Cardiovascular Drug Introduction Cardiovascular medications can be broken down into the following categories Antiarrhythmics Antihypertensives Inotropes Vasodilators Diuretics Antihyperlipidemics Anti-plateletes Thrombolytics Introduction Symptoms of angina due to myocardium oxygen demand exceeding supply Goal is to ↓ myocardial O2 consumption (MVO2) can achieve by reducing end diastolic volume blood pressure heart rate contractility ejection time Can also ↑ O2 supply to myocardium Main drugs include nitrates, beta-blockers, and calcium channel blockers Nitrates Examples nitroglycerin, isosorbide dinitrate (also mononitrate), nitroprusside Mechanism venodilation via generation of endothelial NO results in activation of guanyl cyclase → ↑cGMP → relaxation of smooth muscle dilate veins >> arteries ↓ EDV, ↓ BP → ↓ MVO2 reflex ↑ in HR isosorbide mononitrate has highest oral bioavailability Clinical use angina pulmonary edema aphrodesiac and erection enhancer Toxicity orthostatic hypotension especially in combination with other antihypertensives headache due to vasodilation of cerebral arteries reflex tachycardia tachyphylaxis contraindicated in patients taking vasodilatory medication for erectile dysfunction (e.g. sildenafil) severe hypotension nitroprusside causes cyanide toxicity "Monday disease" in industrial exposure development of tolerance for the vasodilating action during the work week loss of tolerance over the weekend results in tachycardia, dizziness, headache on re-exposure Beta-Blockers Examples propanolol, atenolol, metoprolol Mechanism beta-adrenergic antagonism results in ↓ cAMP ↓ contractility, HR, BP→ ↓ MVO2 Toxicity impotence, depression, bradycardia pindolol and acebutolol are partial β-agonists contraindicated in angina Calcium Channel Blockers Examples nifedipine, verapamil, diltiazem Mechanism ↓ vascular smooth muscle contractility result of inhibition of voltage-gated L-type Ca2+ channels also affects cardiac tissue nifedipine is most selective for vasculature verapamil is most selective for heart "Verapamil works on Ventricles" ↓ afterload, ↓ AV node conduction velocity → ↓ MVO2 Clinical use angina hypertension arrhythmias (not nifedipine) (see Antiarrhythmics) vasospasm Prinzmetal's angina Raynaud's Toxicity cardiac depression peripheral edema AV block flushing dizziness constipation