Anapril/Anapril-S Mechanism of Action

Pharmacodynamics: Mechanism of Action: Enalapril maleate inhibits angiotensin-converting enzyme (ACE) after hydrolysis to enalaprilat. The primary mechanism through which enalapril lowers blood pressure is believed to be suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE blocks the conversion of angiotensin I to angiotensin II resulting in decreased vasopressor activity, decreased aldosterone secretion and increased plasma renin activity.
Cardiovascular Effects: In hypertensive patients, enalapril reduces blood pressure by decreasing total peripheral resistance. The drug causes arterial and possibly venous dilation and generally decreases systolic and diastolic blood pressure by approximately 10-15%.
Blood pressure decreases within 1 hour, with peak antihypertensive effect at 4-8 hours. At recommended doses, antihypertensive and hemodynamic effects have been shown to be maintained for 12-24 hours.
In reducing blood pressure, angiotensin converting enzyme (ACE) inhibitors have been documented to cause a significant regression of pathologic left ventricular hypertrophy in patients with hypertension.
In patients with congestive heart failure, beneficial effects of enalapril lead to both improved symptoms and prolonged survival.
Endothelial Functioning: Microvascular endothelial dysfunction associated with atherosclerosis may be improved by the administration of angiotensin converting-enzyme (ACE) inhibitor therapy.
Renal Effects: With angiotensin converting enzyme (ACE) inhibitor therapy, kidney perfusion is increased and renal vascular resistance is decreased as ACE inhibitors induce vasodilation. Glomerular filtration rate (GFR) will generally increase.
BUN and serum creatinine concentrations have occasionally increased during long-term enalapril therapy.
Pharmacokinetics: Absorption: Enalapril maleate is well absorbed following oral administration. About 60% of dose is absorbed from Gl tract. Food does not affect the absorption of enalapril maleate.
Distribution: Approximately 50-60% of enalapril is bound to plasma proteins. Enalapril and enalaprilat are distributed into milk in trace amounts.
Metabolism: Enalapril is metabolized extensively in the liver to active metabolite enalaprilat, a more potent ACE inhibitor than enalapril but poorly absorbed orally. Peak serum concentrations of enalaprilat occur about 3-4.5 hours after an oral dose.
Excretion: Renal excretion is 61% (enalaprilat 43%, enalapril 18%) and feces excretion is 33% (enalaprilat 27%, enalapril 6%).
The half-life of enalapril is less than 2 hours in healthy individuals and in patients with normal hepatic and renal functions, but may be increased in patients with congestive heart failure or impaired hepatic function.
The effective half-life of enalaprilat following multiple oral doses is 11 hours in subjects with normal renal function.