Pharmacology for Cardiology PDF

Name: Digoxin (Lanoxin) Name: Digitoxin (Crystodigin) Class: CHF Rx (Cardiac Glycoside) Class: CHF Rx (Cardiac Glycoside) Mech.: Inhib. of Na+ /K+ ATPase → ↑ release of Ca2+ from SR → ↑ myocar...

Name: Digoxin (Lanoxin) Name: Digitoxin (Crystodigin) Class: CHF Rx (Cardiac Glycoside) Class: CHF Rx (Cardiac Glycoside) Mech.: Inhib. of Na+ /K+ ATPase → ↑ release of Ca2+ from SR → ↑ myocardial Mech.: Inhib. of Na+ /K+ ATPase → ↑ release of Ca2+ from SR → ↑ myocardial contractility. Also ↑ sensitivity of AV node to vagal stimulation → ↓ contractility. Also ↑ sensitivity of AV node to vagal stimulation → ↓ ventricular rate in atrial flutter or fibrillation (i.e., anti-arrhythmic). ventricular rate in atrial flutter or fibrillation (i.e., anti-arrhythmic). Absorption: Absorption: Dist.: Dist.: Strong protein binding. Metab.: Very little. Metab.: Hepatic metab. Excretion, t_: Urine. Short t_. Excretion, t_: Feces. Longer t_ than digoxin. Toxicity/S.E.s: Low therapeutic index. Toxicity enhanced by hypokalemia. Toxicity/S.E.s: Low therapeutic index. Toxicity enhanced by hypokalemia. Arrhythmias (possibly life-threatening), anorexia, n/v/d, drowsiness, Arrhythmias (possibly life-threatening), anorexia, n/v/d, drowsiness, fatigue, visual disturbances. Verapamil or quinidine → ↑ toxicity. fatigue, visual disturbances. Verapamil or quinidine → ↑ toxicity. Utility: Treat heart failure. DOC for atrial fibrillation/flutter. Utility: Treat heart failure. Special Features: No active metabolites. Shorter t_, less GI absorption, and Special Features: Active metabolites. Longer t_, more GI absorption, and more less protein binding than digitoxin. Only cardiac glycoside routinely protein binding than digoxin. used. Name: Dobutamine (Dobutrex) Name: Dopamine Class: CHF Rx (β-Adrenergic Agonist) Class: CHF Rx (Mixed (α-β) Agonist (Cardioselective)) Mech.: ↓ dose → D1 stim. ↑ dose → β1 stim. Also releases NE from symp. neur. Causes Mech.: Stim. α and β receptors, but not DA. → ↑ CO w/o ↑ HR. ↑ stroke vasodilation in renal, mesenteric, and coronary beds → ↑ renal blood flow, glomerular filtration, and Na+ excretion. Also causes ↓ Na+ and H20 resorption. High doses → ↑ HR. Usu. increases volume. No/little change in peripheral resistance. ↑ cAMP → ↑ systolic BP and pulse pressure. Low-mod. doses → static or decreased vasc. resistance. High contractility. conc. → α1 activation → vasoconstriction → ↑ BP. ↑ cAMP → ↑ contractility. Absorption: IV → rapid onset (1-2 min). Peak effect ~ 10 min. Absorption: No oral. IV. Onset w/in 5 min. Dist.: Dist.: Metab.: Catab. by COMT and MAO, esp. in liver and kidneys. Glucuronidation Metab.: Methylation by COMT. Conjugation and sulfconjugation Excretion, t_: 2 min. Excretion, t_: Duration of action 10 min. t_: 2 min. Toxicity/S.E.s: Nausea, vomiting, tachycardia, anginal pain, arrhythmia, Toxicity/S.E.s: ↑ BP, ↑ HR, tachycardia, ventricular ectopic activity. ↑ headache, hypertension, vasoconstriction. Usu. due to excessive symp myocard. O2 consump. may cause ↑ size MI. Tachyphylaxis to β activity. Treat by stopping admin. or w/α blockers. Local ischemic stim. necrosis. Contraind. w/pheochromocytomas, uncorrected Utility: Short-term treatment of cardiac decompensation after cardiac surgery or tachyarrhythm. or vent. fibrillation, MAO inhibitors, furazolidone. Adjust w/CHF or acute MI. Often DOC after acute MI. Treatment of shock after dose w/tricyclics. correction of hypovolemia. Utility: Some shock (e.g., oliguria and low-normal periph. resist, cardiogenic/septic shock). CHF. www.brain101.info 1 Name: Amrinone (Inocor) Name: Hydralazine Class: CHF Rx (PDE Inhibitor) Class: CHF Rx (Vasodilator) Mech.: Inhib. of PDE III→ ↑ cAMP → ↑ contractility, ↑ stroke volume, ↑ Mech.: Acts directly on smooth muscle cells → vasodilation. Mech. unknown. ejection fraction, ↑ heart rate, ↑ exercise capacity. In smooth muscle, ↓ BP → reflex tachycardia & ↑ CO. ↑ renin concentration. ↑ NE in inhib. → vasodilation. heart failure. Absorption: Absorption: IV only. Dist.: Dist.: Metab.: Metab.: Excretion, t_: Excretion, t_: Toxicity/S.E.s: Reversible lupus-like synd. Headache, nausea, sweating, arrhythmia, angina, tachycardia. Toxicity/S.E.s: ↑ mortality from heart failure (possibly due to arrhythmogenesis). Utility: Treat CHF. Chronic use → reduction in two year mortality by 34%. Utility: Treat CHF. Almost always coadmin. w/β-blocker (to oppose tachycardia) and a diuretic (to decrease Na+ retention). Treat resistant HTN and Special Features: hypertensive emergencies. Special Features: Name: Diazoxide (Hyperstat I.V.) Name: Minoxidil (Loniten) Class: CHF Rx (Vasodilator) (Antihypertensive) Class: CHF Rx (Vasodilator) (Antihypertensive) Mech.: Direct arteriolar vasodilation → ↓ TPR → reflex ↑ in HR & CO. Mech.: Direct arteriolar vasodilation → ↓ TPR → reflex ↑ in HR & CO. Absorption: IV. Absorption: Oral. Dist.: Dist.: Metab.: Metab.: Excretion, t_: Long duration of action. Excretion, t_: Toxicity/S.E.s: Severe tachycardia, prolonged hypotension (possibly resulting Toxicity/S.E.s: Severe tachycardia. Serious Na+ & H2O retention → volume in stroke or MI). overload, edema, CHF. Hypertrichosis. Utility: Treat hypertensive emergencies, hypertensive encephalopathy, and Utility: Treat severe-malignant HTN refractory to other drugs. Male pattern eclampsia. baldness. Special Features: Special Features: Reflex tachycardia may be severe, requiring concomitant use of a diuretic and a β-blocker. www.brain101.info 2  Name: Verapamil (Calan) Name: Nitroprusside (Nipride) Class: Calcium-Entry Blocking Agent (Antidysrhythmic Agent Class IV) Class: Antihypertensive Agent Mech.: Binds to L-type Ca2+ channels → ↓ Ca2+ in arterial smooth muscle cells → vasodilation → Mech.: Stim. membrane-assoc. guanylyl cyclase in vascular smooth muscle ↓ cardiac afterload. Little/no effect on venous vessels. ↓ inotropy, chronotropy, & dromotropy. Net = ↓ HR, ↓ conduction, ↓ contractility, ↓ BP. May inhib. platelet aggreg. cells → ↑ intracellular cGMP → activation of cGMP-dependent protein → Absorption: Oral → nearly complete absorption. 