Quinapril

Usage

• Quinapril is primarily prescribed for the treatment of hypertension (high blood pressure) and congestive heart failure. It can be used as monotherapy or in combination with other antihypertensive medications like thiazide diuretics or beta-blockers. In heart failure, it is typically used adjunctively with diuretics and/or digitalis.
• Pharmacological Classification: Angiotensin-Converting Enzyme (ACE) inhibitor.
• Mechanism of Action: Quinapril, a prodrug, is metabolized to quinaprilat, which inhibits ACE, thereby reducing the production of angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and decreased sodium and water retention, ultimately lowering blood pressure and reducing cardiac workload.

Alternate Names

• International Nonproprietary Name (INN): Quinapril
• Brand Names: Accupril®, Accuretic® (quinapril/hydrochlorothiazide), Quinaretic® (quinapril/hydrochlorothiazide)

How It Works

• Pharmacodynamics: Quinaprilat, the active metabolite of quinapril, primarily works by inhibiting ACE. This leads to a decrease in angiotensin II and aldosterone levels, causing vasodilation, decreased peripheral vascular resistance, and reduced sodium and water retention. These effects contribute to lowering blood pressure and improving cardiac function in heart failure.
• Pharmacokinetics: Quinapril is well-absorbed orally and rapidly hydrolyzed to quinaprilat in the liver. Peak plasma concentrations of quinaprilat are reached within 1-2 hours. Quinaprilat is primarily excreted by the kidneys. The half-life of quinaprilat is prolonged in patients with renal impairment.
• Mode of Action: Quinaprilat competitively binds to and inhibits ACE, preventing the conversion of angiotensin I to angiotensin II. This inhibition reduces the vasoconstricting, sodium-retaining, and aldosterone-secreting effects of angiotensin II.
• Elimination Pathways: Primarily renal excretion.

Dosage

Standard Dosage

Adults:

• Hypertension: Initial dose is 10-20 mg once daily, which can be titrated up to a maximum of 80 mg/day, administered as a single dose or in two divided doses. Patients on diuretics should start with a lower initial dose (5 mg).
• Heart Failure: Initial dose is 5 mg twice daily, which can be titrated up to a maximum of 40 mg/day in two divided doses.

Children:

• Use and dose must be determined by a doctor. Safety and efficacy have not been established in children. Off-label use for hypertension in children aged 6 and older may be considered, starting with a lower dose and titrating based on response.

Special Cases:

• Elderly Patients: Initial dose of 10 mg once daily, titrated based on response.
• Patients with Renal Impairment: Lower initial doses (2.5-5 mg) are recommended and dosage adjustments should be based on creatinine clearance.
• Patients with Hepatic Dysfunction: Use with caution. Dosage adjustments may be necessary.
• Patients with Comorbid Conditions: Individualized dosing should be considered for patients with diabetes, cardiovascular disease, or other comorbid conditions.

Clinical Use Cases

• Quinapril is not typically used in clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary indications are hypertension and congestive heart failure.

Dosage Adjustments

• Dose modifications are necessary based on patient-specific factors like renal or hepatic dysfunction. Close monitoring of renal function and potassium levels is recommended, especially in patients with renal impairment.

Side Effects

Common Side Effects

• Cough, dizziness, lightheadedness, fatigue, nausea, vomiting, stomach discomfort, diarrhea, headache, muscle pain, back pain, skin rash, hypotension.

Rare but Serious Side Effects

• Angioedema (swelling of the face, lips, tongue, or throat), severe hypotension, renal failure, hyperkalemia, neutropenia/agranulocytosis.

Long-Term Effects

• Chronic kidney disease, electrolyte imbalances.

Adverse Drug Reactions (ADR)

• Angioedema, acute renal failure, severe hypotension.

Contraindications

• Hypersensitivity to quinapril or other ACE inhibitors.
• History of angioedema related to ACE inhibitor therapy.
• Pregnancy (especially second and third trimesters).
• Bilateral renal artery stenosis.
• Concomitant use with aliskiren in patients with diabetes or renal impairment.
• Concomitant use with neprilysin inhibitors (e.g., sacubitril/valsartan).

