man comes to the emergency department with severe chest pain. ECG reveals ventricular tachycardia with occasional normal sinus beats, and ST-segment changes suggestive of ischemia. A diagnosis of myocardial infarction is made, and the man is admitted to the cardiac intensive care unit. His arrhythmia should be treated immediately with (A) Adenosine (B) Digoxin (C) Lidocaine (D) Quinidine (E) Verapamil

Answer 37

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

Question 38

Which of the following drugs slows conduction through the AV node and has its primary action directly on L-type calcium channels? (A) Adenosine (B) Amiodarone (C) Diltiazem (D) Esmolol (E) Flecainide (F) Lidocaine (G) Mexiletine (H) Procainamide (I) Quinidine

Answer 38

(C) Diltiazem Diltiazem is the calcium channel blocker in this list. (Beta blockers also slow AV conduction but have much smaller effects on calcium channels.) The answer is C.

Question 39

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

Answer 39

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

Question 40

A drug was tested in the electrophysiology laboratory to determine its effects on the cardiac action potential in normal ventricular cells. The results are shown in the diagram. Which of the following drugs does this agent most resemble? (A) Adenosine (B) Flecainide (C) Mexiletine (D) Procainamide (E) Verapamil

Answer 40

The drug effect shown in the diagram includes slowing of the upstroke of the AP but no significant change in repolariza- tion or AP duration. This is most typical of group 1C drugs. The answer is B, flecainide.

Question 41

A 70-year-old retired businessman is admitted with a history of recurrent heart failure and metabolic derangements. He has marked peripheral edema and metabolic alkalosis. Which of the following drugs is most appropriate for the treatment of his edema? (A) Acetazolamide (B) Digoxin (C) Dobutamine (D) Eplerenone (E) Hydrochlorothiazide

Answer 41

(A) Acetazolamide Although acetazolamide is rarely used in heart failure, car- bonic anhydrase inhibitors are quite valuable in patients with edema and metabolic alkalosis. The high bicarbonate levels in these patients make them particularly susceptible to the action of carbonic anhydrase inhibitors. Digoxin is useful in chronic systolic failure but is not first-line therapy. Dobu- tamine is appropriate only when diuresis has already been accomplished in severe acute failure. Hydrochlorothiazide and spironolactone are not adequate for first-line therapy of edema in failure. The answer is A.

Question 42

A 50-year-old man has a history of frequent episodes of renal colic with calcium-containing renal stones. A careful workup indicates that he has a defect in proximal tubular calcium reabsorption, which results in high concentrations of calcium salts in the tubular urine. The most useful diuretic agent in the treatment of recurrent calcium stones is (A) Chlorthalidone B) Diazoxide (C) Ethacrynic acid (D) Mannitol (E) Spironolactone

Answer 42

(A) Chlorthalidone The thiazides are useful in the prevention of calcium stones because these drugs reduce tubular calcium concentration, probably by increasing passive proximal tubular and distal convoluted tubule reabsorption of calcium. In contrast, the loop agents (choice C) facilitate calcium excretion. Diazoxide is a thiazide-like vasodilator molecule but has no diuretic action; in fact, it may cause sodium retention. It is used in hypertension and insulinoma (see Chapter 11). The answer is A

Question 43

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

Answer 43

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

Question 44

Which drug is correctly associated with its actions in the following table? (+ indicates increase and – indicates decrease.)

