Enalapril, a nonsulfhydryl angiotensin-converting enzyme inhibitor

Abstract

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of enalapril maleate, a nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, are reviewed. Enalapril is rapidly converted by ester hydrolysis to enalaprilat, a potent ACE inhibitor; enalapril itself is only a weak ACE inhibitor. Enalapril lowers peripheral vascular resistance without causing an increase in heart rate. In patients with congestive heart failure, enalapril has beneficial hemodynamic effects based on reduction of both cardiac preload and afterload. Approximately 60% of a dose of enalapril is absorbed after oral administration. Excretion of enalaprilat is primarily renal. Accumulation of enalaprilat occurs in patients with creatinine clearances less than 30 mL/min. Enalapril 10-40 mg per day orally has shown efficacy comparable to that of captopril in treating patients with mild, moderate, and severe hypertension, hypertension caused by renal-artery stenosis, and in congestive heart failure resistant to digitalis and diuretics. When given alone for hypertension, enalapril has efficacy comparable to that of thiazide diuretics and beta blockers. Side effects observed with enalapril have generally been minor. Captopril-associated side effects such as skin rash, loss of taste, and proteinuria have been observed in a small number of patients receiving enalapril to date; neutropenia less than 300/mm3 has been noted with captopril but not enalapril. The incidence of these side effects has been noted to be greatly decreased in patients on low doses of captopril. Enalapril appears to be similar in efficacy to captopril for treating hypertension and congestive heart failure. Whether enalapril is safer than low-dose captopril in patients at high risk for captopril-associated side effects will require further investigation.