The correct answer is B. Digitalis is a cardiac glycoside that slows conduction through the AV node via parasympathomimetic actions, which can be blocked by atropine.

Atropine (choice A) blocks cardiac muscarinic receptors, thereby increasing conduction through the AV node.

Nicotine (choice C) increases conduction by stimulating sympathetic autonomic ganglia and the adrenal medulla.

Norepinephrine (choice D) increases conduction by stimulating cardiac β receptors.

Quinidine (choice E) acts centrally to decrease vagal tone, thereby increasing AV conduction.

The correct answer is C. Hydroxymethyl glutaryl-CoA reductase (HMG-CoA reductase) catalyzes the rate-limiting step in cholesterol synthesis, in which HMG-CoA (formed from 3 acetyl-CoA molecules) is reduced to mevalonic acid, using 2 NADPH. Lovastatin and pravastatin reduce cholesterol synthesis and lower serum cholesterol levels by inhibiting this enzyme. Lovastatin is metabolized by the CYP3A isoform of cytochrome P450. In contrast, gemfibrozil and clofibrate lower cholesterol by increasing the activity of lipoprotein lipase, which is produced by the endothelial cells of the vasculature of adipose and muscle tissue.

Acetyl-CoA carboxylase (choice A) catalyzes the first step in fatty acid synthesis.

Carbamoyl phosphate synthetase (choice B) catalyzes the rate-limiting step in urea synthesis.

Pyruvate dehydrogenase (choice D) catalyzes the transition step between glycolysis and the TCA (Krebs) cycle.

Uridyl transferase (choice E) is employed in galactose metabolism.

The correct answer is E. All of the medications listed as answer choices can be effectively used in the treatment of hypertension. Spironolactone is a "potassium-sparing" diuretic that exerts its action primarily as a competitive inhibitor of aldosterone receptors in the distal nephron. One of the reported side effects of spironolactone is gynecomastia. None of the other choices have gynecomastia as a side effect.

Captopril (choice A) is an angiotensin-converting enzyme (ACE) inhibitor that causes a decrease in plasma angiotensin II concentration, resulting in decreased aldosterone secretion.

Furosemide (choice B) is a "loop diuretic" that acts by inhibiting the reabsorption of sodium and chloride ions in the loop of Henle as well as in the proximal and distal renal tubules.

Hydrochlorothiazide (choice C) is a "thiazide diuretic" that inhibits the reabsorption of sodium and chloride ions in the distal renal tubules.

Metoprolol (choice D) is a beta-adrenergic receptor-blocking agent that has a preferential effect on beta₁ adrenoreceptors, which are mostly located in cardiac muscle.

The correct answer is E. This patient is presenting with the classic signs and symptoms of hypertrophic cardiomyopathy. Patients with this condition often initially present with complaints of dyspnea and chest pain. They also may have experienced recent episodes of post-exertional syncope. On examination, there is usually a sustained apical impulse, loud S₄, and systolic ejection murmur. The echocardiogram is diagnostic for this condition, as it will typically show systolic anterior motion of the mitral valve, asymmetric left ventricular hypertrophy, and early closing followed by the reopening of the aortic valve. Beta-receptor blocking agents, such as metoprolol, are the most commonly used initial agents in symptomatic patients, especially when dynamic outflow is noted on the echocardiogram. Beta-blockers generally prevent the appearance of dyspnea, angina, and arrhythmias in around 50% of all patients. Calcium channel blockers, such as verapamil, have also been effective in symptomatic patients.

Bretylium (choice A) is a class III antiarrhythmic indicated for the treatment of ventricular fibrillation and ventricular tachycardia.

Digoxin (choice B) is an antiarrhythmic used primarily for the treatment of atrial fibrillation and flutter; this agent is also used to decrease the signs and symptoms associated with congestive heart failure.

Enalapril (choice C) is an angiotensin-converting enzyme (ACE) inhibitor indicated for the treatment of hypertension and congestive heart failure (CHF). Note that ACE inhibitors are indicated for the "initial" and chronic treatment of CHF.

Lidocaine (choice D) is a class Ib antiarrhythmic indicated for the treatment of ventricular tachycardia.

The correct answer is B. Niacin, or vitamin B3, is an agent that results in the following physiologic changes: LDL reductions tend to occur in 5-7 days with the maximal effect seen in 3-5 weeks; triglycerides and VLDL are reduced by 20% to 40% in 1-4 days; and HDL levels can increase by 20%. This agent is indicated as adjunctive therapy in patients with elevated cholesterol and triglycerides when diet and other nondrug therapies are inadequate. The most common adverse effect of this agent is generalized flushing with a sensation of warmth, especially in the facial area. This reaction may be so severe in some patients that they discontinue therapy. Other common adverse effects include hepatotoxicity, tachycardia (compare with choice A), hypoalbuminemia (compare with choice C), hyperglycemia (compare with choice D), nausea, vomiting, hyperuricemia, glucose intolerance, pruritus, peptic ulcer disease, and dry skin.