1st pass metab→↓ bioavail. IV. vasodilation of arterial and venous vessels→ reflex tachycardia. Dist.: Significant protein binding. Reduces BP in all pts., regardless of etiology. Decreases afterload and Metab.: Hepatic. Inducible metab. Inhibits hepatic enzymes. Active metabolites. preload. Excretion, t_: 1.5-6 hr. Repeated oral dose → ↑ t_ due to hepatic saturation. Longer t_ in elderly or pts w/hepatic cirrhosis or renal insuff. Absorption: Continuous IV infusion. Oral → cyanide poisoning. Toxicity/S.E.s: Dizziness, hypotension, headache, constipation, gingival hyperplasia, flushing, edema. Aggravation of myocardial ischemia (less than w/DHPs). Serious toxicities (bradycardia, Dist.: transient asystole, exacerbation of heart failure) are rare, but may occur after IV admin; coadmin Metab.: w/β-blocker (c/i); or in pts. w/ventricular dysfxn, conduction disturbances, or systolic BP < 90 mm Hg (c/i). ↑ digoxin levels. C/i w/CHF, quinidine. Excretion, t_: Minutes Utility: Rx angina (stable, variant, unstable), arrhythmias, hypertension. More effective than Toxicity/S.E.s: Tachycardia, hypotension, cyanide toxicity (Rx w/sodium propranolol for unstable angina. DOC (IV) for paroxysmal supraventricular tachycardias. thiosulfate). Reentry arrhythmias. Special Features: Blocking action is frequency and voltage dependent. ∴ more effective in rapidly Utility: Hypertensive emergencies. depolarizing cells. At vasodilatory doses, greater negative chronotropic, dromotropic, and Special Features: inotropic effects than the dihydropyridines. Greatest effect on heart of channel blockers. Name: Nifedipine (Procardia) Name: Diltiazem (Cardizem) Class: Calcium-Entry Blocking Agent (Dihydropyridine) Class: Calcium-Entry Blocking Agent (Antidysrhythmic Agent Class IV) Mech.: Binds to L-type Ca2+ channels → ↓ Ca2+ in arterial smooth muscle cells → vasodilation → Mech.: Binds L-type Ca2+ channels→ ↓ Ca2+ in arterial smooth muscle cells → vasodilation → ↓ ↓ TPR, ↑ coronary blood flow, ↓ cardiac afterload. Little/no effect on venous vessels. No direct TPR, ↑ coronary blood flow, ↓ cardiac afterload. Little/no effect on venous vessels. ↓ effect on conduction or automaticity. Vasodilation → reflex ↑ sympathetic response → ↑ HR, ↑ inotropy, chronotropy, & dromotropy. Net = ↓ HR, ↓ contractility, ↓ BP. May inhib. platelet contractility. Net = ↓ BP, ↑ HR, ↑ contractility, ↑ CO. May inhib. platelet aggreg. aggreg. Absorption: Oral → nearly complete absorption. 1st pass metab→↓ bioavail. IV. Absorption: Oral → nearly complete absorption. 1st pass metab→↓ bioavail. IV. Dist.: Significant protein binding. Dist.: Significant protein binding. Metab.: Hepatic. Inducible metab. Inactive metabolites. Metab.: Hepatic. Inducible metab. Inhib. hepatic enzymes. Active metabolites. Excretion, t_: 1.5-6 hr. Repeated oral dose → ↑ t_ due to hepatic saturation. Longer t_ in elderly Excretion, t_: 1.5-6 hr. Repeated oral dose → ↑ t_ due to hepatic saturation. Longer t_ in elderly or pts w/hepatic cirrhosis or renal insuff. or pts w/hepatic cirrhosis or renal insuff. Toxicity/S.E.s: Dizziness, hypotension, headache, flushing, peripheral edema, gingival Toxicity/S.E.s: Dizziness, hypotension, headache, flushing, edema, constipation (less than hyperplasia. Aggravation of myocardial ischemia, angina. C/i w/CHF. verapamil), bradycardia, gingival hyperplasia. Aggravation of myocardial ischemia (less than Utility: Rx angina (stable, variant, unstable), arrhythmias, hypertension. DOC for stable angina w/DHPs). ↑ digoxin levels. C/i for pts. w/systolic BP30%). Low bioavail: ~30%. Plasma levels vary 7x btwn. Dist.:93% bound to protein. Enters CNS. Metab.: Hepatic Excret., t_: Short t_ (3.5-6 hr). pts. Toxicity/S.E.s: CV—hypotension, bradycardia. C/i for AV. May exacerbate angina (unopposed α Dist.: 30% bound to protein. receptor action). Resp—c/i in asthmatics, COPD, bronchitis, allergic rhinitis. Metab.: Excretion, t_: Renal. Long t_ (14-24 hr). Unchanged in urine. Metab—caution w/diabetics (masks sign of hypoglycemia: tachycardia). CNS—weakness, fatigue, nightmares, depression. GI—n/v (uncommon). Hypersens—rash, hematologic Toxicity/S.E.s: CV—hypotension, bradycardia, c/i for AV block. May exacerbate disorders (rare). angina (unopposed α receptor action). Resp—c/i in asthmatics, COPD, Utility: Mild-mod HTN (↓ CO → ↓ BP; blocks renin release). Adjunct to direct vasodilators for bronchitis, allergic rhinitis. Metab—caution w/diabetics (masks sign of severe HTN (prevents reflex tachycardia). Angina pectoris (prophylactic → ↑ exercise hypoglycemia: tachycardia). CNS—weakness, fatigue, nightmares, tolerance 2° to ↓ O2 demand). Cardiac arrhythmias (esp. supravent. tachyarrhyths). Acute MI depression. GI—n/v (uncommon). Hypersens—rash, hematologic disorders (prophylaxis & reduction of infarct size and failure). Modifies risk factors assoc. (rare). w/atherosclerosis. Increases O2 delivery to ischemic cardiac tissue. Special Features: Abrupt w/drawal may trigger MI. Not as effective against variant angina as Utility: Hypertension (↓ CO → ↓ BP; blocks renin release). Angina pectoris channel blockers and nitrates. Long-term antiarrhythmic β-blocker Rx → ↓ mortality. (prophylactic → ↑ exercise tolerance due to ↓ O2 demand). Cardiac arrhythmias (esp. supravent. tachyarrhyths). Acute MI (prophylaxis and reduction of infarct size and failure). Pheochromocytoma (in comb. w/alpha blocker). Essential tremor. Migraine headache (prophylaxis). Performance anxiety. Special Features: Abrupt w/drawal may trigger MI. Better pt. compliance than w/propranolol. www.brain101.info 7 Name: Timolol (Blocadren) Name: Pindolol (Visken) Class: Nonselective β-Blocking Agent Class: Nonselective β-Blocking Agent (Partial Agonist) Mech.: Competitive blockade of β1 and β2 receptors. No α effect. Absorption: Good oral (>90%). High bioavailability ~75%. Plasma levels vary 7x Mech.: Partial agonists of β1 and β2 receptors. No α effect. Some intrinsic btwn. patients. β-blocking plasma conc. 5-10 ng/mL (low). Eye sympathomimetic activity. drops. Absorption: Dist.: 10% bound to protein. Excretion, t_: Hepatic, renal. Short t_ (3-4 hr). Dist.: Toxicity/S.E.s: CV—hypotension, bradycardia, c/i for AV block. Resp—c/i in Excretion, t_: asthmatics, COPD, bronchitis, allergic rhinitis. Metab—caution w/diabetics (masks sign of hypoglycemia: tachycardia). CNS—weakness, fatigue, Toxicity/S.E.s: Mild chronic fatigue, low exercise tolerance, sedation, nightmares, depression. GI—n/v (uncommon). Hypersens—rash, nightmares, depression, ↑ airway resistance (β2 effect). hematologic disorders (rare). Utility: Hypertension (esp. HTN w/moderate bradycardia). Utility: