IV. ANGIOTENSIN CONVERTING ENZYME INHIBITORS The angiotensin converting enzyme (ACE) inhib

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IV. ANGIOTENSIN CONVERTING ENZYME INHIBITORS The angiotensin converting enzyme (ACE) inhibitors are effective antihypertensive agents and have other indications as well. The 2 avail- able drugs in this group are very similar in their effects and may be discussed together. The major difference between them is that captopril is an active drug with a shorter duration of action 8-12 hours) while enalapril is a prodrug that must be metabolized to the active form, enalaprilat, which has a longer duration of action (12-24 hours). Mechanisms: * Inhibition of angiotensin converting enzyme results in decreased cir- culating levels of angiotensin II as well as increased levels of bradykinin, a vasodilator polypeptide. Indications: * Chronic hypertension. * Captopril is also labeled for the treatment of congestive heart fail- ure that is unresponsive to digitalis and diuretics (see Chapter 4). (PgDn for more text) Contraindications and Warnings: * Hypersensitivity * Blood dyscrasias (Warning) have resulted from the use of ACE in- hibitors, see adverse reactions. * Renal impairment (Warning): These drugs interfere with the action of the renin-angiotensin-aldosterone system and may contribute to a hyper- kalemic state. These drugs should not be given to patients taking potas- sium supplements or potassium-sparing diuretics. Adverse Reactions: * Hematologic: Reversible neutropenia or thrombocytopenia. The effect is more common in patients with elevated BUN or other evidence of impaired renal function (for captopril, 1 case in 500 patients with creatinine above 1.6 mg/dL versus 1 in 8600 patients with normal serum creatinine). * Renal: increased levels of serum creatinine and BUN and, rarely, acute renal failure may occur, especially in patients with bilateral renal artery stenosis. * Electrolyte: elevated serum potassium occurs in about 1% of patients, probably as a result of reduced aldosterone levels. * Dysgeusia, an aberration of taste, has been reported in about 2-4% of patients, a higher rate than for most drugs. * Rash, with or without pruritis, has been reported in 4-7% of patients taking captopril and somewhat less commonly in patients on enalapril. (PgDn for more text) * Nonspecific neurologic and gastrointestinal symptoms occur in 1-3% of patients on either drug. Overdose Toxicity: Hypotension is the major manifestation of serious overdosage. Symptomatic management is usually sufficient (see Chapter 24) but both captopril and enalapril may be removed by hemodialysis if necessary. Interactions: * Other hypotensive agents: predictable additive hypotensive interac- tions, especially in diuretic-induced hypovolemia. * Potassium-sparing diuretics: predictable hyperkalemia occurs. * Aspirin and NSAIDs may interfere with the hypotensive action of these agents (Home key to return to top of file)


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