Answer 44

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

Question 45

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

Answer 45

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

Question 46

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

Answer 46

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

Question 47

A60-year old patient complains of paresthesias and occasional nausea associated with one of her drugs. She is found to have hyperchloremic metabolic acidosis. She is probably taking (A) Acetazolamide for glaucoma (B) Amiloride for edema associated with aldosteronism (C) Furosemide for severe hypertension and heart failure (D) Hydrochlorothiazide for hypertension (E) Mannitol for cerebral edema

Answer 47

Paresthesias and gastrointestinal distress are common adverse effects of acetazolamide, especially when it is taken chronically, as in glaucoma. The observation that the patient has metabolic acidosis also suggests the use of acetazolamide. The answer is A (A) Acetazolamide for glaucoma

Question 48

A 70-year-old woman is admitted to the emergency depart- ment because of a “fainting spell” at home. She appears to have suffered no trauma from her fall, but her blood pres- sure is 120/60 when lying down and 60/20 when she sits up. Neurologic examination and an ECG are within normal limits when she is lying down. Questioning reveals that she has recently started taking “water pills” (diuretics) for a heart condition. Which of the following drugs is the most likely cause of her fainting spell? (A) Acetazolamide (B) Amiloride (C) Furosemide (D) Hydrochlorothiazide (E) Spironolactone

Answer 48

(C) Furosemide The case history suggests that the syncope (fainting) is associ- ated with diuretic use. Complications of diuretics that can result in syncope include both postural hypotension (which this patient exhibits) due to excessive reduction of blood volume and arrhythmias due to excessive potassium loss. Potassium wasting is more common with thiazides (because of their long duration of action), but these drugs rarely cause reduction of blood volume sufficient to result in orthostatic hypotension. The answer is C, furosemide.

Question 49

A 58-year-old woman with lung cancer has abnormally low serum osmolality and hyponatremia. A drug that increases the formation of dilute urine and is used to treat SIADH is (A) Acetazolamide (B) Amiloride (C) Desmopressin (D) Ethacrynic acid (E) Furosemide (F) Hydrochlorothiazide (G) Mannitol (H) Spironolactone (I) Triamterene (J) Tolvaptan

Answer 49

J Tolvaptan Retention of water with hyponatremia and inability to form dilute urine in the fully hydrated condition is characteristic of SIADH. Antagonists of ADH are needed to treat this condition. The answer is J, tolvaptan.

Question 50

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

Answer 50

(A) Acetazolamide Carbonic anhydrase inhibitors are useful in the prevention of altitude sickness. The answer is A.

Question 51

Your 37-year-old patient has been diagnosed with a rare metastatic carcinoid tumor. This neoplasm is releasing sero- tonin, bradykinin, and several unknown peptides. The effects of serotonin in this patient are most likely to include (A) Constipation (B) Episodes of bronchospasm (C) Hypersecretion of gastric acid (D) Hypotension (E) Urinary retention

Answer 51

(B) Episodes of bronchospasm Serotonin causes bronchospasm, but the other effects listed are not observed. Carcinoid is associated with diarrhea and hypertension. The answer is B.

Question 52

A 23-year-old woman suffers from recurrent episodes of angioneurotic edema with release of histamine and other mediators. Which of the following drugs is the most effective physiologic antagonist of histamine in smooth muscle? (A) Cetirizine (B) Epinephrine (C) Granisetron (D) Ranitidine (E) Sumatriptan

Answer 52

(B) Epinephrine The smooth muscle effects of histamine are mediated mainly by H1 receptors. Cetirizine is a pharmacologic antagonist of histamine at these receptors. Granisetron is a 5-HT3 antagonist. Sumatriptan is a 5-HT1D/1B agonist. Ranitidine is a histamine antagonist but blocks the H2 receptor in the stomach and the heart, not H1 receptors in smooth muscle. Epinephrine has a physiologic antagonist action that reverses histamine’s effects on smooth muscle. The answer is B.

Question 52

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

Answer 52

(D) Sedation H1 blockers do not activate muscarinic receptors, mediate vasoconstriction, or cause vertigo. Some relieve vertigo or motion sickness. They do not cause nervousness or anxiety. Diphenhydramine is a potent sedative. The answer is D

Question 53

A laboratory study of new H2 blockers is planned. Which of the following will result from blockade of H2 receptors? (A) Increased cAMP (cyclic adenosine monophosphate) in cardiac muscle (B) Decreased channel opening in enteric nerves (C) Decreased cAMP in gastric mucosa (D) Increased IP3 (inositol trisphosphate) in platelets (E) Increased IP3 in smooth muscle

Answer 53

(C) Decreased cAMP in gastric mucosa H2 receptors are Gs-protein-coupled receptors, like β adrenoceptors. Blockade of this system will cause a decrease in cAMP. The answer is C.

