The quizzes about Cardiovascular Pharmacology – Part 1

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Cardiovascular Pharmacology- Part 1

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Question 1

Your patient i s a 50-year-old man with Type 1 (insulin-requiring) diabetes, normal  renal  function, and no  Although  his HbA1c levels are acceptable, because of his l i festyle  and eating habits  he  has  experienced more  than a  few episodes of symptomatic hypoglycemia following insulin injections. He  currently has asymptomatic hyperuricemia, but he has had several attacks  of acute gout over the  last 5 years. Today you diagnose hypertension that must be treated. Which antihypertensive drug would be  the  most rational  fi rst choice  for starting his antihypertensive therapy?

A	Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker
B	β-adrenergic blocker
C	Nifedipine
D	Thiazide diuretic
E	Verapamil or diltiazem

Question 1 Explanation: 

ACE inhibitors are often selected first for hypertensive patients who also have diabetes mellitus (type 1 or type 2)—provided their renal function is satisfactory (specifically, no severe bilateral renal arterial stenosis, or no inadequate blood flow to one kidney if the other was removed; no albuminuria). Recall that angiotensin II constricts the efferent arterioles in the kidneys, which increases glomerular filtration. So, by reducing angiotensin II synthesis an ACE inhibitor will block this effect and reduce filtration even further. Angiotensin receptor blockers (ARBs, eg, losartan) will do the same but by blocking angiotensin receptors rather than by inhibiting angiotensin synthesis. ACE inhibitors (and ARBs) do not cause any problems with glycemic control or the responses to antidiabetic drugs, and they seem to exert some protective effect that slows or delays diabetes-related nephropathy. Note that either class of angiotensin modifier is contraindicated for patients with severe bilateral renal arterial stenosis, including that which might occur with long-standing and severe diabetes mellitus. In such patients, maintenance on some reasonable degree of renal perfusion and renal function overall depends on the renovascular/postglomerular vasoconstrictor effects of angiotensin. Block angiotensin synthesis (ACE inhibitors) or angiotensin’s ability to activate its receptors (ARBs), and acute renal failure may ensue. β-Adrenergic blockers would not be a good choice if hypertension is accompanied by diabetes mellitus, particularly when insulin is used for glycemic control. Should the diabetic patient experience an episode of hypoglycemia, a β-blocker may delay recovery of blood glucose levels, mask tachycardia that is one symptom of hypoglycemia development, and interact with some antidiabetic drugs (even those used for type 2; to cause excessive blood glucose-lowering). (If the diabetes is well controlled, and if the patient has other disorders for which benefits of β-blockade may outweigh potential problems, such as mild-moderate heart failure or recent myocardial infarction, then a β-blocker may be considered.) Thiazides can elevate blood glucose levels and antagonize the desired effects of antidiabetic drugs (probably by reducing the responsiveness of skeletal muscle cells and adipocytes to insulin). Nonetheless, they might not be a first-choice in the setting of diabetes—at least not for the patient described in the scenario. (Some clinicians may disagree, and consider a thiazide or thiazide-like diuretic (eg, metolazone) a first-choice drug for essential hypertension in most patients.) Verapamil, diltiazem, and nifedipine seem not to complicate blood glucose regulation or interact with antidiabetic drug therapy. Nonetheless, they lack other benefits offered by ACE inhibitors (especially the renal-protective effects) in the setting of diabetes and so would not be a first choice or of special value.

Question 2

A patient i s hospitalized and waiting for coronary His history includes angina pectoris that i s brought on by “modest” exercise, and i s accompanied by transient electrocardiographic changes consistent with myocardial i schemia. There i s no evidence of coronary vasospasm. In the hospital, he i s receiving nitroglycerin and morphine (both by s low IV infusion), plus oxygen via nasal cannula. He suddenly develops episodes of chest discomfort. Heart rate during these episodes ri ses to 170 to 190 beats/min; blood pressure reaches 180  to 200/110 to 120 mm Hg, and prominent findings on the ECG are runs of ventricular ectopic beats that terminate spontaneously, plus ST-segment elevation. Although there are several things that need to be done for immediate care, what drug would you administer to remedy (at least temporarily) the majority of these s igns and symptoms and pose the lowest ri sk of doing further harm?

A	Aspirin
B	Captopril
C	Furosemide
D	Labetalol.
E	Lidocaine
F	Nitroglycerin (increased dose as a bolus)
G	Prazosin

Question 2 Explanation: 

Labetalol is the best choice, assuming no contraindications to β- blockade, such as asthma or second degree or complete heart block. Given its combination of both α-and β-adrenergic (β1 and β2) blocking effect, it offers the best approach for managing the hypertension, the tachycardia, the resulting oxygen supply-demand imbalance that leads to both chest discomfort and the ischemic ST-changes, and the ventricular ectopy (which is probably a reflection of excessive catecholamine stimulation of β1- receptors). If the patient is having an acute myocardial infarction, starting β-blocker therapy early is also decidedly beneficial short term and for the long run. (Most any other β-blocker might be a suitable alternative, but labetalol has the combined α/β-blocking actions that are likely to be of greatest benefit. Carvedilol has the same profile, but it is given orally and in this setting that would not be ideal because of slow onset of action.) Aspirin will do no harm in this situation, but it will also do no good acutely unless there is ongoing platelet aggregation and coronary occlusion. Even if there were, the aspirin would do little to control heart rate, blood pressure, or the ECG changes. Nothing in the scenario suggests that this patient is volume-overloaded or suffering acute pulmonary edema. Therefore, administering the furosemide (c) in such a situation is not appropriate. Moreover, giving it is likely to cause prompt reductions of blood volume and, along with it, of blood pressure. The latter effect is likely to lead to further—and unwanted—reflex sympathetic activation that would make matters worse. Lidocaine (e) might be suitable for the ventricular ectopy. However, I have identified several other important signs and symptoms that would not be relieved by this antiarrhythmic drug. As noted above, the profile of labetalol offers the greatest likelihood of managing multiple problems with one drug. Increasing the dose of nitroglycerin (f; and especially giving it as a bolus) is likely to drop blood pressure acutely, triggering reflex (baroreceptor) stimulation of the heart. The usual “anti-ischemic” effects of the drug would be counteracted by such “pro-ischemic” changes as further rises of heart rate and a probable worsening of the premature ventricular beats. Prazosin (g) would lower blood pressure nicely. However, once again we have to worry about excessive pressure lowering, triggering the baroreceptor reflex, and worsening many of the already worrisome findings (eg, heart rate, PVCs)

Question 3

A 55-year-old woman has just been diagnosed with Stage 2 essential/primary hypertension, and you conclude that i t i s time to start drug therapy for i t. She also tends to be Notes written by her ophthalmologist indicate that she has chronic open-angle glaucoma. Which one of the following drugs would be the most rational choice for this woman, given only the information presented in this question, because i t might help control both the hypertension and the increased intraocular pressure?

A	Captopril
B	Diltiazem
C	Hydrochlorothiazide
D	Timolol
E	Verapamil

Question 3 Explanation: 

Timolol is a nonselective β-adrenergic blocker. Oral dosage forms are approved for managing essential hypertension (and angina). A topical ophthalmic dosage form is indicated for managing some cases of chronic open-angle glaucoma. β-Blockers are not only likely to control blood pressure, and help lower intraocular pressure, but also to reduce catecholamine-induced cardiac stimulation (the tachycardia). Verapamil or diltiazem (b, e), both calcium channel blockers (CCBs) of the nondihydropyridine class, will not only lower blood pressure but also tend to modulate the tachycardia (through direct and β-receptor-independent processes). However, they don’t lower intraocular pressure. All other things being equal, then, the β-blocker would still be a better choice for the hypertensive, tachycardic, glaucomatous patient. Thus, we get three potential benefits from β-blockade and only two with verapamil or diltiazem. ACE inhibitors, such as captopril (a) and thiazide diuretics (c), have no actions that would make them particularly suitable for hypertensive patients who are tachycardic, have glaucoma, or both.

