Altace

[Ramipril]

Clinical Pharmacology
CLINICAL PHARMACOLOGY

Mechanism of Action

Ramipril and ramiprilat inhibit angiotensin-converting enzyme (ACE) in human subjects and animals. 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.

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In hypertensive patients with normal renal function treated with ALTACE alone for up to 56 weeks, approximately 4% of patients during the trial had an abnormally high serum potassium and an increase from baseline greater than 0.75 mEq/ L, and none of the patients had an abnormally low potassium and a decrease from baseline greater than 0.75 mEq/ L. In the same study, approximately 2% of patients treated with ALTACE and hydrochloroth-iazide for up to 56 weeks had abnormally high potassium values and an increase from baseline of 0.75 mEq/ L or greater, and approximately 2% had abnormally low values and decreases from baseline of 0.75 mEq/ L or greater. (See PRECAUTIONS.) Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.

The effect of ramipril on hypertension appears to result at least in part from inhibition of both tissue and cir-culating ACE activity, thereby reducing angiotensin II formation in tissue and plasma. 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 ALTACE remains to be elucidated. While the mechanism through which ALTACE lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, ALTACE has an antihypertensive effect even in patients with low-renin hypertension.

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