The correct answer is A. The patient is presenting with the classic signs and symptoms of congestive heart failure (CHF). Heart failure is a pathologic state in which an abnormality of cardiac function produces a failure of the heart to pump blood throughout the body at a rate sufficient to meet the requirements of the metabolizing tissues. Some of the adaptive mechanisms to compensate for the "failing heart" are increasing pre-load (through the Frank-Starling mechanism), development of myocardial hypertrophy (to restore the increased ventricular wall stress to within normal limits), redistribution of cardiac output from nonvital organs to vital organs, and neurohumoral adjustments. The major criteria for diagnosing heart failure are the appearance of paroxysmal nocturnal dyspnea, neck vein distension, rales, cardiomegaly, acute pulmonary edema, S3 gallop, increased venous pressure (> 16 cm H₂O), and positive hepatojugular reflex. Of the agents listed, only captopril is proven to delay the progression of this condition by protecting the ventricles from remodeling. Captopril is an ACE inhibitor that is now considered to be a standard therapy for the treatment of CHF. In addition to the protective effects, this agent causes vasodilation and blocks the detrimental neurohormonal activity associated with the disorder. None of the other agents have been proven to protect the failing heart in this condition.

Digoxin (choice B) is an agent that produces a positive inotropic effect by increasing the force and velocity of myocardial contraction.

Furosemide(choice C) is also considered to be a first-line agent in the treatment of heart failure. This agent is indicated for the treatment of edema associated with CHF, hepatic cirrhosis, and renal disease, as well as treatment of hypertension (furosemide and torsemide).

Hydrochlorothiazide(choice D) is used in the treatment of heart faioure. This agent is indicated for the treatment of edema associated with CHF as well as treatment of hypertension.

Verapamil (choice E) is a calcium channel blocker indicated for the treatment of hypertension and a variety of cardiac arrhythmias. This agent is contraindicated in the treatment of heart failure, since it has a strong negative inotropic effect on the heart.

The correct answer is A. Beta₁-selective antagonists are often used to control hypertension in patients, such as asthmatics, who might experience bronchoconstriction with non-selective beta antagonists (e.g., propranolol). Remember that beta₁ receptors predominate in the heart, while beta₂ receptors predominate in the lungs. A mnemonic to help you remember the main beta₁ (cardioselective) blockers is "A BEAM": acebutolol, betaxolol, esmolol, atenolol, metoprolol.

Labetalol (choice B) blocks alpha₁, beta₁, and beta₂ receptors, and is useful in treating hypertensive emergencies and the hypertension of pheochromocytoma.

Nadolol (choice C) blocks both beta₁ and beta₂ receptors, and is known for its very long half-life (14-24 hours).

Prazosin (choice D) blocks alpha₁ receptors, and is used primarily in the treatment of hypertension.

Timolol (choice E) blocks both beta₁ and beta₂ receptors and is frequently used for the treatment of open-angle glaucoma.

The correct answer is D. Lidocaine is a class IB antiarrhythmic indicated for the treatment of ventricular tachycardia. This agent blocks sodium channels and shortens the action potential duration. Both mexiletine and tocainide are classified as class IB antiarrhythmic agents that shorten the action potential duration and refractory period and improve the resting potential duration. These agents produce a modest suppression of sinus node automaticity, as well as AV node conduction.

Esmolol (choice A) is a class II antiarrhythmic agent that exerts its action as an ultrashort-acting beta-1 adrenergic blocking agent with cardioselective properties.

Diltiazem (choice B) and verapamil are calcium channel blocking agents and class IV antiarrhythmic agents. As antiarrhythmics, these agents decrease and slow SA and AV node conduction.

Both disopyramide (choice C) and procainamide (choice E) are class IA antiarrhythmics. They decrease myocardial excitability, conduction velocity, contractility, and automaticity. They also prolong the effective refractory period and block vagal stimulation of the AV node.

The correct answer is D. This classic drug response, called epinephrine reversal, is a favorite on the USMLE and in pharmacology classes. Epinephrine, a nonselective alpha and beta adrenergic agonist, increases blood pressure. The unknown drug is an alpha adrenergic antagonist, such as phentolamine, which blocks epinephrine's vasoconstrictive action on arterioles. Subsequent administration of epinephrine produces only beta receptor stimulation, causing vasodilation in skeletal muscle, leading to a decrease in blood pressure. Epinephrine, for all practical purposes, now acts like the nonspecific beta agonist, isoproterenol. This effect is called epinephrine reversal because of the fact that epinephrine originally increases BP and then produces the opposite effect after phentolamine administration.

An acetylcholinesterase inhibitor (choice A) should not affect the subsequent administration of epinephrine.

A nicotinic ganglionic blocker (choice B) may prevent a potential decrease in heart rate due to baroreceptor reflexes, but epinephrine would still cause an increase in blood pressure because its access to end organ receptors would be unaltered.

A nonselective alpha agonist (choice C) might not affect a second administration of epinephrine fifteen minutes later because the agonist effect would probably be gone. But, if there was still some agonist on board at the time of the second administration, it would only serve to enhance epinephrine's increase in blood pressure.

A nonselective beta receptor antagonist (choice E) would enhance epinephrine's increase in blood pressure. After administration of a beta antagonist such as propranolol, epinephrine would only produce alpha receptor stimulation. This would increase blood pressure to a greater extent than epinephrine alone.

