Monopril

[Fosinopril]

Clinical Pharmacology
CLINICAL PHARMACOLOGY

Mechanism of Action

In animals and humans, fosinopril sodium is hydrolyzed by esterases to the pharmacologically active form, fosinoprilat, a specific competitive inhibitor of angiotensin-converting enzyme (ACE). ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium.

Text Continues Below

---

In 647 hypertensive patients treated with fosinopril alone for an average of 29 weeks, mean increases in serum potassium of 0.1 mEq/ L were observed. Similar increases were observed among all patients treated with fosinopril, including those receiving concomitant diuretic therapy. Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity. ACE is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of MONOPRIL remains to be elucidated. While the mechanism through which MONOPRIL lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, MONOPRIL has an antihypertensive effect even in patients with low-renin hypertension.

Although MONOPRIL was antihypertensive in all races studied, black hyper-tensive patients (usually a low-renin hypertensive population) had a smaller average response to ACE inhibitor monotherapy than non-black patients. In patients with heart failure, the beneficial effects of MONOPRIL are thought to result primarily from suppression of the renin-angiotensin-aldosterone system; inhi-bition of the angiotensin-converting enzyme produces decreases in both preload and afterload.

Page:  1 | 2 | 3 | 4 | 5 | Next >>