Question 54

You are asked to consult on a series of cases of drug toxicities. Which of the following is a recognized adverse effect of cimetidine? (A) Blurred vision (B) Diarrhea (C) Orthostatic hypotension (D) P450 hepatic enzyme inhibition (E) Sedation

Answer 54

(D) P450 hepatic enzyme inhibition The older H1 blockers, not H2 blockers, cause blurred vision, orthostatic hypotension, and sedation. Neither group typically causes diarrhea. Cimetidine (unlike other H2 blockers) is a potent CYP3A4 inhibitor. The answer is D.

Question 55

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

Answer 55

(E) Ondansetron Ondansetron and other 5-HT3 antagonists have significant antiemetic effects. Diphenhydramine and prednisone are also used for this purpose. The answer is E.

Question 56

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

Answer 56

(B) Cetirizine: for hay fever Alosetron is indicated in irritable bowel syndrome. Ergonovine is used in uterine bleeding. Ondansetron is useful for chemotherapy-induced emesis. Cetirizine, a second-generation H1 blocker, is used in the treatment of hay fever. The answer is B.

Question 57

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

Answer 57

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

Question 58

A 28-year-old office worker suffers from intense migraine headaches. Which of the following is a serotonin agonist useful for aborting an acute migraine headache? (A) Bromocriptine (B) Cimetidine (C) Ephedrine (D) Ketanserin (E) Loratadine (F) Ondansetron (G) Sumatriptan

Answer 58

(G) Sumatriptan Sumatriptan, an agonist at 5-HT receptors, is indicated 1D for prevention or treatment of migraine and cluster headaches. Ergotamine (not on the list) is also effective for acute migraine but is produced by the fungus Claviceps purpurea. The answer is G

Question 59

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

Answer 59

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

Question 60

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

Answer 60

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

Question 61

In a laboratory study of several peptides, one is found that decreases peripheral resistance but constricts veins. Which of the following causes arteriolar vasodilation and venoconstriction? (A) Angiotensin II (B) Bradykinin (C) Endothelin-1 (D) Substance P (E) Vasoactive intestinal peptide

Answer 61

Substance P is a potent arterial vasodilator and venoconstrictor. The answer is D.

Question 62

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

Answer 62

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

Question 63

A 45-year-old painter presents with respiratory symptoms and careful workup reveals idiopathic pulmonary hypertension. Which of the following binds endothelin receptors and is approved for use in pulmonary hypertension? (A) Aliskiren I (B) Bosentan (C) Capsaicin (D) Losartan (E) Nesiritide

Answer 63

(B) Bosentan Aliskiren,captopril,and losartan are used inprimary hypertension. **Bosentan**, an endothelin antagonist, is used in pulmonary hypertension. The answer is B.

Question 64

60-year-old financial consultant presents with severe pain in a neuronal dermatome region of her chest. This area was previously affected by a herpes zoster rash. Which of the fol- lowing might be of benefit in controlling this post-herpetic pain? (A) Aliskiren (B) Aprepitant (C) Bosentan (D) Capsaicin (E) Captopril (F) Losartan (G) Nesiritide

Answer 64

(D) Capsaicin Substance P is an important pain-mediating neurotransmitter peptide and appears to be involved in post-herpetic pain as well as arthritic pain. Capsaicin can be used topically to deplete substance P stores from sensory nerves. The answer is D.