The correct answer is A. Digoxin is a cardiac glycoside indicated for the treatment of congestive heart failure, atrial fibrillation, and atrial flutter. The therapeutic drug serum levels for digoxin are 0.5-2.2 ng/mL. Toxicity typically occurs when digoxin levels are greater than 2.5 ng/mL; if the patient is hypokalemic, however, toxicity can occur at any therapeutic concentration. Hypokalemia sensitizes the myocardium to digoxin and may reduce the positive inotropic effects of the medication. Other signs and symptoms of digoxin toxicity include nausea, vomiting, anorexia, and appearance of yellow-green halos in the visual field, as well as the development of cardiac arrhythmias.

Although hyponatremia (choice B) and hypophosphatemia (choice C) can result in the development of other pathological disturbances, they do not potentiate digoxin toxicity.

Vitamin B12 deficiency (choice D) is associated with the development of pernicious anemia.

Vitamin K deficiency (choice E) is associated with the development of clotting disorders. Vitamin K deficiency also can potentiate warfarin toxicity.

The correct answer is A. The patient meets the criteria for exertional angina: precordial chest pain precipitated by stress or exertion, generally quickly relieved by rest and/or nitrates. The beta-adrenergic blocking agents prevent angina by decreasing myocardial oxygen requirements during exertion and stress through the reduction of heart rate, myocardial contractility, and blood pressure. Beta-blockers are the only antianginal agents that have been proven to prolong life in patients with coronary disease and are considered to be first-line agents in the treatment of chronic angina. Beta blockers with intrinsic sympathomimetic activity (acebutolol and pindolol) are generally not recommended for patients with angina since they may exacerbate the angina in some patients.

Currently in the U.S., agents indicated for treatment of angina include atenolol (choice B), metoprolol (choice C), nadolol (choice D), and propranolol (choice E).

The correct answer is A. Cocaine is a stimulant that causes hypertension and tachycardia by blocking norepinephrine uptake. This leads to an accumulation of norepinephrine in the synapse, causing greater stimulation of postsynaptic receptors. The receptors that mediate the systemic vasoconstriction are alpha-1 adrenergic receptors, and the receptors that mediate the increases in heart rate and inotropic state are beta-1 adrenergic receptors.

Direct stimulation of alpha-1 receptors (choice B) would increase blood pressure, but this is not cocaine's mechanism of action.

Direct stimulation of beta-1 receptors (choice C) could increase blood pressure by increasing inotropic state, but this is not cocaine's mechanism of action.

Direct stimulation of beta-2 receptors (choice D) would cause vasodilation in the skeletal muscle vasculature, leading to a decrease in blood pressure.

Induction of norepinephrine release (choice E) would increase blood pressure, but this is the mechanism of action of amphetamine, not cocaine.

Cocaine is not metabolized to a false neurotransmitter (choice F).

The correct answer is C. Accessory pathways between the atria and ventricle that avoid the conduction delay of the atrioventricular node may predispose the myocardium to the development of reentrant tachycardias. Examples of these dysrhythmias include atrial fibrillation, atrioventricular reentry tachycardia (AVRT), and atrial flutter. Most commonly, these specific reentry tachycardias make direct connections between the atria and ventricle though the Kent bundles [Wolff-Parkinson-White syndrome (WPWS)]. This produces a short PR interval but an early delta wave at the onset of a wide, slurred QRS complex owing to early ventricular depolarization of the region adjacent to the pathway. In patients with WPWS and atrial fibrillation, digoxin can enhance transmission of impulses through accessory pathways. This may result in an extremely rapid ventricular rate, and even ventricular fibrillation. Digoxin is an antiarrhythmic used primarily for the treatment of atrial fibrillation and flutter. All the other agents can be used to treat supraventricular tachycardias.

Adenosine (choice A) is primarily used for conversion of paroxysmal supraventricular tachycardia (including that associated with accessory bypass tracts of WPWS) to normal sinus rhythm.

Amiodarone (choice B) is a class III/IA antiarrhythmic used in the treatment of refractory ventricular tachycardia and supraventricular tachycardia and in the prevention of ventricular tachycardia and ventricular fibrillation.

Disopyramide (choice D) and quinidine (choice E) are class IA antiarrhythmics used in the treatment of ventricular tachycardia and supraventricular tachycardia and in the prevention of ventricular fibrillation and symptomatic ventricular premature beats.

The correct answer is D. The patient has a ventricular tachycardia as indicated by the electrocardiogram: the appearance of a wide-complex ventricular tachycardia with a rate of 126 beats per minute. Propranolol is a Type II antiarrhythmic agent that acts by decreasing SA node automaticity, increasing AV nodal refractoriness, and decreasing AV nodal conduction velocity. Propranolol is indicated for the treatment of ventricular tachycardias, supraventricular arrhythmias, and for slowing the ventricular rate during atrial fibrillation and atrial flutter.

Amiodarone (choice A) is a Type III antiarrhythmic that acts by prolonging the action potential duration in tissue with fast-response action potentials. Amiodarone is indicated for the treatment of refractory ventricular arrhythmias that are unresponsive to other antiarrhythmics.

