Katzung, Lippincott

Diuretics
 effective in lowering blood pressure by 10–15 mm Hg
 mild or moderate essential hypertension: diuretics alone often provide adequate treatment
 more severe hypertension: diuretics are used in combination with sympathoplegic and vasodilator drugs to control the
tendency toward sodium retention

Thiazide (hydrochlorthizide, chlorthalidone)

 useful in combination therapy with a variety of other antihypertensive agents, including β-blockers, ACE inhibitors,
ARBs, and potassium-sparing diuretic

Potassium-sparing (amiloride, triamterene, spironolactone, eplerenone)

 diuretics are useful both to avoid excessive potassium depletion and to enhance the natriuretic effects of other
diuretics.

Loop diuretics (furosemide, torsemide, bumetanide, and ethacrynic acid)

 act promptly by blocking sodium and chloride reabsorption in the kidneys, even in patients with poor renal function or
those who have not responded to thiazide diuretics   renal vascular resistance and  renal blood flow

ACE Inhibitors
 inhibit the converting enzyme peptidyl dipeptidase that hydrolyzes angiotensin I to angiotensin II and (under the name
plasma kininase) inactivates bradykinin, a potent vasodilator, which works at least in part by stimulating release of nitric
oxide and prostacyclin.
 lower blood pressure by reducing peripheral vascular resistance without reflexively increasing cardiac output, heart
rate, or contractility
 decrease the secretion of aldosterone, resulting in decreased sodium and water retention

enalapril
 oral prodrug that is converted by hydrolysis to a converting enzyme inhibitor, enalaprilat
lisinopril
 lysine derivative of enalaprilat

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Pharmacokinetics:
 All of the ACE inhibitors are orally bioavailable as a drug or prodrug.
 All but captopril and lisinopril undergo hepatic conversion to active metabolites  may be preferred in patients with
severe hepatic impairment.
 Fosinopril is the only ACE inhibitor that is not eliminated primarily by the kidneys and does not require dose adjustment
in patients with renal impairment.
 Enalapril is the only drug in this class available intravenously.

Contraindications:
 second and third trimesters of pregnancy  risk of fetal hypotension, anuria, and renal failure, sometimes associated
with fetal malformations or death
Drug interactions:
 Potassium supplements or potassium-sparing diuretics  hyperkalemia
 Nonsteroidal anti-inflammatory drugs  impair the hypotensive effects of ACE inhibitors by blocking bradykinin
mediated vasodilation, which is at least in part, prostaglandin mediated