====== Lisinopril (Prinivil®, Zestril®) ======

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<WRAP infobox>
| | {{ :cardio:raas:lisinopril_structure.svg |}} |
^ Lisinopril |
| Brand Names | Prinivil®, Zestril® |
| Drug Class | [[cardio:raas:acei|ACE Inhibitor]] |
| Primary Indications | [[cardio:hypertension:start|Hypertension]]; [[cardio:heart_failure:start|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 |
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</WRAP>

===== Overview =====

Lisinopril is a long-acting [[cardio:raas:acei|angiotensin-converting enzyme (ACE) inhibitor]] used in the treatment of [[cardio:hypertension:start|hypertension]], [[cardio:heart_failure:start|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.

<WRAP clear></WRAP>

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===== 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

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===== Indications =====

  * [[cardio:hypertension:start|Hypertension]]
  * [[cardio:heart_failure:start|Heart Failure (HFrEF)]]
  * Post–myocardial infarction with LV dysfunction

Renal protection:
  * Diabetic nephropathy (albuminuria reduction)

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<WRAP blackbox>
===== 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.
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<WRAP contra>
===== Contraindications =====

Absolute:
  * History of ACE inhibitor–induced angioedema
  * Pregnancy
  * Bilateral renal artery stenosis

Relative / Caution:
  * Hyperkalemia
  * Severe renal impairment
  * Volume depletion
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<WRAP details>
===== 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

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<WRAP details>
===== Pharmacokinetics =====

Absorption:
  * Oral

Bioavailability:
  * ~25%

Metabolism:
  * Not metabolized

Half-life:
  * ~12 hours

Elimination:
  * Renal (unchanged)

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<WRAP details>
===== Adverse Effects =====

Common:
  * Dry cough (bradykinin-mediated)
  * Dizziness
  * Hypotension

Electrolyte:
  * Hyperkalemia

Serious:
  * Angioedema
  * Acute kidney injury (in bilateral RAS)

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<WRAP details>
===== Drug Interactions =====

Increased hyperkalemia risk:
  * [[cardio:diuretics:mra|Potassium-Sparing Diuretics]]
  * Potassium supplements

Renal function risk:
  * NSAIDs
  * Volume depletion

Avoid combination:
  * ACE inhibitor + [[cardio:raas:arb|ARB]]
  * ACE inhibitor + [[cardio:raas:direct_renin_inhibitor|Direct Renin Inhibitor]]

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<WRAP monitoring>
===== Monitoring =====

Labs:
  * Serum creatinine
  * Potassium

Vitals:
  * Blood pressure

Clinical:
  * Cough
  * Angioedema symptoms

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<WRAP pearls>
===== 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

</WRAP>

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===== Comparison Within Class =====

Compared to other [[cardio:raas:acei|ACE inhibitors]]:

  * Not a prodrug (active form)
  * Long duration (once-daily dosing)
  * Fully renally cleared
  * Similar mortality benefit to enalapril in HFrEF

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===== Related =====

  * [[cardio:raas:acei|ACE Inhibitors]]
  * [[cardio:hypertension:start|Hypertension Module]]
  * [[cardio:heart_failure:start|Heart Failure Module]]
  * [[cardio:intro:start|Cardiovascular Pharmacology]]