Disopyramide (choice B) is a Type IA antiarrhythmic that reduces the maximal velocity of phase 0 depolarization by blocking the inward sodium current in tissue with fast-response action potentials. It also increases the action potential duration. Disopyramide is indicated for the treatment of atrial and ventricular extrasystoles and atrial and ventricular tachyarrhythmias.

Lidocaine (choice C) is a Type IB agent that attenuates phase 4 depolarization, decreases automaticity and cases a decrease in excitability and membrane responsiveness. This agent raises the ventricular fibrillation threshold as well as suppresses arrhythmias casued by abnormal automaticity. Lidocaine is used in the treatment of the acute management of ventricular arrhythmias that occur during periods of cardiac ischemia, such as cardiac surgery or secondary to an acute MI.

Verapamil (choice E), a Type IV antiarrhythmic agent, blocks calcium channels, thereby decreasing conduction velocity and increasing refractoriness in tissue with slow-response action potentials. Verapamil is indicated for the treatment of atrial fibrillation and flutter as well as other atrial tachycardias.

The correct answer is E. Verapamil is a "first-generation" calcium channel blocker that has been associated with an accelerated progression of CHF in certain patients. This agent has a strong negative inotropic effect, which leads to a decrease in the force and velocity of myocardial contraction. Hence, this agent would most likely exacerbate the patient's heart failure. As a general rule, the use of calcium channel blockers in CHF is reserved for patients who also have hypertension and/or anginal symptoms.

Amlodipine (choice A) and felodipine (choice C) are the most commonly used calcium channel blocking agents in patients with CHF. These two medications may actually produce a small increase in myocardial contractility and cardiac output.

Diltiazem (choice B) is generally avoided in patients with CHF, since it has mild-to-moderate negative inotropic effects leading to a small decrease in myocardial contractility. However, the negative inotropic effects of verapamil are much greater than those seen with diltiazem.

Isradipine (choice D) is a calcium channel blocker that can safely be used at lower doses in patients with CHF; it seems to have no net effect on myocardial contractility.

The correct answer is B. The effect of digoxin on the myocardium is dose-related and involves both a direct and indirect action on the cardiac muscle. The indirect actions involve a vagomimetic action, which decreases the conduction rate through the atrioventricular node (AV node), and a depression of the sinoatrial node. Digoxin is indicated for the treatment of atrial fibrillation, especially when the ventricular rate is elevated. Digoxin is also indicated for the treatment of congestive heart failure and atrial flutter, although electrical cardioversion is often the treatment of choice for atrial flutter.

Atropine (choice A) is an anticholinergic agent that has been used in the treatment of atrioventricular heart block to increase conduction through the AV node when increased vagal tone is a major factor in the conduction defect.

Lidocaine (choice C) is an antiarrhythmic agent indicated for the treatment of ventricular arrhythmias. Lidocaine has a variable effect on AV node conduction. For the most part, conduction through the AV node remains unchanged.

Procainamide (choice D) is a class IA antiarrhythmic agent indicated for the treatment of ventricular arrhythmias. It often causes AV node conduction to be slightly increased.

Quinidine (choice E) is indicated for the conversion of atrial fibrillation/flutter. However, quinidine exerts an indirect anticholinergic effect that will decrease vagal tone and may facilitate conduction in the AV node.

The correct answer is B. Angiotensin converting enzyme (ACE) inhibitors, such as enalapril, captopril and fosinopril, block the conversion of angiotensin I to angiotensin II. These agents are indicated for the treatment of hypertension, myocardial infarction, diabetic neuropathy and heart failure. With respect to heart failure, ACE inhibitors improve hemodynamic measures and congestive symptoms, reduce cardiovascular events and hospitalization, and improve survival (decrease morbidity and mortality).

Blocking catecholamine release from peripheral sympathetic nerves (choice A) is the antihypertensive effect seen with peripherally acting adrenergic neuron blockers (e.g., guanethidine and bretylium).

Atenolol is a beta1-adrenergic receptor blocking agent used in the treatment of hypertension. Medications in this drug class lower blood pressure by reducing both cardiac output (choice C) and decreasing renin release from the kidney (to a lesser extent).

Diuretics decrease intravascular volume (choice D), which ultimately leads to a reduction in blood pressure.

Increasing renin release from the kidney (choice E) would increase, not decrease, blood pressure.

The correct answer is E. Amlodipine is a calcium channel-blocking agent indicated for the treatment of mild to moderate hypertension and angina. Amlodipine selectively blocks calcium ion influx across the membranes of cardiac and vascular smooth muscle cells without changing serum calcium concentrations.

Terazosin is an example of an alpha-1 adrenergic receptor-blocking agent (choice A) that is indicated for the treatment of hypertension and benign prostatic hypertrophy.

Enalapril is an example of an angiotensin converting enzyme (ACE) inhibitor (choice B) indicated for the treatment of hypertension and congestive heart failure. When ACE is inhibited, it prevents the conversion of angiotensin I to angiotensin II, leading to a decrease in aldosterone levels.

Propranolol is an example of a non-selective beta-1 receptor (choice C) and beta-2 receptor (choice D) blocking agent indicated for the treatment of hypertension. Beta-1 receptor blockade leads to negative inotropic and chronotropic effects on the heart. Beta-2 receptor blockade causes bronchoconstriction.

