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Victus quoque rationem ad aegrotantium salutem pro facultate, judicioque meo adhibebo, noxamvero et maleficium propulsabo. Also I ­ will, according to my ability and judgment, prescribe a regimen for the health of the sick; but I ­ will utterly reject harm and mischief. Hippocratic oath INTRODUCTION Of the top 20 individual medi­ cations by prescription volume in 2014, eight (40%)­ were cardiovascular agents (1). ­ These agents are ubiquitous in the care of patients. All medi­ cations have the potential to cause iatrogenic effects, and clinicians need to be vigilant in determining their presence. The recent Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive control to a systolic less than 120 mmHg may reduce the rate of major cardiovascular events, both fatal and nonfatal , and all-­ cause mortality. However, control does come at a cost of increasing the rates of some adverse events, most notably hypotension, syncope, electrolyte abnormalities , and acute kidney injury or failure (2). This chapter utilizes a drug category–­ based approach in identifying commonly occurring or impor­ tant adverse events to cardiovascular agents. The classes covered include loop diuretics, thiazide diuretics, potassium-­ sparing diuretics, beta-­ blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin-­ receptor blockers (ARBs), direct renin inhibitors, calcium channel blockers, alpha-­ blockers, and direct vasodilators. ­ Table 11-1 summarizes common agents for each class. Each class is evaluated for the common and concerning adverse reactions or iatrogenic disorders. ­ Table 11-2 provides an overview of reactions by class. Annually, more than 2 million serious adverse events are reported, resulting in 100,000 deaths. It is estimated that the cost associated with adverse drug reactions (ADRs) is $136 billion per year. The impact of ADRs is significant; annually, they cause CHAPTER 11 Iatrogenicity of Cardiovascular Drugs Associated With Cardiac and Noncardiac Toxicities Antihypertensive Agents and Biologics Evelyn R. Hermes-­ DeSantis and Joseph A. Barone Loop Diuretics / 117 injury or death to one out of five hospitalized patients. In addition, ADRs double the mean length of stay, costs, and mortality compared with control patients (3). LOOP DIURETICS Loop diuretics work on the Na+-­K+-2Cl-­ contransporter , inhibiting the ions’ reabsorption, in the thick ascending limb of the loop of Henle. They cause rapid diuresis and are a first-­ line treatment option for symptomatic management of volume overload in conditions such as heart failure and pulmonary edema. Pos­ si­ ble adverse events include renal insufficiency, hearing damage at high doses, hypotension, hypokalemia, and hypomagnesemia (4).­TABLE 11-1 Antihypertensive agents by class [generic name (brand name)] Loop diuretics • bumetanide (Bumex) • ethacrynic acid (Edecrin) • furosemide (Lasix) • torsemide (Demadex) Thiazide diuretics • chlorthalidone (Hygroton) • chlorothiazide (Diuril) •  hydrochlorothiazide (Esidrix, Hydrodiuril, Microzide) • indapamide (Lozol) • metolazone (Zaroxolyn) Potassium-­sparing diuretics • amiloride (Midamor) • eplerenone (Inspra) • spironolactone (Aldactone) • triamterene (Dyrenium) Beta-­blockers • acebutolol (Sectral) • atenolol (Tenormin) • betaxolol (Kerlone) • bisoprolol fumarate (Zebeta) • carteolol hydrochloride (Cartrol) • carvedilol (Coreg) •  labetalol hydrochloride (Normodyne, Trandate) • metoprolol succinate (Toprol-­ XL) • metoprolol tartrate (Lopressor) • nadolol (Corgard) • penbutolol sulfate (Levatol) • pindolol (Visken) • propranolol hydrochloride (Inderal) • sotalol (Betaspace) Angiotensin converting enzyme (ACE) inhibitors • benazepril hydrochloride (Lotensin) • captopril (Capoten) • enalapril maleate (Vasotec) • fosinopril sodium (Monopril) • lisinopril (Prinivel, Zestril) • moexipril (Univasc) • perindopril (Aceon) • quinapril hydrochloride (Accupril) • ramipril (Altace) • trandolapril (Mavik) Angiotensin-­ receptor blockers (ARBs) • candesartan (Atacand) • eprosartan mesylate (Teveten) • irbesarten (Avapro) • losartan potassium (Cozaar) • olmesartan (Benicar) • telmisartan (Micardis) • valsartan (Diovan) Direct renin inhibitors • aliskiren (Tekturna) Calcium channel blockers (DHP) • amlodipine besylate (Norvasc, Lotrel) • felodipine (Plendil) • isradipine • nicardipine (Cardene SR) • nifedipine (Adalat CC, Procardia XL) • nisoldipine (Sular) Calcium channel blockers (non-­ DHP) •  diltiazem hydrochloride (Cardiezem, Cartia, Dilacor, Diltia, Tiazac, Taztia) •  verapamil hydrochloride (Calan SR, Covera HS, Isoptin SR, Verelan) Alpha-­blockers • doxazosin mesylate (Cardura) • prazosin hydrochloride (Minipress) • terazosin hydrochloride (Hytrin) Direct vasodilators • hydralazine hydrochloride (Apresoline) • minoxidil (Loniten) ­TABLE 11-2 Adverse reactions or iatrogenic disorders by drug class Adverse reactions or iatrogenic disorders Loop Diuretics Thiazide Diuretics Potassium-­ S paring Diuretics Beta-­ B lockers ACE Inhibitors Angiotensin-­ Receptor Blockers Direct Renin Inhibitors (Aliskiren) Calcium Channel Blockers Alpha-­ B lockers Direct Vasodilators Cardiovascular effects Dehydration and hypovolemia X X X Noncardiogenic pulmonary edema and shock X Arrhythmia X Coronary artery spasm X Orthostatic hypotension X X Hypotension X X X Peripheral edema X X Myo­car­dial infarction X Angina X Pericardial effusions X Respiratory effects Angioedema X X X Cough X X CNS disturbances Ototoxicity X Musculoskeletal symptoms X Fatigue, somnolence, dizziness X X Confusion X Depression X Hallucination X Headache X Peripheral neuropathy X Electrolyte disturbances Hypomagnesemia X X Hypokalemia X X Hypocalcemia X Hyponatremia X X X Hypercalcemia X Hyperuricemia and ­ gout X Hyperkalemia X X X X Acid...


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