Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor prescribed primarily for the management of hypertension, heart failure, and post-myocardial infarction care. It works by inhibiting the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby promoting vasodilation and reducing peripheral arterial resistance. This mechanism not only lowers blood pressure but also decreases cardiac afterload, making it a cornerstone therapy in cardiovascular medicine. Its well-established efficacy, once-daily dosing convenience, and extensive clinical evidence base solidify its position as a first-line treatment option in numerous clinical guidelines worldwide.

Features

• Pharmacological Class: Angiotensin-converting enzyme (ACE) inhibitor
• Available Formulations: Oral tablets in strengths of 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, and 40 mg
• Mechanism of Action: Competitive inhibition of ACE, preventing the conversion of angiotensin I to angiotensin II
• Bioavailability: Approximately 25%, with significant inter-patient variability
• Protein Binding: Minimal
• Onset of Action: Antihypertensive effects begin within 1 hour; peak effect at 6 hours
• Half-Life: 12 hours, permitting once-daily dosing in most patients
• Metabolism: Not metabolized by the liver; excreted unchanged primarily by the kidneys
• FDA-Approved Indications: Hypertension, adjunctive therapy for heart failure, post-MI to improve survival in clinically stable patients

Benefits

• Significant Blood Pressure Reduction: Effectively lowers both systolic and diastolic blood pressure, reducing long-term cardiovascular risk.
• Improved Survival in Heart Failure: Demonstrated to reduce mortality and hospitalization rates in patients with systolic heart failure.
• Cardioprotective Post-Myocardial Infarction: Shown to improve survival and reduce the incidence of heart failure in stable patients following an acute MI.
• Renoprotective Effects: Slows the progression of renal disease in hypertensive patients with diabetes and proteinuria.
• Favorable Safety Profile: Generally well-tolerated with a predictable side effect profile when appropriately dosed and monitored.
• Once-Daily Dosing: Enhances patient adherence and simplifies treatment regimens.

Common use

Lisinopril is predominantly used in the management of essential hypertension, either as monotherapy or in combination with other antihypertensive agents such as thiazide diuretics. It is a fundamental component of guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF), where it improves symptoms, functional capacity, and survival. Following an acute myocardial infarction, lisinopril is initiated in hemodynamically stable patients to prevent ventricular remodeling and subsequent heart failure. Off-label uses include the treatment of diabetic nephropathy, particularly in patients with albuminuria, due to its ability to reduce protein excretion and slow the decline in glomerular filtration rate.

Dosage and direction

Dosage must be individualized based on the patient’s clinical condition, renal function, and blood pressure response.

Hypertension:

• Initial dose: 10 mg orally once daily in patients not on diuretics.
• Maintenance dose: 20–40 mg once daily. Dosage may be titrated at intervals of at least 2 weeks.
• Dosage in volume-depleted patients (e.g., on diuretics): Start with 5 mg once daily under close medical supervision.

Heart Failure:

• Initial dose: 2.5–5 mg once daily under close medical observation for hypotension.
• Target maintenance dose: 20–40 mg once daily, as tolerated. Titration should be performed over several weeks.

Acute Myocardial Infarction:

• Initiate within 24 hours in hemodynamically stable patients.
• Initial dose: 5 mg orally, followed by 5 mg after 24 hours, 10 mg after 48 hours, then 10 mg once daily.
• Maintenance therapy should continue for at least 6 weeks post-infarction.

Dosing in Renal Impairment: Dosage adjustment is required based on creatinine clearance (CrCl):

• CrCl >30 mL/min: Standard dosing.
• CrCl 10–30 mL/min: Initial dose 5 mg daily.
• CrCl <10 mL/min (or on dialysis): Initial dose 2.5 mg daily. Lisinopril is dialyzable.

The tablet should be taken with a glass of water, with or without food, at approximately the same time each day.

Precautions

• Hypotension: Symptomatic hypotension may occur, particularly following the first dose, in volume-depleted patients (e.g., those on diuretic therapy), or with heart failure. Correct volume depletion prior to initiation, if possible.
• Renal Function Impairment: May cause elevated BUN and serum creatinine, especially in patients with pre-existing renal disease, renal artery stenosis, or those receiving concomitant diuretics. Monitor renal function before and during therapy.
• Hyperkalemia: Elevations in serum potassium can occur. Risk is increased in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium. Monitor potassium levels.
• Cough: A persistent, dry, non-productive cough may develop and is a class effect of ACE inhibitors. It usually resolves upon discontinuation of therapy.
• Angioedema: Can occur at any time during treatment, involving the face, extremities, lips, tongue, glottis, and/or larynx. Discontinue lisinopril immediately and provide appropriate emergency care if airway obstruction is threatened.
• Surgery/Anesthesia: ACE inhibitors may potentiate the hypotensive effects of anesthesia. The cardiothoracic anesthesia community often recommends withholding ACE inhibitors for 24 hours prior to major surgery, but this should be individualized.
• Hepatic Impairment: Use with caution; rare cases of cholestatic jaundice and hepatitis have been reported.
• Neutropenia/Agranulocytosis: Has been reported; risk may be increased in patients with collagen vascular disease or renal impairment. Monitor CBC with differential in at-risk populations.