Question 65

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

Answer 65

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

Question 66

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

Answer 66

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

Question 67

Which of the following is an **antagonist at NK1** receptors and is used to prevent or reduce chemotherapy-induced nausea and vomiting? (A) Angiotensin I (B) Aprepitant (C) Bosentan (D) Bradykinin (E) Brain natriuretic peptide (F) Enalapril (G) Ondansetron

Answer 67

(B) Aprepitant Aprepitant and ondansetron are both used to reduce or prevent chemotherapy-induced nausea and vomiting. Ondansetron is an antagonist at 5-HT3 receptors. The answer is B.

Question 68

A 50-year-old woman with moderately severe arthritis has been treated with nonsteroidal anti-inflammatory drugs for 6 mo. She now complains of heartburn and indigestion. 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 com- plaining that your last prescription has caused severe diarrhea. Which of the following is most likely to be associated with increased gastrointestinal motility and diarrhea? (A) Aspirin (B) Famotidine (C) Leukotriene LTB4 (D) Misoprostol (E) Zileuton

Answer 68

(D) Misoprostol Aspirin and zileuton rarely cause diarrhea. LTB4 is a chemotactic factor. Famotidine is an H2 blocker that does not cause diarrhea (Chapter 16). The answer is D

Question 69

Which of the following drugs inhibits thromboxane synthesis much more effectively than prostacyclin synthesis? (A) Aspirin (B) Hydrocortisone (C) Ibuprofen (D) Indomethacin (E) Zileuton

Answer 69

(A) Aspirin 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. The answer is A.

Question 70

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) Angiotensin II (B) Ergotamine (C) Prostaglandin PGF2α (D) Prostacyclin (E) Thromboxane

Answer 70

(D) Prostacyclin Prostacyclin (PGI2) is a very potent **vasodilator**. All the other choices in the list are vasoconstrictors. The answer is D.

Question 71

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

Answer 71

(D) Prostaglandin PGF2α Although serotonin and, in some species, histamine may cause uterine stimulation, these substances 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

Question 72

Inflammation is a complex tissue reaction that includes the release of cytokines, leukotrienes, prostaglandins, and pep- tides. Prostaglandins 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

Answer 72

(B) Cyclooxygenase-2 See Figure 18–1. Phospholipase A converts membrane phospholipid to arachidonic acid. Cyclooxygenases convert arachidonic acid to prostaglandins. COX-1 products appear to be important in normal physiologic processes. COX-2 is the enzyme responsible for this reaction in inflammatory cells. The answer is B.

Question 73

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

Answer 73

(D) Prostaglandin PGE1 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. In the meantime, 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.

Question 74

A patient with a bleeding tendency presents in the hematology 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

Answer 74

(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.

Question 75

Whichofthefollowingisacomponentofslow-reactingsub- stance of anaphylaxis (SRS-A)? (A) Alprostadil (B) Aspirin (C) Leukotriene LTB4 (D) Leukotriene LTC4 (E) Misoprostol 2 (F) Prednisone (G) Prostacyclin (H) Zafirlukast (I) Zileuton

Answer 75

(D) Leukotriene LTC4 The leukotriene C and D series are major components of SRS-A. Leukotriene LTB4 is a chemotactic eicosanoid. The answer is D.

Question 76

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

Answer 76

(D) Leukotriene LTC4 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 bronchocon- striction often observed in this condition. The answer is D.

Question 77

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

Answer 77

(E) Montelukast Zileuton blocks the synthesis of leukotrienes. Montelukast and zafirlukast block LTD4 receptors. The answer is E.

Question 78

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

Answer 78

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

Question 79

A molecule that releases nitric oxide in the blood is (A) Citrulline (B) Histamine (C) Isoproterenol (D) Nitroglycerin (E) Nitroprusside

Answer 79

(E) Nitroprusside Nitroprusside is the only molecule in this list that spontaneously releases NO in the bloodstream. The answer is E.

