Vasotec
Vasotec
Generic Name
Vasotec
Brand Names
for lisinopril, a potent angiotensin‑converting enzyme (ACE) inhibitor used widely in cardiovascular therapy.
Mechanism
- Inhibits ACE: Blocks the conversion of angiotensin I → angiotensin II, reducing a key vasoconstrictor.
- Decreases Aldosterone: Lower angiotensin II levels blunt mineralocorticoid-mediated sodium/water retention.
- Raises Bradykinin: Inhibition of ACE elevates bradykinin, leading to vasodilation and potential cough.
- Low Lipophilicity: Predominantly exerts systemic effects rather than central nervous system actions.
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Pharmacokinetics
- Absorption: Rapid oral absorption; peak plasma at 1–4 h. Bioavailability: ~60–70 %.
- Distribution: ↓ Protein binding; volumes of distribution ∼5 L.
- Metabolism: Non‑enzymatic amino‑acid hydrolysis (no major CYP involvement).
- Elimination: Renally excreted as unchanged drug; mean half‑life 13 h (healthy adults).
- Special Populations:
- *Renal impairment*: Dose reduction or interval extension.
- *Hepatic impairment*: Generally tolerated; no dose adjustment needed.
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Indications
- Essential hypertension (monotherapy or combination).
- New‑onset or established heart failure (HF) with reduced ejection fraction (EF < 40 %).
- Post‑myocardial infarction secondary prevention of ventricular remodeling.
- Diabetic nephropathy: Slows progression, often combined with ACE‑feedback.
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Contraindications
| Category | Key Points |
| Contraindications |
• History of angioedema related to any ACE inhibitor or ARB. • Severe renal artery stenosis. • Pregnant women (category X). |
| Cautions |
• Hyperkalemia risk—monitor potassium. • Elderly or patients on potassium‑sparing diuretics: increased serum K⁺. • Recent ACE inhibitor withdrawal can cause angioedema. |
| Drug Interactions |
• NSAIDs → ↓ ACE inhibition, ↑ serum K⁺. • Diuretics (e.g., spironolactone) → additive hyperkalemia. • Potassium supplements or salt substitutes → ↑ K⁺. |
| Monitoring | See section “Monitoring Parameters.” |
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Dosing
| Condition | Starting Dose | Titration | Maintenance Dose |
| Hypertension (adult) | 10 mg PO once daily | Increase by 10 mg every 2–4 weeks up to 40 mg | 20–40 mg daily (dose individualized) |
| Heart Failure (adult) | 5 mg PO once daily | Increase by 5 mg every 2–4 weeks up to 40 mg | 20–40 mg daily (titrate to tolerable maximum) |
| Post‑MI | 5 mg PO once daily | Increase by 5 mg every 2 weeks up to 40 mg | 10–20 mg daily (balance β blocker/ACE) |
| CKD | Start at 5 mg, monitor eGFR | Titrate same as above | 5–20 mg (often lower) |
• Take with food or a meal to reduce gastrointestinal upset.
• Do not abruptly discontinue; taper to avoid rebound hypertension or angioedema.
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Adverse Effects
| Category | Examples |
| Common |
• Dry cough (35–50 % incidence). • Dizziness/orthostatic hypotension (~15 %). • Headache, fatigue. |
| Serious |
• Angioedema (rare, <1 %)—swelling of lips, tongue, airway. • Hypersensitivity rash, anaphylaxis. • Hyperkalemia (K⁺ > 5.5 mmol/L). • Acute renal failure (esp. with volume depletion). |
| Monitoring Mechanisms | Discuss in next section. |
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Monitoring
| Parameter | Frequency | Target/Reference |
| Blood pressure | Before first dose and at each follow‑up visit | Goal: <140/90 mm Hg (or <130/80 mm Hg in diabetics) |
| Serum electrolytes (K⁺, Na⁺) | Baseline, then 2–4 weeks after dosage change, then every 3 months | K⁺ 3.5–5.0 mmol/L |
| Serum creatinine & eGFR | Baseline, 2–4 weeks post‑dose increase, then every 3 months | Increase ≤30 % from baseline |
| Urinalysis (proteinuria) | Baseline, then every 6–12 months | Reduce albuminuria |
| Pregnancy test | Female of childbearing potential | Avoid therapy in pregnancy |
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Clinical Pearls
- Cough Dilemma: Persistent cough >2 weeks → consider switch to *ARB* (e.g., losartan) because ARBs do not raise bradykinin.
- Dose Titration Timing: Use a conservative 2–6 week window between increases; this pacing reduces cough and hyperkalemia risk.
- Renal Protection: In early diabetic nephropathy, lisinopril slows progression even when urine albumin <300 mg/day—start early if creatinine <2.0 mg/dL.
- ACE Withdrawal Syndrome: Abrupt cessation can precipitate angioedema; if forced discontinuation, include a 48‑hour waiting period before alternative ACE inhibitor initiation.
- Drug‑Drug Bleeding: When combined with warfarin, monitor INR; ACE inhibitors can modestly elevate INR through increased plasma volume reduction.
- Food & Timing: For patients on high‑potassium diets, schedule lisinopril dose after meals to mitigate peak serum K⁺ spikes.
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