====== 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 * ↓ VasoconstrictionBradykinin 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 ===== * Hypertension * Heart Failure (HFrEF) * Post–myocardial infarction with LV dysfunctionRenal 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 hypoplasiaDiscontinue immediately if pregnancy is detected.

—-

===== Contraindications =====Absolute: * History of ACE inhibitor–induced angioedema * Pregnancy * Bilateral renal artery stenosisRelative / Caution: * Hyperkalemia * Severe renal impairment * Volume depletion

—-

===== Dosing =====Hypertension: * Initial: 10 mg daily * Typical: 20–40 mg daily * Max: 40 mg dailyHeart Failure: * Initial: 2.5–5 mg daily * Titrate upward as toleratedRenal adjustment: * Required in reduced eGFR

—-

===== Pharmacokinetics =====Absorption: * OralBioavailability: * ~25%Metabolism: * Not metabolizedHalf-life: * ~12 hoursElimination: * Renal (unchanged)

—-

===== Adverse Effects =====Common: * Dry cough (bradykinin-mediated) * Dizziness * HypotensionElectrolyte: * HyperkalemiaSerious: * Angioedema * Acute kidney injury (in bilateral RAS)

—-

===== Drug Interactions =====Increased hyperkalemia risk: * Potassium-Sparing Diuretics * Potassium supplementsRenal function risk: * NSAIDs * Volume depletionAvoid combination: * ACE inhibitor + ARB * ACE inhibitor + Direct Renin Inhibitor

—-

===== Monitoring =====Labs: * Serum creatinine * PotassiumVitals: * Blood pressureClinical: * 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—-===== Related ===== * ACE Inhibitors * Hypertension Module * Heart Failure Module * Cardiovascular Pharmacology