Brands, Medical Use, Clinical Data
Drug Category
- Antihypertensive Agents
- Angiotensin-converting Enzyme Inhibitors
Dosage Forms
- Tablet (5 mg, 10 mg, 20 mg, 40 mg)
Brands / Synonyms
Amlobenz; Benazepril HCl; Benazepril Hydrochloride; Benazeprilum [Latin]; Briem; Cibacen; Cibacene; Lotensin; Lotensin
; Lotensin HCT; Lotrel
Indications
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.
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.
Toxicity
Symptoms of overdose include swelling of face, mouth, hands, or feet, trouble in swallowing or breathing (sudden), hoarseness, fever and chills.
Biotrnasformation / Drug Metabolism
Cleavage of the ester group (primarily in the liver) converts benazepril to its active metabolite, benazeprilat.
Contraindications
Lotensin is contraindicated in patients who are hypersensitive to this product or to any other ACE
inhibitor.
Drug Interactions
Diuretics
Patients on diuretics, especially those in whom diuretic therapy was recently instituted, may
occasionally experience an excessive reduction of blood pressure after initiation of therapy with Lotensin. The
possibility of hypotensive effects with Lotensin can be minimized by either discontinuing the diuretic or increasing
the salt intake prior to initiation of treatment with Lotensin. If this is not possible, the starting dose should be
reduced.
Potassium Supplements and Potassium-Sparing Diuretics
Lotensin can attenuate potassium loss caused by thiazide diuretics. Potassium-sparing diuretics
(spironolactone, amiloride, triamterene, and others) or potassium supplements can increase the risk of hyperkalemia.
Therefore, if concomitant use of such agents is indicated, they should be given with caution, and the patient’s
serum potassium should be monitored frequently.
Oral Anticoagulants
Interaction studies with warfarin and acenocoumarol failed to identify any clinically important
effects on the serum concentrations or clinical effects of these anticoagulants.
Lithium
Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients
receiving ACE inhibitors during therapy with lithium. These drugs should be coadministered with caution, and frequent
monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may be
increased.
Other
No clinically important pharmacokinetic interactions occurred when Lotensin was administered
concomitantly with hydrochlorothiazide, chlorthalidone, furosemide, digoxin, propranolol, atenolol, naproxen, or
cimetidine.
Lotensin has been used concomitantly with beta-adrenergic-blocking agents, calcium-channel-blocking
agents, diuretics, digoxin, and hydralazine, without evidence of clinically important adverse interactions.
Benazepril, like other ACE inhibitors, has had less than additive effects with beta-adrenergic blockers, presumably
because both drugs lower blood pressure by inhibiting parts of the renin-angiotensin system.
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