The correct answer is D. The question states that the patient began antihypertensive therapy 3 months earlier and now has elevated total cholesterol, LDL, and triglyceride levels, as well as a low HDL level. Therefore, there is a strong possibility that the antihypertensive medication caused the dyslipidemia. Metoprolol is a beta-adrenergic blocking agent that is known to cause dyslipidemias in patients. None of the other medications are associated with the development of dyslipidemias.

Benazepril (choice A), an ACE inhibitor, and diltiazem (choice B), a calcium-channel blocker, are both used to treat essential hypertension, and are not associated with the development of dyslipidemias.

Both guanfacine (choice C), a centrally acting alpha-2-receptor agonist, and prazosin (choice E), a peripherally acting alpha-1-receptor blocking agent, can be used to treat hypertension. However, due to their side-effect profiles, these agents are generally used in patients unresponsive to other antihypertensive therapies.

The correct answer is B. First, eliminate all answers in which Drug X does not produce an increase in blood pressure (BP). Choice A should be eliminated because acetylcholine stimulates the noninnervated muscarinic (M3) receptors that are located on endothelial cells of the vasculature. Stimulation of these receptors releases endothelial-derived relaxing factor (EDRF; nitric oxide), which produces a relaxation of the neighboring smooth muscle cells, leading to a decrease in BP. Choice C should be eliminated because isoproterenol (a nonspecific beta agonist) decreases BP by stimulating beta-2 receptors in the vasculature.

Epinephrine, norepinephrine, and phenylephrine all increase BP, so the remaining answers must be eliminated by examining the effects of Drug Y on Drug X. Start with choice B: Epinephrine is an agonist at alpha-1, alpha-2, beta-1, and beta-2 receptors; phentolamine is an antagonist at alpha-1 and alpha-2 receptors. Therefore, after the administration of phentolamine, epinephrine can stimulate only beta receptors, which would produce a decrease in BP. Epinephrine is now acting like isoproterenol. This is called epinephrine reversal (the name stems from the fact that epinephrine originally increases BP and then produces the opposite effect after phentolamine administration). Therefore, choice B is correct.

Choice D: Norepinephrine is an agonist at alpha-1, alpha-2, and beta-1 receptors; propranolol is a nonselective beta antagonist. After administration of propranolol, norepinephrine can stimulate only alpha receptors, which will still cause vasoconstriction (primarily via alpha-1 stimulation in the vasculature) and therefore increase BP.

Choice E: Phenylephrine is an alpha-1 agonist; hexamethonium is a nicotinic ganglionic blocker. Hexamethonium administration would be predicted to eliminate the baroreceptor response after the second phenylephrine administration by blocking the peripheral ganglia. However, phenylephrine will still reach the alpha-1 receptors on the vasculature to produce an increase in blood pressure.

The correct answer is A. This question is essentially asking for the mechanism of action of the patient's medication. Amiodarone is a class III (with IA properties as well) antiarrhythmic that blocks potassium channels, prolongs repolarization, widens the QRS, and prolongs the QT interval. Amiodarone is used in the treatment of refractory ventricular tachycardia and supraventricular tachycardia, and in the prevention of ventricular tachycardia and ventricular fibrillation.

Lidocaine (choice B) is a class IB antiarrhythmic indicated for the treatment of ventricular tachycardia. This agent blocks sodium channels and shortens the action potential duration.

Propranolol (choice C) is a beta-receptor blocking agent and class II antiarrhythmic that decreases automaticity and prolongs atrioventricular conduction and refractoriness. It is indicated for the treatment of supraventricular tachycardia.

Quinidine (choice D) is a class IA antiarrhythmic used in the treatment of ventricular tachycardia and supraventricular tachycardia, and in the prevention of ventricular fibrillation and symptomatic ventricular premature beats. It blocks sodium channels, slows the rate of rise of the action potential, and prolongs its duration.

Verapamil (choice E) is a calcium channel blocker and a class IV agent. It decreases automaticity and slows atrioventricular conduction. This agent is indicated for the treatment of supraventricular tachycardias.

The correct answer is E. The ductus arteriosus is an arterial channel connecting the aorta with the pulmonary trunk during intrauterine life. Closure of this embryonal vessel occurs in the first few days after birth. Patency of the ductus is maintained by prostaglandins, more specifically prostaglandin E. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin (choice B), promote closure of this structure since NSAIDs inhibit prostaglandin synthesis. Prostaglandin E and NSAIDs can be used therapeutically to maintain a patent ductus arteriosus or to promote its closure.

Glucocorticoids (choice A) can accelerate pulmonary maturation and stimulate production of surfactant, but do not affect the ductus arteriosus.

Insulin (choice C) inhibits surfactant production, but has no effect on the ductus arteriosus.

Oxytocin (choice D) is a hypothalamic hormone that stimulates contraction of smooth muscle in the uterus and mammary glands. It has no effect on the ductus arteriosus.

The correct answer is A. The angiotensin-converting enzyme (ACE) inhibitors are indicated for the treatment of hypertension, heart failure, and diabetic nephropathy. These agents may cause hyperkalemia and mild hyponatremia (compare to choice B), as well as neutropenia, anaphylactoid reactions, angioedema, chronic cough, and fetal abnormalities. Laboratory evaluation should be performed periodically, especially for patients at risk for the development of hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and use of potassium-containing products, including salt substitutes. These agents do not affect phosphate (choices C and E) blood levels.