Question 4

Nebivolol i s a fairly new and rather selective β₁-adrenergic blocker that i s indicated for managing essential The drug allegedly causes fewer s ide effects than most other β-blockers, and orthostatic hypotension does not occur even with full therapeutic doses. The  drug has no effects on changes of total peripheral resistance induced by infusion of phenylephrine or administration an amphetamine. Nebivolol’s antihypertensive mechanism of action clearly involves those common to all β-blockers, but another mechanism contributes to the overall effect. Given your general knowledge of blood pressure control and of auto-nomic/cardiovascular pharmacology, which one of the following i s the other most l ikely mechanism by which nebivolol helps lower TPR and blood pressure?

A	Competitively blocks postsynaptic (α1) adrenergic receptors
B	Competitively blocks presynaptic (α2) adrenergic receptors
C	Increases nitric oxide formation
D	Increases synthesis of thromboxane A2
E	Inhibits catechol O-methyltransferase (COMT)

Question 4 Explanation: 

Even if you know nothing specifically about nebivolol you should be able to conclude that increased formation or activity of nitric oxide (a vasodilator, among other things) is the only reasonable answer. A drug that competitively blocks α1 receptors (a; for example phentolamine or prazosin) would, indeed, lower blood pressure (BP). However, the question stated that nebivolol had no effect on the vasoconstrictor effects of either phenylephrine (direct α-agonist) or amphetamines (indirect-acting sympathomimetics; release neuronal norepinephrine). (Recall that labetalol and carvedilol are the β-blockers that also block α1 adrenergic receptors.) Competitive blockade of α2 receptors (b) cannot be correct. Blocking the presynaptic α-receptors would inhibit released norepinephrine’s usual ability to “feedback inhibit” further NE release upon an action potential. Had nebivolol blocked the α2 receptors, then, the most likely response would be a rise, not a fall, of peripheral resistance and BP. Thromboxane A2 (d) is a vasoconstrictor (among other things).Increasing its synthesis would tend to raise BP/peripheral resistance also. COMT (e) inhibits the metabolic inactivation of catecholamines in the GI tract, liver, and elsewhere. In theory, COMT inhibitors also would raise BP caused by its substrates. Finally, β-blockers are not catecholamines, and so are not substrates for COMT.

Question 5

A 44-year-old woman i s transported to the emergency department after consuming what might be a lethal dose of a β-adrenergic blocker that has no intrinsic vasodilator Despite administration of large doses of i soproterenol to overcome the blockade, her cardiac output i s dangerously low because heart rate and stroke volume are profoundly depressed. Which one of the following approaches i s most l ikely to prove beneficial, i f not l i fesaving?

A	Administer glucagon
B	Administer phenylephrine
C	Administer phentolamine
D	Switch from i soproterenol to ephedrine
E	Switch from i soproterenol to epinephrine

Question 5 Explanation: 

β1 activation, whether in contractile, nodal, or conducting tissues of the heart, leads to and requires increased production of cyclic AMP. Those responses will be inhibited in the presence of excessive doses of a β- blocker. Glucagon, a parenteral drug normally used for managing severe and acute hypoglycemia, can directly increase c-AMP levels in the heart, even in the presence of β-blockade. It has the best chance of helping to restore (or at least improve) cardiac function—even in the presence of profound β-blockade. Phenylephrine (b), the prototype α-agonist, would either not affect the already high TPR, or might increase it further. Giving it in this case would not only be irrational, but also dangerous. Phentolamine (c), the prototype α-antagonist, would lower TPR, but it is still unlikely that the heart can generate sufficient CO to perfuse the tissues adequately. Ephedrine (d), a drug that works in part by releasing norepinephrine, would be of little if any benefit. If it were given CO would still be depressed owing to the β-blockade, and α-receptor activation would cause phenylephrine-like effects on the peripheral vasculature. As noted above, those peripheral vasoconstrictor effects are precisely what we don’t need or want to cause. Epinephrine (e) would also cause not-needed/unwanted peripheral vasoconstriction; it is not likely to do better at activating cardiac β-receptors, and improving CO, than isoproterenol already has.

Question 6

At high (but not necessarily toxic) blood levels, a cardiovascular drug causes many s igns and symptoms that resemble what you see with “low- grade” aspirin toxicity (salicylism): l ight-headedness, tinnitus, and visual disturbances such as What drug most l ikely caused these responses?

A	Atropine
B	Captopril
C	Dobutamine
D	Propranolol
E	Quinidine

Question 6 Explanation: 

Many of the signs and symptoms of salicylism are similar to those caused by high blood levels of quinidine (antiarrhythmic, no longer a first-line antiarrhythmic) or quinine (mainly used as an antimalarial). Quini-dine, quinine, and related drugs are called cinchona alkaloids, and the low grade toxicity syndrome caused by these drugs is called cinchonism. (These drugs were originally obtained from a plant known, generically, as Cinchona.) Aspirin and the cinchona alkaloids are chemically similar in some important chemical and pharmacologic ways. The common signs and symptoms include light-headedness, tinnitus, and visual disturbances such as diplopia.

Question 7

A patient has periodic episodes of paroxysmal supraventricular tachycardia (PSVT). What drug would be most suitable for outpatient prophylaxis of these worrisome electrophysiologic events?

A	Adenosine
B	Lidocaine
C	Nifedipine
D	Nitroglycerin
E	Verapamil

Question 7 Explanation: 

Verapamil, a nondihydropyridine calcium channel blocker (CCB), depresses both the SA node and the AV node and would be effective for prophylaxis of paroxysmal atrial or supraventricular tachycardia. Nifedipine (c), the prototypic dihydropyridine CCB, has little effect on SVT because it and the other dihydropyridines lack cardiac depressant effects. Moreover, if we chose a fast-/immediate-acting dosage form of nifedipine, we would probably trigger substantial reflex cardiac stimulation. The increased sympathetic tone to the heart could worsen the PSVT. Nitroglycerin (d) is mainly a venodilator, but it can cause falls of arterial blood pressure sufficient to trigger reflex cardiac activation that would exacerbate the tachycardia. Adenosine (a) may be useful in diagnosing whether ventricular tachycardia is of supraventricular or ventricular origin, because it effectively slows AV nodal conduction. It is also used as acute therapy for PSVT. However, it is a fast- and short-acting parenteral drug, which renders it unsuitable for the condition I stated: outpatient prophylaxis. Lidocaine (b) is mainly used for ventricular tachyarrhythmias, not those of supraventricular origin. Both adenosine and lidocaine are parenteral drugs with short half-lives; neither property makes them suitable for outpatient prophylactic use.

Question 8

You and a colleague are discussing which α-blocker to use, adjunctively, to control blood pressure in a pheochromocytoma patient before surgery for an adrenalectomy can be Your colleague correctly states that phenoxybenzamine i s the “preferred” drug. You state that prazosin would be a better choice. Which statement about prazosin i s correct in comparison with phenoxybenzamine, and might actually support your proposal that i t would be a better choice?

