Cardio Pharm Qs - CHF, Diuretics, Anti-anginal, Anti-arrhythmics, Lipid Lowering

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

A

A 67-year-old man with a long history of heart failure was admitted to the hospital because of a heart failure exacerbation. His present medications included furosemide, captopril and carvedilol. On admission the patient showed the following hemodynamic profile: BP 100/60 mm Hg, pulse 118/min, cardiac output 2.6 L/min. The clinical examination confirmed the diagnosis of acute decompensated heart failure and an IV infusion of milrinone was started. What molecular event can most likely mediate the positive inotropic action of the drug? a. Activation of 1Ca + + /3Na + antiport b. cAMP-mediated increase in cardiac intracellular Ca + + levels c. cGMP-mediated dephosphorylation of myosin light chain d. Increased binding of Ca + + to calmodulin e. Opening of K + channels in cardiac cell membraneD.

A patient with acute decompensated heart failure usually needs positive inotropic agents. In a patient under beta-blockers phosphodiesterase inhibitors are preferred over dobutamine. Phosphodiesterase inhibitors inhibit the phosphodiesterase 3 isozyme with a consequent increase of cAMP levels. The cascade of events that follows this increase is equal to the one triggered by other inotropic drugs (i.e beta-1 agonists, glucagon etc.) that also increase (even if by a different mechanism) cAMP levels. It involves opening of voltage-gated Ca++channels which in turn increase intracellular Ca++ levels. Phosphodiesterase type 3 inhibitors do not inhibit cGMP phosphodiesterase isozyme, and the dephosphorylation of myosin light chain would lead to relaxation, not contraction, of muscle cells. The increased cAMP level does not trigger the opening of K+ channels, and this opening would cause hyperpolarization of the cell membrane, which would adversely affect myocyte contractility

A 33-year-old woman with known hypertension is now 2 weeks pregnant. What antihypertensive drug classes are absolutely contraindicated in this woman? a. ACE-inhibitors b. Alpha-1 blockers c. Ca++ channel blockers d. Central sympatholytics e. Potassium channel openers

A. ACE-inhibitors are known to cause various malformations, growth retardation and fetal death, when given during the second and third trimester. They are category D (positive evidence of human risk) in FDA classification.

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

A. Acetazolamide is rarely used in heart failure, but CA inhibitors are valuable in patients with edema & metabolic alkalosis. The high bicarb levels in these patients make them susceptible to the action of CA inhibitors. (Digoxin is useful in chronic systolic failure but is not first-line therapy. Dobutamine is appropriate only when diuresis has already been accomplished in severe acute failure. HCTZ & spironolactone are NOT adequate for first-line therapy of edema in failure.)

A 66-year-old man presents to your office with a 5-month history of dry cough. He denies any other symptoms. His past medical history includes a recent MI, after which he was placed on several medications. He does not smoke, nor has he had a history of asthma. You decide that a medication side effect is the most likely cause of this patient's symptoms. Which medication might this be? (A) Lisinopril (B) Nitroglycerin (C) Lovastatin (D) Digoxin (E) Quinidine

A. Angiotensin-converting enzyme (ACE) inhibitors commonly cause dry nonproductive cough. Nitroglycerin can cause headaches. Lovastatin commonly causes liver dysfunction. Digoxin can cause arrhythmias, and quinidine is known to cause muscle weakness.

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

A. CA inhibitors are useful in preventing altitude sickness

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

A. Calcium channel blockers are effective in supraventricular AV nodal tachycardias. However, adenosine is just as effective in most acute nodal tachycardias and is less toxic because of its extremely short duration of action.

A 75-year-old woman, who is admitted for the management of her recent stroke, develops increased BP, up to 195/105, with a HR of 95. Her physician is worried about the possibility of cerebral hemorrhage into the preexisting infarct and decides to administer a fast-acting vasodilating agent, which is also commonly used for severe decompensated CHF. Which medication did the doctor use? (A) Nitroprusside (B) Furosemide (C) Dobutamine (D) Losartan (E) Digoxin

A. Nitroprusside is a vasodilating agent that can be used in hypertensive emergencies. Furosemide is used for long-term treatment of congestive heart failure (CHF). Dobutamine does not significantly affect the vessels to produce vasodilation. Losartan is an angiotensin-converting enzyme (ACE) inhibitor that is used in long-term care of CHF. Digoxin is another long-term agent used in CHF and certain arrhythmias.

7. A 60-year-old patient complains of paresthesias and occasional nausea associated with one of her drugs. She is found to have hyperchloremic metabolic acidosis. She is probably taking (A) Acetazolamide for glaucoma (B) Amiloride for edema associated with aldosteronism (C) Furosemide for severe hypertension and heart failure (D) Hydrochlorothiazide for hypertension (E) Mannitol for cerebral edema

A. Paresthesias and GI distress are common adverse effects of acetazolamide, especially when taken chronically, as in glaucoma. The observation that the patient has metabolic acidosis also suggests the use of acetazolamide.

A 60yo man presents to his PCP w/ a c/o severe CP when he walks uphill to his home in cold weather. The pain disappears when he rests. After evaluation and discussion of treatment options, a decision is made to treat him with nitroglycerin. 4. If a β blocker were to be used for prophylaxis, what is the most probable mechanism of action in angina? (A) Block of exercise-induced tachycardia (B) Decreased end-diastolic ventricular volume (C) Increased double product (D) Increased cardiac force (E) Decreased ventricular ejection time

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

A 57-year-old man with atrial flutter is initially treated with quinidine to control the arrhythmia. He is released from the hospital, and while his condition improves, sporadic arrhythmias continue. Which of the following drugs might be used as an adjunct to quinidine in the treatment of the atrial flutter? (A) Digitalis (B) Lidocaine (C) Procainamide (D) Nifedipine (E) Propranolol

A. Quinidine acts to prolong refractoriness and slow conduction rather than as a negative inotropic agent. The ability of digitalis to decrease conduction through the atrioventricular (AV) node makes its effects compatible with quinidine to reduce atrial flutter. Lidocaine must be administered parenterally. The effects of procainamide are synergistic with quinidine, increasing the risk of toxicity; nifedipine has little antiarrhythmic effect.

A patient with a long history of cardiovascular disease develops worsening ventricular arrhythmias. Which of the following drugs is most likely to be the cause of the arrhythmia? (A) Quinidine (B) Propanolol (C) Dobutamine (D) Methyldopa

A. Quinidine is associated with a prolonged QT interval & torsade de point arrhythmias. Propranolol can cause heart block. Dobutamine rarely causes ventricular arrhythmias.

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

A. Several β blockers, including carvedilol, have been shown to prolong life in heart failure patients even though these drugs have a negative inotropic action on the heart.

