Lisinopril

Generic Name: Lisinopril
Drug Class: Angiotensin-Converting Enzyme (ACE) Inhibitor
Pharmacological Class: Antihypertensive, cardioprotective agent
ATC Code: C09AA03
Regulatory Status: Prescription-only (Rx)
Common Brand Names: Zestril, Prinivil, Carace, Linopril (region-specific)

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Mechanism of Action

Lisinopril is a long-acting, orally active ACE inhibitor that blocks the conversion of angiotensin I to angiotensin II by inhibiting the angiotensin-converting enzyme (ACE). This results in:

• Vasodilation: Reduced levels of angiotensin II lead to relaxation of arteriolar smooth muscle

• Reduced aldosterone secretion: Leading to decreased sodium and water retention

• Lowered sympathetic activity

• Preservation of bradykinin: Lisinopril slightly increases bradykinin levels, contributing to vasodilation but also responsible for cough and angioedema in some patients

Outcome: Decreased systemic vascular resistance, reduced blood pressure, improved cardiac output, and renal protection in specific populations.

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Therapeutic Indications

1. Hypertension (essential or renovascular):

   • First-line or adjunctive therapy for blood pressure control in adults and children ≥6 years

2. Heart Failure with Reduced Ejection Fraction (HFrEF):

   • Reduces afterload and preload, improving cardiac performance and survival

3. Post-Myocardial Infarction:

   • Initiated early post-MI in hemodynamically stable patients to reduce mortality and prevent ventricular remodeling

4. Diabetic Nephropathy or Proteinuric Chronic Kidney Disease:

   • Delays progression of renal damage, especially in type 1 diabetics with microalbuminuria

5. Left Ventricular Dysfunction (Asymptomatic):

   • Prevents progression to symptomatic heart failure

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Formulations and Strengths

• Tablets: 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg

• Combination Products:

  • Lisinopril + hydrochlorothiazide (e.g., Zestoretic): 10/12.5 mg, 20/12.5 mg, 20/25 mg

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Dosage and Administration

Adults:

Hypertension (monotherapy):

• Initial dose: 10 mg once daily

• Usual maintenance dose: 20–40 mg once daily

• Max dose: 80 mg once daily

Heart Failure:

• Initial dose: 2.5–5 mg once daily

• Target dose: 20–40 mg/day (based on tolerability and renal function)

Post-Myocardial Infarction:

• Initial dose: 5 mg within 24 hours, followed by 5 mg after 24 hours, then titrate to 10 mg once daily

Diabetic Nephropathy or CKD:

• Initial dose: 10 mg daily

• Titrate up to: 20–40 mg daily to reduce proteinuria

Children (≥6 years, with hypertension):

• Initial dose: 0.07 mg/kg once daily

• Max dose: 0.61 mg/kg/day or 40 mg/day (whichever is lower)

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Pharmacokinetics

• Absorption: ~25% bioavailable orally; not affected by food

• Onset of action: 1 hour

• Peak effect: 6–8 hours

• Duration: 24 hours (once-daily dosing)

• Protein Binding: Negligible

• Metabolism: Not metabolized; excreted unchanged

• Half-life: ~12 hours

• Excretion: Renal (unchanged in urine)

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Contraindications

• Hypersensitivity to lisinopril or any ACE inhibitor

• History of angioedema associated with prior ACE inhibitor therapy

• Hereditary or idiopathic angioedema

• Concomitant use with aliskiren in patients with diabetes or renal impairment (eGFR <60 mL/min/1.73 m²)

• Pregnancy (second and third trimesters)

• Bilateral renal artery stenosis

• Severe hypotension or hemodynamic instability

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Warnings and Precautions

1. Angioedema:

   • Can be life-threatening; more common in Black patients

   • Discontinue immediately if facial, lip, or airway swelling occurs

2. Hyperkalemia:

   • Risk increased in renal impairment, diabetes, elderly, and when used with potassium-sparing diuretics or supplements