A	Causes not only peripheral α-blockade but also suppresses adrenal epinephrine release
B	Has a longer duration of action, which enables less frequent dosing
C	Has good intrinsic β-blocking activity, phenoxybenzamine does not
D	Overdoses, and the hypotension i t may cause, are easier to manage pharmacologically
E	Will not cause orthostatic hypotension, which i s a common consequence of phenoxybenzamine

Question 8 Explanation: 

Prazosin causes competitive α-blockade. This is in stark contrast with phenoxybenzamine, which causes insurmountable (noncompetitive) and long-lasting blockade of α-receptors by alkylating them. Phenoxybenzamine is classified as a haloalkylamine. You probably don’t need to remember that, but perhaps it will help you realize that the drug alkylates the α-adrenergic receptors. This covalent interaction, in comparison with typical weak ionic interactions between most drugs and their receptors, accounts for phenoxybenzamine’s long-lasting (not shorter-acting; a) and noncompetitive blockade. As a result of altering receptor confirmation, not merely occupying them as prazosin and most other α-blockers do, phenoxybenzamine renders largely ineffective α- agonists that ordinarily would be used to counteract effects of excessive receptor blockade. Thus, if the patient became hypotensive in response to phenoxybenzamine, raising pressure with typical and usually effective drugs may not succeed. Neither drug has intrinsic β-blocking activity (b), and so regardless of which of these drugs we use for the pheochromocytoma patient, a β-blocker will need to be used adjunctively to control (primarily) heart rate and contractility. Neither drug suppresses epinephrine release from the adrenal/suprarenal medulla (c); both tend to cause orthostatic hypotension by blocking peripheral α-mediated vasoconstriction that occurs upon standing up suddenly

Question 9

A patient with a history of atrial fibrillation develops acute coronary syndrome and i s admitted to the hospital’s coronary care As of today, he has been receiving otherwise “proper” doses of a drug for 5 days straight. Dosing was done correctly, starting with usual maintenance doses; no loading dose strategy was used. Then, and rather precipitously, the patient develops s igns and symptoms of widespread thrombotic events, and platelet counts decline s ignificantly concomitant with the thrombosis. The patient dies within 24 hours of the onset of s igns and symptoms. What drug most l ikely caused these ultimately fatal responses?

A	Abciximab
B	Clopidogrel
C	Heparin (unfractionated)
D	Nifedipine
E	Warfarin

Question 9 Explanation: 

This brief scenario describes heparin-induced thrombocytopenia (HIT). It is an immune-mediated thrombocytopenia that is accompanied by a paradoxical increase in thrombotic events (eg, in limbs, brain, lungs, and heart). It affects about 1% to 3% of patients receiving heparin for more than about 4 days in a row. The cause appears to involve formation of antibodies that develop to heparin-platelet complexes. This leads to substantial increases of platelet activation that, in turn, leads to thrombosis, vascular damage, and eventually significant declines in the number of functional circulating platelets (since platelets have been consumed in widespread thrombotic events). This phenomenon is not associated with any of the other drugs listed in the question. Important note: Warfarin can also cause a paradoxical prothrombotic state, probably due to suppressed protein C activity. It is most likely to occur if loading doses are used, rather than starting with the anticipated maintenance dose. If you do some checking on the web or in medicine texts, you will probably find several algorithms for calculating warfarin loading doses. The safest advice is not to use any loading doses: always get the initial anticoagulation with a heparin, start warfarin simultaneously, then continue the heparin for at least 5 days and until the INR reaches the desired range. Using warfarin loading dose strategies does not hasten warfarin’s antithrombotic effect.

Question 10

A 65-year-old man with heart failure i s unable to cl imb a fl ight of stairs without experiencing After several years of therapy with carvedilol, captopril, low doses of labetalol, and furosemide, the therapeutic plan probably needs to change now. You empirically add digoxin to improve cardiac muscle contractility. Within 4 weeks, he has a marked improvement in his symptoms. What best describes the main cellular action of digoxin that accounts for i ts ability to improve his cardiovascular function and overall hemodynamic status?

A	Activates β1-adrenergic receptors
B	Facilitates GTP binding to specific G proteins
C	Increases mitochondrial calcium (Ca 2+) release
D	Inhibits sarcolemmal Na+-K+-ATPase
E	Stimulates cyclic adenosine 5′-monophosphate (cAMP) synthesis

Question 10 Explanation: 

Digoxin inhibits the sarcolemmal Na+, K+-ATPase (“sodium pump”). This reduces the active (ATP-dependent) extrusion of intracellular Na+. The relative excess of intracellular Na+ competes with intracellular Ca2+ for sites on a sarcolemmal 2Na-Ca exchange diffusion carrier, such that less Ca2+ is extruded from the cells. The net results include a rise of free [Ca2+]i and greater actin-myosin interactions (ie, a positive inotropic effect that increases cardiac output through an increase of stroke volume).

Question 11

A patient with newly diagnosed essential (primary) hypertension starts treatment with a commonly used antihypertensive  drug at a  dose that i s considered to be therapeutic for the vast majority of Soon after starting therapy the patient experiences crushing chest discomfort. ECG changes show myocardial i schemia. Studies in the cardiac cath lab show episodes of coronary vasospasm, and i t i s l ikely the  antihypertensive drug provoked the vasospasm. Which antihypertensive drug or drug class most l ikely caused the i schemia and the angina?

A	Atenolol
B	Diltiazem
C	Hydrochlorothiazide
D	Losartan
E	Metolazone

Question 11 Explanation: 

β-Blockers (represented in this question by atenolol) should not be administered (especially by a systemic route) to patients with vasospastic angina unless for a medical emergency that requires β-blockade as a life-saving measure. Recall the dual roles of adrenergic receptors in the coronary vasculature. Activation of β2-adrenergic receptors causes vasodilation. Activation of α-adrenergic receptors in the coronary (and other) vasculature favors vasoconstriction or—in the setting of variant angina— vasospasm. Normally these receptors are exposed to circulating epinephrine, which causes the opposing vasodilator (β2) and vasoconstrictor (α) effects. Norepinephrine is also activating α-adrenergic receptors. Block only the β2 (vasodilator) effects in the coronaries and the constrictor (and spasm-favoring) effects of the α receptors are left unopposed. Diltiazem (b), a nondihydropyridine calcium channel blocker, would not only lower blood pressure but also suppress the tendency for coronary vasoconstriction or spasm by blocking vascular smooth muscle calcium influx. Hydrochlorothiazide (c) is the prototype thiazide diuretic, andmetolazone (e) is thiazide-like in terms of most of its pharmacologic profiles. Neither is at all likely to cause or favor vasoconstriction in the coronary vessels or elsewhere. Losartan (d) is an angiotensin receptor blocker. It not only has good antihypertensive activity, but also is apt to suppress any coronary vasoconstrictor influences of circulating angiotensin.

Question 12

A patient with chronic-stable (“effort-induced”) angina i s on prophylactic β-blocker (propranolol) therapy, with sublingual nitroglycerin (NTG) used as needed for managing acute One day he experiences particularly severe angina and takes the usually recommended dose of sublingual NTG. His discomfort i s not reduced at all. Seeking relief, he repeats  the  usual recommended NTG dose frequently over a  period of about 10 minutes, and now has taken far too much of the nitrovasodilator. An electrocardiogram taken by the paramedics, who were called for the patient’s emergency, shows changes consistent with severe myocardial i schemia. The patient goes into cardiac arrest and cannot be resuscitated. What i s the most l ikely cause of or contributing factor to the patient’s responses to the excessive dosage of NTG?

