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Classes of Drugs Used to Treat Myocardial Infarction Classes of drugs used in the treatment of myocardial infarction are given below. Clicking on the drug class will link you to the page describing the pharmacology of that drug class. Vasodilators (dilate arteries and veins) - nitrodilators o isosorbide dinitrate o isosorbide mononitrate o nitroglycerin o erythrityl tetranitrate o pentaerythritol tetranitrate o sodium nitroprusside - angiotensin converting enzyme inhibitors (ACE inhibitors) (to treat hypertension & heart failure) o o o o o o o o benazepril captopril enalapril fosinopril lisinopril moexipril quinapril ramipril - angiotensin receptor blockers (ARBs) o These drugs have very similar effects to angiotensin converting enzyme (ACE) inhibitors and are used for the same indications (hypertension, heart failure, post- myocardial infarction). o o o o o o o candesartan eprosartan irbesartan losartan olmesartan telmisartan valsartan Cardiac depressant drugs (reduce heart rate and contractility) o Cardioinhibitory drugs depress cardiac function by decreasing heart rate (chronotropy) and myocardial contractility (inotropy), which decreases cardiac output and arterial pressure. These cardiac changes reduce the work of the heart and myocardial oxygen consumption. The mechanisms of action of these drugs also lead to depressed electrical conduction (dromotropy) within the heart. Some of these drugs may also impair relaxation (lusitropy). o The mechanical and metabolic effects of these drugs make them very suitable for treating hypertension, angina caused by coronary artery disease, and myocardial infarction. Furthermore, their effects on electrical activity make them good candidates for the treatment of cardiac Page 2, Classes of Drugs Used to Treat Myocardial Infarction arrhythmias. Finally, some cardioinhibitors, notably certain beta-blockers, are used in the treatment of heart failure. - beta-blockers Clinical Uses HTN Angina Arrhy MI CHF Comments Class/Drug Non-selective β1/β2 carteolol carvedilol labetalol nadolol penbutolol pindolol propranolol sotalol timolol β1-selective acebutolol atenolol betaxolol bisoprolol esmolol metoprolol X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X ISA X MSA X X X nebivolol ISA; long acting; also used for glaucoma α-blocking activity ISA; α-blocking activity long acting ISA ISA; MSA MSA; prototypical beta-blocker several other significant mechanisms primarily used for glaucoma ultra short acting; intra or postoperative HTN MSA relatively selective in most patients; vasodilating (NO release) Abbreviations: HTN, hypertension; Arrhy, arrhythmias; MI, myocardial infarction; CHF, congestive heart failure; ISA, intrinsic sympathomimetic activity. - calcium channel blockers amlodipine felodipine isradipine nicardipine nifedipine nimodipine nitrendipine Page 3, Classes of Drugs Used to Treat Myocardial Infarction - centrally-acting sympatholytics clonidine guanabenz guanfacine α-methyldopa Antiarrhythmics (if necessary) Antiarrhythmic drug classes: Class I – Sodium-channel blockers Class IA: atrial fibrillation, flutter; supraventricular & ventricular tachyarrhythmias cinchonism (blurred vision, tinnitus, headache, psychosis); anticholinergic (moderate) quinidine* cramping and nausea; enhances digitalis toxicity anticholinergic (weak); lupus-like syndrome in 25-30% of patients procainamide relatively short half-life negative inotropic effect disopryamide anticholinergic (strong) Class IB: ventricular tachyarrhythmias (VT) IV only; VT and PVCs good efficacy in ischemic myocardium lidocaine* orally active lidocaine analog can cause pulmonary fibrosis tocainide orally active lidocaine analog good efficacy in ischemic myocardium mexiletine Class IC: life-threatening supraventricular tachyarrhythmias (SVT) and ventricular tachyarrhythmias (VT) SVT can induce life-threatening VT flecainide* β-blocking and Ca++-channel blocking activity can worsen propafenone SVT & VT; heart failure VT; IB activity moricizine * prototypical drug Abbreviations: IV, intravenous; PVC, premature ventricular complex. Page 4, Classes of Drugs Used to Treat Myocardial Infarction Class II – Beta-blockers (see chart above) Class III – Potassium-channel blockers Drug Therapeutic Uses ventricular tachycardia, includuing ventricular amiodarone fibrillation; atrial fibrillation and flutter (off-label use) Comments very long half-life (25-60 days); Class I, II, III & IV