Zestril
Zestril
Generic Name
Zestril
Brand Names
for the antihypertensive drug *lisinopril*, a potent, long‑acting ACE inhibitor.
Mechanism
* ACE inhibition – Zestril blocks the conversion of angiotensin I to angiotensin II by inhibiting angiotensin‑converting enzyme (ACE).
* Decreased angiotensin II – leads to vasodilation, lowered aldosterone secretion, and reduced sympathetic tone.
* Increased bradykinin – accumulation of bradykinin contributes to vasodilatory effects and can cause the characteristic ACE‑inhibitor cough.
Pharmacokinetics
| Parameter | Typical Value (Standard Dose) |
| Absorption | Oral, peak plasma ~1‑2 h, ~60‑70 % bioavailability |
| Distribution | Vd ≈ 15 L; limited protein binding (~10 %) |
| Metabolism | Minimal hepatic metabolism; largely unchanged in plasma |
| Excretion | Renal (≈80 %) via glomerular filtration and tubular secretion; half‑life ~12 h (shorter in renal impairment) |
| Special Populations |
• Renal dysfunction → dose adjustment • Pregnancy (category D) → avoid • Elderly → monitor renal function |
Indications
* Hypertension – both monotherapy and in combination regimens.
* Heart Failure – improves survival and reduces hospitalizations.
* Post‑myocardial infarction – attenuation of remodeling, cardiovascular mortality benefit.
* Diabetic nephropathy – slows progression of kidney disease in type 2 diabetes.
Contraindications
* Contraindications
• History of angioedema related to previous ACE‑inhibitor or cystic fibrosis.
• Bilateral renal artery stenosis or unilateral kidney removal.
• Pregnancy (avoid; fetal harm).
* Warnings
• Renal insufficiency – dose reduction; monitor serum creatinine and potassium.
• Hyperkalemia risk – particularly with concomitant potassium‑sparing diuretics, NSAIDs, or potassium supplements.
• Hypotension – especially in volume‑depleted patients or when combined with other antihypertensives.
• Cough – may progress to refractory cough; consider switching to ARB if persistent.
Dosing
| Condition | Starting Dose | Titration | Max Dose (allowable) |
| Hypertension (adult) | 5 mg PO daily | +5 mg every 2‑4 weeks to target BP | 40 mg/day |
| Heart Failure | 5 mg PO daily | +5 mg every 2‑4 weeks, usually reaching 20‑40 mg | 40 mg/day |
| Post‑MI | 5 mg PO daily | ±5 mg every 2‑4 weeks | 40 mg/day |
| Type 2 DM nephropathy | 5 mg PO daily | titrate to 20 mg daily | 40 mg/day |
| Renal impairment (CrCl 30‑59 mL/min) | 2.5 mg daily or 5 mg every 48 h | titrate sparingly | 20 mg/day |
| Pregnancy | None – contraindicated |
*Take orally with or without food. Avoid patient‑specific elimination factors (e.g., high diuretic use).*
Adverse Effects
Common
* Dry cough (≈10 %)
* Dizziness/hypotension (5–10 %)
* Headache (5–10 %)
* Ankle edema (≤3 %)
Serious
* Angioedema (rare but life‑threatening)
* Hyperkalemia (esp. with renal impairment or potassium‑sparing agents)
* Acute kidney injury (marked rise in creatinine ≥50 % or oliguria)
* Severe hypotension (especially in volume‑depleted states)
Monitoring
* Baseline and every 4–8 weeks: serum creatinine, BUN, eGFR, serum potassium.
* Blood pressure at each visit.
* After initiation or dose change: monitor for cough, angioedema signs.
* In patients with diabetes: hemoglobin A1c, urinary albumin‑creatinine ratio.
Clinical Pearls
- ACE‑inhibitor cough – check for hyperkalemia or drug interactions before labeling as “cough”; consider ARB switch (Benazepril or losartan).
- Renal adjustment – stagger dosing (e.g., 5 mg every other day) in CrCl 30‑50 mL/min rather than immediately lowering dose.
- Combination with beta‑blockers – can blunt the rise in intrarenal renin, reducing the risk of acute kidney injury.
- Office vs. home BP – Zestril’s onset is ~4–8 h; advise patients to take the dose at bedtime to match the rhythm of nocturnal BP dips.
- Pregnancy avoidance – even a single dose in the first trimester can cause fetal renal dysgenesis; patients should be advised to use reliable contraception.
- Potassium‑sparing diuretics – avoid concurrent use unless absolutely necessary; if unavoidable, close serum potassium checks.
- Angioedema – if swelling occurs, immediate discontinuation and ENT evaluation; epinephrine & steroids are standard treatment.
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