Hypertension (↓ CO → ↓ BP; blocks renin release). Angina pectoris Special Features: Much less effect on HR and CO compared to other β-blockers. (prophylactic → ↑ exercise tolerance due to ↓ O2 demand). Cardiac Less disturbance of lipid and carbohydrate metab. compared to arrhythmias (esp. supravent. tachyarrhyths). Acute MI (prophylaxis and reduction of infarct size and failure). Pheochromocytoma (in comb. w/alpha other β-blockers. blocker). Essential tremor. Migraine headache (prophylaxis). Performance anxiety. Eyedrops for open-angle glaucoma (↓ production of aqueous humor). Spec. Features: Abrupt w/drawal may trigger MI. 6-10x as potent orally as others. Name: Metoprolol (Lopressor) Name: Labetalol (Trandate) Class: Cardioselective β1-Blocking Agent Class: Nonselective β and α1 Blocking Agent Mech.: Selective blockade of β1 (heart, kidney) w/rel. sparing of β2. No α effect. Mech.: Competitive blockade of β1, β2, and α receptors. Absorption: Good oral (>95%). Bioavailability ~50%. Plasma levels vary 10x Absorption: btwn. patients. Dist.: Dist.: 12% bound to protein. Metab.: Hepatic Excretion, t_: Short t_ (3-4 Metab.: hr). Excretion, t_: Toxicity/S.E.s: CV—hypotension, bradycardia, c/i for AV block. Resp—c/i in Toxicity/S.E.s: CV—orthostatic hypotension, sexual dysfxn, bradycardia, c/i for asthmatics, COPD, bronchitis, allergic rhinitis. Metab—caution w/diabetics AV block. Resp—c/i in asthmatics, COPD, bronchitis, allergic rhinitis. (masks sign of hypoglycemia: tachycardia). CNS—weakness, fatigue, Metab—caution w/diabetics (masks sign of hypoglycemia: tachycardia). nightmares, depression. GI—n/v (uncommon). Hypersens—rash, CNS—weakness, fatigue, nightmares, depression. GI—n/v (uncommon). hematologic disorders (rare). Hypersens—rash, hematologic disorders (rare). Also α effects. Utility: Hypertension (↓ CO → ↓ BP; blocks renin release). Angina pectoris Utility: Hypertension (↓ CO → ↓ BP; blocks renin release). Angina pectoris (prophylactic → ↑ exercise tolerance due to ↓ O2 demand). Cardiac (prophylactic → ↑ exercise tolerance due to ↓ O2 demand). Cardiac arrhythmias (esp. supravent. tachyarrhyths). Acute MI (prophylaxis and arrhythmias (esp. supravent. tachyarrhyths). Acute MI (prophylaxis and reduction of infarct size and failure). Pheochromocytoma (in comb. w/alpha reduction of infarct size and failure). Pheochromocytoma (in comb. w/alpha blocker). Essential tremor. Migraine headache (prophylaxis). Performance blocker). Essential tremor. Migraine headache (prophylaxis). Performance anxiety. anxiety. Special Features: Abrupt w/drawal may trigger MI. Cardioselectivity not great. Features: Abrupt w/drawal may trigger MI. More α side effects. Widely used. May be advantageous in asthmatic or diabetic hypertensives. www.brain101.info 8 Name: Captopril (Capoten) Name: Enalapril (Vasotec) Class: ACE Inhibitor Class: ACE Inhibitor Mech.: Inhib. production of angiotensin II → block of vasoconstriction and Mech.: Inhib. production of angiotensin II → block of vasoconstriction and aldosterone stim. → ↓ TPR, ↓ Na+ /H20 retention → ↓ BP. Also blocks aldosterone stim. → ↓ TPR, ↓ Na+ /H20 retention → ↓ BP. Also blocks inactivation of bradykinin → vasodilation. Diminishes normal ↑ in inactivation of bradykinin → vasodilation. Diminishes normal ↑ in epinephrine and aldosterone seen in CHF. epinephrine and aldosterone seen in CHF. Absorption: Absorption: Dist.: Dist.: Metab.: Metab.: Excretion, t_: Excretion, t_: Toxicity/S.E.s: Postural hypotension, renal insufficiency, hyperkalemia, Toxicity/S.E.s: Postural hypotension, renal insufficiency, hyperkalemia, persistent dry cough, rash, angioneurotic edema. C/i in 2nd & 3rd trimesters persistent dry cough, rash, angioneurotic edema. C/i in 2nd & 3rd trimesters of pregnancy. Prob. not a great idea for 1st trimester either. of pregnancy. Prob. not a great idea for 1st trimester either. Utility: Treat HTN, CHF, MI. Utility: Treat HTN, CHF, MI. Special Features: Special Features: Inactive prodrug. Converted to enalaprilat (acts like captopril). Name: Lisinopril (Zestril, Prinivol) Name: Losartan (Cozaar) Class: ACE Inhibitor Class: Angiotensin II Antagonist Mech.: Inhib. production of angiotensin II → block of vasoconstriction and Mech.: Competitive inhib. of angiotensin II → smooth muscle relaxation aldosterone stim. → ↓ TPR, ↓ Na+ /H20 retention → ↓ BP. Also blocks (vasodilation), ↓ Na+ & H20, ↓ plasma volume → ↓ BP. inactivation of bradykinin → vasodilation. Diminishes normal ↑ in Absorption: Oral. epinephrine and aldosterone seen in CHF. Dist.: Absorption: Metab.: Dist.: Excretion, t_: Metab.: Toxicity/S.E.s: Hyperkalemia, fetal toxicity (c/i in 2nd & 3rd trimesters). Excretion, t_: Utility: Treat hypertension. Toxicity/S.E.s: Postural hypotension, renal insufficiency, hyperkalemia, Special Features: Angioneurotic edema and dry cough of ACE inhibitors not persistent dry cough, rash, angioneurotic edema. C/i in 2nd & 3rd trimesters manifested. of pregnancy. Prob. not a great idea for 1st trimester either. Utility: Treat HTN, CHF, MI. Special Features: Lysine derivative of enalaprilat. www.brain101.info 9 Name: Lovastatin (Mevacor) Name: Pravastatin (Pravochol) Class: Blood Lipid-Lowering Agent (HMG CoA Reductase Inhibitor) Class: Blood Lipid-Lowering Agent (HMG CoA Reductase Inhibitor) Mech.: Inhib. of HMG CoA reductase → ↓ cholesterol pool, ↑ apoB/E receptor Mech.: Inhib. of HMG CoA reductase → ↓ cholesterol pool, ↑ apoB/E receptor activity, ↑ LDL clearance. Large reduction of cholesterol and LDL. activity, ↑ LDL clearance. Large reduction of cholesterol and LDL. Little/no ↓ in TGs, little/no ↑ in HDL, no change in VLDL. Little/no ↓ in TGs, little/no ↑ in HDL, no change in VLDL. Absorption: Dist.: Metab.: Excretion, t_: Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Common mild GI disturbances. Reversible elevations of liver Toxicity/S.E.s: Common mild GI disturbances. Reversible elevations of liver enzymes in 4-7% (if AST or ALT > 3x normal, discontinue). Possible muscle enzymes in 4-7% (if AST or ALT > 3x normal, discontinue). Possible muscle damage—much more likely w/concurrent cyclosporine, gemfibrozil, niacin, or damage—much more likely w/concurrent cyclosporine, gemfibrozil, niacin, or erythromycin; or if pt has hepatic disease, a severe infxn, or renal erythromycin; or if pt has hepatic disease, a severe infxn, or renal