Generic Name

Lisinopril

Mechanism

Lisinopril is an orally active, irreversible angiotensin‑converting enzyme (ACE) inhibitor.
• It blocks the conversion of angiotensin I → angiotensin II, the potent vasoconstrictor.
• Resulting in:
• ↓ vasoconstriction → lower systemic vascular resistance.
• ↓ renin‑angiotensin‑aldosterone system (RAAS) activation → decreased aldosterone release, natriuresis, and diuresis.
• Sustained reduction of blood pressure and cardiac afterload, reducing myocardial oxygen demand and improving cardiac remodeling.

Pharmacokinetics

• Absorption: 30–50 % bioavailability; peak plasma levels 1–2 h post‑dose.
• Distribution: Volume of distribution ≈ 0.5 L/kg; minimal protein binding.
• Metabolism: Not appreciably metabolized; active metabolites contribute to effect.
• Elimination: Renal excretion (≈70 % unchanged); half‑life 11 h (shorter in renal impairment).
• Drug interactions: ↑ plasma levels with ACE–I or ARB combinations; caution with potassium‑S‑paring agents or NSAIDs (exacerbates hyperkalemia/renal dysfunction).

Indications

• Hypertension – first‑line or adjunct therapy.
• Heart failure – reduces morbidity/mortality; improves ejection fraction.
• Left ventricular dysfunction post‑myocardial infarction.
• Diabetic nephropathy – preserves renal function in type 2 diabetes.
• Proteinuria – useful in chronic kidney disease irrespective of etiology.

Contraindications

• Contraindicated:
• History of angioedema related to previous ACE‑I.
• Pregnancy (especially 2nd–3rd trimester).
• Warnings:
• ACE‑I/ARB-induced hyperkalemia – monitor serum K⁺.
• Renal impairment – dose adjustment in CrCl < 30 mL/min.
• Hypotensive episodes – especially after first dose.
• Cough – non‑productive, dry.
• Renal artery stenosis – careful use; benefit vs. risk.

Dosing

• Initiation:
• Adult 40 kg–60 kg: 10 mg once daily.
• Adult > 60 kg: 20 mg once daily.
• Maintenance:
• Titrate every 4–6 weeks by 5–10 mg increments to target BP/efficacy.
• Max daily dose 80 mg (as monotherapy).
• Renal impairment:
• CrCl 30–49 mL/min: start 10 mg, max 20 mg daily.
• CrCl < 30 mL/min: use 5–10 mg with close monitoring.
• Administration advice: Take ≥ 30 min before a meal; chew/disintegrate tablets if dysphagia (not to be crushed).

Adverse Effects

• Common (≥ 1 %):
• Dry cough
• Hypotension, dizziness
• Hyperkalemia
• Elevated serum creatinine
• Fatigue, headache
• Serious (≤ 0.1 %):
• Angioedema (acute swelling of lips, tongue, throat).
• Severe hypotension; syncope.
• Severe renal dysfunction (acute kidney injury).
• Unexplained GI bleeding (rare).

Monitoring

Clinical Pearls

• First‑Dose “Cough” Check: A patient’s first cough often settles within 2–4 weeks; advise them to wait before discontinuing.
• Renal Protection Strategy: In diabetics with proteinuria, initiate lisinopril at a low dose (5 mg) and titrate gradually to avoid abrupt creatinine rise.
• Hyperkalemia Hot‑Spot: Combine with a low‑potassium diet and avoid supplements with potassium or K⁺‑sparingly used diuretics (e.g., spironolactone) unless closely monitored.
• Pregnancy Switch‑Guide: If a patient becomes pregnant, switch promptly to an ARB or other non‑ACE‑I antihypertensive; avoid abrupt withdrawal of lisinopril to minimize rebound hypertension risk.
• Interaction Alert: Concomitant NSAIDs (e.g., diclofenac) blunt ACE‑I natriuretic effect; reduce NSAID dose or use COX‑2 selective agents to preserve renal perfusion.

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• *Prepared for medical students and clinicians seeking a concise, evidence‑based reference on Lisinopril.*