Anti-hypertensive-Drugs.pdf

ANTI-HYPERTENSIVE DRUGS Subclass, Drug Mechanism of Action Effects Clinical Applications Pharmacokinetics, Toxicities,...

ANTI-HYPERTENSIVE DRUGS Subclass, Drug Mechanism of Action Effects Clinical Applications Pharmacokinetics, Toxicities, Interactions DIURETICS Thiazides: Block Na/Cl transporter in Reduce blood volume and Hypertension Hydrochlorothiazide renal distal convoluted poorly understood Mild heart failure Chlorthalidone tubule vascular effects Loop diuretics: Block Na/K/2Cl Like thiazides, greater Severe hypertension See Chapter 15 Furosemide transporter in renal loop efficacy Heart failure of Henle Spironolactone, Block aldosterone Increase Na and Aldosteronism eplerenone receptor in renal decrease K excretion, Heart failure collecting tubule poorly understood Hypertension reduction in heart failure mortality ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS Captopril, many others Inhibit Reduce: Hypertension Oral angiotensin-converting angiotensin II levels, Heart failure, Diabetes Toxicity: Cough, enzyme vasoconstriction and angioedema aldosterone secretion Hyperkalemia Renal impairment Increase bradykinin Teratogenic ANGIOTENSIN RECEPTOR BLOCKERS (ARBs): Losartan, many others Block AT1 angiotensin Same as ACE inhibitors Hypertension Oral receptors but no increase in Heart failure Toxicity: Same as bradykinin ACE inhibitors but less cough RENIN INHIBITOR Aliskiren Inhibits enzyme activity of Reduces: Hypertension Oral renin - Angiotensin I and Toxicity: Hyperkalemia, II and renal impairment aldosterone Potential teratogen SYMPATHOPLEGICS, CENTRALLY ACTING Clonidine Activate α2 Reduces: Hypertension, clonidine Oral, clonidine also as Methyldopa adrenoceptors - Central also used in withdrawal patch sympathetic from abused drugs Toxicity: sedation outflow Methyldopa hemolytic - Norepinephrine anemia release from noradrenergic nerve endings SYMPATHETIC NERVE TERMINAL BLOCKERS Reserpine Blocks vesicular amine Reduces: Hypertension but rarely Oral, long duration (days) transporter in - All sympathetic used Toxicity: psychiatric noradrenergic nerves and effects, especially depression, depletes transmitter cardiovascular, gastrointestinal stores and reduce blood disturbances pressure Guanethidine Interferes with amine Same as reserpine Same as reserpine Severe orthostatic Guanadrel release and replaces hypotension norepinephrine in Sexual dysfunction, vesicles availability limited α BLOCKERS Prazosin Selectively block α1 Prevent sympathetic Hypertension Oral Terazosin adrenoceptors vasoconstriction Benign prostatic Toxicity: orthostatic Doxazosin Reduce prostatic smooth hyperplasia hypotension muscle tone β BLOCKERS Metoprolol, others Block β1 receptors; Prevent sympathetic Hypertension See Chapter 10 - carvedilol also cardiac stimulation Heart failure blocks α Reduce renin secretion Coronary disease receptors; - nebivolol also releases nitric oxide *Propranolol :Nonselective prototype β blocker *Metoprolol and atenolol: Very widely used β1-selective blockers VASODILATORS Verapamil, Diltiazem Nonselective block of Reduce: Hypertension See Chapter 12 L-type calcium channels - cardiac rate and Angina output Arrhythmias - vascular resistance Nifedipine, amlodipine, Block vascular calcium Reduce vascular Hypertension See Chapter 12 other dihydropyridines channels > cardiac resistance Angina calcium channels Hydralazine Causes nitric oxide Vasodilation Hypertension Oral Minoxidil release Reduces vascular Minoxidil also used to Toxicity: angina, Metabolite opens K resistance treat hair loss tachycardia channels in vascular Arterioles more sensitive Hydralazine: lupus-like smooth muscle than veins syndrome Reflex tachycardia Minoxidil: hypertrichosis PARENTERAL AGENTS Nitroprusside Releases nitric oxide Powerful vasodilation Hypertensive Parenteral emergencies Short duration Diazoxide: used only in Toxicity: excessive hypoglycemia hypotension, shock Fenoldopam Activates D1 receptors Diazoxide Opens K channels Labetalol α, β blocker