insufficiency. Continued use w/myopathy may → severe myositis, insufficiency. Continued use w/myopathy may → severe myositis, rhabdomyolysis, or acute renal failure. Can shorten sleep period by up to 18%. rhabdomyolysis, or acute renal failure. C/i in kids & preg. E. C/i in kids & preg. E. Utility: Treat pts. w/type IIA/IIB hyperlipidemia refractory to diet and other Utility: Treat pts. w/type IIA/IIB hyperlipidemia refractory to diet and other drugs. May not be useful for pts. w/homozygous familial drugs. May not be useful for pts. w/homozygous familial hypercholesterolemia. hypercholesterolemia. Special Features: Most effective drug class for lowering LDL. Probably better Special Features: Most effective drug class for lowering LDL. Probably better tolerated than other cholesterol lowering drugs. Synergistic effects w/resins tolerated than other cholesterol lowering drugs. Synergistic effects w/resins and niacin. If taken once/day, take at night (peak cholesterol synth. and niacin. If taken once/day, take at night (peak cholesterol synth. occurs between 12:00-3:00 a.m.). occurs between 12:00-3:00 a.m.). Name: Simvastatin (Zocor) Name: Cholestyramine (Cholybar) Class: Blood Lipid-Lowering Agent (HMG CoA Reductase Inhibitor) Class: Blood Lipid-Lowering Agent (Resin) Mech.: Inhib. of HMG CoA reductase → ↓ cholesterol pool, ↑ apoB/E receptor Mech.: Binds bile acids in intestine → ↑ defecation of bile acids, ↑ conversion activity, ↑ LDL clearance. Large reduction of cholesterol and LDL. of cholesterol to bile acids, ↓ pool of hepatic cholesterol, ↑ activity of Little/no ↓ in TGs, little/no ↑ in HDL, no change in VLDL. apoB/E receptor, ↑ LDL clearance, ↓ plasma cholesterol. Moderate ↓ in Absorption: Dist.: Metab.: Excretion, t_: cholesterol & LDL. Mild ↑ in HDL. Zero-moderate ↑ in TG & VLDL. Toxicity/S.E.s: Common mild GI disturbances. Reversible elevations of liver Absorption: Oral. No absorption. enzymes in 4-7% (if AST or ALT > 3x normal, discontinue). Possible muscle Dist.: Metab.: Excretion, t_: damage—much more likely w/concurrent cyclosporine, gemfibrozil, niacin, or Toxicity/S.E.s: Up to 50% refuse to continue Rx. Flatulence, constipation, erythromycin; or if pt has hepatic disease, a severe infxn, or renal gas, n/v, steatorrhea. Supersaturation of cholesterol in bile → gallstones, insufficiency. Continued use w/myopathy may → severe myositis, need for cholecystectomy. ↓ bile → ↓ absorption of lipid-soluble rhabdomyolysis, or acute renal failure. Can shorten sleep period by up to 18%. drugs/vitamins. Binds acidic drugs. Weak stim. of VLDL synth. Do not C/i in kids & preg. E. use in pts. w/hyperTG w/o concurrent TG-lowering agent. Utility: Treat hyperlipidemia IIA/IIB refractory to diet and other drugs. May not Utility: Treat hyperlipidemia IIA/IIB. Use alone or w/niacin, probucol, or HMG be useful for pts. w/homozygous familial hypercholesterolemia. CoA reductase inhib. Special Features: Most effective drug class for lowering LDL. Probably better Special Features: GI S.E.s reduced if taken immediately prior to meals. _ tolerated than other cholesterol lowering drugs. Synergistic effects w/resins and niacin. If taken once/day, take at night (peak cholesterol synth. dose + Metamucil™ → ↓ constipation & bloating, but sim. occurs between 12:00-3:00 a.m.). efficacy. www.brain101.info 10 Name: Colestipol (Colestid) Name: Nicotinic Acid (Niacin) Class: Blood Lipid-Lowering Agent (Resin) Class: Blood Lipid-Lowering Agent Mech.: Binds bile acids in intestine → ↑ defecation of bile acids, ↑ conversion Mech.: Reduces synth. rate of VLDL. Inhib. lipolysis of TG in adipocytes. of cholesterol to bile acids, ↓ pool of hepatic cholesterol, ↑ activity of Large ↓ in TG. Moderate ↓ in cholesterol & VLDL. Mild ↓ in LDL. Zero- apoB/E receptor, ↑ LDL clearance, ↓ plasma cholesterol. Moderate ↓ in moderate ↑ in HDL. Absorption: cholesterol & LDL. Mild ↑ in HDL. Zero-moderate ↑ in TG & VLDL. Dist.: Metab.: Absorption: Oral. No absorption. Excretion, t_: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Cutaneous flushing (92%), itching (49%), rashes (20%). Toxicity/S.E.s: Flatulence, constipation, gas, n/v, steatorrhea. Reduce w/aspirin pretreatment, admin. after meals, small init. dose gradually Supersaturation of cholesterol in bile → gallstones, need for increased in size. Pruritis, dry skin, ↑ pigmentation, hepatotoxicity, n/v, cholecystectomy. ↓ bile → ↓ absorption of lipid-soluble drugs/vitamins. dyspepsia, peptic ulceration, ↑ urinary frequency, dysuria, gout. High doses Binds acidic drugs. Weak stim. of VLDL synth. Do not use in pts. w/hyperTG w/o concurrent TG-lowering agent. → hepatic/pancreatic dysfxn. Coadmin. anti-hypertensives → dizziness, Utility: Treat hyperlipidemia IIA/IIB. Use alone or w/niacin, probucol, or HMG syncope. Sustained-release preparations more commonly assoc. CoA reductase inhib. w/hepatotoxicity, dry eyes, ↑ pigmentation, hyperglycemia. Special Features: GI S.E.s reduced if taken immediately prior to meals. _ Utility: Prob. DOC for hyperlipidemias IV and V. Very useful for III. Can be dose + Metamucil™ → ↓ constipation & bloating, but sim. used for II. Synergy w/resins. efficacy. Special Features: Name: Gemfibrozil (Lopid) Name: Clofibrate (Atromid-S) Class: Blood Lipid-Lowering Agent (Fibric Acid Derivative) Class: Blood Lipid-Lowering Agent (Fibric Acid Derivative) Mech.: ↑ catabolism of VLDL, in part 2° to ↑ activity of lipoprotein lipase in Mech.: ↑ catabolism of VLDL, in part 2° to ↑ activity of lipoprotein lipase in adipose tissue. Moderate ↓ in TG & VLDL. Mild ↓ in LDL and adipose tissue. Moderate ↓ in TG & VLDL. Zero-mild ↓ in cholesterol. cholesterol. Moderate ↑ in HDL. Zero-mild ↑ in HDL. Mild ↑ or ↓ in LDL. Absorption: Absorption: Dist.: Dist.: Metab.: Glucuronide conjugation. Metab.: Glucuronide conjugation. Excretion, t_: Renal excretion. Excretion, t_: Renal excretion. Toxicity/S.E.s: Generally well tolerated. GI distress, rash, musculoskeletal Toxicity/S.E.s: Generally well tolerated. Gallstones, nausea, diarrhea, pain, blurred vision, anemia, leukopenia, gallstones. Adjust dose abdominal discomfort. Displaces weakly acidic drugs (T3, T4, in pts. w/renal insufficiency. warfarin, phenytoin) from plasma proteins. Binds cholestyramine. Utility: DOC for hyperlipidemia III. Better tolerated than niacin for type IV, Utility: Treat severe hyperlipidemia IV