What is quinapril (ACE inhibitor)?

What is Quinapril?

Quinapril is an ACE inhibitor that is converted to its active metabolite quinaprilat, used primarily for treating hypertension and heart failure by inhibiting angiotensin-converting enzyme, thereby reducing angiotensin II formation and aldosterone secretion. 1

Mechanism of Action

Quinapril is a prodrug that undergoes hepatic deesterification to quinaprilat, which is approximately 3 times more potent as an ACE inhibitor than the parent compound 1, 2. The drug works through several key mechanisms:

• Inhibits conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion 1
• Reduces aldosterone secretion, which may result in small increases in serum potassium (mean increase 0.07 mmol/L in hypertension trials) 1
• Does not affect pressor response to angiotensin II, norepinephrine, or epinephrine 1
• Inhibits kininase II (identical to ACE), which degrades bradykinin, a potent vasodilator, though the therapeutic contribution of increased bradykinin levels remains unclear 1
• Binds strongly to tissue ACE in kidney, heart, and brain, allowing once-daily dosing despite a short elimination half-life 3, 4

Pharmacokinetics

• Absorption: At least 60% oral bioavailability, with peak quinapril concentrations at 1 hour and peak quinaprilat concentrations at 2 hours post-dose 1, 2
• Food effect: Unlike captopril, quinapril absorption is only moderately diminished (25-30%) by high-fat meals 1, 2
• Protein binding: Approximately 97% of quinapril or quinaprilat is protein-bound 1
• Elimination half-life: Quinaprilat has an effective accumulation half-life of 3 hours with a prolonged terminal phase of 25 hours 1, 3
• Excretion: Primarily renal (up to 96% of IV dose), with 61% of oral dose excreted in urine 1, 2

Clinical Indications

Hypertension

• Effective as monotherapy at 10-40 mg daily for mild to severe hypertension, with some patients requiring up to 80 mg daily 5, 6, 7
• Initial dose: 5 mg twice daily, with maximum dose of 20 mg twice daily 5
• Combination therapy with hydrochlorothiazide provides significantly greater blood pressure reduction than either drug alone 7
• Reduces microalbuminuria in patients with hypertension and/or diabetes mellitus 7

Heart Failure with Reduced Ejection Fraction

• Reduces morbidity and mortality in patients with prior or current symptoms of chronic HFrEF 5
• Dosing for heart failure: Start at 5 mg twice daily, titrate to target of 20 mg twice daily 5
• Produces beneficial hemodynamic changes, improves exercise tolerance, symptoms, and functional class at doses ≤40 mg/day 6, 7
• Comparable efficacy to captopril (10-20 mg twice daily vs. captopril 25-50 mg twice daily) in well-designed trials 7

Post-Myocardial Infarction

• Reduces ischemic events after coronary artery bypass grafting at 40 mg/day 7
• Note: Lower doses (20 mg/day) showed no effect on ischemic events in patients undergoing coronary angioplasty 7

Dosing Adjustments

Renal Impairment

• Linear correlation between plasma quinaprilat clearance and creatinine clearance 1
• Dose reduction recommended for creatinine clearance ≤0.50 mL/sec 2
• Hemodialysis or peritoneal dialysis has little effect on elimination of quinapril and quinaprilat 1

Elderly Patients

• Reduced elimination of quinaprilat in patients ≥65 years, attributable to decreased renal function 1

Hepatic Impairment

• Impaired hydrolysis of quinapril to quinaprilat in cirrhosis, resulting in lower plasma quinaprilat concentrations and up to 2-fold increase in quinapril half-life 2

Adverse Effects and Precautions

Common Adverse Effects

• Cough: Occurs in 2-4.3% of patients (lower than some ACE inhibitors due to kininase inhibition) 5, 4
• Hypotension: <1% in hypertension, 2.9% in heart failure 4
• Headache: Up to 4.7% of patients 4
• Dizziness and somnolence: >1% incidence 4

Serious Adverse Effects

• Angioedema: Occurs in <1% of patients, more frequent in blacks and women; constitutes absolute contraindication to all ACE inhibitors if it occurs 5
• Hyperkalemia: Monitor serum potassium, especially in patients with renal insufficiency or those taking potassium-sparing agents 5
• Renal insufficiency: Use with caution in patients with baseline renal impairment 5

Absolute Contraindications

• History of angioedema with previous ACE inhibitor exposure 5
• Pregnancy: Risk of fetal and neonatal morbidity and death 5, 3

Monitoring Requirements

• Renal function and serum potassium: Check within 1-2 weeks of initiation and periodically thereafter 5
• Blood pressure: Monitor at each dose adjustment 5
• Avoid abrupt withdrawal: Can lead to clinical deterioration in heart failure patients 5

Key Clinical Pearls

• Titrate to target doses proven in clinical trials (20 mg twice daily for heart failure), not just symptom control 5
• Asymptomatic hypotension does not require dose reduction or discontinuation 5
• ACE inhibitor-induced cough rarely requires discontinuation; exclude pulmonary edema first before attributing cough to the medication 5
• Once-daily dosing is sufficient for hypertension due to strong tissue ACE binding, but twice-daily dosing is typically used for heart failure 6, 7