A 55-year-old woman complained to her physician of palpitations, flushing of the face and vertigo. The woman, also suffering from diabetes mellitus, was giving herself three daily doses of insulin. She had been recently diagnosed with exertional angina and nitrate therapy was started with transdermal nitroglycerin and oral isosorbide mononitrate. After three weeks of therapy anginal attacks were less frequent but not completely prevented. What would be an appropriate therapeutic conduct for this patient a. Add diltiazem b. Add nifedipine c. Add propranolol d. Reduce the dosage of both nitrates e. Stop isosorbide mononitrate

A. The symptoms referred by the patient are most likely due to nitrate therapy. The addition of a calcium channel blocker with cardiac activity, such as diltiazem, can attenuate the nitrate-induced reflex tachycardia and reflex increase in cardiac contractility. Beta-blockers are relatively contraindicated in patients receiving insulin treatment because they can mask some symptoms of hypoglycemia and inhibit gluconeogenesis impairing the body capacity to recover from hypoglycemia. Nifedipine could increase palpitations because it can cause reflex tachycardia. Because anginal attacks are not completely prevented it is useless to reduce nitrate dosage, which would decrease adverse effects but also therapeutic effects.

A 16-year-old boy is brought to the hospital by ambulance following a car accident causing serious head injuries. His blood pressure is 220/170 mmHg. Fundoscopy reveals retinal damage, and you administer nitroprusside via infusion. Control of the hypertension requires 72 hours and you notice the patient becoming increasingly fatigued and nauseous. The mostly likely cause of these symptoms is (A) Production of thiocyanate from nitroprusside (B) Negative inotropic activity of nitroprusside (C) Renal precipitation of nitroprusside (D) Accumulation of nitroprusside because of its long half-life (E) Production of hydroxocobalamin

A. The toxicity of nitroprusside is caused by the release of cyanide and the accumulation of thiocyanate. Hydroxocobalamin is used to reduce the toxicity of nitro- prusside through the formation of the less toxic cyanocobalamin.

A 63-year-old man who had been suffering from hypertension and mild cardiac failure for three years, had been recently diagnosed with sustained atrial fibrillation. The arrhythmia was refractory to therapy with digoxin and verapamil and was only partially controlled by sotalol. What drug would be most appropriate to prescribe to the patient at this time? a. Amiodarone b. Diltiazem c. Lidocaine d. Mexiletine e. Propranolol

Amiodarone is considered a second choice drug in any instance of atrial fibrillation and can be a first choice drug in patients with concomitant hypertension and left ventricular dysfunction. It is therefore an appropriate drug to be tried in the present case. Mexitelene and lidocaine are not effective in supraventricular arrhythmias. Sotalol was only partially effective therefore it is not appropriate to try another beta-blocker. Verapamil was not effective, and therefore is unwise to try another drug (diltiazem) with the same mechanism of action.

A 35-year-old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cholesterol, LDL, and triglyceride are elevated. Her serum concentration of HDL is somewhat reduced. Which of the following is a major toxicity associated with gemfibrozil therapy? (A) Bloating and constipation (B) Cholelithiasis (C) Hyperuricemia (D) Liver damage (E) Severe cardiac arrhythmia

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

A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL, VLDL, and triglycerides are normal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. 9. After being counseled about lifestyle and dietary changes, the patient was started on atorvastatin. During his treatment with atorvastatin, it is important to routinely monitor serum concentrations of which of the following? (A) Blood urea nitrogen (B) Alanine and aspartate aminotransferase (C) Platelets (D) Red blood cells (E) Uric acid

B - LFTs The 2 primary adverse effects of the HMG-CoA reductase inhibitors are hepatotoxicity and myopathy. Patients taking these drugs should have liver function tests performed before starting therapy, and at regular intervals during therapy. Serum concentrations of alanine and aspartate aminotransfer- ase are used as markers of hepatocellular toxicity.

A 35-year-old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cholesterol, LDL, and triglyceride are elevated. Her serum concentration of HDL is somewhat reduced. 3. Which of the following drugs is most likely to increase this patient's triglyceride and VLDL cholesterol concentrations when used as monotherapy? (A) Atorvastatin (B) Cholestyramine (C) Ezetimibe (D) Gemfibrozil (E) Niacin

B - Resins In some patients with familial combined hyperlipidemia and elevated VLDL, the resins increase VLDL and triglyceride concentrations even though they also lower LDL.

A 59-year-old man presented to the hospital complaining of pruritic swelling of the eyelids, nose, lips, hands, feet, and genitalia. The man, recently discharged from the hospital after an acute myocardial infarction, was prescribed an appropriate multidrug treatment. He referred that the swelling appeared few hours after starting the therapy. What drug most probably caused the patient's disorder? a. Atenolol b. Captopril c. Clopidogrel d. Isosorbide mononitrate e. Lovastatin

B.

1. A 32-year-old woman with hypertension wishes to become pregnant. Her physician informs her that she will have to switch to another antihypertensive drug. Which of the following drugs is absolutely contraindicated in pregnancy? (A) Atenolol (B) Captopril (C) Methyldopa (D) Prazosin (E) Propranolol

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

A 55-year-old man recently diagnosed with congestive heart failure, started a therapy which included furosemide. Acetazolamide was also added to counteract the potential metabolic alkalosis induced by furosemide. What molecular action most likely mediated the therapeutic effect of acetazolamide in this patient? a. Inhibition of carbonic acid dehydration in the tubular lumen b. Inhibition of Na+ reabsorption in the early distal tubule c. Stimulation of bicarbonate reabsorption in the proximal tubule d. Stimulation of carbonic acid formation inside the tubular cells e. Stimulation of H+ reabsorption in the proximal tubule

B. Acetazolamide is a carbonic anhydrase inhibitor. By blocking the enzyme it blocks the re-absorption of bicarbonate and Na+, resulting in an increase in diuresis. Acetazolamide causes an inhibition, not a simulation of bicarbonate reabsorption. Acetazolamide causes an inhibition, not stimulation, of carbonic acid formation inside the tubular cells. Hydrogen is not reabsorbed by the kidney. By inhibiting carbonic anhydrase, acetazolamide inhibits the formation of carbonic acid inside the tubular cells, which in turn inhibits the secretion of hydrogen into the lumen.

4. A 65yo woman has been admitted to the coronary care unit with a left ventricular MI. She develops acute severe HF with marked pulmonary edema, but no evidence of peripheral edema or weight gain. Which one of the following drugs would be most useful? (A) Digoxin (B) Furosemide (C) Minoxidil (D) Propranolol (E) Spironolactone

B. Acute severe congestive failure with pulmonary edema often requires a vasodilator that reduces intravascular pressures in the lungs. Pulmonary edema also involves a shift of fluid from the intravascular compartment to the lungs. Pulmonary vasodilation and removal of edema fluid by diuresis are accomplished by furosemide

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

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

A 60-year-old man presents to his PCP w/ a c/o severe CP when he walks uphill to his home in cold weather. The pain disappears when he rests. After evaluation and discussion of treatment options, a decision is made to treat him with nitroglycerin. 3. 1yr later, the pt returns complaining that his nitroglycerin works well when he takes it for an acute attack but that he is now having more frequent attacks and would like something to prevent them. Useful drugs for the prophylaxis of angina of effort include (A) Amyl nitrite (B) Diltiazem (C) Esmolol (D) Sublingual isosorbide dinitrate (E) Sublingual nitroglycerin

B. Ca channel blockers & β blockers are generally effective in reducing the # of attacks of angina of effort & most have durations of 4-8 h. Oral and transdermal nitrates have similar or longer durations. Amyl nitrite, the sublingual nitrates, and esmolol (an intravenous β blocker) have short durations of action and are of no value in prophylaxis.