The correct answer is C. Tissue plasminogen activator (tPA) is produced by recombinant DNA technology. It is indicated in the management of acute myocardial infarction, acute ischemic stroke, and pulmonary embolism. The agent is known as a "clot buster," because of its mechanism of action: it binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin, which initiates fibrinolysis and essentially dissolves the thrombus. Since tPA is a thrombolytic, bleeding (or hemorrhage) is the most common complication. The bleeding caused by tPA can be divided into two broad categories: 1) internal bleeding involving the gastrointestinal, genitourinary, and respiratory tracts, as well as intracranial sites, and 2) superficial bleeding.

Since tPA is produced by recombinant DNA technology, the incidence of anaphylactic reactions (choice A) is very low. In other words, this compound is essentially the same as the tPA produced in the human body.

Cardiac arrhythmias (choice B) have occurred with tPA use secondary to thrombolysis with reperfusion; however, the incidence is very low.

Hypotension (choice D) is also a rare side effect of tPA therapy.

Although the mechanism of tPA is to "dissolve blood clots," there is a very low occurrence of thrombosis (choice E) secondary to the use of this agent.

The correct answer is B. The question is essentially asking, "Which of the following agents would be recommended in a women with diabetic nephropathy and hyperuricemia?" The angiotensin-converting enzyme (ACE) inhibitors, such as captopril, are commonly recommended for the treatment of hypertension in diabetic patients, especially those with renal complications, since these agents have been shown to delay the progression of renal disease. Furthermore, these agents are generally well tolerated.

Atenolol (choice A) is a beta-1 adrenergic antagonist that is generally not recommended for diabetic patients since it can "block" the appearance of the normal signs and symptoms of hypoglycemia.

The thiazide diuretics, such as hydrochlorothiazide (choice C) and indapamide (choice D), are commonly associated with hyperuricemia. Furthermore, they can precipitate an acute gout attack in patients with hyperuricemia.

Minoxidil (choice E) is a direct acting vasodilator most commonly used in the treatment of severe refractive hypertension because of its profound side effect profile. This agent is rarely used as an initial treatment agent.

The correct answer is A. The disease is adult polycystic kidney disease. The cysts impair perfusion of glomeruli, which triggers the secretion of renin by the juxtaglomerular complexes. The renin secretion triggers the renin/angiotensin/aldosterone system. ACE (angiotensin-converting enzyme) inhibitors directly interrupt this system by blocking the conversion of angiotensin I to angiotensin II.

Calcium channel blockers (choice B) (e.g., nifedipine. verapamil, diltiazem) control hypertension by blocking calcium entry into cells, thereby inhibiting vascular smooth muscle contraction.

Centrally acting sympatholytics (choice C) (e.g., clonidine) lower blood pressure by stimulating adrenergic receptors (alpha 2) in the brain, thus reducing sympathetic outflow.

Nitrates (choice D) (e.g., nitroglycerin) release nitric oxide in smooth muscle cells, stimulating guanylate cyclase. The subsequent increase in cGMP leads to smooth muscle relaxation and vasodilation.

Thiazide diuretics (choice E) (e.g., hydrochlorothiazide) act on the early distal tubule, and would not directly address the cause of the hypertension.

The correct answer is E. The patient is presenting with signs and symptoms of drug-induced lupus. This complication is associated with procainamide and other agents, including hydralazine, chlorpromazine, isoniazid, methyldopa, and quinidine. Procainamide is a class IA agent, similar in action to quinidine, and is indicated for the treatment of ventricular arrhythmias. This agent is has also been associated with agranulocytosis, bone marrow depression, neutropenia, hypoplastic anemia, and thrombocytopenia.

Digoxin (choice A) is a cardiac glycoside used for congestive heart failure (CHF), atrial fibrillation, and atrial flutter. Signs and symptoms of digoxin toxicity include nausea, vomiting, anorexia, appearance of yellow-green halos in the visual field, and the development of cardiac arrhythmias.

Disopyramide (choice B) is a class IA agent indicated for the treatment of documented ventricular arrhythmias. It possesses strong anticholinergic effects and is associated with the development of atrial tachyarrhythmias, heart block, and conduction abnormalities.

Flecainide (choice C) is a class IC agent indicated for the treatment of life-threatening ventricular arrhythmias. It is associated with paresthesias, ataxia, flushing, vertigo, tinnitus, depression, and a worsening of cardiac arrhythmias.

Mexiletine (choice D) is a class IB agent indicated for the treatment of life-threatening ventricular arrhythmias. It is associated with the development of palpitations, chest pain, CHF, edema, arrhythmias, tremor, nervousness, blurred vision, CNS stimulation, and convulsions.

