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Lisinopril

Lisinopril

Zestril Prinivil Qbrelis

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Updated: December 06, 2025

Overview

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor widely used in cardiovascular medicine. It effectively lowers blood pressure by inhibiting the renin-angiotensin-aldosterone system (RAAS), reducing vasoconstriction and aldosterone secretion. This results in decreased peripheral vascular resistance without increasing heart rate. As a long-acting ACE inhibitor, lisinopril is administered once daily and exhibits linear pharmacokinetics. Unlike some ACE inhibitors, it is not a prodrug and is excreted unchanged in urine, making it particularly useful in patients with hepatic impairment but requiring dose adjustments in renal dysfunction.

Drug Class

• Therapeutic: Antihypertensive • Pharmacologic: Angiotensin-converting enzyme (ACE) inhibitor • Chemical Class: Lysine analog of enalaprilat

Mechanism of Action

Lisinopril competitively inhibits angiotensin-converting enzyme (ACE), preventing the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor). This results in: 1. Reduced angiotensin II-mediated vasoconstriction 2. Decreased aldosterone secretion (reducing sodium/water retention) 3. Increased bradykinin levels (contributing to vasodilation) 4. Reduced degradation of substance P Collectively, these effects lower systemic vascular resistance without reflex tachycardia.

Pharmacokinetics

Absorption: Bioavailability 25% (food does not affect absorption). Peak plasma concentration: 7 hours Distribution: Minimal plasma protein binding (<10%). Volume of distribution: 1.7 L/kg Metabolism: Not metabolized in the liver. Does not undergo significant first-pass metabolism Excretion: Primarily renal (100% as unchanged drug). Elimination half-life: 12 hours (prolonged in renal impairment) Half-life: 12 hours (allows once-daily dosing)

Pharmacodynamics

• Cardiovascular: Reduces systemic vascular resistance (afterload), improves cardiac output in heart failure • Renal: Dilates efferent glomerular arterioles, reducing intraglomerular pressure • Endocrine: Suppresses aldosterone secretion, potentially causing hyperkalemia • Kinin system: Increased bradykinin causes dry cough (up to 35% patients)

Indications

• Hypertension: First-line therapy for essential hypertension as monotherapy or combination • Heart failure: Improves survival and symptoms in systolic heart failure (NYHA Class II-IV) • Acute myocardial infarction: Reduces mortality when started within 24 hours in hemodynamically stable patients • Diabetic nephropathy: Renoprotective in type 1 diabetes with proteinuria

Contraindications

Absolute: • History of angioedema related to ACE inhibitors • Concomitant aliskiren in diabetic patients • Pregnancy (second/third trimester) Relative: • Renal artery stenosis (bilateral or unilateral in solitary kidney) • Aortic stenosis/hypertrophic cardiomyopathy • Hyperkalemia (K⁺ >5.5 mEq/L) • Severe renal impairment (CrCl <30 mL/min)

Dosage & Administration

Hypertension: • Initial: 10 mg PO daily (5 mg in volume-depleted patients) • Maintenance: 20-40 mg daily (max 80 mg) Heart Failure: • Initial: 2.5-5 mg PO daily • Maintenance: Titrate to 20-40 mg daily (target dose) Acute MI: • Start within 24 hours: 5 mg PO, then 5 mg after 24h, 10 mg after 48h, then 10 mg daily Renal impairment: • CrCl 10-30 mL/min: Start 2.5-5 mg daily • CrCl <10 mL/min: Start 2.5 mg daily

Special Populations

Pediatric: Not recommended <6 years. Hypertension dosing (≥6 years): 0.07 mg/kg PO daily (max 5 mg), titrate q1-2 weeks Geriatric: Start with 2.5-5 mg daily due to decreased renal function Renal impairment: Reduce dose based on CrCl (see dosage section). Contraindicated in anuria Hepatic impairment: No adjustment needed (non-hepatic metabolism)

Adverse Effects

Common (>10%): • Dry cough (up to 35%): Bradykinin-mediated, resolves after discontinuation • Dizziness (15%): Due to hypotension, especially with initial doses • Hyperkalemia (10-15%): Monitor potassium, especially with NSAIDs or potassium-sparing diuretics Serious (<1%): • Angioedema (0.1-0.7%): Potentially life-threatening, requires immediate discontinuation • Acute renal failure: Especially in renal artery stenosis • Neutropenia/agranulocytosis: Higher risk in collagen vascular disease or immunosuppression • Fetal toxicity: Causes fetal malformations in 2nd/3rd trimester

Drug Interactions

• Diuretics: Potentiate hypotensive effects (discontinue diuretic 2-3 days before initiation) • NSAIDs: Reduce antihypertensive effect, increase renal toxicity risk • Potassium supplements/spironolactone: Significant hyperkalemia risk • Lithium: Increased lithium levels and toxicity • Aliskiren: Contraindicated in diabetes - increases hyperkalemia, hypotension, renal impairment

Warnings & Precautions

• Black Box Warning: Fetal toxicity - discontinue immediately if pregnancy detected • Angioedema: Can occur at any time during treatment (monitor airway) • Hypotension: Risk increased in volume-depleted or heart failure patients • Hyperkalemia: Monitor potassium, especially in renal impairment or diabetes • Neutropenia: Higher risk in collagen vascular disease (monitor CBC) • Hepatic failure: Rare cholestatic jaundice (monitor LFTs)

Pregnancy & Lactation

Pregnancy: FDA Category D (1st trimester), Category D (2nd/3rd trimester). Causes fetal skull hypoplasia, oligohydramnios, and renal failure. Contraindicated in 2nd/3rd trimester Lactation: Excreted in breast milk (infant plasma 0.1% of maternal). AAP considers compatible but monitor infant for hypotension

Monitoring Parameters

• Blood pressure (standing/supine) at initiation and monthly • Serum creatinine and potassium within 1-2 weeks of initiation and dose changes • Urine protein in diabetic patients (annually) • CBC in collagen vascular disease patients • Signs of angioedema (face/lip swelling, dyspnea)

Patient Counseling

• Take at same time daily, with/without food • Report any swelling of face/lips or difficulty breathing immediately • Rise slowly to minimize dizziness • Monitor for persistent dry cough • Avoid potassium supplements/salt substitutes unless prescribed • Report pregnancy or pregnancy planning immediately • Regular blood pressure and lab monitoring required

Storage & Stability

Store at 20-25°C (68-77°F). Protect from moisture and light. Dispense in tight container. Stable for 30 days after opening.

Clinical Pearls

• 'First-dose hypotension' uncommon but monitor high-risk patients for 2 hours after initial dose • Cough typically develops weeks-months after initiation • Discontinue if serum creatinine increases >30% from baseline • Consider in hypertensive patients with diabetes/proteinuria for renal protection • ACE inhibitor-induced angioedema has higher incidence in African Americans

References

• Drugs.com. (2023). Lisinopril: Uses, Dosage, Side Effects. Retrieved from https://www.drugs.com/lisinopril.html • Whelton PK, et al. (2017). 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J Am Coll Cardiol. 71(19):e127-e248 • CONSENSUS Trial Study Group. (1987). Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med. 316(23):1429-35