3. Which one of the following is characteristic of captopril treatment in patients with essential hypertension? (A) Competitively blocks angiotensin II at its receptor (B) Decreases [angiotensin II] in the blood (C) Decreases [renin] in the blood (D) Increases sodium and decreases potassium in the blood (E) Decreases sodium and increases potassium in the urine

B. Converting enzyme inhibitors act on the enzyme, not on the receptor. Plasma renin levels may increase as a compensatory response to reduced angiotensin II. ACE inhibitors increase blood potassium and urine sodium.

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

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

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

B. Dobutamine is the only inotropic drug in this list (DDD MI)

A 47-year-old woman is admitted for the treatment of acute myocardial ischemia. Her prior medication included digoxin for A-fib. She also suffers from HTN, for which she is currently not taking anything. Before you discharge her, you decide to add a medication that works well for HTN. While she is still on the floor she develops a dangerous arrhythmia, which you are fortunately able to treat promptly. Which medication you added likely increased the effects of digoxin that this patient was already taking? (A) Valsartan (B) Hydrochlorothiazide (C) Hydralazine (D) Tadalafil (E) Lovastatin

B. HCTZ, is known to cause hypokalemia, a state in which the actions of digoxin can be potentiated to a dangerous level. Valsartan is generally not used as a sole agent for HTN. Hydralazine lowers BP, but it doesn't generally cause marked electrolyte disturbances.

A woman who is undergoing an endocrine work-up to diagnose the cause of a large multinodular goiter develops A-fib. Which of the following would be best to treat this arrhythmia? (A) Verapamil (B) Propranolol (C) Digitalis (D) Bretylium (E) Tocainide

B. Hyperthyroidism apparently increases β-adrenoceptors. β-Adrenoceptor antagonists such as propranolol can actually decrease symptoms of hyperthyroidism.

A 55-year-old woman is admitted to the surgical ICU after having a quadruple CABG. Overnight she develops hypotension, and her CO, as measured by the Swan-Ganz catheter, is significantly lower than it had been post-surgery. You decide to give her a dose of milrinone. This results in an increase in her CO. How does this medication work? (A) It is a cholinergic agonist (B) It reduces left ventricular filling pressure (C) It potentiates cardiac phosphodiesterase type 3 (D) It decreases (cAMP) (E) It decreases intracellular calcium

B. Milrinone reduces left ventricular filling pressure and thus enhances CO. It is related to the anticholinergic agent biperiden. Milrinone inhibits cardiac phosphodiesterase type 3. It increases cyclic AMP (cAMP), and therefore intracellular calcium.

A 24-year-old man presented to the emergency department with a chief complain of palpitations for three hours. He had experienced no prior symptoms and had no significant past medical history. Vital signs were: HR 190 bpm, BP 100/60 mm Hg, RR14/min. An ECG showed a picture compatible with Wolff-Parkinson-White syndrome. An appropriate therapy was instituted which included an IV administration of a drug. What drug was most likely given? a. Digoxin b. Procainamide c. Propranolol d. Nifedipine e. Verapamil

B. Of the FDA approved drugs, procainamide, which prolongs the refractory period of the accessory pathways, is considered by many the drug of choice. Digoxin, calcium channel blockers and beta-blockers may be dangerous by blocking the AV node and redirecting impulses down the bypass tract. Nifedipine has no direct action on the heart and the reflex tachycardia it induces may worsen the arrhythmia.

2. After your patient has been receiving digoxin for 3 wks, he presents to the ED with an arrhythmia. Which one of the following is most likely to contribute to the ARRHYTHMOGENIC effect of digoxin? (A) Increased parasympathetic discharge (B) Increased intracellular calcium (C) Decreased sympathetic discharge (D) Decreased intracellular ATP (E) Increased extracellular potassium

B. The effects of digitalis include increased vagal action on the heart (not arrhythmogenic) & increased intracellular Ca, including calcium overload, the most important cause of toxicity. Decreased sympathetic discharge and increased extracellular potassium and magnesium reduce digitalis arrhythmogenesis. (A, C, E are all effects of digoxin BUT not the cause of arrhythmias)

A 65-year-old woman was found to have a blood pressure of 165/90 during a routine visit. Past history of the patient was significant for a second-degree heart block and for osteoporosis. One year ago she had suffered from a severe episode of angioedema. What antihypertensive drug would be most appropriate for this patient? a. Captopril b. Hydrochlorothiazide c. Minoxidil d. Propranolol e. Verapamil

B. The patient has stage 2 essential hypertension and in addition to lifestyle modification antihypertensive medication is recommended. The patient is a good candidate for a thiazide diuretic for several reasons. First these drugs are usually the most appropriate initial choice in case of uncomplicated hypertension because they decrease morbidity and mortality. Secondly the woman is suffering from osteoporosis and thiazides can cause retention of calcium, a potentially beneficial effect. ACE-inhibitors are contraindicated because of the past episode of angioedema. Beta-blockers and verapamil are contraindicated because of the heart block. Minoxidil is never a drug of first choice for antihypertensive therapy.

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

C. Antagonists of ADH are needed to treat this condition.

A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL cholesterol, VLDL cholesterol, and triglycerides are nor- mal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. 10. Six months after beginning atorvastatin, the patient's total and LDL cholesterol concentrations remained above normal, and he continued to have anginal attacks despite good adherence to his antianginal medications. His physician decided to add ezetimibe. Which of the following is the most accurate description of ezetimibe's mechanism of an action? (A) Decreased lipid synthesis in adipose tissue (B) Decreased secretion of VLDL by the liver (C) Decreased gastrointestinal absorption of cholesterol (D) Increased endocytosis of HDL by the liver (E) Increased lipid hydrolysis by lipoprotein lipase

C - The major recognized effect of ezetimibe is inhibition of absorption of cholesterol in the intestine.

1. Increased serum levels of which of the following is associated with a decreased risk of atherosclerosis? A. Cholesterol B. LDL C. HDL D. Triglyceride E. VLDL

C- HDL Increased serum concentrations of LDL and total cholesterol are associated with increased risk of atherosclerosis. High serum concentration of HDL cholesterol is associated with a decrease in the risk of atherosclerotic disease.

6. A 55-year-old man is admitted to the ED & has an abnormal ECG. Overdose of an anti-arrhythmic drug is considered. Which of the following drugs is correctly paired with its ECG effects? (A) Quinidine: Increased PR and decreased QT intervals (B) Flecainide: Increased PR, QRS, and QT intervals (C) Verapamil: Increased PR interval (D) Lidocaine: Decreased QRS and PR interval (E) Metoprolol: Increased QRS duration

C. All the associations listed are incorrect except verapamil (see Table 14-1). This group 4 drug increases PR interval and has little effect on the other ECG variables.

A 22-year-old previously healthy woman was brought to the emergency department because she had collapsed while jogging. She denied orthopnea, paroxysmal nocturnal dyspnea, chest pain or edema. Her younger brother was known to have had two episodes of syncope after exertion. The ECG indicated left ventricular hypertrophy and the echocardiogram showed a normal ejection fraction and an asymmetric septal hypertrophy. What drug would be most appropriate for this patient? a. Digoxin b. Furosemide c. Metoprolol d. Nitroglycerin e. Prazosin

C. Beta blockers and calcium channel blockers that act on the heart (verapamil, diltiazem) are drugs of choice in this disease because they decrease cardiac contractility and increase diastolic ventricular filling. All the other listed drugs are contraindicated in hypertrophic obstructive cardiomyopathy because either they decrease venous return (prazosin, nitrates, diuretics) or increase contractile function (inotropic agents).