A	Cyanide, a toxic metabolite of NTG, accumulated
B	Nitroglycerin directly induced coronary vasoconstriction
C	The NTG lowered arterial pressure excessively
D	The patient has vasospastic (variant or Prinzmetal) angina, not chronic-stable
E	The β-blocker’s intrinsic vasodilator activity potentiated that of the NTG

Question 12 Explanation: 

At usual therapeutic doses, nitroglycerin (NTG) acts primarily as a peripheral venodilator. At higher doses arterial dilation also occurs. The net effect is that, particularly with excessive doses, peripheral vasodilation occurs and blood pressure (BP) falls. Critical among these pressure changes is a fall of diastolic BP. I say critical because DBP is the main driving force for blood flow through the coronary vasculature. Up to a point autoregulation of coronary flow may help maintain cardiac perfusion, but once DBP reaches a certain lower level coronary blood flow is inadequate to meet the oxygen demands of the myocardium (ie, ischemia has developed). Add to the underperfusion of the heart by reduced DBP the fact that if BP falls by a sufficient amount, and sufficiently fast, the baroreceptor reflex is activated. That, in turn, increases heart rate and contractility—an increase of myocar-dial oxygen demand simultaneous with reduced oxygen supply due to the decreased coronary perfusion. Nitroglycerin is not metabolized to cyanide (a). If you selected that possibility as your preferred answer you are confusing NTG with another nitrovasodilator that clearly does form cyanide: nitroprusside. NTG does not, cannot, induce coronary vasoconstriction or spasm directly (b). NTG is often used, with success and no extra risk, for patients with coronary vasospasm (d). For such individuals NTG is mainly used for acute management of an ongoing attack (as applies to virtually all angina patients who take the drug), with long-term suppression of vasospasm provided by a calcium channel blocker. Finally, for patients with angina that does not involve vasospasm, NTG is frequently prescribed with a β- adrenergic blocker (e). Here again, the NTG is used mainly for acute symptom control and the β-blocker for prophylaxis. As an aside, if you indeed chose answer e, that the β-blocker’s “intrinsic vasodilator activity potentiated that of the NTG,” I think you should be prepared to cite a specific β-blocker with that property. The β-blocker named in the question, propranolol, has absolutely no intrinsic vasodilator activity. Indeed, of the long list of β-blockers on the market, only three have the ability to cause vasodilation. Labetalol and carvedilol have some α-blocking activity that causes vasodilation, but the effect is weak. Then there is nebivolol, which causes some vasodilation through its metabolism to nitric oxide. Note: There is an interesting and somewhat controversial phenomenon ascribed to NTG and some other vasodilator drugs: coronary steal. In essence, vasodilation shunts or diverts (steals) blood flow from areas of low perfusion (eg, a stenotic coronary vessel) to areas of high perfusion. The postulated outcome is that poorly perfused vessels (and the tissues served by them) become even less well perfused, thereby causing or worsening distal tissue ischemia.

Question 13

A 50-year-old man has a long history of asymptomatic hyperuricemia (elevated uric acid levels), and you are about to start therapy for newly diagnosed essential hypertension (BP 136/90 mm Hg, based on repeated measurements with the patient supine and at rest). Which antihypertensive drug i s most l ikely to increase his uric acid levels further, and in doing so, be most l ikely to cause the most common cl inical presentation of the hyperuricemia—gout?

A	Hydrochlorothiazide
B	Labetalol
C	Losartan
D	Ramipril
E	Verapamil

Question 13 Explanation: 

Thiazide diuretics tend to raise uric acid concentration in the blood, probably by inhibiting tubular secretion of urate. The elevations of urate may be of little concern for patients with no history of hyperuricemia or gout, but for those with such a history it can be a problem that is not associated with any of the other answer choices given. Thiazides can be administered to hyperuricemic/gouty patients, but that may require another drug (allopurinol or febuxostat, which are xanthine oxidase inhibitors) to counteract diureticinduced rises of urate levels. If one can avoid the problems by avoiding the thiazide, and the possible need for adding a second drug to counteract the hyperuricemia, why not do just that? That is one of many reasons why we might use another class of antihypertensive drugs (eg, angiotensin modifiers, calcium channel blockers, many more) that don’t have negative effects on urate levels. None of the other answer choices have any appreciable desired or untoward effects on urate levels, renal handling of urate, or the incidence or severity of gout.

Question 14

We conduct an experiment to assess the effects of other drugs on the anti-platelet aggregatory effects of In each case we sample venous blood from an otherwise healthy patient, centrifuge the blood to obtain a platelet-rich fraction, and put samples of the platelets into an instrument that accurately measures platelet aggregation in vitro. We then activate the platelets by adding ADP (or collagen; makes no difference). Results are graphed below. The control (top l ine) condition reflects results from the patients who has been taking no drugs at all. The bottom trace shows aggregation of platelets i solated from the patient after they have taken aspirin (ASA; 81 mg/day) for 14 days in a row. We stop aspirin for 2 weeks to ensure that the patient has no aspirin in their blood. Then we restart 81 mg/day aspirin plus an unknown drug taken with each aspirin tablet for final 2 weeks. The platelets taken at the end of the 14 days show only s l ight inhibition of platelet aggregation—results not s ignificantly from control. The results are shown here: Which drug was taken with the aspirin and inhibited i ts aggregatory effects in response to ADP or collagen?

A	Acetaminophen
B	Clopidogrel
C	Dabigatran
D	Ibuprofen
E	Warfarin

Question 14 Explanation: 

These in vitro responses, showing that ibuprofen (or another NSAID, naproxen) can significantly antagonize the antiplatelet effects of aspirin, are clinically relevant. Both ibuprofen and aspirin compete for the same binding sites on both COX-1 and COX-2. Aspirin’s interaction is covalent, and irreversible. Ibuprofen, however, binds to the same COX sites as aspirin. Its antiplatelet effects are comparatively weak and reversible. More importantly, the bound ibuprofen prevents the ability of aspirin to bind to same critical enzyme site. If aspirin therapy is stopped, COX-1 activity will increase by about 10% per day, and just 20% of baseline COX activity—that is, skipping aspirin for more than 2 to 3 days—may be enough to enable sufficient COX activity to be restored and the protective antiplatelet effects lost. Using ibuprofen for more than a few days in a row is likely to do the same. In short, the interaction should be avoided. And remember: ibuprofen (and naproxen) is available OTC, and unless you explicitly tell your patients to avoid it, your pharmacologic efforts to afford cardioprotection may be for naught. Such NSAIDs as diclofenac, and many others, do not interfere with aspirin’s antiplatelet effects. Acetaminophen (a), in dosages of about 1 g/day or more, taken for more than 7 days in a row, may potentiate warfarin’s anticoagulant effects. However, it does not interfere with aspirin’s antiplatelet effects; and it has no anticoagulant or antithrombotic effects in its own right. Clopidogrel (b), a platelet ADP receptor blocker that is used as an antiplatelet drug in lieu of aspirin (for some patients), does not block aspirin’s antiplatelet effects, because the mechanisms of action of clopidogrel and aspirin are synergistic and different. Dabigatran (c) is an oral anticoagulant, sometimes used as an alternative to warfarin (e). It is classified as a direct-acting thrombin inhibitor. Neither dabigatran nor warfarin counteracts aspirin’s antiplatelet effects.

Question 15

A 57-year-old patient complains of muscle aches, pain, and tenderness. These affect the legs and There i s no fever, bruising, or any recent history of muscle trauma or strains (as from excessive exercise). He has myoglobinuria, a cl inically s ignificant fall of creatinine clearance, and a ri se of plasma creatine kinase (CK) to levels nearly ten times the upper l imit of normal. Which drug i s the most l ikely cause of these findings?

A	Aspirin (low dose) for i ts cardioprotective/antiplatelet effects
B	Captopril for hypertension and heart failure
C	Carvedilol for hypertension, heart failure, and angina prophylaxis
D	Furosemide as adjunctive management of his heart failure
E	Rosuvastatin to control his hypercholesterolemia and the associated ri sks

Question 15 Explanation: 

The findings are consistent with statin-induced myositis and myopathy, which seem to have progressed to rhabdomyolysis and renal failure—both potentially fatal. This syndrome (and hepatotoxicity) is the most serious adverse response to the statins. It is more prevalent in older patients, those with multiple illnesses, and especially those with renal or liver disease. Coadministration of most other lipid-lowering drugs (none of which are in the above list) increases the risk of rhabdomyolysis, hepatotoxicity, or both. As an aside, the risk of rhabdomyolysis (or lesser skeletal muscle changes) is not too much different between the currently available statins. However, it was (allegedly) such a problem with one relatively recent drug, cerivastatin, that the drug was pulled from the market. Note: Never been taught specifically about rosuvastatin? Well, the drug name ends in “-statin” so you should automatically know quite a bit about it.