Question 80

The inducible isoform of nitric oxide synthase (iNOS, iso- form 2) is found primarily in which of the following? (A) Cartilage (B) Eosinophils (C) Macrophages (D) Platelets (E) Vascular endothelial cells

Answer 80

(C) Macrophages The inducible form of NOS is associated with inflammation, and the enzyme is found in highest concentration in macrophages, cells that are particularly involved in inflammation. The answer is C.

Question 81

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

Answer 81

(C) Arginine

Question 82

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

Answer 82

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

Question 83

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

Answer 83

(D) Hemoglobin Heme and hemoglobin inactivate NO. The answer is D.

Question 84

Which of the following drugs accelerates the conversion of plasminogen to plasmin? (A) Aminocaproic acid (B) Heparin (C) Argatroban (D) Reteplase (E) Warfarin

Answer 84

(D) Reteplase Reteplase is the only thrombolytic drug listed. Heparin and warfarin are anticoagulants. Argatroban is a direct inhibitor of thrombin, and aminocaproic acid is an inhibitor, not an activator, of the conversion of plasminogen to plasmin. The answer is D.

Question 85

If a fibrinolytic drug is used for treatment of this man’s acute myocardial infarction, which of the following adverse drug effects is most likely to occur? (A) Acute renal failure (B) Development of antiplatelet antibodies (C) Encephalitis secondary to liver dysfunction (D) Hemorrhagic stroke (E) Neutropenia

Answer 85

(D) Hemorrhagic stroke The most common serious adverse effect of the fibrinolytics is bleeding, especially in the cerebral circulation. The fibrinolytics do not usually have serious effects on the renal, hepatic, or hematologic systems. Unlike heparin, they do not induce antiplatelet antibodies. The answer is D.

Question 86

If this patient undergoes a percutaneous coronary angiography procedure and placement of a stent in a coronary blood vessel, he will need to be on dual antiplatelet therapy. eg, aspirin and clopidogrel for at least a year. Which of the following most accurately describes the mechanism of action of clopidogrel? (A) Clopidogrel directly binds to the platelet ADP receptors (B) Clopidogrel irreversibly inhibits cyclooxygenase (C) Clopidogrel facilitates the action of antithrombin III (D) The active metabolite of clopidogrel binds to the platelet ADP receptors (E) The active metabolite of clopidogrel binds to the platelet glycoprotein IIb/IIIa receptors

Answer 86

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

Question 87

The above graph shows the plasma concentration of free warfarin as a function of time for a patient who was treated with 2 other agents, drugs B and C, on a daily basis at constant dosage starting at the times shown. Which of the following is the most likely explanation for the observed changes in warfarin concentration? (A) Drug B displaces warfarin from plasma proteins; drug C displaces warfarin from tissue-binding sites (B) Drug B inhibits hepatic metabolism of warfarin; drug C displaces drug B from tissue-binding sites (C) Drug B stimulates hepatic metabolism of warfarin; drug C displaces warfarin from plasma protein (D) Drug B increases renal clearance of warfarin; drug C inhibits hepatic metabolism of drug B

Answer 87

(C) Drug B stimulates hepatic metabolism of warfarin; drug C displaces warfarin from plasma protein A drug that increases metabolism (clearance) of the antico- agulant lowers the steady-state plasma concentration (both free and bound forms), whereas one that displaces the antico- agulant increases the plasma level of the free form only until elimination of the drug has again lowered it to the steady- state level. The answer is C.