actions and therefore decreases phase 4 slope and conduction velocity; potentially serious side effects (e.g., pulmonary fibrosis; hypothyroidism) structurally related to amiodarone, but has a much smaller volume of distribution and shorter elimination half-life (13-19 hr); Class I, II, III & IV actions; containdicated in severe or recently decompensated, symptomatic heart failure; based on results from atrial fibrillation (nondronedarone the PALLAS trial in 2011, the FDA has concluded there are permanent) and flutter concerns regarding increased risk for severe liver injury and serious cardiovascular adverse events in patients with permanent atrial fibrillation, and therefore, this drug should be used only in patients in sinus rhythm with a history of non-permanent atrial fibrillation life-threatening ventricular IV only; initial sympathomimetic effect (norepinephrine release) bretylium tachycardia and fibrillation followed by inhibition, which can lead to hypotension ventricular tachycardia; sotalol also has Class II activity atrial flutter and fibrillation slow inward Na+ activator, which delays repolarization; –inhibits ibutilide atrial flutter and fibrillation Na+-channel inactivation, which increases ERP; IV only; can cause life-threatening ventricular arrhythmias very selective K+-channel blocker; can cause life-threatening dofetilide atrial flutter and fibrillation ventricular arrhythmias Class IV – Calcium-channel blockers Dihydropyridines include the following specific drugs: (Go to www.rxlist.com for specific drug information) amlodipine felodipine isradipine nicardipine nifedipine nimodipine nitrendipine Page 5, Classes of Drugs Used to Treat Myocardial Infarction Non-dihydropyridines, of which there are only two currently used clinically, comprise the other two classes of CCBs. Verapamil (phenylalkylamine class), is relatively selective for the myocardium, and is less effective as a systemic vasodilator drug. This drug has a very important role in treating angina (by reducing myocardial oxygen demand and reversing coronary vasospasm) and arrhythmias. Diltiazem (benzothiazepine class) is intermediate between verapamil and dihydropyridines in its selectivity for vascular calcium channels. By having both cardiac depressant and vasodilator actions, diltiazem is able to reduce arterial pressure without producing the same degree of reflex cardiac stimulation caused by dihydropyridines. Miscellaneous – Adenosine Electrolytes (magnesium and potassium salts) hypomagnesemia (serum concentration <1.5 mg/dl) and hypokalemia (serum concentration <3.5 mg/dl; severe hypokalemia, <2.5 mg/dl) can precipitate cardiac arrhythmias, which include ventricular tachycardia and fibrillation, premature ventricular complexes, supraventricular tachycardias (e.g., WolffParkinson-White Syndrome), atrial tachycardias, including flutter and fibrillation, and arrhythmias associated with digitalis toxicity. For treating hypomagnesemiaassociated arrhythmias, magnesium sulfate may by administered intravenously. Oral magnesium supplementation can be administered using magnesium gluconate, oxide or hydroxide salts. Potassium chloride may be administered intravenously or orally. Digitalis compounds (cardiac glycosides) atropine (muscarinic receptor antagonist) Page 6, Classes of Drugs Used to Treat Myocardial Infarction Anti-arrhythmics by type of arrhythmia… Condition Sinus tachycardia Drug Comments Class II, IV Other underlying causes may need treatment Class IA, IC, II, III, IV Ventricular rate control is important goal; Atrial fibrillation/flutter digitalis anticoagulation required adenosine Paroxysmal supraventricular Class IA, IC, II, III, IV tachycardia adenosine AV block atropine Acute reversal Ventricular tachycardia Class I, II, III Class II, IV Premature ventricular complexes PVCs are often benign and not treated Mg++ salts Class IB Digitalis toxicity Mg++ salts; KCl Anti-thrombotics (prevent thrombus formation) - anticoagulant o Warfarin - anti-platelet drugs o o Aspirin Ticagrelor (trade name Brilinta in the US Thrombolytics (dissolve clots - i.e., "clot busters") -- Thrombolytic drugs are used to dissolve (lyse) blood clots (thrombi). o There are three major classes of fibrinolytic drugs: tissue plasminogen activator (tPA), streptokinase (SK), and urokinase (UK). - plasminogen activators o Analgesics (reduce pain) - morphine Adapted from: http://www.cvpharmacology.com/clinical%20topics/myocardial%20infarction-3 , accessed 10-21-15