Contraindications

• History of angioedema related to previous ACE inhibitor therapy.
• Hereditary or idiopathic angioedema.
• Hypersensitivity to lisinopril or any other ACE inhibitor.
• Concomitant use with aliskiren in patients with diabetes.
• Concomitant use with sacubitril/valsartan (must allow a 36-hour washout period when switching).
• Second and third trimester of pregnancy (can cause injury and even death to the developing fetus).

Possible side effect

Most side effects are generally mild and transient. Common adverse reactions (≥1%) include:

• Dizziness (12%)
• Headache (6%)
• Persistent dry cough (up to 5%)
• Fatigue (3%)
• Nausea (2%)
• Orthostatic hypotension (2%)
• Diarrhea (2%)
• Rash (1%)
• Hyperkalemia (1-10%, depending on population)
• Elevated BUN/creatinine (2%)

Less common but serious side effects require immediate medical attention:

• Angioedema (0.1-0.7%)
• Severe hypotension
• Jaundice or signs of hepatic failure
• Symptoms of infection (e.g., fever, sore throat - possible neutropenia)
• Oliguria or progressive renal impairment

Drug interaction

Lisinopril has several clinically significant interactions:

• Diuretics: Potentiates hypotensive effect. Risk of first-dose hypotension. Consider withholding diuretic for 2-3 days before starting lisinopril.
• Potassium-Sparing Diuretics (e.g., spironolactone, amiloride), Potassium Supplements, Salt Substitutes: Increased risk of hyperkalemia.
• Lithium: Increased lithium levels and toxicity. Monitor lithium levels closely.
• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): May diminish the antihypertensive effect of lisinopril and increase the risk of renal functional deterioration, especially in the elderly or volume-depleted.
• Aliskiren: Contraindicated in patients with diabetes; increased risk of renal impairment, hypotension, and hyperkalemia in others.
• Sacubitril/Valsartan: Concomitant use is contraindicated due to increased risk of angioedema.
• Oral Hypoglycemics and Insulin: ACE inhibitors may enhance hypoglycemic effects.
• Gold Injections: Nitritoid reactions (flushing, nausea, hypotension) have been reported with sodium aurothiomalate.
• MTOR Inhibitors (e.g., temsirolimus): Increased risk of angioedema.

Missed dose

If a dose is missed, it should be taken as soon as remembered on the same day. If it is almost time for the next scheduled dose, the missed dose should be skipped. Do not double the dose to make up for a missed one. Maintaining a consistent daily schedule is important for stable blood pressure control.

Overdose

The most likely manifestation of overdose is severe hypotension, which may lead to circulatory shock. Other signs may include bradycardia, electrolyte disturbances (hyperkalemia), and renal failure. Management: Place patient in supine position and initiate supportive measures. Primary treatment is volume expansion with intravenous normal saline. Vasopressor therapy (e.g., norepinephrine) may be required. Lisinopril is removed by hemodialysis. Bradycardia may be treated with atropine. Serum electrolytes and creatinine should be monitored.

Storage

Store at controlled room temperature, 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F and 86°F). Keep the container tightly closed to protect from moisture and light. Keep out of reach of children and pets. Do not use after the expiration date printed on the bottle.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting or changing any treatment regimen. Never disregard professional medical advice or delay in seeking it because of something you have read here. Dosage and indications may vary based on individual patient factors and latest clinical guidelines.

Reviews

Clinical Perspective: “Lisinopril remains a foundational therapy in cardiology and hypertension management. Its mortality benefit in heart failure and post-MI patients is robust and well-documented in major trials like SOLVD and GISSI-3. The once-daily dosing and generic availability make it highly accessible. The side effect profile is manageable with appropriate patient selection and monitoring, though the cough and risk of angioedema require patient education.” – Cardiologist, 15 years experience.

Patient Experience (Aggregated): Many patients report effective blood pressure control and appreciate the convenience of once-daily dosing. The dry cough is a frequently cited reason for discontinuation among a minority of users. Those with heart failure often note an improvement in symptoms like shortness of breath and exercise tolerance. Common feedback highlights the importance of regular blood tests to monitor kidney function and potassium levels.