Question 16

A coronary artery sample was removed from a healthy animal, put inside a suitable oxygenated salt and nutrient solution, and connected to a transducer that measured increases (contraction) or decreases (relaxation) of smooth muscle tension (force). ACh was then added to give the cumulative concentrations shown As expected, in the control setting (left) ACh caused concentration-dependent vasorelaxation (equivalent to vasodilation in the intact animal). The ACh was washed out several times, control conditions returned. The conditions were manipulated, and then the ACh  dose-response experiment was repeated (right). Now the data show increased tension developed by the muscle sample (vasoconstriction in vivo) in response to ACh and incremental increases of i ts concentration. Which one of the following summarizes what was most l ikely done to the vessel under the experimental conditions, before retesting the responses to added ACh? Assume that the vascular responses in this animal model are identical to those that would occur in a human.

A	Endothelium was removed mechanically
B	Isoproterenol was added right before ACh
C	Muscarinic receptors were blocked with atropine
D	Sample was pretreated with prazosin
E	Tissue was pretreated with botulinum toxin

Question 16 Explanation: 

ACh causes vasodilation only when the vascular endothelium is intact functionally and anatomically. The normal response, initiated by ACh acting as an agonist on muscarinic receptors, involves endothelium-derived relaxing factor/nitric oxide (EDRF/NO) that is generated in and released from the endothelium (that is why it’s called “endothelium-derived”). The NO diffuses into the adjacent vascular smooth muscle cells and increases cGMP formation. That, in turn, causes extrusion of Ca2+ and relaxation of the muscle (vasodilation in the intact animal). When the endothelium is removed (actually quite easy to do experimentally) or damaged, ACh causes concentration-dependent increases of smooth muscle tension. Isoproterenol (b) is a β1/β2 agonist. Added to an in vitro preparation such as the one used here, it would only cause smooth muscle relaxation (β2 effect) unless the β-receptors were blocked; it does not alter the contractile responses to added ACh. Blockade of muscarinic receptors (c) cannot be correct. If that were the case, particularly under control conditions, contractile response to ACh would be diminished or abolished, andcontraction shown under the experimental conditions would not be changed from what is shown in the figure. Prazosin (d) cannot be correct. It is an α 1 receptor blocker, and pretreating with it would not cause vasoconstriction with or without added ACh. Botulinum toxin (e) blocks ACh release from cholinergic nerves. Although there may be some postganglionic para-sympathetic (and sympathetic) nerve “endings” in the tissue sample, the responses shown above were caused by adding ACh directly to the tissue bath and so they are independent of any residual autonomic neural influences.

Question 17

A 28-year-old woman i s receiving drug therapy for essential (primary) She subsequently becomes pregnant. You realize that the drug she’s been taking for her high blood pressure can have serious, i f not fatal, effects on the fetus (i t i s in pregnancy category X). As a result, you stop the current antihypertensive drug and substitute another that i s deemed to be equiefficacious in terms  of her blood pressure, and safer for the fetus. Which drug was she most l ikely taking before she became pregnant?

A	α-Methyldopa
B	Captopril
C	Furosemide
D	Labetalol.
E	Verapamil

Question 17 Explanation: 

ACE inhibitors (and angiotensin receptor blockers, ARBs, eg, losartan) are contraindicated in pregnancy (category X), and should not be administered to “women of childbearing potential”—not just women who are pregnant—in the first place. Normal in utero development of the kidneys and other urogenital structures seems to be angiotensindependent. ACE inhibitors, or ARBs, given during the second or third trimesters (not the first) have been associated with severe and sometimes fatal developmental anomalies of these structures. Cranial hypoplasia, and neonatal hyperkalemia and hypotension, have also been reported. α-Methyldopa (a) is considered one of the preferred antihypertensive drugs for pregnant women. It not only controls maternal blood pressure well, but also is remarkably free of adverse effects on the fetus. (Indeed, it is the most likely drug that we would prescribe for this hypertensive and now pregnant woman.) β-Blockers such as labetalol (d) are sometimes used during pregnancy, posing no specific or significant risks to the mother or the fetus, provided that adequate perinatal care is given and blood pressure doesn’t fall excessively. None of the calcium channel blockers (including verapamil, e) seem to have any significant benefits or risks during pregnancy, compared with other drugs. (Verapamil, for example, is in pregnancy category C.) One theoretical concern with verapamil and diltiazem is a prolongation of labor as parturition draws near, due to suppression of uterine contractility. There are concerns with using diuretics during pregnancy. Furosemide (c) or other loop diuretics pose relatively significant fetal risks. However, that is related to potential maternal hypovolemia and hypotension that may lead to placental underperfusion. There is no teratogenic or embryopathic risk on par with that associated with the angiotensin modifiers (ACE inhibitors or ARBs). Moreover, when the goal is treating essential hypertension in the absence of hypervolemia, edema, ascites, and so on, loop diuretics seldom are used. Instead, thiazide or thiazidelike diuretics are the ones usually chosen. Nevertheless, the thiazides also pose a risk of placental underperfusion, and so they are not preferred or ideal antihypertensives for the pregnant woman. Note: It is not necessary (now) for you to memorize the pregnancy classifications of the nonteratogenic drugs listed above. What you need to know is that ACE inhibitors and ARBs are absolutely contraindicated. So is warfarin, at least during the first 12 weeks of gestation, which is addressed in Question 199.

Question 18

We treat a patient with a drug that affects the clotting-thrombolytic systems for a time sufficient to let the drug’s effects and blood levels stabilize at a therapeutic We then i solate platelets from a blood sample and test their in vi tro aggregatory responses to ADP, collagen, PAF, and thromboxane A₂. Aggregatory responses to ADP are inhibited; responses to the other platelet proaggregatory agonists are unaffected. Which drug exhibits these properties?

A	Aspirin
B	Bivalirudin
C	Clopidogrel
D	Heparin
E	Warfarin

Question 18 Explanation: 

Clopidogrel (and the much lesser-used drug ticlopidine) is a noncompetitive antagonist of ADP. This prodrug (it must be metabolically activated) causes largely irreversible (ie, for the lifetime of the platelet) inhibition of platelet aggregation by blocking ADP binding to the Gi coupled P2Y(AC) receptor. It has no effect on platelet activation and amplification caused by such other proaggregatory agonists as collagen, thromboxane A2, thrombin, PAF, serotonin, or epinephrine. Aspirin (a) inhibits platelet aggregation caused by thromboxane A2 (TXA2) only, and does so only by inhibiting TXA2 synthesis via cyclooxygenase, not by blocking TXA2 receptors. Bivalirudin (b) is a synthetic hirudin derivative (you may recall that hirudin is produced by the medicinal leach, Hirudo medicinalis). It is classified as an anticoagulant, not as an antiplatelet drug. It is a direct-acting inhibitor of free and clot-bound thrombin, which leads to two main effects: (1) decreased conversion of fibrinogen to fibrin; and (2) reduced activation of Factor XIIIa, which in turn decreases conversion of soluble fibrin monomers to insoluble (polymerized) fibrin. Bivalirudin is given IV as an alternative to heparin (both drugs bind to free thrombin, but bivalirudin also interacts with clot-bound thrombin), mainly along with aspirin for patients with unstable angina who are undergoing angioplasty. It is also used to help treat heparin-induced thrombocytopenia; and seems to be more effective than heparin when given postmyocardial infarction. A related drug is argatroban. Heparin and warfarin (d, e) have no direct effects on platelets. (You should also recall that since warfarin’s site of action is the liver, it has no anticoagulant effects when tested in vitro (ie, added to a tube of whole blood). Note: I mentioned that ticlopidine is much lesser-used than clopidogrel. Actually, it’s seldom used. The reason? A greater risk of thrombotic thrombocytopenic purpura (TTP) and/or neutropenia.

