indication

For the treatment of hypertension. It may be used alone or in combination with thiazide diuretics.

pharmacology

Benazepril, an angiotensin-converting enzyme (ACE) inhibitor, is a prodrug which, when hydrolyzed by estarases to its active Benazeprilat, is used to treat hypertension and heart failure, to reduce proteinuria and renal disease in patients with nephropathies, and to prevent stroke, myocardial infarction, and cardiac death in high-risk patients. Benazepril and Benazeprilat 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.

mechanism of action

Benazeprilat, the active metabolite of Benazepril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion. Benazeprilat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.

toxicity

Most likely symptom of overdosage is severe hypotension. Most common adverse effects include headache, dizziness, fatigue, somnolence, postural dizziness, nausea, and cough.

biotransformation

Cleavage of the ester group (primarily in the liver) converts benazepril to its active metabolite, benazeprilat. Benazepril and benazeprilat may be conjugated to glucuronic acid prior to urinary excretion.

absorption

Peak in plasma within 0.5-1.0 hours. The extent of absorption is at least 37% as determined by urinary recovery and is not significantly influenced by the presence of food in the GI tract.

half life

10-11 hours

route of elimination

Benazepril and benazeprilat are cleared predominantly by renal excretion in healthy subjects with normal renal function. Nonrenal (i.e., biliary) excretion accounts for approximately 11%-12% of benazeprilat excretion in healthy subjects.

drug interactions

Amiloride: Increased risk of hyperkalemia

Drospirenone: Increased risk of hyperkalemia

Lithium: The ACE inhibitor increases serum levels of lithium

Potassium: Increased risk of hyperkalemia

Spironolactone: Increased risk of hyperkalemia

Tizanidine: Tizanidine increases the risk of hypotension with the ACE inhibitor

Tobramycin: Increased risk of nephrotoxicity

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Triamterene: Increased risk of hyperkalemia