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

C. Beta blockers are the most effective agents in acute thyrotoxic arrhythmias. Esmolol is a parenteral, rapid-acting β blocker.

8. A patient with hypertension is to receive a Ca channel blocker. Verapamil is associated with which one of the following? (A) Diarrhea (B) Hypoglycemia (C) Increased PR interval (D) Tachycardia (E) Thyrotoxicosis

C. Ca ch blockers don't cause diarrhea & are sometimes associated with constipation, probably through inhibition of calcium influx in intestinal SM. Hypoglycemia is not a common effect of any of the anti-hypertensive drugs. Thyroid disorders are not associated with Ca blockers. However, Ca blockers, especially verapamil and diltiazem, are associated with depression of Ca-dependent processes in the heart, for ex, contractility, HR, & AV conduction. Therefore, bradycardia and increased PR interval may be expected. The dihydropyridines don't often cause cardiac depression, probably bc they evoke increased sympathetic outflow as a result of their dominant vascular effects.

5. A significant # of patients started on ACE inhibitors for HTN are intolerant & must be switched to a different class of drug. What is the most common manifestation of this intolerance? (A) Diarrhea (B) Glaucoma (C) Incessant cough (D) Lupus-like syndrome (E) Vomiting

C. Chronic cough is an important adverse effect of captopril & other ACE inhibitors. It may be relieved by prior administration of ASA. These drugs are very commonly used in hypertensive diabetic patients because of their proven benefits in reducing diabetic renal damage. ACE inhibitors don't cause glaucoma or GI disturbances.

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

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

You are taking care of a 64-year-old man who had just undergone a right hemicolectomy for colon cancer. His blood pressure has been low, and you want to find out whether the shock that this patient is experiencing is related to a possible intraab- dominal infection as a consequence of his surgery or is due to his preexisting congestive heart failure (CHF). After analyzing the Swan-Ganz catheter measurements, you deduce that the picture is most compatible with cardiogenic shock. You recall from your pharmacology class that dobutamine can be used successfully for such patients. Which of the following is true regarding dobutamine? (A) It acts on dopamine receptors (B) It activates α-receptors (C) It activates cyclic AMP (cAMP)-related pathways (D) It increases peripheral resistance (E) It produces bradycardia

C. Dobutamine increases cyclic AMP (cAMP)-mediated phosphorylation and the activity of Ca channels. It doesn't act on dopamine receptors or α-receptors; it only acts on β1-receptors. Dobutamine does not substantially affect peripheral resistance. This agent produces mild tachycardia

6. Which one of the following is a significant unwanted effect of the drug named? (A) Heart failure with hydralazine (B) Hemolytic anemia with atenolol (C) Fetal damage with losartan (D) Lupus-like syndrome with hydrochlorothiazide (E) Tachycardia with verapamil

C. Hydralazine (A) is sometimes used in HF. B-blockers (B) aren't associated with hematologic abnormalities, but methyldopa is. Thiazide diuretics (D) often cause mild hyperglycemia, hyperuricemia, and hyperlipidemia but not lupus; hydralazine is associated with a lupus-like syndrome. Verapamil (E) often causes bradycardia. ARBs (C) may cause damage to the fetal kidney, and they are contraindicated in pregnancy.

A 63-year-old woman was brought to the emergency department by family members because she had become more lethargic and unresponsive over the past several days. Her past medical history was significant for bone metastases from breast cancer. Physical examination revealed a dehydrated, cachectic female responsive only to painful stimuli. Pertinent laboratory values were: Na+ 138 mEq/L, K + 4.5 mEq/L, Ca + + 19.2 mg/dL. An intravenous saline infusion was started and a diuretic was given concurrently. What diuretic was most likely administered? a. Acetazolamide b. Amiloride c. Furosemide d. Hydrochlorothiazide e. Spironolactone

C. Lab values of this patient indicate very high Ca++ levels and her symptoms and history are in accordance with the diagnosis of profound hypercalcemia. The first-line emergency treatment for this disorder is hydration and volume expansion because these patients are volume depleted due to the accompanied polyuria, nausea and vomiting. Furosemide is administered because it can increase urinary Ca++ excretion.

7. A 60-year-old man comes to the ED with severe CP. ECG reveals V-tach with occasional normal sinus beats, and ST-segment changes suggestive of ischemia. A diagnosis of MI is made & the man is admitted to the cardiac ICU. His arrhythmia should be treated immediately with (A) Adenosine (B) Digoxin (C) Lidocaine (D) Quinidine (E) Verapamil

C. Lidocaine: emergency treatment of myocardial infarction arrhythmias is one of the most important uses. Lidocaine is also useful in digoxin-induced arrhythmias. After recovery from the acute phase of a myocardial infarction, β blockers are used for 2 yrs or more to prevent sudden death arrhythmias.

Since the side effects of the medication you prescribed preclude the patient in the above scenario (dry cough) from taking it, you switch him to therapy with an agent that is said to produce similar mortality benefits, while working via a slightly different mechanism of action. What agent is it? (A) Furosemide (B) Captopril (C) Losartan (D) Esmolol (E) Ezetimibe

C. Losartan is an angiotensin receptor blocker (ARB) that produces effects similar to those of angiotensin-converting enzyme (ACE) inhibitors while causing less cough and angioedema. Furosemide is a loop diuretic that is used in congestive heart fail- ure. Captopril is an example of another ACE inhibitor. Esmolol is an antiarrhythmic agent. Ezetimibe is a lipid-lowering drug.

A 35-year-old woman in her 29 week of gestation was found to have a positive direct Coombs' test during a routine prenatal visit. Two months after she became pregnant, she was diagnosed with stage 1 hypertension and started an antihypertensive therapy. What drug was she most likely taking? a. Captopril b. Losartan c. Methyldopa d. Nifedipine e. Prazosin f. Propranolol

C. Methyldopa is the most commonly used drug for chronic treatment of hypertension in pregnancy in the US. This is mainly because of the largest experience with this drug during pregnancy. Positive Coombs' reaction occurs in up to 30% of patients treated for more than 6 months, but hemolytic anemia occurs only in 1-5% of cases.

2. A patient is admitted to the ED with severe tachycardia after a drug OD. His family reports that he has been depressed about his hypertension. Which one of the following drugs increases the heart rate in a dose-dependent manner? (A) Captopril (B) Hydrochlorothiazide (C) Minoxidil (D) Prazosin (E) Verapamil

C. Neither ACE inhibitors (A) nor diuretics (B) significantly increase HR. Although dihydropyridine calcium channel blockers do not usually reduce rate markedly (and may increase it), verapamil and diltiazem do inhibit the SA node & predictably decrease rate. Direct vasodilators (C) and α blockers (D) regularly increase heart rate but minoxidil, a very efficacious vasodilator causes severe tachycardia that must be controlled with β blockers.