refractory to gemfibrozil or niacin. although less effective. Decreases frequency of CHD-related incidents. Special Features: Does not appear to decrease frequency of CHD-related Special Features: incidents. www.brain101.info 11 Name: Probucol (Lorelco) Name: Nitroglycerin (Nitro-Bid) Class: Blood Lipid-Lowering Agent (Fibric Acid Derivative) Class: Antianginal Agent (Organonitrate) Mech.: Stim. LDL clearance by non-receptor pathways. May reduce risk of Mech.: Converted to NO → activation of cytosolic guanylate cyclase → ↑ atherogenesis w/o altering serum cholesterol levels. May block cGMP → activation of cGMP-dependent protein kinase → smooth muscle oxidation of LDL. Moderate ↓ in cholesterol, LDL, & HDL. No effect on relaxation → vasodilation. Greater effect in veins & large arteries than in TG or VLDL. resistance vessels → ↓↓ preload, ↓ afterload → ↓ work → ↓ O2 demand. Absorption: Inhib. of platelet fxn. Dist.: Stored in fat. Absorption: Sublingual preferred. IV. Oral → ↑ 1st pass metab, low bioavail. Metab.: Excretion, t_: Buccal/transdermal → slow absorption. Toxicity/S.E.s: Generally very well tolerated (2-6% incidence). Flatulence, Dist.: n/v/d, abd. pain, headache, rash. C/i in monkeys (cardiac arrhythmias). Metab.: Hepatic (glutathione-organic nitrate reductase), extra-hepatic. Plasma clearance >> C.O. Stored in fat. ∴ E advised to wait 6 mo. after last dose before becoming Excretion, t_: Renal. 3 min. Short duration of action (20-30 min.). pregnant. Toxicity/S.E.s: Orthostatic hypotension, tachycardia, severe throbbing Utility: Treat hyperlipidemia IIA/IIB, but prob. not drug o’ first choice. May be headache, dizziness, flushing, syncope. C/i w/elevated ICP. useful for homozygous familial hypercholesterolemia (IIA). May cause Utility: Treat angina. Subling. not suitable for maintenance therapy. IV for regression of xanthomas. severe recurrent unstable angina. Oral/buccal/transdermal for Special Features: ↓ in LDL takes 1-3 mo., but some pts. don’t respond. Does prophylaxis, but may → tolerance. not further reduce LDL when used w/lovastatin. Special Features: 8+ hr. breaks necessary to avoid tolerance from slow absorp. Name: Isosorbide Dinitrate (Isordil) Name: Amyl Nitrate Class: Antianginal Agent (Organonitrate) Class: Antianginal Agent (Organonitrate) Mech.: Converted to NO → activation of cytosolic guanylate cyclase → ↑ cGMP → activation of cGMP-dependent protein kinase → smooth muscle Mech.: Converted to NO → activation of cytosolic guanylate cyclase → ↑ relaxation → vasodilation. Greater effect in veins & large arteries than in cGMP → activation of cGMP-dependent protein kinase → smooth muscle resistance vessels → ↓↓ preload, ↓ afterload → ↓ work → ↓ O2 demand. relaxation → vasodilation. Greater effect in veins & large arteries than in Inhib. of platelet fxn. resistance vessels → ↓↓ preload, ↓ afterload → ↓ work → ↓ O2 demand. Absorption: Sublingual preferred → complete absorption. Oral → ↑ 1st pass Inhib. of platelet fxn. metab, low bioavail. Buccal/transdermal → slow absorption. Absorption: Inhalation → rapid onset. Dist.: Dist.: Metab.: 80% converted to active metabolite 5-ISMN before entering systemic Metab.: Hepatic inactivation via glutathione-organic nitrate reductase. circulation. Hepatic inactivation via glutathione-organic nitrate reductase. Excretion, t_: Renal. Short duration of action (3-5 min.). Excretion, t_: Renal. 10 min. Short duration of action (20-30 min.). Toxicity/S.E.s: Orthostatic hypotension, tachycardia, severe throbbing Toxicity/S.E.s: Orthostatic hypotension, tachycardia, severe throbbing headache, dizziness, flushing, syncope. C/i w/elevated ICP. headache, dizziness, flushing, syncope. C/i w/elevated ICP. Utility: Treat angina. Not suitable for maintenance therapy. Utility: Treat angina. Subling. not suitable for maintenance therapy. Special Features: Oral/buccal/transdermal for prophylaxis, but may → tolerance Special Features: 8+ hr. breaks necessary to avoid tolerance from slow absorp. www.brain101.info 12 Name: Acetylsalicylic Acid (Aspirin) Name: Dipyridamole (Persantine) Class: Antithrombotic Agent (Antiplatelet Agent) Class: Antithrombotic Agent (Antiplatelet Agent) Mech.: Irrevers. acetylation of cyclooxygenase → ↓ platelet thromboxane synth. Mech.: Inhib. PDE in platelets → ↑ cAMP → inhib. of platelet activation. Absorption: Oral → rapid absorption. Absorption: Dist.: Dist.: Metab.: Metab.: Excretion, t_: Toxicity/S.E.s: GI hemorrhage, hemorrhagic stroke. Use w/caution in pts on Excretion, t_: long-term oral anticoagulants. Hypersensitivity rxns—generalized urticaria, Toxicity/S.E.s: bronchial asthma, laryngeal edema, bronchoconstriction, hypotension, Utility: Prevention of systemic embolism in pts. w/prosthetic heart valves. shock—may occur in 20-25% of pts w/asthma, nasal polyps, or chronic Admin. in combination w/warfarin. urticaria. Special Features: When used alone, ineffective for Rx of cerebral or CV Utility: Acute MI, stable/unstable angina, 2° prevention in MI survivors. TIA. thrombotic events. Not proven to be of additional benefit 2° prevention in nondisabling ischemic stroke. Prevention of saphenous when admin. w/aspirin. Antithrombotic use is primarily for vein bypass graft occlusion. Post-coronary angioplasty. 1° MI arterial thromboses. prophylaxis (325 mg/d) adjunctive to risk factor management. Headache. Special Features: Low dose Rx optimal—75-325 mg/d. Antithrombotic use is primarily for arterial thromboses. Name: Ticlopidine (Ticlid) Name: Abciximab (Reo-Pro) Class: Antithrombotic Agent (Antiplatelet Agent) Class: Antithrombotic Agent (Antiplatelet Agent) Mech.: Unknown. Through some effect on platelet membranes, blocks ADP- Mech.: Monoclonal antibody to GPIIb/IIIa. Interferes w/platelet-adhesive induced aggregation. Interacts w/membrane glycoprotein IIb/IIIa. protein interactions. Absorption: Absorption: Dist.: Metab.: Dist.: Excretion, t_: Metab.: Toxicity/S.E.s: Diarrhea, GI cramping, rash, ↑ LDL & VLDL, leukopenia, Excretion, t_: agranulocytosis, pancytopenia. Toxicity/S.E.s: Utility: Treat thromboses in patients unable to take aspirin. May be more Utility: Treat high risk angioplasty pts. effective than aspirin in 2° prevention of stroke in pts w/previous TIA. Special Features: Special Features: Several days required for effects to develop. Effects persist for several days after cessation of treatment. As