Quinapril is a new non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor. Quinapril is used to treat high blood pressure and congestive heart failure. The drug decreases certain chemicals that constrict the blood vessels so that blood flows more smoothly. The drug undergoes hepatic hydrolysis into its major active diacid metabolite, quinaprilat, and two minor inactive metabolites. On a weight basis quinaprilat is three times as potent an ACE inhibitor as quinapril. Approximately 60 percent of an oral dose of quinapril is absorbed. In contrast with captopril, the absorption of quinapril is unaffected by food. Peak serum concentrations of quinapril and quinaprilat are achieved within one and two hours, respectively. Approximately 61 percent of an orally administered dose is excreted in the urine, principally as quinaprilat.
Quinapril belongs in a class of drugs called angiotensin converting enzyme (ACE) inhibitors. ACE inhibitors are used for treating high blood pressure and heart failure and for preventing kidney failure due to hypertension and diabetes. Other drugs in this class are enalapril (Vasotec), ramipril (Altace), captopril (Capoten), fosinopril (Monopril), benazepril (Lotensin), lisinopril (Zestril, Prinivil), moexipril (Univasc) and trandolapril (Mavik). Angiotensin converting enzyme is important because it produces angiotensin II. Angiotensin II contracts the muscles of the arteries in the heart and the rest of the body, narrowing the arteries and thereby elevating blood pressure. In the kidney, the narrowing caused by angiotensin II decreases blood flow and increases the filtration pressure in the kidney. ACE inhibitors such as quinapril lower blood pressure by inhibiting the formation of angiotensin II, thereby relaxing the arterial muscles and enlarging the arteries. This increases the flow of blood and oxygen to the heart so that it can pump blood more efficiently. The enlargement of the arteries elsewhere in the body also makes it easier for the heart to pump blood. This is particularly beneficial when there is heart failure. In the kidneys this increases blood flow and reduces the filtration pressure in the kidneys
Quinapril is deesterified to the principal metabolite, quinaprilat, which is an inhibitor of ACE activity in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor, angiotensin II. The effect of quinapril in hypertension and in congestive heart failure (CHF) appears to result primarily from the inhibition of circulating and tissue ACE activity, thereby reducing angiotensin II formation. Quinapril inhibits the elevation in blood pressure caused by intravenously administered angiotensin I, but has no effect on the pressor response to angiotensin II, norepinephrine or epinephrine. Angiotensin II also stimulates the secretion of aldosterone from the adrenal cortex, thereby facilitating renal sodium and fluid reabsorption. Reduced aldosterone secretion by quinapril may result in a small increase in serum potassium. In controlled hypertension trials, treatment with quinapril HCl alone resulted in mean increases in potassium of 0.07 mmol/L (see PRECAUTIONS.) Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity (PRA).
While the principal mechanism of antihypertensive effect is thought to be through the renin-angiotensin-aldosterone system, quinapril exerts antihypertensive actions even in patients with low renin hypertension. Quinapril HCl was an effective antihypertensive in all races studied, although it was somewhat less effective in blacks (usually a predominantly low renin group) than in nonblacks. ACE is identical to kininase II, an enzyme that degrades bradykinin, a potent peptide vasodilator; whether increased levels of bradykinin play a role in the therapeutic effect of quinapril remains to be elucidated.