A 53-year-old man, suffering from exertional angina, was prescribed inhaled nitroglycerin and oral isosorbide mononitrate. What are the molecular actions that most likely mediated the therapeutic efficacy of these drugs in the patient's disease? a. Conversion of nitrite ions into nitrous oxide (N2O) b. Decreased synthesis of guanylyl-cyclase c. Dephosphorylation of myosin light chain d. Increased intracellular Ca++ concentration e. Phosphorylation of myosin light chain kinase

C. Nitrates release free nitrite ions which in turn are converted to nitric oxide. NO causes the activation of guanylyl-cyclase causing an increase in cGMP. This second messenger causes dephosphorylation of myosin light chain. Myosin is no longer able to interact with actin and vascular smooth muscle relaxes. Intracellular Ca++ concentration is actually reduced by nitrates. Phosphorylation of myosin light chain kinase would increase, not decrease, smooth muscle contraction.

A 53-year-old woman suffering from hypertension still had a blood pressure of 156/92 mm Hg after three months of therapy with hydrochlorotiazide and losartan. His physician decided to add a third drug which acts by decreasing central sympathetic outflow. What are the adverse effects most likely to occur after few days of therapy with the new drug? a. Megaloblastic anemia b. Palpitations c. Pronounced sedation d. Severe postural hypotension e. Sialorrhea

C. Sedation is a frequent, and sometimes pronounced, adverse effect of central sympathoplegic antihypertensive drugs (methyldopa and clonidine), most likely related to the decreased adrenergic transmission in the CNS. Hemolytic, not megaloblastic, anemia occasionally occurs with methyldopa. Methyldopa and clonidine tend to decrease the heart rate so palpitations are unlikely. Postural hypotension is an uncommon and usually slight adverse effect of methyldopa and clonidine, since the basal central adrenergic tone is reduced but the baroreceptor reflex is still operative. Methyldopa and clonidine frequently cause xerostomia, not sialorrhea. The mechanism of the effect is still uncertain.

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

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

A 47-year-old man, recently diagnosed with exertional angina, started a treatment with nitroglycerin by transdermal route and oral propranolol. What is the most likely main purpose of the combination therapy in this case? a. To enhance nitrate-induced coronary vasodilation b. To prevent nitrate-induced decrease in arterial pressure c. To prevent nitrate-induced tachycardia d. To enhance propranolol-induced decrease in cardiac rate e. To enhance propranolol-induced decrease in cardiac contractility

C. The three classes of antianginal drugs utilize different mechanisms of action, and combination of two of these agents can increase the effectiveness and reduce the incidence of adverse effects. Sometimes beta-blockers are associated with nitrates in the therapy of exertional angina because: 1) beta-blockers can offset the nitrate-induced increase in cardiac contractility and rate. 2) nitrates can prevent the beta-blocker-induced increase in end diastolic volume and ejection time. Beta-blockers cause vasoconstriction of coronary vessels, mainly as a consequence of the reduced heart rate. Beta-blockers do not prevent the nitrate-induced decrease in arterial pressure. This is a useful effect of nitrates and would be irrational to prevent it. Nitrates do not enhance, but rather counteract, the effect of propranolol on cardiac rate and contractility.

A 50yo man has a hx of frequent episodes of renal colic with Ca-containing renal stones. Workup indicates that he has a defect in proximal tubular Ca reabsorption, which results in [high] of calcium salts in the tubular urine. The most useful diuretic agent in the treatment of recurrent calcium stones is (A) Acetazolamide (B) Furosemide (C) Hydrochlorothiazide (D) Mannitol (E) Spironolactone

C. Thiazides are useful in PREVENTING calcium stones because they reduce tubular [Ca], probably by increasing passive proximal tubular and distal convoluted tubule reabsorption of calcium. In contrast, the loop agents facilitate calcium excretion. (NOT B)

A 35-year-old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cholesterol, LDL, and triglyceride are elevated. Her serum concentration of HDL is somewhat reduced. 5. The patient is started on gemfibrozil. Which of the following is a major mechanism of gemfibrozil's action? (A) Increased excretion of bile acid salts (B) Increased expression of high-affinity LDL receptors (C) Increased secretion of VLDL by the liver (D) Increased triglyceride hydrolysis by lipoprotein lipase (E) Reduced uptake of dietary cholesterol

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

A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL, VLDL, and triglycerides are normal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. 8. If the patient has a history of gout, which of the following drugs is most likely to exacerbate this condition? (A) Colestipol (B) Ezetimibe (C) Gemfibrozil (D) Niacin (E) Simvastatin

D - Niacin can exacerbate both hyper-uricemia and glucose intolerance.

1. Which of the following is the best documented mechanism of beneficial action of cardiac glycosides? A. Decreased calcium uptake by the SR B. Increased ATP synthesis C. Modification of the actin molecule D. Increased systolic cytoplasmic calcium levels E. Blockage of cardiac β adrenoceptors

D, The most accurate description of digoxin's mechanism in this list is that it increases systolic cytoplasmic calcium indirectly by inhibiting Na+/K+ ATPase and altering Na/Ca exchange.

A 54-year-old woman is diagnosed with congestive heart failure (CHF). You prescribe captopril, a medication proven to reduce her mortality. This agent delivers several benefits to patients with CHF. Which of the following effects is caused by this drug? (A) It has a high affinity for angiotensin II receptors (B) It promotes increased peripheral vascular resistance (C) It decreases cardiac output and increases afterload (D) It causes venodilation and induces natriuresis (E) It increases preload

D. ACE inhibitors cause venodilation and induce natriuresis, thereby reducing preload. A high affinity for angiotensin II receptors represents the mechanism of action of angiotensin-receptor blockers. ACE inhibitors counteract increased peripheral resistance, increase cardiac output, and decrease afterload.

8. A 45-year-old woman with hyperlipidemia and frequent migraine headaches develops angina of effort. Which of the following is relatively contraindicated because of her migraines? (A) Amlodipine (B) Diltiazem (C) Metoprolol (D) Nitroglycerin (E) Verapamil

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

While doing your medicine clerkship, you hear an announcement that a CPR team should immediately report to the room of one of the patients. You decide to observe how the code team manages this unfortunate patient's CPR. The rhythm monitor displays V-fib that is quickly converted to atrial fibrillation with rapid ventricular response. The senior resident orders amiodarone to be administered to this patient. Since you forgot how this agent works, you ask one of the residents to explain how this medication works. The resident replies that he is busy, but tells you it is a class III antiarrhythmic agent. What is the MOA of this medicine? A. It is a β-receptor antagonist B. It blocks fast sodium channels C. It decreases refractoriness D. It interferes with outward potassium current E. It has a relatively short half-life

D. Amiodarone is a class III antiarrhythmic agent that interferes with outward potassium current. β-Receptor antagonists are considered class II antiarrhythmics. Class I antiarrhythmics block fast sodium channels. Amiodarone prolongs the effective refractory period. It has a rather long half-life, up to 100 days.

