Anti-Hypertensive Drug Classes Diuretics Sympatholytics Vasodilators Calcium Angiotensin Channel Converting Blockers Enzyme (ACE) Inhibitor

Diuretics Thiazides Hydrochlorothiazide (HydroDIURIL) Chlorthalidone (Hygroton) Chlorothiazide (Diuril) Indapamide (Lozol) Metolazone (Zaroxolyn) Potassium Sparing Amiloride (Midamor) Spironolactone (Aldactone) Triamterene (Dyrenium) Loop Diuretics Furosemide (Lasix), Bumetanide (Bumex), Ethacrynic acid (Edecrin) Torsemide (Demadex)

Furosemide (Lasix), Bumetanide (Bumex),Ethacrynic acid (Edecrin) Furosemide (Lasix), bumetanide (Bumex), and ethacrynic acid (Edecrin) are "high-ceiling" loop diuretics acting primarily at the ascending limb of the loop of Henle. o The effectiveness of these agents is related to their site of action because reabsorption of about 30 - 40% of the filtered sodium and chloride load occurs at the ascending loop. o Distal sites are not able to compensate completely for this magnitude of reduction of NaCl reabsorption. Loop diuretics increase urinary Ca2+ in contrast to the action of thiazides. Loop diuretics also increase renal blood flow by decreasing renal vascular resistance. These drugs are rarely used in the management of hypertension because of their short duration of action and the availability of better drugs. Adverse Effects o Ototoxicity o Furosemide (Lasix) and ethacrynic acid (Edecrin) block renal excretion of uric acid by competition with renal secretory and biliary secretory systems.Therefore these agents can precipitate gout. o Potassium depletion. Sympatholytics Centrally Active Clonidine (Catapres) Methyldopa Adrenergic Neuron Blocker Guanadrel (Hylorel) Adrenoceptor Antagonists Labetalol (Trandate,

(Aldomet) Guanabenz (Wytensin) Guanfacine (Tenex)

Guanethidine (Ismelin) Reserpine

Normodyne) (alpha & beta) Prazosin (Minipress) (alpha), Terazosin (Hytrin) (alpha)

Clonidine (Catapres) (Sympatholytic) o Antihypertensive: Clonidine (Catapres) acts in the brain, inhibiting adrenergic outflow from the brainstem. Inhibition of sympathetic outflow results in a decrease in blood pressure. Mechanism of action: centrally acting selective a 2 adrenergic agonist. Especially effective in management of severe hypertension or in renin-dependent hypertension Transdermal clonidine (Catapres) patch: useful for surgical patients unable to take oral formulation Clonidine (Catapres) reduces cardiac output (by reducing both stroke volume and heart rate) and peripheral resistance. Reduction in stoke volume occurs due to increased venous pooling (decreased preload). Clonidine (Catapres) does not interfere with cardiovascular responses to exercise. Renal blood flow and function is maintained during clonidine treatment. Clonidine (Catapres) has minimal or no effect on plasma lipids.

Vasodilators
Diazoxide Hydralazine (Hyperstat) (Apresoline)

Minoxidil (Loniten)

Nitroprusside sodium (Nipride)

Diazoxide (Hyperstat), Nitroprusside sodium (Nipride)

o o

Vasodilators used for acute management of hypertensive crisis or malignant hypertension include sodium nitroprusside and diazoxide. Nitroprusside sodium (Nipride) is the agent of choice. Administered by a continuously variable rate i.v. infusion pump, precise blood pressure control can be obtained. Nitroprusside sodium (Nipride), a nitrovasodilator, is metabolized by smooth muscle cells to nitric oxide which dilates both arterioles and venules. Side effects are mainly due to excessive vasodilation. Much less commonly, toxicity may result from conversion of nitroprusside to cyanide and thiocyanate. Risk of toxicity due to thiocyanate increases after 24 to 48 hours. Nitroprusside sodium (Nipride) can worsen arterial hypoxemia in patients with obstructive pulmonary airway disease since nitroprusside will

interfere with hypoxic pulmonary vasoconstriction. A result is increasing ventilation-perfusion mismatching.

Calcium Channel Blockers

Dihydropyridines o Amlodipine (Norvasc), Felodipine (Plendil) o Nimodipine o Isradipine o Nicardipine o Nifedipine

Non-Dihydropyridines o Bepridil (Vascor) o Diltiazem (Cardiazem) o Verapamil (Isoptin, Calan)

Amlodipine (Norvasc) Felodipine (Plendil)

o o

o o o

Calcium channel blockers are effective in treating hypertension because they reduce peripheral resistance. Amlodipine (Norvasc) and Felodipine (Plendil) have relatively little effects on reducing myocardial contractility compared to verapamil (Isoptin, Calan) or diltiazem (Cardiazem). Arteriolar vascular tone depends on free intracellular Ca2+ concentration. 2+ Calcium channel blockers reduce transmembrane movement of Ca reduce the amount reaching intracellular sites and therefore reduce vascular smooth muscle tone. All calcium channel blocks appear similarly effective for management of mild to moderate hypertension. For low-renin hypertensive patients (elderly and African-American groups), Ca2+ channel blockers appear good choices for monotherapy (single drug) control. Adverse Effects SA nodal inhibition may lead to bradycardia or SA nodal arrest. This effect is more prominent if beta adrenergic antagonists are concurrently administered. GI reflux. Negative inotropic are augmented if beta-adrenergic receptor antagonists are concurrently administered. Calcium channel blockers should not be administered if the patient has SA or AV nodal abnormalities or in patients with significant congestive heart failure.

Angiotensin Converting Enzyme Inibitors

Benazepril Moexipril (Lotensin) (Univasc) Captopril Quinapril (Capoten) (Accupril) Enalapril (Vasotec) Ramipril (Altace) Fosinopril Losartin (Cozaar), (Monopril) Irbesartin*** *** Lisinopril (Prinvivil, Zestril) ***angiotensin receptor blocker

Captopril and other Angiotensin Converting Enzyme Inhibitors

o

Pharmacological Properties

Angiotensin II, a potent vasoconstrictor, is produced by the action of angiotensin converting enzyme (ACE) on the substrate angiotensin I. Angiotensin II activity produces a rapid pressor response a slow pressor response and vascular and cardiac hypertrophy and remodeling. Antihypertensive effects of ACE inhibitors are due to the reduction in the amount of angiotensin II produced. ACE inhibitors are efficacious in management of hypertension and have a favorable side effect profile. ACE inhibitor are advantageous in management of diabetic patients by reducing the development of diabetic neuropathy and glomerulosclerosis. ACE inhibitor are probably the antihypertensive drug of choice in treatment of hypertensive patient who have hypertrophic left ventricles. Hypertensive patients who have ischemic heart disease with impaired left ventricular function also benefit from ACE inhibitor treatment. ACE inhibitors reduce the normal aldosterone response to sodium loss (normally aldosterone opposes diuretic-induced sodium loss). Therefore, the use of ACE inhibitors enhance the efficacy of diuretic treatment, allowing the use of lower diuretic dosages and improving control of hypertension. If diuretics are administered at higher dosages in combination with ACE inhibitors significant and undesirable hypotensive reactions can occur with attendant excessive sodium loss. Reduction in aldosterone production by ACE inhibitors also affects potassium levels. The tendency is for potassium retention, which may be serious in patients with renal disease or if the patient is also taking potassium sparing diuretics, nonsteroidal anti-inflammatory agents or potassium supplements.