Question 87

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

Answer 87

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

Question 88

She tells you that her main reason for not wanting oral anti- coagulation is that she does not want to come to clinic for frequent blood draws. You agree on an oral alternative and start her on apixaban. You counsel her extensively on the importance of taking the medication each day, as suddenly stopping can lead to (A) Anaphylaxis (B) Excess bleeding (C) Increase in INR (D) Stroke (E) Thrombocytopenia

Answer 88

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

Question 89

She is excited about not having to come in for blood tests but wonders if there is a test, just in case the doctors need to know. Which of the following tests would provide accurate information about the coagulation status of a patient taking apixaban? (A) aPTT (B) Factor X test (C) INR (D) PT test

Answer 89

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

Question 90

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

Answer 90

(A) Can be used without monitoring the patient’s aPTT Enoxaparin is an LMW heparin. LMW heparins have a longer half-life than standard heparin and a more consistent relationship between dose and therapeutic effect. Enoxaparin is given subcutaneously, not intravenously. It is less, not more, likely to cause thrombosis and thrombocytopenia. Neither LMW heparins nor standard heparin are teratogenic. The aPTT is not useful for monitoring the effects of LMW heparins. The answer is A.

Question 90

During the next week, the patient was started on warfarin and her enoxaparin was discontinued. Two months later, she returned after a severe nosebleed. Laboratory analysis revealed an INR (international normalized ratio) of 7.0 (INR value in such a warfarin-treated patient should be 2.0–3.0). To prevent severe hemorrhage, the warfarin should be discontinued and this patient should be treated immediately with which of the following? (A) Aminocaproic acid (B) Desmopressin (C) Factor VIII (D) Protamine (E) Vitamin K1

Answer 90

(E) Vitamin K1

Question 91

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

Answer 91

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

Question 92

PJ is a 4.5-year-old boy. At his checkup, the pediatri- cian notices cutaneous xanthomas and orders a lipid panel. Repeated measures confirm that the patient’s serum cholesterol levels are high (936 mg/dL). Further testing confirms a diagno- sis of homozygous familial hypercholesterolemia. Which of the following interventions will be least effective in this patient? (A) Atorvastatin (B) Ezetimibe (C) Lomitapide (D) Mipomersen (E) Niacin

Answer 92

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

Question 93

A 46-year-old woman with a history of hyperlipidemia was treated with a drug. The chart below shows the results of the patient’s fasting lipid panel before treatment and 6 mo after initiating drug therapy. Normal values are also shown. Which of the following drugs is most likely to be the one that this patient received? (A) Colestipol (B) Ezetimibe (C) Gemfibrozil (D) Lovastatin (E) Niacin

Answer 93

(E) Niacin This patient presents with striking hypertriglyceridemia, elevated VLDL cholesterol, and depressed HDL cholesterol. Six months after drug treatment was initiated, her triglyceride and VLDL cholesterol have dropped dramatically and her HDL cholesterol level has doubled. The drug that is most likely to have achieved all of these desirable changes, particularly the large increase in HDL cholesterol, is niacin. Although gemfibrozil lowers triglyceride and VLDL concentrations, it does not cause such large increases in HDL cholesterol and decreases in LDL cholesterol. The answer is E.

Question 94

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

Answer 94

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

Question 95

If this patient is pregnant, which of the following drugs should be avoided because of a risk of harming the fetus? (A) Cholestyramine (B) Ezetimibe (C) Fenofibrate (D) Niacin (E) Pravastatin

Answer 95

(E) Pravastatin The HMG-CoA reductase inhibitors are contraindicated in pregnancy because of the risk of teratogenic effects. The answer is E.

Question 96

The patient is started on gemfibrozil. Which of the following is a major mechanism of gemfibrozil’s action? (A) Increased excretion of bile acid salts (B) Increased expression of high-affinity LDL receptors (C) Increased secretion of VLDL by the liver (D) Increased triglyceride hydrolysis by lipoprotein lipase (E) Reduced uptake of dietary cholesterol

Answer 96

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

Question 97

Which of the following is a major toxicity associated with gemfibrozil therapy? (A) Bloating and constipation (B) Cholelithiasis (C) Hyperuricemia (D) Liver damage (E) Severe cardiac arrhythmia

Answer 97

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

Question 98

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

Answer 98

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

Question 99

If the patient has a history of gout, which of the following drugs is most likely to exacerbate this condition? (A) Colestipol (B) Ezetimibe (C) Gemfibrozil (D) Niacin (E) Simvastatin