7. Comparison of prazosin with atenolol shows that (A) Both decrease heart rate (B) Both increase cardiac output (C) Both increase renin secretion (D) Both increase sympathetic outflow from the CNS (E) Both produce orthostatic hypotension

D. Atenolol, but not prazosin, may decrease HR (A). Prazosin—but not atenolol—may increase CO (B). Prazosin may increase renin output, but β blockers inhibit its release by the kidney (C). By reducing BP, both may increase central sympathetic outflow. Beta blockers do not cause orthostatic hypotension

A 38-year-old man was diagnosed with hypertension (156/95 mm Hg) during a routine visit. Subsequent exams indicated he was affected by hypertrophic cardiomyopathy. What antihypertensive drug would be most appropriate for this patient? a. Aliskiren b. Clonidine c. Diazoxide d. Metoprolol e. Minoxidil f. Prazosin

D. Beta blockers are drug of choice in hypertrophic cardiomyopathy because they increase the duration of diastole, decrease left ventricular contractility and myocardial wall stress during systole. In the present case they can also reduce the high blood pressure and are therefore the most appropriate drugs for this patient.

5. A new 60-year-old patient presents to the medical clinic with hypertension & angina. In considering adverse effects of possible drugs for these conditions, you note that an adverse effect that nitroglycerin and prazosin have in common is (A) Bradycardia (B) Impaired sexual function (C) Lupus erythematosus syndrome (D) Orthostatic hypotension (E) Throbbing headache

D. Both drugs cause venodilation and reduce venous return sufficiently to cause some degree of postural hypotension. Throbbing headache is a problem only with the nitrates.

A patient is admitted into the ED & manifests v-tach following an acute MI. This arrhythmia is life-threatening and must be controlled immediately. Which of the following drugs would be best to quickly control the condition? (A) Dobutamine (B) Digitalis (C) Quinidine (D) Lidocaine (E) Atropine

D. Lidocaine is the best agent for the management of V- tach associated with acute MI. Dobutamine, digitalis, quinidine, and atropine can all induce tachyarrhythmias. Lidocaine does not slow conduction and has little effect on atrial function

3. A 57-year-old man is admitted to the ED with an irregular HR. The ECG shows an inferior MI & V-tach. Lidocaine is ordered. When used as an antiarrhythmic drug, lidocaine typically A. Increases action potential duration B. Increases contractility C. Increases PR interval D. Reduces abnormal automaticity E. Reduces resting potential

D. Lidocaine reduces automaticity in the ventricles; the drug does not alter resting potential or AP duration and does not increase contractility

A 60yo man presents to his PCP w/ a c/o severe CP when he walks uphill to his home in cold weather. The pain disappears when he rests. After evaluation and discussion of treatment options, a decision is made to treat him with nitroglycerin. 2. In advising the patient about the adverse effects he may notice, you point out that nitroglycerin in moderate doses often produces certain symptoms. Which of the following effects might occur due to the mechanism listed? (A) Apnea due to cranial vasodilation (B) Dizziness due to reduced cardiac force of contraction (C) Diuresis due to sympathetic discharge (D) Headache due to meningeal vasodilation (E) Hypertension due to reflex tachycardia

D. Nitroglycerin causes hypotension as a result of arterial and venous dilation. Dilation of arteries in the head has no effect on CNS function but does cause headache.

A 60-year-old man presents to his PCP with a complaint of severe chest pain when he walks uphill to his home in cold weather. The pain disappears when he rests. After evaluation and discussion of treatment options, a decision is made to treat him with nitroglycerin. 1. Which of the following is a common direct or reflex effect of nitroglycerin? (A) Decreased heart rate (B) Decreased venous capacitance (C) Increased afterload (D) Increased cardiac force (E) Increased diastolic myocardial fiber tension

D. Nitroglycerin increases heart rate and venous capacitance and decreases afterload and diastolic fiber tension. It increases cardiac contractile force because the decrease in blood pres- sure evokes a compensatory increase in sympathetic discharge.

Which of the following drugs can cause polymorphic ventricular tachycardia (torsade de pointes) in patients a. Atenolol b. Digoxin c. Lidocaine d. Sotalol e. Phenytoin

D. The The ECG hallmark of torsade de pointes (TdP) is a long Q-T interval. Prolongation of Q-T interval indicates prolongation of action potential duration, which is related to a decreased outward potassium current during the phase 3 of the action potential. Long Q-T interval is present prior to the onset of tachycardia and is due to hereditary or acquired potassium channel defects. Hereditary Q-T syndromes are due to some rare mutations of the genes encoding potassium channels. However the importance TdP in everyday practice is its provocation by diseases or drugs that prolong Q-T interval. Diseases include hypothyroidism, subarachnoid hemorrhage, myocarditis, hypokalemia and hypomagnesemia. Drugs include class Ia and class III antiarrhythmic drugs. All these drugs are able to increase action potential duration by blocking or modifying potassium channels. High doses of these drugs can trigger torsade de pointes in patients at risk. Sotalol is the only beta-blocker that can block potassium channels (a property not related to beta receptor blockade) and it can cause TdP.

A female patient with a history of bronchospasm complains she felt short of breath accompanied with nausea when playing softball. During her history, she admits that she has felt like that before when walking up a few flights of stairs. You schedule a stress test and the results confirm stable angina. Which of the following drugs would be the best choice for long-term management of this patient? (A) Nitroprusside (B) Sildenafil (C) Metolazone (D) amilodipine (E) Propranolol

D. The calcium-channel blocker amlodipine. Nitroprusside must be given by IV infusion. Sildenafil is useful for erectile dysfunction and pulmonary hypertension. The thiazide-like metolazone would not be of particular benefit. Propranolol is an appropriate choice for treating angina in some patients, but not in the presence of a lung disorder.

A Purkinje fiber was isolated from an animal heart and placed in a recording chamber. Action potentials were recorded before and after a low dose of quinidine was added to the perfusate. Which of the following was an electrophysiological action of quinidine on this preparation? a. Decreased action potential duration b. Increased slope of phase 3 c. Decreased effective refractory period d. Decreased slope of phase 0 e. Increased slope of phase 4

D. The higher the number of sodium channels that are in the open state, the higher the sodium current and the steeper the slope of phase zero. By blocking activated sodium channels (the number of channels that are blocked is dose-dependent) the sodium current will be less intense and the slope of phase zero decreases By blocking K+ channels quinidine slows down repolarization and therefore action potential duration is increased, the slope of phase 3 is decreased and the effective refractory period is increased. The slope of phase 4 is related to automaticity (the steeper the slope the higher the automaticity). Most antiarrhythmic drugs decrease the slope of phase 4, unless toxic doses are given.

3. A patient who has been taking digoxin for several years for a-fib and CHF is about to receive atropine for another condition. A common effect of digoxin (at therapeutic blood levels) that can be almost entirely blocked by atropine is A. Decreased appetite B. Headaches C. Increased atrial contractility D. Increased PR interval on ECG E. Tachycardia

D. The only parasympathomimetic effect in the list provided is increased PR interval, representing slowing of AV conduction. Can be blocked by muscarinic blockers (Atropine)

6. What are the major effects of full therapeutic doses of digoxin on the AV node and the ECG? (AV refractory period, QT interval, T wave)

Digoxin increases AV node refractory period. Shorten the action potential & QT interval. It also flattens or inverses the T wave.

