For the treatment of essential or renovascular hypertension and symptomatic congestive heart failure. It may be used alone or in combination with thiazide diuretics.
There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Enalaprilat, the principle active metabolite of enalapril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Enalapril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors. Enalaprilat's affinity for ACE is approximately 200,000 times greater than that of ATI and 300-1000 times greater than that enalapril.
Overdosage may result in marked hypotension and stupor. Most common adverse effects include hypotension, headache, dizziness and fatigue.
55-75%, absorption is unaffected by food; enalaprilat (clinically administered IV) is poorly absorbed, 3-12%, due to its high polarity.
< 2 hours for unchanged enalapril in health individuals, may be increased in those with congestive heart failure (3.4 and 5.8 hours for single 5- and 10-mg doses, respectively). The average terminal half life of enalaprilat is 35-38 hours. The effective half life following multiple doses is 11-14 hours.
Excretion of enalapril is primarily renal.