Answer 99

(D) Niacin

Question 100

After being counseled about lifestyle and dietary changes, the patient was started on atorvastatin. During his treatment with atorvastatin, it is important to routinely monitor serum concentrations of which of the following? (A) Blood urea nitrogen (B) Alanine and aspartate aminotransferase (C) Platelets (D) Red blood cells (E) Uric acid

Answer 100

(B) Alanine and aspartate aminotransferase The 2 primary adverse effects of the HMG-CoA reductase inhibitors are hepatotoxicity and myopathy. Patients taking these drugs should have liver function tests performed before starting therapy, and at regular intervals as needed during therapy. Serum concentrations of alanine and aspartate ami- notransferase are used as markers of hepatocellular toxicity. The answer is B.

Question 101

Six months after beginning atorvastatin, the patient’s total and LDL cholesterol concentrations remained above normal, and he continued to have anginal attacks despite good adher- ence to his antianginal medications. His physician decided to add ezetimibe. Which of the following is the most accurate description of ezetimibe’s mechanism of an action? (A) Decreased lipid synthesis in adipose tissue (B) Decreased secretion of VLDL by the liver (C) Decreased gastrointestinal absorption of cholesterol (D) Increased endocytosis of HDL by the liver (E) Increased lipid hydrolysis by lipoprotein lipase

Answer 101

(C) Decreased gastrointestinal absorption of cholesterol The major recognized effect of ezetimibe is inhibition of absorption of cholesterol in the intestine. The answer is C.

Question 102

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

Answer 102

(A) Irreversibly inhibits its target enzyme Aspirin differs from other NSAIDs by irreversibly inhibiting cyclooxygenase. The answer is A.

Question 103

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

Answer 103

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

Question 104

A 16-year-old girl comes to the emergency department suffering from the effects of an aspirin overdose. Which of the following syndromes is this patient most likely to exhibit as a result of this drug overdose? (A) Bone marrow suppression and possibly aplastic anemia (B) Fever, hepatic dysfunction, and encephalopathy (C) Hyperthermia, metabolic acidosis, and coma (D) Rapid, fulminant hepatic failure (E) Rash, interstitial nephritis, and acute renal failure

Answer 104

(C) Hyperthermia, metabolic acidosis, and coma Salicylate intoxication is associated with metabolic acidosis, dehydration, and hyperthermia. If these problems are not corrected, coma and death ensue. The answer is C.

Question 105

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

Answer 105

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

Question 106

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

Answer 106

(D) Is available in a parenteral formulation that can be injected intramuscularly or intravenously Ketorolac exerts typical NSAID effects. It prolongs the bleed- ing time and can impair renal function, especially in a patient with preexisting renal disease. Its primary use is as a paren- teral agent for pain management, especially for treatment of postoperative patients. The answer is D.

Question 107

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

Answer 107

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

Question 108

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

Answer 108

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

Question 109

Over the next 7 mo, the patient had 2 more attacks of acute gout. Her serum concentration of uric acid was elevated. The decision was made to put her on chronic drug therapy to try to prevent subsequent attacks. Which of the following drugs could be used to decrease this woman’s rate of production of uric acid? (A) Allopurinol (B) Aspirin (C) Colchicine (D) Hydroxychloroquine E) Probenecid

Answer 109

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

Question 110

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

Answer 110

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

Question 111

Although the patient’s disease was adequately controlled with an NSAID and methotrexate for some time, her symptoms began to worsen and radiologic studies of her hands indicated progressive destruction in the joints of several fingers. Treatment with another second-line agent for rheumatoid arthritis was considered. Which of the following is a par- enterally administered DMARD whose mechanism of anti- inflammatory action is antagonism of tumor necrosis factor? (A) Cyclosporine (B) Etanercept (C) Penicillamine (D) Phenylbutazone (E) Sulfasalazine

Answer 111

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