A 66-year-old man was admitted to the coronary unit with an acute inferior myocardial infarction. In spite of the initial therapy his condition deteriorated and two hours after admission he had the following hemodynamic profile: BP 94/50, CO 2.9 L/min, cardiac index 1.5 L/min/m2 (normal, 2.6 - 4.2). An IV infusion of dobutamine was started. What action most likely mediates the positive inotropic action of dobutamine? a. Activation of phospholipase A2 b. Inhibition of Ca + + /Na + exchanger in cardiac cell membrane c. Inhibition of Na + /K + ATPase in cardiac cell membrane d. Inhibition of phosphodiesterase e. Protein kinase-mediated increase in cytoplasmic Ca + + availability

Dobutamine activates mainly beta-1 receptors. The subsequent activation of a cAMP-dependent protein kinase A increases the opening of membrane voltage-gated calcium channels (causing an increased speed and strength of myocyte contraction) as well as the opening of sarcoplasmic calcium channels (causing and increased reuptake of Ca++ by the sarcoplasmic reticulum). Therefore both the speed of contraction and the speed of relaxation of myocytes are increased.

2. A 58-year-old man with a history of hyperlipidemia was treated with a drug. The patient's fasting lipid panel before treatment (Trigs - 1000, Total Chol - 640, LDL 120, VLDL - 500, HDL - 20) and 6 mo after initiating drug therapy (Trigs - 300, Total Chol - 275, LDL - 90, VLDL - 150, HDL - 40). Which of the following drugs is most likely to be the one that this man received? (A) Colestipol (B) Ezetimibe (C) Gemfibrozil (D) Lovastatin (E) Niacin

E - Niacin Striking hypertriglyceridemia, elevated VLDL, and depressed HDL. Six months after drug treatment was initiated, his trig & VLDL dropped dramatically and HDL level has doubled. The drug that is most likely to have achieved all of these desirable changes, particularly the LARGE increase in HDL, is niacin. Although gemfibrozil lowers triglyceride and VLDL concentrations, it DOES NOT cause such large increases in HDL and decreases in LDL.

A 35-year-old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cholesterol, LDL, and triglyceride are elevated. Her serum concentration of HDL is somewhat reduced. 4. If this patient is pregnant, which of the following drugs should be avoided because of a risk of harming the fetus? (A) Cholestyramine (B) Ezetimibe (C) Fenofibrate (D) Niacin (E) Pravastatin

E - Statins

A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL, VLDL, and triglycerides are normal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. 7. Consumption of alcohol is associated with which of the following changes in serum lipid concentrations? (A) Decreased chylomicrons (B) Decreased HDL cholesterol (C) Decreased VLDL cholesterol (D) Increased LDL cholesterol (E) Increased triglyceride

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

A 52-year-old woman was discharged from the hospital after recovery from an acute myocardial infarction. Her post-discharge medications included captopril. What action most likely contributes to mortality reduction obtained by the use of ACE inhibitors in myocardial infarction? a. Coronary vasodilation b. Decreased cardiac contractility c. Decreased ventricular automaticity d. Increased preload e. Reduction of myocardial remodeling

E. ACE inhibitors block the vasoconstricting activity of angiotensin II reducing both preload and afterload, which in turn reduces the workload of the heart. In addition they reduce the growth effects of angiotensin II on cardiac myocytes and attenuates the cardiac fibrosis induced by angiotensin II. - By decreasing the workload of the heart ACE inhibitors can indirectly cause coronary vasoconstriction. - ACE inhibitors do not appreciably affect cardiac contractility - By blocking aldosterone formation ACE inhibitors decrease, not increase, preload - ACE inhibitors have negligible effects on ventricular automaticity.

A 77-year-old woman was brought to the emergency department with an acute myocardial infarction. Six months ago she suffered from a myocardial infarction and began taking propranolol, aspirin and lovastatin. Her current medications also included captopril and hydrochlorothiazide for hypertension. Two days ago she became nauseous and vomited and she stopped taking all her medications. The abrupt withdrawal from what drug most likely triggered the recent myocardial infarction? a. Aspirin b. Captopril c. Hydrochlorothiazide d. Lovastatin e. Propranolol

E. Abrupt discontinuation of beta-blockers can precipitate myocardial infarction and can increase the risk of sudden death in cardiac patients. There is enhanced sensitivity to beta-adrenergic agonists in patients who have undergone long-term treatment with beta blockers, likely due to up-regulation of beta receptors. Abrupt withdrawal from the beta-blocker allows an increased number of receptors to be exposed to norepinephrine. This supersensitivity can be attenuated by tapering the dose of the beta-blocker for several week before discontinuation.

A 60-year-old male suffering from hypertension had been taking hydrochlorothiazide and propranolol for two months but the therapy failed to completely control his blood pressure. The man was recently diagnosed with benign prostatic hyperplasia and experienced frequent nocturia. His physician decided to add a third drug which could also help the patient's difficulty in urinating. A drug from which of the following drug classes was most likely prescribed? a. ACE inhibitors b. Alpha 2 agonists c. Beta blockers d. Calcium channel blockers e. Alpha-1 blockers

E. Alpha-1 blockers (prazosin, terazosin, etc.) are used as antihypertensive drugs mainly in men with prostatic hyperplasia since they relax the internal sphincter of the bladder and the prostate capsule.

A 61-year-old man presented to the hospital with shortness of breath, decreased exercise capacity and distended neck veins. The man had a history of severe hypertension currently treated with hydrochlorothiazide and captopril. However, despite the treatment, his blood pressure was still 170/110. After physical examination and laboratory tests a diagnosis of diastolic cardiac failure was made. What would be a useful drug to add to the patient's therapeutic regimen? a. Digoxin b. Dobutamine c. Mannitol d. Milrinone e. Metoprolol

E. Beta blockers are drug of choice in diastolic heart failure because: 1) They slow the heart rate allowing more time for complete ventricular filling. 2) They increase heart relaxation, counteracting the stiffness of the ventricular wall. 3) They reduce myocardial oxygen demand. Inotropic drugs are usually contraindicated in diastolic heart failure because they do not relieve the high end diastolic pressure and may induce arrhythmias. Mannitol is an osmotic diuretic which can be dangerous in patient with heart failure.

A 57-year-old man suffering from persistent atrial fibrillation started a treatment with digoxin, one tablet daily. What mechanism of action most likely mediates the therapeutic effect of digoxin in the present case? a. Blockade of Ca++/Na+ exchanger b. Blockade of Na+/K+ pump c. Inhibition of phosphodiesterase d. Opening of Ca++ channels of cardiac cell membranes e. Stimulation of vagal activity

E. Digoxin is still used in persistent atrial fibrillation (it is not a first-line therapy) because it can decrease the AV conduction, decreasing the high ventricular rate. This is accomplished by a stimulation of vagal activity due to: 1) stimulation of vagal nucleus 2) sensitization of carotid sinus baroreceptors 3) facilitation of muscarinic transmission at the cardiac muscle cells. Cardiac glycosides do not inhibit phosphodiesterase. Digoxin does have all the other actions but these are important for the positive inotropic activity, not for the decrease in the AV conduction.

A 76-year-old man has suffered from a-fib for many years. This condition has been under good control with amiodarone and diltiazem until recently, when he started experiencing palpitations and came back to see you. You decide to start the patient on digoxin therapy. How does this medication work? (A) It decreases intracellular Na+ and increases intracellular K+ (B) It lowers intracellular Ca2+ (C) It decreases SV & CO (D) It diminishes elimination of Na+ & H2O (E) It increases vagal activity & decreases sympathetic tone

E. Digoxin, a cardiac glycoside, increases vagal activity, resulting in inhibition of the (SA) node & delayed conduction through the (AV) node. It also decreases sympathetic tone. Cardiac glycosides increase intracellular sodium while decreasing intracellular potassium; increase intracellular calcium; and increase stroke volume and therefore cardiac output. Cardiac glycosides enhance elimination of sodium and water.