3. Renal Impairment:

   • Monitor creatinine and eGFR regularly

   • Temporary rise in creatinine expected; persistent elevations require dosage adjustment or discontinuation

4. Hypotension:

   • Common after first dose, especially in sodium-depleted, dehydrated, or heart failure patients

   • Start low, especially if patient is on diuretics

5. Hepatic Dysfunction:

   • Rarely, hepatocellular injury and cholestatic jaundice may occur

6. Neutropenia/Agranulocytosis:

   • Rare, more common in patients with collagen vascular disease or renal dysfunction

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Adverse Effects

Very Common (≥10%):

• Dizziness (due to vasodilation)

• Headache

• Cough (dry, persistent; due to bradykinin)

Common (1–10%):

• Hypotension

• Hyperkalemia

• Fatigue

• Nausea

• Renal function impairment

• Diarrhea

Uncommon to Rare (<1%):

• Angioedema

• Rash or urticaria

• Taste disturbances

• Depression

• Erectile dysfunction

• Increased liver enzymes

• Blood dyscrasias (anemia, leukopenia)

Severe:

• Anaphylaxis

• Acute kidney injury

• Pancreatitis

• Hepatic failure (rare)

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Drug Interactions

Increased Risk of Hyperkalemia:

• Potassium supplements, potassium-sparing diuretics (e.g., spironolactone)

• Salt substitutes containing potassium

Increased Hypotensive Effect:

• Diuretics (especially loop/thiazide; caution for first-dose hypotension)

• Vasodilators, other antihypertensives

• Alcohol

Reduced Antihypertensive Effect:

• NSAIDs (especially with diuretics → risk of renal failure and reduced effect)

Lithium:

• Decreased clearance → lithium toxicity

• Monitor serum lithium if coadministered

Dual RAAS Blockade:

• Avoid combination with ARBs or aliskiren due to increased risk of hypotension, hyperkalemia, and renal dysfunction

Antidiabetic Agents (insulin and oral hypoglycemics):

• Risk of enhanced hypoglycemic effect, especially in early treatment

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Monitoring Parameters

Parameter	Frequency
Blood pressure	Baseline, then periodically
Serum creatinine and eGFR	Baseline, 1–2 weeks after initiation/dose changes, then every 3–6 months
Serum potassium	Baseline and periodically
Signs of angioedema	Ongoing
CBC (for leukopenia)	In patients with autoimmune disease or renal impairment
Urine protein (in nephropathy)	Periodically if indicated

Pregnancy and Lactation

Pregnancy:

• Contraindicated, especially in 2nd and 3rd trimesters

• Causes fetal hypotension, renal failure, skull hypoplasia, and death

• Discontinue immediately if pregnancy detected

Lactation:

• Not recommended

• Lisinopril is present in human milk in low levels; monitor infant for hypotension and renal function if used

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Comparison with Similar Agents

Property	Lisinopril	Ramipril	Enalapril	Losartan (ARB)
Class	ACE inhibitor	ACE inhibitor	ACE inhibitor	ARB
Prodrug	No	Yes	Yes	No
Dosing	Once daily	Once daily	BID	Once daily
Cough risk	Yes	Yes	Yes	Rare
Renal protection	Yes	Yes	Yes	Yes
Duration	24 hrs	24 hrs	12–24 hrs	24 hrs

Patient Counseling Points

• Take at the same time each day, with or without food

• Do not stop abruptly unless advised by a physician

• Report persistent dry cough, facial/lip swelling, or signs of low blood pressure

• Stay hydrated, but avoid excess potassium (diet or supplements)

• Avoid NSAIDs unless approved by your doctor

• Routine blood tests are essential for monitoring kidney and potassium levels

• Inform all healthcare providers you are taking an ACE inhibitor

• Not suitable during pregnancy or breastfeeding

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Storage

• Store at 20–25°C

• Keep in a dry, cool place away from sunlight

• Protect from moisture

• Keep out of reach of children