This is an old revision of the document!
Lisinopril (Prinivil®, Zestril®)
 | |
| Lisinopril | |
|---|---|
| Brand Names | Prinivil®, Zestril® |
| Drug Class | ACE Inhibitor |
| Primary Indications | Hypertension; Heart Failure (HFrEF); Post-MI |
| Blood Pressure Effect | ↓ SVR |
| Mortality Benefit | Yes (HFrEF, post-MI) |
| Elimination | Renal |
| Black Box Warning | Fetal Toxicity |
| FDA Approval | 1987 |
Overview
Lisinopril is a long-acting angiotensin-converting enzyme (ACE) inhibitor used in the treatment of hypertension, heart failure with reduced ejection fraction, and post–myocardial infarction ventricular dysfunction.
It reduces systemic vascular resistance, decreases aldosterone-mediated sodium retention, and mitigates maladaptive neurohormonal activation. Lisinopril improves survival in HFrEF and post-MI patients and remains a cornerstone agent in cardiometabolic therapy.
Mechanism of Action
Primary Molecular Target
- Inhibition of angiotensin-converting enzyme (ACE)
RAAS Effects
- ↓ Conversion of Angiotensin I → Angiotensin II
- ↓ Aldosterone secretion
- ↓ Vasoconstriction
Bradykinin Effect
- ↑ Bradykinin levels (due to reduced breakdown)
Net Physiologic Outcomes
- ↓ Systemic vascular resistance (afterload)
- ↓ Sodium and water retention
- ↓ Ventricular remodeling
- Improved cardiac output in HFrEF
Indications
- Post–myocardial infarction with LV dysfunction
Renal protection:
- Diabetic nephropathy (albuminuria reduction)
Black Box Warning
ACE inhibitors can cause fetal toxicity when administered during pregnancy.
Mechanism:
- Disruption of fetal RAAS
- Risk of renal failure, oligohydramnios, skull hypoplasia
Discontinue immediately if pregnancy is detected.
Contraindications
Absolute:
- History of ACE inhibitor–induced angioedema
- Pregnancy
- Bilateral renal artery stenosis
Relative / Caution:
- Hyperkalemia
- Severe renal impairment
- Volume depletion
Dosing
Hypertension:
- Initial: 10 mg daily
- Typical: 20–40 mg daily
- Max: 40 mg daily
Heart Failure:
- Initial: 2.5–5 mg daily
- Titrate upward as tolerated
Renal adjustment:
- Required in reduced eGFR
Pharmacokinetics
Absorption:
- Oral
Bioavailability:
- ~25%
Metabolism:
- Not metabolized
Half-life:
- ~12 hours
Elimination:
- Renal (unchanged)
Adverse Effects
Common:
- Dry cough (bradykinin-mediated)
- Dizziness
- Hypotension
Electrolyte:
- Hyperkalemia
Serious:
- Angioedema
- Acute kidney injury (in bilateral RAS)
Drug Interactions
Increased hyperkalemia risk:
- Potassium supplements
Renal function risk:
- NSAIDs
- Volume depletion
Avoid combination:
- ACE inhibitor + ARB
- ACE inhibitor + Direct Renin Inhibitor
Monitoring
Labs:
- Serum creatinine
- Potassium
Vitals:
- Blood pressure
Clinical:
- Cough
- Angioedema symptoms
Clinical Pearls
- Mortality benefit in HFrEF
- Renoprotective in diabetes
- Cough due to bradykinin accumulation
- First-line in many hypertension guidelines
- Hold during acute kidney injury or dehydration
Comparison Within Class
Compared to other ACE inhibitors:
- Not a prodrug (active form)
- Long duration (once-daily dosing)
- Fully renally cleared
- Similar mortality benefit to enalapril in HFrEF