Introduction
Zestril (lisinopril) is an angiotensin-converting enzyme (ACE) inhibitor widely used in cardiovascular medicine. As a long-acting ACE inhibitor, it plays a crucial role in managing hypertension, heart failure, and post-myocardial infarction care. Originally developed from snake venom peptides, lisinopril represents a significant advancement in renin-angiotensin-aldosterone system (RAAS) modulation.
Mechanism of Action
Zestril exerts its therapeutic effects by competitively inhibiting angiotensin-converting enzyme (ACE). This inhibition prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, and reduces the degradation of bradykinin, a vasodilator. The resulting effects include:
- Vasodilation of arterial and venous beds
- Reduced aldosterone secretion
- Decreased sodium and water retention
- Attenuation of adverse cardiac remodeling
Indications
FDA-approved indications:
- Hypertension (monotherapy or combination therapy)
- Heart failure (as adjunctive therapy)
- Acute myocardial infarction (within 24 hours in hemodynamically stable patients)
- Diabetic nephropathy in hypertensive patients with type 1 diabetes
Off-label uses may include:
- Chronic kidney disease progression delay
- Migraine prophylaxis
- Scleroderma renal crisis prevention
Dosage and Administration
Hypertension:- Initial dose: 10 mg once daily
- Maintenance: 20-40 mg once daily
- Maximum: 80 mg daily
- Initial: 2.5-5 mg once daily
- Titrate upward as tolerated
- Target: 20-40 mg daily
- Initial: 5 mg within 24 hours
- Subsequent: 5 mg daily for 2 days, then 10 mg daily
- Renal impairment: Adjust based on creatinine clearance
- Elderly: Start with lower doses (2.5-5 mg daily)
- Volume-depleted patients: Consider 2.5 mg starting dose
Pharmacokinetics
Absorption: ~25% bioavailability, not significantly affected by food Distribution: Volume of distribution: 0.5 L/kg; minimal protein binding Metabolism: Not metabolized by cytochrome P450 system Elimination: Primarily renal excretion unchanged; half-life: 12 hours Onset: 1 hour; Peak effect: 6 hours; Duration: 24 hoursContraindications
- History of angioedema related to previous ACE inhibitor therapy
- Hereditary or idiopathic angioedema
- Concomitant use with aliskiren in patients with diabetes
- Hypersensitivity to lisinopril or other ACE inhibitors
- Pregnancy (second and third trimesters)
Warnings and Precautions
Black Box Warnings:- Fetal toxicity and mortality when used during pregnancy
- Angioedema: Can occur at any time during therapy
- Hypotension: Particularly in volume-depleted patients
- Impaired renal function: Monitor in patients with renal artery stenosis
- Hyperkalemia: May occur, especially with renal impairment or concomitant potassium-sparing diuretics
- Neutropenia/agranulocytosis: Rare but serious
Drug Interactions
Significant interactions:- Diuretics: Enhanced hypotensive effect
- NSAIDs: Reduced antihypertensive effect; increased renal risk
- Potassium-sparing diuretics/potassium supplements: Increased hyperkalemia risk
- Lithium: Increased lithium levels and toxicity
- Aliskiren: Increased renal impairment, hyperkalemia, and hypotension
- Gold injections: Nitritoid reactions reported
Adverse Effects
Common (≥1%):- Cough (dry, persistent) (5-35%)
- Dizziness (5-19%)
- Headache (5-14%)
- Fatigue (3-8%)
- Nausea (3-6%)
- Angioedema
- Acute renal failure
- Severe hypotension
- Hyperkalemia
- Neutropenia/agranulocytosis
- Hepatic failure
- Pancreatitis
Monitoring Parameters
Baseline:- Blood pressure
- Renal function (BUN, creatinine, electrolytes)
- Pregnancy test in women of childbearing potential
- Blood pressure at each visit
- Renal function and electrolytes within 2-4 weeks of initiation/dose change, then periodically
- Potassium levels, especially with renal impairment or concomitant medications
- CBC with differential if collagen vascular disease present
- Monitor for signs of angioedema
Patient Education
Key points:- Take medication at the same time each day
- Report any swelling of face, lips, tongue, or difficulty breathing immediately
- Persistent dry cough may occur and should be reported
- Rise slowly from sitting/lying position to prevent dizziness
- Avoid potassium supplements or salt substitutes without medical advice
- Notify all healthcare providers of ACE inhibitor use
- Use effective contraception; report suspected pregnancy immediately
- Regular blood pressure monitoring is essential
- Do not discontinue medication without medical guidance
References
1. FDA Prescribing Information: Zestril (lisinopril) 2. Williams B, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-3104 3. Yancy CW, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. J Am Coll Cardiol. 2017;70(6):776-803 4. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3(1):1-150 5. Israili ZH, et al. Clinical pharmacokinetics of angiotensin converting enzyme (ACE) inhibitors in renal disease. Clin Pharmacokinet. 1992;22(1):22-37 6. Brown NJ, Vaughan DE. Angiotensin-converting enzyme inhibitors. Circulation. 1998;97(14):1411-1420 7. McMurray JJ, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. Eur Heart J. 2012;33(14):1787-1847