Drug Interactions

• Potassium supplements, salt substitutes, potassium-sparing diuretics (e.g., spironolactone), lithium, NSAIDs, other antihypertensives (including ARBs), antacids, antipsychotics, immunosuppressants, alcohol.
• CYP450 interactions: Quinapril is primarily metabolized to quinaprilat, but CYP-mediated interactions are not clinically significant.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: D (contraindicated in the second and third trimesters).
• Fetal Risks: Fetal renal dysfunction, oligohydramnios, skull hypoplasia, anuria, hypotension, renal failure, death.
• Breastfeeding: Quinapril is excreted in breast milk. Use is not recommended.

Drug Profile Summary

• Mechanism of Action: ACE inhibitor, reducing angiotensin II and aldosterone levels.
• Side Effects: Cough, dizziness, hypotension, angioedema, renal dysfunction, hyperkalemia.
• Contraindications: Hypersensitivity, angioedema history, pregnancy, bilateral renal artery stenosis, concomitant use with aliskiren (in diabetes or renal impairment) or neprilysin inhibitors.
• Drug Interactions: Diuretics, potassium supplements, lithium, NSAIDs, other antihypertensives.
• Pregnancy & Breastfeeding: Contraindicated in pregnancy (second and third trimesters); not recommended during breastfeeding.
• Dosage: Hypertension: 10-80 mg/day; Heart failure: 5-40 mg/day. Adjustments needed for renal impairment and elderly.
• Monitoring Parameters: Blood pressure, renal function, potassium levels.

Popular Combinations

• Hydrochlorothiazide (Accuretic®, Quinaretic®): Combines the antihypertensive effects of quinapril with the diuretic action of hydrochlorothiazide for enhanced blood pressure control.

Precautions

• Monitor renal function, potassium levels, and blood pressure.
• Assess for signs of angioedema.
• Caution in patients with renal or hepatic impairment.
• Avoid in pregnancy and breastfeeding.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Quinapril?

A: For hypertension, the initial dose is 10-20 mg once daily, titratable up to 80 mg/day. For heart failure, the initial dose is 5 mg twice daily, titratable up to 40 mg/day. Adjustments are necessary for renal impairment and elderly patients.

Q2: What is the mechanism of action of Quinapril?

A: Quinapril is an ACE inhibitor. Its active metabolite, quinaprilat, blocks the conversion of angiotensin I to angiotensin II, leading to vasodilation and reduced blood pressure.

Q3: What are the common side effects of Quinapril?

A: Common side effects include cough, dizziness, lightheadedness, fatigue, headache, and gastrointestinal upset.

Q4: What are the serious side effects of Quinapril?

A: Serious side effects include angioedema, severe hypotension, renal impairment, and hyperkalemia.

Q5: Can Quinapril be used during pregnancy?

A: Quinapril is contraindicated during the second and third trimesters of pregnancy due to the risk of fetal harm. Its use in the first trimester is not recommended.

Q6: How should Quinapril be administered?

A: Quinapril is administered orally, usually once or twice daily. It can be taken with or without food.

Q7: Does Quinapril interact with other medications?

A: Yes, Quinapril can interact with several medications, including diuretics, potassium supplements, NSAIDs, lithium, and other antihypertensive drugs.

Q8: What should be monitored in patients taking Quinapril?

A: Blood pressure, renal function (serum creatinine and creatinine clearance), and potassium levels should be regularly monitored in patients receiving quinapril.

Q9: What is the difference between Quinapril and other ACE inhibitors?

A: While all ACE inhibitors share a similar mechanism of action, they differ in their pharmacokinetic properties, such as absorption, metabolism, and elimination. This can influence the dosing frequency and potential for drug interactions. Clinically, the choice of ACE inhibitor may depend on patient-specific factors and tolerability.

Q10: When should Quinapril be discontinued?

A: Quinapril should be discontinued immediately if signs of angioedema develop (swelling of the face, lips, tongue, throat, or extremities). It should also be stopped if severe hypotension or significant renal dysfunction occurs. Any decision to discontinue quinapril should be made in consultation with a physician.