Benazepril
Benazepril
Generic Name
Benazepril
Mechanism
- Inhibits ACE: Blocks conversion of angiotensin‑I → angiotensin‑II, a potent vasoconstrictor and aldosterone‑stimulating peptide.
- Reduces Angiotensin‑II Levels: Decreases systemic vascular resistance, promotes renal sodium excretion, and suppresses sympathetic activation.
- Increases Bradykinin: By preventing its degradation, leading to vasodilation and natriuresis; also contributes to the classic ACE‑inhibitor cough.
- Metabolite Contribution: The β‑hydroxy acid metabolite has higher ACE affinity, prolonging the drug’s effect.
Pharmacokinetics
| Parameter | Detail |
| Absorption | Oral bioavailability ~57%; peak plasma concentration at 0.5–1 hr post‑dose. |
| Distribution | Protein‑binding ~50%; penetrates glomerular filtrate; not extensively lipid‑soluble. |
| Metabolism | Hydrolyzed to benazepril‑β‑hydroxy acid in the liver; minor glucuronidation. |
| Elimination | Dual renal and fecal routes; renal excretion accounts for ~60% of dose; half‑life 9–10 hrs (parent) and 10–12 hrs (metabolite). |
| Dose Adjustments | Reduce dose in moderate‑to‑severe chronic kidney disease (eGFR <30 mL/min/1.73 m²). |
Indications
- Hypertension: Effective as monotherapy or as part of dual therapy.
- Post‑MI & Chronic Heart Failure: Improves survival and reduces remodeling when added within 72 h of infarction.
- Diabetic Nephropathy: Slows albuminuria progression in type‑2 diabetes with hypertension.
Contraindications
- Pregnancy: Category X—contraindicated during all trimesters due to teratogenic risk (fetal renal dysgenesis).
- Cystic Fibrosis: No evidence of benefit; avoid due to reduced drug exposure.
- Hypersensitivity: Known allergy to benazepril or other ACE inhibitors.
- Renal or Hepatic Impairment: Use cautiously; consider alternate agents if eGFR <30 mL/min.
- Hyperkalemia Risk: Monitor serum potassium; contraindicated with potassium‑sparing diuretics or potassium supplements without adjustment.
- Angioedema: Patients with prior ACE‑inhibitor‑induced angioedema should avoid.
Dosing
| Condition | Initial Dose | Titration | Max Dose |
| Hypertension | 10 mg PO daily (often 7.5 mg or 5 mg for sensitive patients) | Increase by 10 mg increments every 2–4 weeks | 40 mg PO daily |
| Post‑MI / CHF | 10 mg PO daily | Increase after 2–4 weeks based on BP and tolerability | 40 mg PO daily |
| Renal Function | 10 mg PO daily (if eGFR 30–60 mL/min) | Titrate cautiously | 30 mg PO daily (if eGFR <30 mL/min) |
• Administration: Oral tablets with or without food. Take at the same time daily.
• Drug Interactions: Avoid concomitant use with potassium‑sparing diuretics, NSAIDs (reduce renal clearance), or other ACE inhibitors/ARBs (risk of hyperkalemia and renal dysfunction).
Adverse Effects
- Common (≥5%) |
- Dry, persistent cough
- Dizziness or fatigue (hypotension)
- Headache
- Elevated serum potassium
- Mild GI upset (nausea, diarrhea)
- Serious (≤1%) |
- Angioedema (rapid swelling of lips, tongue, throat)
- Severe hyperkalemia (especially with concurrent potassium‑sparing agents)
- Acute kidney injury (particularly in volume depletion)
- Severe hypotension (orthostatic)
- Hypersensitivity reactions (anaphylaxis)
Monitoring
- Vital Signs: Blood pressure, heart rate (baseline, 1–2 h after dose, 24‑h interval).
- Renal Function: Serum creatinine and eGFR at baseline, 4 weeks post‑initiation, then every 6–12 months during maintenance.
- Serum Potassium: Baseline, 1 week after dose change, quarterly thereafter.
- Electrocardiogram (ECG): For patients with baseline cardiac disease or symptomatic arrhythmias.
- Orthostatic Vital Signs: To detect malignant hypotension.
- Albuminuria: For diabetic nephropathy monitoring (proteinuria trend).
Clinical Pearls
- Start Low, Go Slow: A 5‑mg formulation helps mitigate the cough and studies show good tolerability.
- Cough vs. Angioedema: A dry cough is common (~10–15%) and often benign; angioedema is rare (<1%) but requires immediate discontinuation and emergency care.
- Kidney Protection: Post‑MI patients benefit from a dual ACE‑inhibitor strategy, but close monitoring prevents renal deterioration.
- Combination with Metformin: Benazepril doesn’t interfere with metformin; however, monitor renal function to avoid lactic acidosis risks when eGFR <30 mL/min.
- Pediatric Use: Not approved for children; risk of hypotension and bradycardia; use with caution only under strict supervision.
- Pregnancy Awareness: Always counsel patients with a bar graph indicating teratogenicity; use contraceptive monitoring if pregnant or planning.
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• References
• U.S. Food & Drug Administration (FDA) Benazepril Labeling (2024).
• UpToDate: Benazepril – Pharmacology and Clinical Use.
• American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Management of Hypertension (2023).
*Prepared for medical students and healthcare professionals; ideal for quick reference and exam revision.*