Question 19

Your newly diagnosed hypertensive patient has vasospastic angina. Which drug or drug class would be the most rational for starting anti- hypertensive therapy because i t exerts not only antihypertensive effects, but also directly lowers myocardial oxygen demand and consumption and tends to inhibit cellular processes that otherwise favor coronary vaso-spasm? Assume there are no other specific contraindications to the drug you

A	Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker
B	β-Adrenergic blocker
C	Nifedipine
D	Thiazide diuretic
E	Verapamil (or diltiazem)

Question 19 Explanation: 

The vascular calcium channel-blocking actions of verapamil or diltiazem (nondihydropyridine class) will not only lower systemic blood pressure, but also tend to counter coronary arterial calcium influx that favors vasospasm. Thus, in this setting we can expect both antihypertensive and antianginal effects from one drug. One might argue that nifedipine (answer c) would be a reasonable alternative. However, recall that the dihydropyridines (which is the class to which nifedipine belongs) lack cardiac depressant actions. Rapidly acting formulations of a dihydropyridine, even if given orally, are likely to lower blood pressure (the desired antihypertensive effect), but lacking cardiac-depressant actions are liable to trigger reflex (sympathetic/baroreceptor) cardiac stimulation. The resulting increases of either or both cardiac rate and contractility (mediated, reflexly, by sympathetic activation) necessarily may raise myocardial oxygen demand sufficient to cause myocardial ischemia, and/or may trigger coronary vasospasm. (The degree to which a dihydropyridine will cause unwanted reflex cardiac stimulation depends on the drug, the dose, and even the dosage form [eg, immediate-acting vs extended-acting].) Nonetheless, a nondihydropyridine would have a much better overall profile of cardiac/vascular actions. ACE inhibitors or an ARB (a), or a thiazide (d), might cause no particular problems for a patient with vasospastic angina, but they also have no actions that would help that comorbidity. Why select one of them when a nondihydropyridine calcium channel blocker might be beneficial for both problems? β-Blockers (b) would be a poor choice. Recall that the coronary vasculature constricts in response to α-adrenergic influences, while vascular β2 receptor activation tends to cause coronary vasodilation. Patients with vasospastic angina depend on β-mediated vasodilatory influences, and are at greater risk of ischemic events if the β-receptors are blocked.

Question 20

You are reviewing the medication history of a 59-year-old He has been taking ramipril and pravastatin for the last 5 years. Other medications include metformin for type 2 diabetes mellitus, and escitalopram to help manage his depression. At his last cl inic vis i t, a year ago, he was told to continue his current medications but he was also started on s low-release niacin because diet, exercise and other l i festyle modifications, and his current medications were not adequate. What was the most l ikely reason for adding the niacin?

A	Counteract deficiencies of B-vitamin absorption caused by the antidepressant
B	Counteract polyphagia, and over-eating, caused by the metformin.
C	Lower HDL and triglyceride levels that did not respond adequately to the statin
D	Prevent statin-induced neuropathy
E	Slow the progression of diabetic nephropathy caused by the ACE inhibitor

Question 20 Explanation: 

Answering this question correctly indeed depends on your knowledge of several drugs, and their prototype or representative agents, that goes beyond “cardiovascular” (since I included a diabetes drug [metformin] and an antidepressant [escitalopram] as possible answer choices). Nonetheless, niacin (nicotinic acid; vitamin B3) is often added-on—in dosages higher than those recommended for vitamin supplementation— mainly to lower HDL and triglyceride levels, particularly in patients with the classic mixed hyperlipidemia characterized by elevated cholesterol and triglyceride levels (Type IIb) and who aren’t adequately managed with a statin. The primary effect of niacin is to decrease production of VLDLs(mainly by inhibiting lipolysis in adipocytes). Since LDLs are by-products of VLDL degradation, the fall in VLDL levels causes LDL levels to fall as well. Lastly, recall that VLDLs deliver triglycerides to and increase their storage in adipose tissue. By decreasing VLDL production, then, niacin indirectly counters triglyceride accumulation and favors triglyceride clearance (elimination). See the answer for Question 258 for more information about niacin’s more common side effects. Pravastatin and other statins (HMG CoA reductase inhibitors), while mainly used for hypercholesterolemia (to lower LDL-cholesterol levels), often concomitantly raise HDL and lower triglyceride levels adequately. When statins and lifestyle modifications fail to control triglyceride levels adequately, adding niacin is usually a reasonable next step. Citalopram (a), escitalopram, and other SSRI-antidepressants have no known effects on altered vitamin absorption or on the cardiovascular system. Metformin (b), the prototype biguanide often used for managing type 2 diabetes mellitus, typically suppresses (not increases) appetite. Statins do not cause peripheral neuropathy (d); and ACE inhibitors (ramipril and others; e) do not cause diabetic nephropathy, although they are clearly contraindicated for patients with severe bilateral renal arterial stenosis, such as that associated with severe and poorly controlled diabetes mellitus.

Question 21

Quinidine i s ordered for a patient with recurrent atrial fibrillation and who refuses any interventions other than drugs in an attempt to terminate and control the He has some pulmonary fibrosis and a thyroid disorder—both leading you to conclude that amiodarone therapy might not be the best approach. Which statement applies to the quinidine?

A	Decreases SA nodal automaticity due to a strong anticholinergic/vagolytic effect
B	Is l ikely to increase blood pressure via a direct vasoconstrictor effect
C	Is contraindicated i f the patient also requires anticoagulant therapy
D	Tends to increase electrical impulse conduction velocity through the AV node
E	Will increase cardiac contractility (positive inotropic effect) independent of i ts antiarrhythmic effects

Question 21 Explanation: 

Quinidine is becoming an outmoded drug, but it is, of course, still being used. It may be described as a broad-spectrum antiarrhythmic (that does not mean it is indicated or safe for all arrhythmias and all etiologies). It is mainly used for long-term management of supraventricular and ventricular arrhythmias: atrial flutter and fibrillation; and sustained ventricular tachycardia. The drug’s effects reflect direct ion channel-blocking actions plus a variety of receptor-blocking effects that may counteract the direct effects. Direct blockade of sodium channels (a “major” action of Class I antiarrhythmics) slows impulse conduction in the atria, ventricles, and HisPurkinje system. Repolarization at those sites tends to be delayed, presumably by blockade of potassium channels. Among other changes, the ECG shows widened QRS complexes and prolonged QT intervals (which may predispose patients, particularly those with long QT syndrome, to some serious arrhythmias, including torsades). Quinidine has strong anticholinergic (vagolytic) effects that are particularly apparent at the SA node (increased automaticity, tends to predominate over direct depressant effects from sodium channel blockade) and the AV node (increased conduction velocity, correct answer d). (Recall that vagal tone on the SA node slows spontaneous depolarization and heart rate; the vagolytic effects of quinidine will therefore do the opposite.) The effects on AV conduction are a main reason why, when quinidine therapy is to be started and atrial rates are still high, we pretreat the patient with a dose of a drug that “blocks down” the AV node: digoxin, sometimes verapamil, and occasionally a β-blocker. The main reason why ventricular rates aren’t identical (or close to) atrial rates during atrial fibrillation is because the AV node cannot transmit impulses at such high rates. This protective effect depends on AV nodal refractoriness and a relative inability to transmit too many impulses per time. If we did not suppress the AV node before giving quinidine, the AV nodal “conduction-stimulating” effects of the quinidine might increase AV nodal transmission; ventricular rates might rise to dangerous levels as the atrial rate slows in response to the quinidine. Quinidine is not likely to increase blood pressure (b), or worsen preexisting hypertension. Quite the contrary: the predominant vascular effect of the drug is dilation, and blood pressure falls, due to peripheral vascular α-adrenergic blocking activity. Likewise, quinidine exerts a negative inotropic effect—not a positive one (e)—on ventricular muscle. That, too, can contribute to a fall of blood pressure. For long-term management of a patient with atrial fibrillation, anticoagulants are important (not contraindicated, c) for prophylaxis of venous thrombosis; the use of quinidine does not contraindicate that.