3. Which of the following is an important effect of chronic therapy with loop diuretics? (A) Decreased urinary excretion of calcium (B) Elevation of blood pressure (C) Elevation of pulmonary vascular pressure (D) Metabolic acidosis (E) Ototoxicity

E. Loop diuretics INCREASE urinary Ca excretion & decrease BP (in HTN) & pulmonary vascular pressure. They cause metabolic ALKALOSIS and also ototoxicity

5. An 82-year-old woman has long-standing heart failure. Which one of the following drugs has been shown to reduce mortality in chronic heart failure? (A) Atenolol (B) Digoxin (C) Dobutamine (D) Furosemide (E) Spironolactone

E. Only spironolactone has been shown to reduce mortality in this highly lethal disease. Digoxin, dobutamine, and furosemide are used in the management of symptoms.

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

E. Osmotic diuretics are needed to remove water from the cells of the edematous brain and reduce intracranial pressure rapidly.

A 76yo patient with RA & chronic heart disease is being considered for treatment with procainamide. She is already receiving digoxin, HCTZ, & K+ supps for her cardiac condition. If this patient should take an OD & manifest severe acute procainamide toxicity with markedly prolonged QRS, which of the following should be given immediately? (A) A calcium chelator such as EDTA (B) Digitalis (C) Nitroprusside (D) Potassium chloride (E) Sodium lactate

E. The most effective therapy for procainamide toxicity appears to be concentrated sodium lactate. This drug may (1) increase sodium current by increasing the ionic gradient and (2) reduce drug-receptor binding by alkalinizing the tissue.

A 60-year-old man was admitted to the hospital because of symptoms of episodic weakness, polydipsia and polyuria over the last two weeks. Vital signs on admission were: BP 136/95 mm Hg, HR 80 bpm, RR 13 breaths/min. Significant blood tests results on admission were: K+ 3.1 mEq/L, aldosterone 45 ng/Dl (normal 7-30). A CT scan showed bilateral adrenal hyperplasia. What drug was most likely included in the therapeutic regimen of this patient? a. Hydrochlorotiazide b. Fenoldopam c. Furosemide d. Mannitol e. Nitroprusside f. Spironolactone

F

10. Certain drugs can cause severe hypotension when combined with nitrates. Which of the following interacts with nitroglycerin by inhibiting the metabolism of cGMP? (A) Atenolol (B) Hydralazine (C) Isosorbide mononitrate (D) Nifedipine (E) Ranolazine (F) Sildenafil (G) Terbutaline

F. Sildenafil inhibits phosphodiesterase 5, an enzyme that inactivates cGMP. The nitrates (via NO) increase the synthesis of cGMP. This combination is synergistic.

8. A 38-year-old man who has been running a marathon collapses and is brought to the emergency department. He is found to have a left ventricular myocardial infarction and heart failure with significant pulmonary edema. The first-line drug of choice in most cases of heart failure is (A) Atenolol (B) Captopril (C) Carvedilol (D) Digoxin (E) Diltiazem (F) Dobutamine (G) Enalapril (H) Furosemide (I) Metoprolol (J) Spironolactone

H. In both systolic and diastolic heart failure, the initial treatment of choice is usually furosemide.

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

H. The two agents in this list that act via a NO mecha- nism are hydralazine and nitroprusside. However, hydralazine has a duration of action of hours, whereas nitroprusside acts for seconds to minutes and must be given by IV infusion.

A 76-year-old patient with rheumatoid arthritis and chronic heart disease is being considered for treatment with procainamide. She is already receiving digoxin, hydrochlorothiazide, and potassium supplements for her cardiac condition. In deciding on a treatment regimen with procainamide for this patient, which of the following statements is most correct? (A) A possible drug interaction with digoxin suggests that digoxin blood levels should be obtained before and after starting procainamide (B) Hyperkalemia should be avoided to reduce the likelihood of procainamide toxicity (C) Procainamide cannot be used if the patient has asthma because it has a β-blocking effect (D) Procainamide has a duration of action of 36-40 h (E) Procainamide is not active by the oral route

HyperK facilitates procainamide toxicity. Procainamide is active by the oral route and has a duration of action of 2-4 h (in the prompt-release form). Procainamide has NO SIGNIFICANT documented interaction with digoxin and little or no β-blocking action.

7. Another patient is admitted to the ED after a drug OD. He is noted to have hypotension and severe tachycardia. He has been receiving therapy for HTN & angina. Which of the following drugs often causes tachycardia? (A) Clonidine (B) Diltiazem (C) Isosorbide dinitrate (D) Propranolol (E) Verapamil

Isosorbide dinitrate (like all the nitrates) can cause reflex tachycardia, but all the other drugs listed here slow heart rate. The answer is C.

4. A 73yo man with a history of falling at home is found to have moderately severe HTN. Which of the following drug groups is most likely to cause postural hypotension and thus an increased risk of falls? (A) ACE inhibitors (B) Alpha-receptor blockers (C) Arteriolar dilators (D) Beta1-selective receptor blockers (E) Nonselective β blockers

Postural (orthostatic) hypotension is usually due to venous pooling. Venous pooling is normally prevented by α-receptor activation. The answer is B. (Postural hypotension may also occur in patients with hypovolemia owing to excessive diuretic treatment.)

A 66-year-old woman is admitted to the emergency department with a myocardial infarction. She develops sustained ventricular tachycardia. Neither amiodarone nor lidocaine is effective so the cardiologist decides to administer another drug. This drug acts by blocking activated Na+ channels and K+ channels. Which drug is it? a. Adenosine b. Mexiletine c. Sotalol d. Verapamil e. Procainamide

Procainamide is a class 1a antiarrhythmic. Drugs is this class block activated sodium channels and potassium channels. Procainamide can be used in acute treatment and prevention of supraventricular and ventricular arrhythmias when other drugs are poorly tolerated or ineffective

6. A man is admitted to the ED with a brownish cyanotic appearance, marked shortness of breath, and hypotension. Which of the following is most likely to cause methemoglobinemia? (A) Amyl nitrite (B) Isosorbide dinitrate (C) Isosorbide mononitrate (D) Nitroglycerin (E) Sodium cyanide

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

A 56-year-old alcoholic man presented to the ED with chest palpitations for 3 hours. Vital signs were: BP 170/90, pulse 170 beats/min. An ECG confirmed A-Fib and the physician considered prescribing one of the following drugs: metoprolol, verapamil, or digoxin. What action best explains a common effect of all these drugs in atrial fibrillation? a. Decreased AV conduction b. Decreased cardiac preload c. Increased intra-atrial conduction d. Increased myocardial contractility e. Increased ventricular refractoriness

The first treatment goal in atrial fibrillation (AF) is to slow the ventricular rate, allowing the ventricles to contract and empty more effectively. Digoxin, beta blockers and calcium channel blockers, all can be used effectively because they can cause an incomplete AV block, allowing less atrial impulses to pass into the ventricle.


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