The correct answer is D. Dilated (congestive) cardiomyopathy results in a diminution in the contractile function of the left, right, or even both ventricles of the heart. The loss of heart muscle function frequently results in the development of congestive heart failure. This patient is presenting with classic signs and symptoms of congestive cardiomyopathy/congestive heart failure; orthopnea, paroxysmal nocturnal dyspnea, nocturia, tachycardia, pulmonary rales, and a third heart sound (S3) are noted. The anthracycline antibiotics doxorubicin and daunomycin both are commonly associated with the development of congestive cardiomyopathy; however, the incidence is much higher with doxorubicin therapy. Doxorubicin is an antibiotic antineoplastic agent commonly used in the treatment of sarcomas, multiple myeloma, malignant lymphoma, acute leukemias, and ovarian, breast, testicular, gastric, bladder, and throat cancer.

Bleomycin (choice A) is classified as an anticancer antibiotic and is one of the few chemotherapeutic agents that does not cause bone marrow suppression. Bleomycin, along with busulfan, carmustine (BCNU), and methotrexate, are commonly associated with the development of pulmonary toxicity. Bleomycin is indicated for the treatment of squamous cell carcinomas of the head, neck, penis, cervix, and vulva, as well as several types of lymphomas.

Carmustine (BCNU; choice B) is an alkylating agent commonly used in the treatment of Hodgkin's disease and other lymphomas. The most notable side effects of this agent are "delayed" myelosuppression and pulmonary toxicity.

Cisplatin (choice C) is an alkylating agent indicated for the treatment of metastatic testicular and ovarian tumors in combination with other agents. This agent can cause severe bone marrow suppression as well as profound renal toxicity.

Methotrexate (choice E) is an antimetabolite and folic acid antagonist commonly used in various neoplastic disorders, such as pediatric acute lymphocytic leukemia, Burkitt's lymphoma, non-Hodgkin's lymphoma, breast, head, neck, and small cell lung cancer. The most common side effects seen with this agent are mucositis, gastrointestinal ulcer, hepatotoxicity, bone marrow suppression, and pulmonary toxicity.

The correct answer is C. Lovastatin is an agent that competitively inhibits the enzyme HMG-CoA reductase, which catalyzes the rate-limiting step in cholesterol biosynthesis. The result is an increase in HDL and decrease in LDL, VLDL, and triglycerides. Statins such as lovastatin, simvastatin, and pravastatin are indicated for the treatment of hypercholesterolemia, atherosclerosis, and to slow the progression of coronary atherosclerosis in patients with coronary artery disease.

Resins such as cholestyramine act by binding bile acids (choice A). They cause the liver to use cholesterol for the synthesis of new bile acids.

Inhibition of hepatic VLDL secretion (choice B) is the mechanism of action of niacin.

Both niacin and gemfibrozil stimulate HDL production (choice D); however, this is not their main mechanism of action.

Gemfibrozil (as well as clofibrate) works by increasing the activity of lipoprotein lipase (choice E), leading to increased clearance of VLDL, which is elevated in familial hypertriglyceridemia.

The correct answer is A. Indapamide is classified as a thiazide diuretic. Thiazide diuretics, such as indapamide, hydrochlorothiazide, and metolazone, are commonly used to treat various forms of edema and essential hypertension. One of the unlabeled uses of this medication is for the adjunctive treatment/prevention of osteoporosis in postmenopausal women with hypertension. Thiazides are effective in reducing the risk of osteoporosis because they decrease the elimination of calcium.

Indapamide, like other thiazide diuretics, increases the elimination of chloride (choice B), magnesium (choice C), potassium (choice D), and sodium (choice E). Since potassium loss can be substantial, patients are generally advised to take this medication with food products high in potassium, such as bananas or orange juice.

The correct answer is A. Losartan competitively inhibits angiotensin II at the AT-1 receptor. Angiotensin II is the most powerful sodium-retaining hormone of the body. The effects of angiotensin II can be attributed to (1) direct stimulation of sodium reabsorption in the proximal and distal tubules of the kidney; (2) stimulation of aldosterone secretion, which is another sodium-retaining hormone; and (3) constriction of the efferent arterioles in the kidney, which increases peritubular colloid osmotic pressure, thereby enhancing reabsorption of salt and water from the proximal tubule. Therefore, when the effects of angiotensin II are blocked with losartan, the ability of the kidneys to excrete sodium increases greatly.

Because angiotensin II normally stimulates aldosterone (choice B) secretion, losartan decreases plasma aldosterone levels.

The decrease in arterial pressure (choice C) caused by losartan (because of its effect to increase the loss of salt and water) should also decrease the total peripheral resistance by an autoregulatory mechanism. That is, when arterial pressure is lowered, the arterioles dilate, which maintains blood flow at a constant level in the peripheral tissues.

Overstretching of the two atria, usually as a result of increased blood volume, causes atrial natriuretic peptide (choice D) to be released into the blood. Because losartan increases the ability of the kidneys to excrete sodium (and therefore water), the blood volume should decrease, and the plasma levels of atrial natriuretic peptide should decrease.

Angiotensin II is a potent vasoconstrictor. Blocking its effects with losartan would be expected to decrease total peripheral resistance (choice E).

The correct answer is D. Pregnant women with chronic hypertension "require" antihypertensive therapy when the diastolic pressure is greater than 100 mm Hg; however, some clinicians may decide to treat patients with diastolic blood pressures less than 100 mm Hg. For the initiation of therapy, methyldopa is still considered to be the agent of choice. Methyldopa is converted intraneuronally to α-methylnorepinephrine, an alpha-2 adrenergic agonist, which is subsequently released. Release of α-methylnorepinephrine in the medulla leads to a decrease in sympathetic outflow, thus lowering blood pressure. Methyldopa has been safely used in the treatment of hypertension during pregnancy; this agent is not associated with the development of teratogenic or other fetal abnormalities.