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Part 1 | Part 2 | Part 3 | Part 4

II. Preview all questions below

1.;Your patient i s a 50-year-old man with Type 1 (insulin-requiring) diabetes, normal  renal  function, and no  Although  his HbA1c levels are acceptable, because of his l i festyle  and eating habits  he  has  experienced more  than a  few episodes of symptomatic hypoglycemia following insulin injections. He  currently has asymptomatic hyperuricemia, but he has had several attacks  of acute gout over the  last 5 years. Today you diagnose hypertension that must be treated. Which antihypertensive drug would be  the  most rational  fi rst choice  for starting his antihypertensive therapy?

1. Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker
2. β-adrenergic blocker
3. Nifedipine
4. Thiazide diuretic
5. Verapamil or diltiazem

2. A patient i s hospitalized and waiting for coronary His history includes angina pectoris that i s brought on by “modest” exercise, and i s accompanied by transient electrocardiographic changes consistent with myocardial i schemia. There i s no evidence of coronary vasospasm. In the hospital, he i s receiving nitroglycerin and morphine (both by s low IV infusion), plus oxygen via nasal cannula.

He suddenly develops episodes of chest discomfort. Heart rate during these episodes ri ses to 170 to 190 beats/min; blood pressure reaches 180  to 200/110 to 120 mm Hg, and prominent findings on the ECG are runs of ventricular ectopic beats that terminate spontaneously, plus ST-segment elevation.

Although there are several things that need to be done for immediate care, what drug would you administer to remedy (at least temporarily) the majority of these s igns and symptoms and pose the lowest ri sk of doing further harm?

1. Aspirin
2. Captopril
3. Furosemide
4. Labetalol. Lidocaine
5. Nitroglycerin (increased dose as a bolus)
6. Prazosin

3. A 55-year-old woman has just been diagnosed with Stage 2 essential/primary hypertension, and you conclude that i t i s time to start drug therapy for i t. She also tends to be Notes written by her ophthalmologist indicate that she has chronic open-angle glaucoma. Which one of the following drugs would be the most rational choice for this woman, given only the information presented in this question, because i t might help control both the hypertension and the increased intraocular pressure?

1. Captopril
2. Diltiazem
3. Hydrochlorothiazide
4. Timolol
5. Verapamil

4. Nebivolol i s a fairly new and rather selective β₁-adrenergic blocker that i s indicated for managing essential The drug allegedly causes fewer s ide effects than most other β-blockers, and orthostatic hypotension does not occur even with full therapeutic doses. The  drug has no effects on changes of total peripheral resistance induced by infusion of phenylephrine or administration an amphetamine. Nebivolol’s antihypertensive mechanism of action clearly involves those common to all β-blockers, but another mechanism contributes to the overall effect. Given your general knowledge of blood pressure control and of auto-nomic/cardiovascular pharmacology, which one of the following i s the other most l ikely mechanism by which nebivolol helps lower TPR and blood pressure?

1. Competitively blocks postsynaptic (α₁) adrenergic receptors
2. Competitively blocks presynaptic (α₂) adrenergic receptors
3. Increases nitric oxide formation
4. Increases synthesis of thromboxane A₂
5. Inhibits catechol O-methyltransferase (COMT)

5. A 44-year-old woman i s transported to the emergency department after consuming what might be a lethal dose of a β-adrenergic blocker that has no intrinsic vasodilator Despite administration of large doses of i soproterenol to overcome the blockade, her cardiac output i s dangerously low because heart rate and stroke volume are profoundly depressed. Which one of the following approaches i s most l ikely to prove beneficial, i f not l i fesaving?

1. Administer glucagon
2. Administer phenylephrine
3. Administer phentolamine
4. Switch from i soproterenol to  ephedrine
5. Switch from i soproterenol to epinephrine

6. At high (but not necessarily toxic) blood levels, a cardiovascular drug causes many s igns and symptoms that resemble what you see with “low- grade” aspirin toxicity (salicylism): l ight-headedness, tinnitus, and visual disturbances such as What drug most l ikely caused these responses?

1. Atropine
2. Captopril
3. Dobutamine
4. Propranolol
5. Quinidine

7. A patient has periodic episodes of paroxysmal supraventricular tachycardia (PSVT). What drug would be most suitable for outpatient prophylaxis of these worrisome electrophysiologic events?

1. Adenosine
2. Lidocaine
3. Nifedipine
4. Nitroglycerin
5. Verapamil

8. You and a colleague are discussing which α-blocker to use, adjunctively, to control blood pressure in a pheochromocytoma patient before surgery for an adrenalectomy can be Your colleague correctly states that phenoxybenzamine i s the “preferred” drug. You state that prazosin would be a better choice. Which statement about prazosin i s correct in comparison with phenoxybenzamine, and might actually support your proposal that i t would be a better choice?

1. Causes not only peripheral α-blockade but also suppresses adrenal epinephrine release
2. Has a longer duration of action, which enables less frequent dosing
3. Has good intrinsic β-blocking activity, phenoxybenzamine does not
4. Overdoses, and the hypotension i t may cause, are easier to manage pharmacologically
5. Will not cause orthostatic hypotension, which i s a common consequence of phenoxybenzamine

9. A patient with a history of atrial fibrillation develops acute coronary syndrome and i s admitted to the hospital’s coronary care As of today, he has been receiving otherwise “proper” doses of a drug for 5 days straight. Dosing was done correctly, starting with usual maintenance doses; no loading dose strategy was used. Then, and rather precipitously, the patient develops s igns and symptoms of widespread thrombotic events, and platelet counts decline s ignificantly concomitant with the thrombosis. The patient dies within 24 hours of the onset of s igns and symptoms. What drug most l ikely caused these ultimately fatal responses?

1. Abciximab
2. Clopidogrel
3. Heparin (unfractionated)
4. Nifedipine
5. Warfarin

10. A 65-year-old man with heart failure i s unable to cl imb a fl ight of stairs without experiencing After several years of therapy with carvedilol, captopril, low doses of labetalol, and furosemide, the therapeutic plan probably needs to change now. You empirically add digoxin to improve cardiac muscle contractility. Within 4 weeks, he has a marked improvement in his symptoms. What best describes the main cellular action of digoxin that accounts for i ts ability to improve his cardiovascular function and overall hemodynamic status?

1. Activates β₁-adrenergic receptors
2. Facilitates GTP binding to specific G proteins
3. Increases mitochondrial calcium (Ca 2+) release
4. Inhibits sarcolemmal Na+-K+-ATPase
5. Stimulates cyclic adenosine 5′-monophosphate (cAMP) synthesis

11. A patient with newly diagnosed essential (primary) hypertension starts treatment with a commonly used antihypertensive  drug at a  dose that i s considered to be therapeutic for the vast majority of Soon after starting therapy the patient experiences crushing chest discomfort. ECG changes show myocardial i schemia. Studies in the cardiac cath lab show episodes of coronary vasospasm, and i t i s l ikely the  antihypertensive drug provoked the vasospasm. Which antihypertensive drug or drug class most l ikely caused the i schemia and the angina?

