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Active ingredient: Quinapril - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Antihypertensive Agents
  • Angiotensin-converting Enzyme Inhibitors

Dosage Forms

  • Tablets

Brands / Synonyms

Accupril; Accuprin; Accupro; Accuretic; Acequin; Acuitel; Korec; Quinapril; Quinapril and Hydrochlorothiazide; Quinapril Hcl; Quinapril Hydrochloride; Quinapril Hydrochloride: Accupril; Quinaprilum [Latin]; Quinaretic; Quinazil

Indications

For the treatment of hypertension and chronic heart failure.

Pharmacology

Quinapril, an angiotensin-converting enzyme (ACE) inhibitor, is used to treat hypertension and heart failure. Like ramipril, quinapril is a prodrug that, upon deesterification, is converted to the active metabolite quinaprilat. 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.

Mechanism of Action

Quinaprilat competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to 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. Quinaprilat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.

Absorption

Following oral administration, peak plasma quinapril concentrations are observed within one hour. Based on recovery of quinapril and its metabolites in urine, the extent of absorption is at least 60%. The rate and extent of quinapril absorption are diminished moderately (approximately 25-30%) when ACCUPRIL tablets are administered during a high-fat meal.

Toxicity

Overdose may lead to severe hypotension. LD50=1739mg/kg (orally in mice).

Biotrnasformation / Drug Metabolism

Hepatic.

Contraindications

ACCUPRIL is contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an ACE inhibitor.

Drug Interactions

Concomitant diuretic therapy

As with other ACE inhibitors, patients on diuretics, especially those on recently instituted diuretic therapy, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with ACCUPRIL. The possibility of hypotensive effects with ACCUPRIL may be minimized by either discontinuing the diuretic or cautiously increasing salt intake prior to initiation of treatment with ACCUPRIL. If it is not possible to discontinue the diuretic, the starting dose of quinapril should be reduced.

Agents increasing serum potassium

Quinapril can attenuate potassium loss caused by thiazide diuretics and increase serum potassium when used alone. If concomitant therapy of ACCUPRIL with potassium-sparing diuretics (eg, spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes is indicated, they should be used with caution along with appropriate monitoring of serum potassium.

Tetracycline and other drugs that interact with magnesium

Simultaneous administration of tetracycline with ACCUPRIL reduced the absorption of tetracycline by approximately 28% to 37%, possibly due to the high magnesium content in ACCUPRIL tablets. This interaction should be considered if coprescribing ACCUPRIL and tetracycline or other drugs that interact with magnesium.

Lithium

Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy. These drugs should be coadministered with caution and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, it may increase the risk of lithium toxicity.

Other agents

Drug interaction studies of ACCUPRIL with other agents showed:

· Multiple dose therapy with propranolol or cimetidine has no effect on the pharmacokinetics of single doses of ACCUPRIL.

· The anticoagulant effect of a single dose of warfarin (measured by prothrombin time) was not significantly changed by quinapril coadministration twice-daily.

· ACCUPRIL treatment did not affect the pharmacokinetics of digoxin.

· No pharmacokinetic interaction was observed when single doses of ACCUPRIL and hydrochlorothiazide were administered concomitantly.

· Co-administration of multiple 10 mg doses of atorvastatin with 80 mg of ACCUPRIL resulted in no significant change in the steady-state pharmacokinetic parameters of atorvastatin.

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