effective in E as in G. Antithrombotic use is primarily for arterial thromboses. www.brain101.info 13 Name: Heparin Name: Enoxaparin (Lovenox) Class: Antithrombotic Agent (Anticoagulant) Class: Antithrombotic Agent (Anticoagulant) (Low Molecular Weight Heparin) Mech.: Catalyzes complex formation btwn. plasma antithrombin III and various serine proteases Mech.: Catalyzes complex formation btwn. plasma antithrombin III and various serine proteases of the coagulation pathway, including thrombin and activated factors IX, X, XI, & XII. Effect of the coagulation pathway, including thrombin and activated factors IX, X, XI, & XII. Effect primarily due to thrombin inhib. Prevents further clot formation and thrombus propagation. Does primarily due to thrombin inhib. Less effect on thrombin than heparin. Prevents further clot not alter organized clots. formation and thrombus propagation. Does not alter organized clots. Absorp.: IV, continuous IV→immed. onset. SC→1-2 hr onset w/variable bioavail. Absorp.: SC → better bioavail. than heparin. Daily SC injxn has sim. efficacy to 2-3 injxns/d of Dist.: Metab.: Hepatic. heparin. Excretion, t_: Rel. short t_. ↓ t_ w/pulm. embolism. ↑ t_ w/hepatic cirrhosis or end-stage renal Dist.: Metab.: Hepatic. disease. Excretion, t_: Longer t_ than heparin. ↓ t_ w/pulm. embolism. ↑ t_ w/hepatic cirrhosis or end- Toxicity/S.E.s: 1° = bleeding. Thrombocytopenia (bovine > porcine)—mild, severe (delayed stage renal disease. onset; can occur w/heparin resistance → thromboembolism & DIC). Long-term use → Toxicity/S.E.s: 1° = bleeding. Thrombocytopenia (bovine > porcine)—mild, severe (delayed osteoporosis. Non-teratogenic, but discontinue prior to delivery. onset; can occur w/heparin resistance → thromboembolism & DIC). Long-term use → Utility: Symptomatic calf vein thrombi or thrombi extending above the popliteal vein, pulm. embolus, osteoporosis. Non-teratogenic, but discontinue prior to delivery. atrial fibrillation, valvular heart disease, CAD, adjunct to post-MI thrombolytic therapy. Use in Utility: 1° prevention of DVT after hip replacement surgery. general surgery for E on oral contraceptives. Special Features: Primarily used for venous thromboses. Monitor PTT to achieve desired Special Features: Primarily used for venous thromboses. Most widely used antithromb. agent. dose—1.5-2.5x normal PTT is therapeutic. ↑ recurrence rate if PTT < 1.5 x normal or if Monitor PTT to achieve desired dose—1.5-2.5x normal PTT is therapeutic. ↑ recurrence rate if therapeutic levels aren’t achieved w/in 24 hr. Few drug interactions. Lower rate of bleeding than PTT < 1.5 x normal or if therapeutic levels aren’t achieved w/in 24 hr. Few drug interactions. w/heparin. Name: Protamine Sulfate Name: Antithrombin III (ATnativ) Class: Anticoagulant Antagonist Class: Antithrombotic Agent (Coagulation Inhibitor) Mech.: Binds tightly to heparin and rapidly reverses its effects. Also interacts Mech.: Prepared from pooled human plasma. Inhibits coagulation factors w/platelets, fibrinogen, and other plasma proteins → anticoagulant (thrombin, IXa, Xa, XIIa). effect. Absorption: Absorption: IV infusion—slow rate. Dist.: Dist.: Metab.: Metab.: Excretion, t_: Excretion, t_: Toxicity/S.E.s: Toxicity/S.E.s: Utility: Treat pts w/hereditary AT-III deficiency and neonates w/a family history of AT-III deficiency. Prophylaxis for deficient pts who are undergoing Utility: Treat life-threatening hemorrhage 2° to heparin use. surgery or delivery at term. Special Features: Use minimal effective dose. Special Features: www.brain101.info 14 Name: Warfarin (Coumadin) Name: Vitamin K1 (Phytonadione) Class: Antithrombotic Agent (Oral Anticoagulant) Class: Anticoagulant Antagonist Mech.: Vitamin K antagonist → ↓ γ-carboxylation of thrombin, factors, VII, IX, Mech.: Vit. K is necessary for γ-carboxylation of thrombin, factors VII, IX, & X, & X, and proteins C & S → inhib. of synth. of active coagulation factors. and proteins C & S. The γ-carboxylated residues are required for binding Does not alter organized clots. Ca2+, which is essential for their activity. Absorption: Oral. Absorption: Oral or SC preferred. IV admin. may cause shock or anaphylaxis. Dist.: Almost completely bound (99%) to plasma proteins (mainly albumin). Metab.: Microsomal enzymes in liver and kidneys. Dist.: Excretion, t_: Urine and stool. Metab.: Toxicity/S.E.s: Hemorrhage, hypersensitivity rxns., fetal toxicity. “Purple Toe” Excretion, t_: synd. (necrosis) assoc. w/protein C deficiency. During Toxicity/S.E.s: IV admin. may cause shock or anaphylaxis. pregnancy, can cause birth defects and abortion. Many drug interactions. Utility: Reverse excessive bleeding due to warfarin—indicated for severe or continued bleeding if warfarin dosage adjustment is unsuccessful. Utility: Prevention of recurrent thrombotic events following acute Rx w/heparin. Valvular heart disease, prosthetic cardiac valves, AMI, atrial fibrillation. Special Features: Significant improvement in hemostasis may require as long as 24 hr. If immediate hemostasis is necessary, fresh frozen Special Features: Max. effects require 2-7 days. Init. response may be plasma should be infused. procoagulant due to inhib. of protein C. Should have 6 day overlap w/heparin. Monitor PT. Name: Streptokinase (Streptase) Name: Anistreplase/APSAC (Eminase) Class: Antithrombotic Agent (Thrombolytic Agent) Class: Antithrombotic Agent (Thrombolytic Agent) Mech.: Derived from β-hemolytic streptococci. Forms a complex w/plasminogen, Mech.: Acylated plasminogen-streptokinase activator complex. Plasminogen exposing its active site. Poor thrombus specificity—catalyzes conversion of active site is protected from inactivation. Poor thrombus specificity—catalyzes circulating and fibrin-bound plasminogen—results in a systemic lytic state. conversion of circulating & fibrin-bound plasminogen—results in a systemic lytic Absorption: IV. Admin. w/large loading dose to overcome plasma antibodies. state. Dist.: Absorption: IV. Admin. w/large loading dose to overcome plasma antibodies. Metab.: Dist.: Metab.: Excretion, t_: Excretion, t_: Longer t_ than streptokinase → sustained fibrinolytic effect. Toxicity/S.E.s: Hemorrhage. Allergic rxns—pruritis, flushing, urticaria. Higher Toxicity/S.E.s: Hemorrhage. Allergic rxns—pruritis, flushing, urticaria. Higher incidence of allergic rxns. w/readministration. Pronounced