1. Atenolol
2. Diltiazem
3. Hydrochlorothiazide
4. Losartan
5. Metolazone

12. A patient with chronic-stable (“effort-induced”) angina i s on prophylactic β-blocker (propranolol) therapy, with sublingual nitroglycerin (NTG) used as needed for managing acute One day he experiences particularly severe angina and takes the usually recommended dose of sublingual NTG. His discomfort i s not reduced at all. Seeking relief, he repeats  the  usual recommended NTG dose frequently over a  period of about 10 minutes, and now has taken far too much of the nitrovasodilator. An electrocardiogram taken by the paramedics, who were called for the patient’s emergency, shows changes consistent with severe myocardial i schemia. The patient goes into cardiac arrest and cannot be resuscitated. What i s the most l ikely cause of or contributing factor to the patient’s responses to the excessive dosage of NTG?

1. Cyanide, a toxic metabolite of NTG, accumulated
2. Nitroglycerin directly induced coronary vasoconstriction
3. The NTG lowered arterial pressure excessively
4. The patient has vasospastic (variant or Prinzmetal) angina, not chronic-stable The β-blocker’s intrinsic vasodilator activity potentiated that of the NTG

13. A 50-year-old man has a long history of asymptomatic hyperuricemia (elevated uric acid levels), and you are about to start therapy for newly diagnosed essential hypertension (BP 136/90 mm Hg, based on repeated measurements with the patient supine and at rest). Which antihypertensive drug i s most l ikely to increase his uric acid levels further, and in doing so, be most l ikely to cause the most common cl inical presentation of the hyperuricemia—gout?

1. Hydrochlorothiazide
2. Labetalol
3. Losartan
4. Ramipril
5. Verapamil

14. We conduct an experiment to assess the effects of other drugs on the anti-platelet aggregatory effects of In each case we sample venous blood from an otherwise healthy patient, centrifuge the blood to obtain a platelet-rich fraction, and put samples of the platelets into an instrument that accurately measures platelet aggregation in vitro. We then activate the platelets by adding ADP (or collagen; makes no difference). Results are graphed below.

The control (top l ine) condition reflects results from the patients who has been taking no drugs at all. The bottom trace shows aggregation of platelets i solated from the patient after they have taken aspirin (ASA; 81 mg/day) for 14 days in a row. We stop aspirin for 2 weeks to ensure that the patient has no aspirin in their blood. Then we restart 81 mg/day aspirin plus an unknown drug taken with each aspirin tablet for final 2 weeks. The platelets taken at the end of the 14 days show only s l ight inhibition of platelet aggregation—results not s ignificantly from control.

The results are shown here:

Which drug was taken with the aspirin and inhibited i ts aggregatory effects in response to ADP or collagen?

1. Acetaminophen
2. Clopidogrel
3. Dabigatran
4. Ibuprofen
5. Warfarin

15. A 57-year-old patient complains of muscle aches, pain, and tenderness. These affect the legs and There i s no fever, bruising, or any recent history of muscle trauma or strains (as from excessive exercise). He has myoglobinuria, a cl inically s ignificant fall of creatinine clearance, and a ri se of plasma creatine kinase (CK) to levels nearly ten times the upper l imit of normal. Which drug i s the most l ikely cause of these findings?

1. Aspirin (low dose) for i ts cardioprotective/antiplatelet effects
2. Captopril for hypertension and heart failure
3. Carvedilol for hypertension, heart failure, and angina prophylaxis
4. Furosemide as adjunctive management of his heart failure
5. Rosuvastatin to control his hypercholesterolemia and the associated ri sks

16. A coronary artery sample was removed from a healthy animal, put inside a suitable oxygenated salt and nutrient solution, and connected to a transducer that measured increases (contraction) or decreases (relaxation) of smooth muscle tension (force). ACh was then added to give the cumulative concentrations shown

As expected, in the control setting (left) ACh caused concentration-dependent vasorelaxation (equivalent to vasodilation in the intact animal).

The ACh was washed out several times, control conditions returned. The conditions were manipulated, and then the ACh  dose-response experiment was repeated (right). Now the data show increased tension developed by the muscle sample (vasoconstriction in vivo) in response to ACh and incremental increases of i ts concentration.

Which one of the following summarizes what was most l ikely done to the vessel under the experimental conditions, before retesting the responses to added ACh? Assume that the vascular responses in this animal model are identical to those that would occur in a human.

1. Endothelium was removed mechanically
2. Isoproterenol was added right before ACh
3. Muscarinic receptors were blocked with atropine
4. Sample was pretreated with prazosin
5. Tissue was pretreated with botulinum toxin

17. A 28-year-old woman i s receiving drug therapy for essential (primary) She subsequently becomes pregnant. You realize that the drug she’s been taking for her high blood pressure can have serious, i f not fatal, effects on the fetus (i t i s in pregnancy category X). As a result, you stop the current antihypertensive drug and substitute another that i s deemed to be equiefficacious in terms  of her blood pressure, and safer for the fetus. Which drug was she most l ikely taking before she became pregnant?

1. α-Methyldopa
2. Captopril
3. Furosemide
4. Labetalol.
5. Verapamil

18. We treat a patient with a drug that affects the clotting-thrombolytic systems for a time sufficient to let the drug’s effects and blood levels stabilize at a therapeutic We then i solate platelets from a blood sample and test their in vi tro aggregatory responses to ADP, collagen, PAF, and thromboxane A₂. Aggregatory responses to ADP are inhibited; responses to the other platelet proaggregatory agonists are unaffected. Which drug exhibits these properties?

1. Aspirin
2. Bivalirudin
3. Clopidogrel
4. Heparin
5. Warfarin

19. Your newly diagnosed hypertensive patient has vasospastic angina. Which drug or drug class would be the most rational for starting anti- hypertensive therapy because i t exerts not only antihypertensive effects, but also directly lowers myocardial oxygen demand and consumption and tends to inhibit cellular processes that otherwise favor coronary vaso-spasm? Assume there are no other specific contraindications to the drug you

1. Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker
2. β-Adrenergic blocker
3. Nifedipine
4. Thiazide diuretic
5. Verapamil (or diltiazem)

20. You are reviewing the medication history of a 59-year-old He has been taking ramipril and pravastatin for the last 5 years. Other medications include metformin for type 2 diabetes mellitus, and escitalopram to help manage his depression. At his last cl inic vis i t, a year ago, he was told to continue his current medications but he was also started on s low-release niacin because diet, exercise and other l i festyle modifications, and his current medications were not adequate. What was the most l ikely reason for adding the niacin?

1. Counteract deficiencies of B-vitamin absorption caused by the antidepressant
2. Counteract polyphagia, and over-eating, caused by the metformin.
3. Lower HDL and triglyceride levels that did not respond adequately to the statin
4. Prevent statin-induced neuropathy
5. Slow the progression of diabetic nephropathy caused by the ACE inhibitor

21. Quinidine i s ordered for a patient with recurrent atrial fibrillation and who refuses any interventions other than drugs in an attempt to terminate and control the He has some pulmonary fibrosis and a thyroid disorder—both leading you to conclude that amiodarone therapy might not be the best approach. Which statement applies to the quinidine?

1. Decreases SA nodal automaticity due to a strong anticholinergic/vagolytic effect
2. Is l ikely to increase blood pressure via a direct vasoconstrictor effect
3. Is contraindicated i f the patient also requires anticoagulant therapy
4. Tends to increase electrical impulse conduction velocity through the AV node
5. Will increase cardiac contractility (positive inotropic effect) independent of i ts antiarrhythmic effects