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Accupril

Generic Name: quinapril hydrochloride
Dosage Form: tablet, film coated
USE IN PREGNANCY


When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, Accupril should be discontinued as soon as possible. See WARNINGS, Fetal/Neonatal Morbidity and Mortality.
Accupril Description

Accupril® (quinapril hydrochloride) is the hydrochloride salt of quinapril, the ethyl ester of a non-sulfhydryl, angiotensin-converting enzyme (ACE) inhibitor, quinaprilat.

Quinapril hydrochloride is chemically described as [3S-[2[R*(R*)], 3R*]] - 2 - [2 - [[1 - (ethoxycarbonyl) - 3 - phenylpropyl]amino] - 1 - oxopropyl] - 1,2,3,4 - tetrahydro - 3 - isoquinolinecarboxylic acid, monohydrochloride. Its empirical formula is C25H30N2O5•HCl and its structural formula is:


Quinapril hydrochloride is a white to off-white amorphous powder that is freely soluble in aqueous solvents.

Accupril tablets contain 5 mg, 10 mg, 20 mg, or 40 mg of quinapril for oral administration. Each tablet also contains candelilla wax, crospovidone, gelatin, lactose, magnesium carbonate, magnesium stearate, synthetic red iron oxide, and titanium dioxide.
Accupril - Clinical Pharmacology
Mechanism of Action

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 Accupril 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. Accupril 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.
  
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