incidence of allergic rxns. w/readministration. Pronounced hypotension (usu. transient). Delayed fever and arthralgia. hypotension (usu. transient). Delayed fever and arthralgia. Utility: Treat acute MI (w/in 6 hr. of symptoms), massive PE, acute proximal Utility: Treat acute MI (w/in 6 hr. of symptoms), massive PE, acute proximal vein thromboses, occlusion of dialysis access sites and indwelling vein thromboses, occlusion of dialysis access sites and indwelling catheters, occlusion of prosthetic heart valves. catheters, occlusion of prosthetic heart valves. Special Features: Best results in pts. that receive therapy < 1 hr. after onset Special Features: Best results in pts. that receive therapy < 1 hr. after onset of symptoms and that achieve successful reperfusion. Pts. of symptoms and that achieve successful reperfusion. Pts. w/antibodies can develop therapeutic resistance. w/antibodies can develop therapeutic resistance. www.brain101.info 15 Name: Tissue Plasminogen Activator, tPA (Activase) Name: Urokinase (Abbokinase) Class: Antithrombotic Agent (Thrombolytic Agent) Class: Antithrombotic Agent (Thrombolytic Agent) Mech.: Recombinant product identical to endothelial tPA. Preferentially Mech.: Urinary-type single chain plasminogen activator. Isolated from cultured activates plasminogen that is bound to fibrin → greater clot specificity human kidney cells. and potentially less systemic fibrinolysis than w/streptokinase. Absorption: Absorption: IV. Prolonged admin. necessary (generally given over 3 hr.). Dist.: “Accelerated” regimen admin. over 90 min. (2/3 given w/in 1st 30 min.) Metab.: Dist.: Metab.: Excretion, t_: Excretion, t_: Short t_. Toxicity/S.E.s: Hemorrhage. Toxicity/S.E.s: Hemorrhage. Utility: Treat acute MI (w/in 6 hr. of symptoms), massive PE, acute proximal Utility: Treat acute MI (w/in 6 hr. of symptoms), massive PE, acute proximal vein thromboses, occlusion of dialysis access sites and indwelling vein thromboses, occlusion of dialysis access sites and indwelling catheters, occlusion of prosthetic heart valves. catheters, occlusion of prosthetic heart valves. Special Features: Best results in pts. that receive therapy < 1 hr. after onset Special Features: Best results in pts. that receive therapy < 1 hr. after onset of symptoms and that achieve successful reperfusion. Generally non- of symptoms and that achieve successful reperfusion. antigenic. Does not cause allergic rxns. Expensive—several times more costly than streptokinase. Name: Aminocaproic Acid (Amicar) Name: Tranexamic Acid (Amstat) Class: Thrombolytic Agent Antagonist Class: Thrombolytic Agent Antagonist Mech.: Lysine analog. Binds to lysine sites on plasminogen and plasmin → Mech.: Competitive inhib. of plasminogen activation. blocks binding of plasmin to fibrin. Absorption: Oral. Absorption: IV (slow injxn). Dist.: Dist.: Metab.: Metab.: Excretion, t_: Excretion, t_: Toxicity/S.E.s: Toxicity/S.E.s: Thrombi that form during treatment are not lysed. Thrombosis Utility: Used for hemostasis in pts. undergoing oral surgery who are being may become a problem. treated w/oral anticoagulants. Utility: Treat bleeding from fibrinolytic therapy. Special Features: Special Features: www.brain101.info 16 Name: Quinidine (Quinidex) Name: Procainamide (Pronestyl) Class: Antidysrhythmic Agent (Class IA) Class: Antidysrhythmic Agent (Class IA) Mech.: Binds to open and inactivated Na+ channels and prevents Na+ influx → Mech.: Binds to open and inactivated Na+ channels and prevents Na+ influx → slowing of the rapid upstroke during phase 0. Also decreases the slope of slowing of the rapid upstroke during phase 0. Also decreases the slope of phase 4 spontaneous depolarization. Prolongs repolarization. Inhibits phase 4 spontaneous depolarization. Prolongs repolarization. Inhibits arrhythmias due to ↑ normal automaticity. Intermed. speed of dissociation arrhythmias due to ↑ normal automaticity. Intermed. speed of dissociation from Na+ channels. from Na+ channels. Absorption: Oral → rapid, nearly complete absorption. Absorption: Oral. IV rarely used, as hypotension occurs w/too rapid infusion. Dist.: Metab.: Excretion, t_: Dist.: Excretion, t_: Urine. 2-3 hr. Toxicity/S.E.s: Proarrhythmic effects, negative inotropy, infranodal conduction Metab.: Hepatic → active metabolite NAPA (↑ duration of action potential). block, DILQT. Cinchonism—n/v/d, tinnitus, headache, vertigo, Toxicity/S.E.s: Proarrhythmic effects, negative inotropy, infranodal conduction auditory/visual disturbances. Hypotension (α-blocking activity). ↑ block, DILQT. Hypotension (ganglion-blocking activity). Chronic use → digoxin levels. Hypersensitivity rxns—rash, fever, angioneurotic edema, reversible SLE-like synd. Depression, hallucination, psychosis, giddiness. hepatitis. Reversible thrombocytopenia. Less GI intolerance than quinidine. Hypersensitivity rxns—fever, Utility: Treat atrial, AV junctional, & ventricular tachyarrhythmias. Maintain agranulocytosis, Raynaud’s synd., myalgias, rashes, digital vasculitis. sinus rhythm after direct current cardioversion of atrial flutter or Utility: Treat atrial, AV junctional, & ventricular tachyarrhythmias. Maintain fibrillation. Prevent frequent ventricular tachycardia. sinus rhythm after direct current cardioversion of atrial flutter or Special Features: fibrillation. Prevent frequent ventricular tachycardia. Special Features: Name: Disopyramide (Norpace) Name: Lidocaine (Zylocaine) Class: Antidysrhythmic Agent (Class IA) Class: Antidysrhythmic Agent (Class IB) Mech.: Binds to open and inactivated Na+ channels and prevents Na+ influx → Mech.: Shortens phase 3 repolarization. Little change in action potential slowing of the rapid upstroke during phase 0. Also decreases the slope of duration. Inhibits arrhythmias caused by abnormal automaticity. Rapid phase 4 spontaneous depolarization. Prolongs repolarization. Inhibits speed of dissociation from Na+ channels. Absorption: IV arrhythmias due to ↑ normal automaticity. Intermed. speed of dissociation Dist.: from Na+ channels. Peripheral vasoconstriction. The stereoisomers have Metab.: Hepatic. opposite effects on repolarization. Excretion, t_: Absorption: Toxicity/S.E.s: Fairly wide therapeutic index. Proarrhythmic effects, negative Dist.: inotropy, infranodal conduction block. Drowsiness, slurred speech, Metab.: Hepatic. paresthesia, agitation, confusion, convulsions, resp. depression, tinnitus, Excretion, t_: Urine. Toxicity/S.E.s: Proarrhythmic effects, negative inotropy, infranodal conduction muscle twitching, psychosis, seizures. ↑ CNS toxicity if used w/tocainide or block, DILQT. Anticholinergic effects—dry mouth, urinary mexiletine (e.g., seizures). retention, blurred vision, constipation. N/v/d, abd. pain. Less GI Utility: DOC for sustained ventricular tachycardia. Treat ventricular intolerance than quinidine. arrhythmias arising during myocardial ischemia or digitalis-induced VA. Utility: Alt. to procainamide or quinidine for treatment of ventricular arrhythmia. Special Features: Class IB drugs have the lowest potency as Na+ channel Special Features: blockers. www.brain101.info 17 Name: Tocainide (Tonocard) Name: Mexiletine (Mexitil) Class: Antidysrhythmic Agent (Class IB) Class: Antidysrhythmic Agent (Class IB) Mech.: Shortens phase 3 repolarization. Little change in action potential Mech.: Shortens phase 3 repolarization. Decreases action potential duration. duration. Inhibits arrhythmias caused by abnormal automaticity. Rapid Inhibits arrhythmias caused by abnormal automaticity. Rapid speed of speed of dissociation from Na+ channels. dissociation from Na+ channels. Absorption: Oral Absorption: Oral Dist.: Dist.: Metab.: Metab.: Excretion, t_: Excretion, t_: Toxicity/S.E.s: Proarrhythmic effects, negative inotropy, infranodal conduction Toxicity/S.E.s: Proarrhythmic effects, negative inotropy, infranodal conduction block. N/v, dizziness, disorientation, tremor. Hematologic effects block. N/v, dizziness, disorientation, tremor. (agranulocytosis, bone marrow suppression, thrombocytopenia) can be fatal. Utility: Chronic treatment of ventricular arrhythmias assoc. w/previous Utility: Treat ventricular tachyarrhythmias (only as a last resort). myocardial infarction. Special Features: Concurrent use w/quinidine may be effective at lower doses Special Features: Concurrent use w/quinidine may be effective at lower doses than either alone → ↓ adverse effects of each. than either alone → ↓ adverse effects of each. Name: Flecainide (Tambocor) Name: Sotalol (Betapace) Class: Antidysrhythmic Agent (Class IC) Class: Antidysrhythmic Agent (Class III) Mech.: Slow dissociation from Na+ channels → marked suppression of phase 0 upstroke → marked slowing of conduction. ↑ threshold potential → ↓ Mech.: Blocks rapid outward K+ current (delayed rectifier) → prolonged automaticity. repolarization and action potential → ↑ effective refractory period. Little Absorption: Oral. effect on rate of depolarization. L-isomer is a potent β-blocker. Dist.: Absorption: Metab.: Minimal. Excretion, t_: 16-20 hr. Dist.: Toxicity/S.E.s: Long-term Rx → ↑ mortality. Dizziness, blurred vision, tremor, Metab.: agitation, headache, nausea. Aggravation of preexisting arrhythmias, Excretion, t_: negative inotropy, induction of life-threatening ventricular tachycardia (CAST Toxicity/S.E.s: Rel. low rate of adverse effects. DILQT synd., sinus proarrhythmia), aggravation of CHF, infranodal conduction block. bradycardia. Utility: Treat refractory ventricular arrhythmias. Suppress premature ventricular contraction. Treat AV nodal reentry, WPW-related Utility: Long-term therapy to decrease the rate of sudden death following acute arrhythmia. MI. Modest ability to suppress ectopic beats and ↓ O2 demand. Strong Special Features: Class IC drugs have the highest potency as Na+ channel antifibrillary effect. Prevents arrhythmia and decreases mortality in pts. blockers w/sustained ventricular tachycardia. Special Features: www.brain101.info 18 Name: Amiodarone (Cordarone) Name: Adenosine (Adrenocard) Class: Antidysrhythmic Agent (Class III) Class: Antidysrhythmic Agent Mech.: Structurally related to thyroxine. 1° effect is prolongation of action potential and refractory period. Antiarrhythmic activity and antianginal Mech.: High doses → ↓ conduction velocity, ↑ refractory period, ↓ automaticity activity. in the AV node. Absorption: Oral. Absorption: IV Dist.: Dist.: Metab.: Excretion, t_: 25-110 days. Metab.: Toxicity/S.E.s: Common (>75% of pts). Interstitial pulmonary fibrosis, GI Excretion, t_: Extremely short duration of action (15 sec.). intolerance, tremor, ataxia, dizziness, depression, nightmares, Toxicity/S.E.s: Low toxicity. Flushing, chest pain, hypotension, transient hallucinations, hyper/hypothyroidism, liver toxicity, photosensitivity, periph. dyspnea, non-myocardial chest discomfort, metallic taste. neuropathy, muscle weakness, blue skin (I2), possibly irreversible hepatic dysfxn. DILQT synd., sinus bradycardia. Asympt. corneal deposits in all Utility: DOC for acute supraventricular tachycardia. Treat AV nodal reentry, orthodromic tachycardia. pts. Substantial ↑ in LDL. Phospholipidosis. Enhances effect of warfarin. Special Features: ↑ conc. of digoxin, quinidine, procainamide, et. al. Utility: Treat severe refractory supraventricular and ventricular tachyarrhythmia. Special Features: Usefulness limited by toxicity. Full effects may take up to 6 weeks to manifest. Name: Magnesium Class: Antidysrhythmic Agent Hope. Pandora brought the box containing the evils and opened it. It was the gift Mech.: of the gods to mankind, outwardly a fair, seductive gift and named the ‘box of Absorption: good fortune’. Then all the evils, living winged creatures, flew out; since then Dist.: they have been hovering about doing harm to men by day and night. A single evil had not yet slipped out of the box; then, by the will of Zeus, Pandora shut the Metab.: lid, and thus it remained within. Now man has the box of good fortune forever in Excretion, t_: the house and is amazed at the treasure he possesses in it; it stands at his service, Toxicity/S.E.s: he reaches for it when he desires to do so; for he does not know that the box Utility: DOC for torsades de pointes (DILQT synd). Treat pts w/digitalis- Pandora brought was the box of evil and regards the evil that has remained behind induced arrhythmia if hypomagnesemia is present. as the greatest piece of good fortune - it is hope. For what Zeus wanted was that Special Features: man, though never so tormented by the other evils, should nonetheless not throw life away but continue to let himself be tormented. To that end he gives men hope: it is in truth the worst of all evils, because it protracts the torment of men. - Nietzsche www.brain101.info 19