Diuretics, such as bumetanide (choice A) and hydrochlorothiazide (choice C), are often avoided since these agents can produce hypovolemia, leading to reduced uterine blood flow. Although these agents can be used during pregnancy, methyldopa and hydralazine are the drugs of choice for hypertension during pregnancy.

Fosinopril (choice B) is an angiotensin-converting enzyme (ACE) inhibitor that should not be administered to pregnant women, especially in the second or third trimesters. These agents have been associated with severe fetal and neonatal injury, such as hypotension, neonatal skull hypoplasia, anuria, renal failure, and death.

Along the same lines, the use of the angiotensin II receptor antagonists, such as valsartan (choice E), is not recommended since these agents cause fetal complications similar to the ACE inhibitors.

The correct answer is D. Acute gouty arthritis (AGA) is characterized by the rapid onset of pain, swelling, and inflammation. The attack is often monoarticular at first, affecting the first metatarsophalangeal (MTP) joint, eventually it may involve the insteps, ankles, heels, knees, wrist, fingers, and elbows. Note: > 90% of all gouty patients experience attacks in the great toe. Uric acid levels are generally > 7.5 mg/dL when an attack occurs. The predilection of acute gout for the peripheral joints of the lower extremities is related to the lower average temperature of these joints, as well as the higher intra-articular urate concentrations of these joints. Synovial effusions are postulated to occur in weight-bearing joints during the day; water is then absorbed from the effusion in the night, leaving a supersaturated solution of monosodium urate, which leads to an attack. Note that the patient is awakened from sleep in terrible pain. With respect to crystal-induced inflammation, phagocytosis of the urate crystals by leukocytes leads to rapid lysis of cells, which subsequently leads to an inflammatory reaction causing intense joint pain, erythema, warmth, and swelling. Factors that increase AGA attacks include: stress, trauma, alcohol, surgery, and a rapid lowering of serum uric acid. The thiazide diuretics are a common cause of drug-induced gout, causing hyperuricemia, as well as hypokalemia, hyponatremia, hypochloremia, hypomagnesemia, hypercalcemia, and glucose intolerance.

Atenolol (choice A) is a beta1-receptor blocking agent that can cause bradycardia, dizziness, vertigo, impotence in males, and bronchospasm in asthmatics.

Enalapril (choice B) is an angiotensin converting enzyme inhibitor that is associated with anaphylactoid reactions, angioedema, hypotension, hyperkalemia and cough, especially in asthmatic patients.

Both felodipine (choice C) and verapamil (choice E) are calcium channel blocking agents that are associated with hypotension and dizziness.

The correct answer is B. Patients who develop digoxin toxicity gradually during chronic therapy are often hypokalemic and hypomagnesemic secondary to concurrent diuretic therapy. Toxicity can also occur in those with concomitant ventricular dysrhythmias. In this case, the patient's premature ventricular contractions (PVCs) are most likely related to the development of hypokalemia secondary to the overuse of furosemide, a loop diuretic. All the other agents are associated with reducing digoxin blood levels, which would decrease the risk for digoxin toxicity.

Colestipol (choice A) is a bile-acid-binding resin that is indicated for the treatment of hypercholesteremia. When given with digoxin, this agent will bind in the intestinal tract and, hence, decrease the absorption of the drug into the body.

Glyburide (choice C) is a sulfonylurea indicated for the treatment of type 2 diabetes. Medications such as glyburide and sulfasalazine, which have "sulfa" components, are associated with the lowering of serum digoxin levels.

Phenytoin (choice D) is a hydantoin antiepileptic agent indicated for the treatment of tonic-clonic and partial complex seizures. This agent increases the metabolism of digoxin; hence, it will lower digoxin levels.

Sulfasalazine (choice E) is an agent indicated for the treatment of ulcerative colitis and rheumatoid arthritis, and lowers serum digoxin levels.

The correct answer is B. Captopril, an angiotensin-converting enzyme inhibitor (ACE inhibitor), reduces the mortality associated with myocardial infarction. ACE inhibitors decrease the amount of ventricular remodeling after infarction and reduce the risk of congestive heart failure; they may also diminish the risk of a second heart attack. ACE inhibitors are known to frequently cause a dry cough. They also cause headache, diarrhea, fatigue, nausea, and dizziness. All of the other agents might be prescribed in this setting, but dry cough is only associated with captopril.

Aspirin (choice A) is a nonsteroidal anti-inflammatory drug associated with increased bleeding time, gastrointestinal bleeding, and tinnitus.

Metoprolol (choice C), a beta-1 antagonist, can cause hypoglycemia, peripheral vasoconstriction, and CNS side effects.

Procainamide (choice D) is a group IA antiarrhythmic that can cause antimuscarinic and direct depressant effects on the heart, and may produce a reversible syndrome similar to lupus erythematosus.

Warfarin (choice E) is an oral anticoagulant that can cause bleeding at therapeutic doses, and bone defects in the developing fetus.