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# ACE Inhibitors
## Overview
Angiotensin-Converting Enzyme (ACE) inhibitors are a class of drugs used to treat hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced blood pressure.
## Primary Indications
* Hypertension
* Heart failure (systolic dysfunction)
* Post-myocardial infarction (to improve survival)
* Diabetic nephropathy (proteinuria reduction)
## Adult Dosing
Dosing varies significantly by specific ACE inhibitor. Common starting doses and maximum daily doses (examples):
* **Enalapril:** Start 2.5-5 mg once or twice daily; titrate up to a usual dose of 10-20 mg once or twice daily, max 40 mg/day.
* **Lisinopril:** Start 5-10 mg once daily; titrate up to a usual dose of 20-40 mg once daily, max 80 mg/day.
* **Ramipril:** Start 2.5-5 mg once daily; titrate up to a usual dose of 10 mg once daily, max 20 mg/day.
Titration is typically based on patient response and tolerability.
## Pediatric Dosing
ACE inhibitors are used in pediatrics for hypertension and heart failure. Dosing is weight-based and requires careful titration.
* **Enalapril:** For hypertension, usual dose 0.04-0.2 mg/kg/day divided every 12-24 hours. For heart failure, 0.1 mg/kg/dose every 12-24 hours. Max doses vary by indication and age.
* **Lisinopril:** For hypertension, usual dose 0.07-0.2 mg/kg/day once daily. Max doses vary.
*Specific pediatric dosing requires consultation with specialized resources or local protocols.*
## Dose Adjustments
* **Renal Impairment:** Dose reduction is often necessary in patients with renal insufficiency, especially those with creatinine clearance < 30 mL/min. Consult specific drug monographs for precise adjustments.
* **Hepatic Impairment:** Use with caution. Enalapril is a prodrug requiring hepatic activation; metabolism may be reduced.
## Contraindications
* History of angioedema related to prior ACE inhibitor treatment.
* Hereditary or idiopathic angioedema.
* Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment.
* Pregnancy (especially second and third trimesters).
## Adverse Effects
* **Cough:** Dry, persistent cough is common (up to 10-20%).
* **Hypotension:** Especially after the first dose or in volume-depleted patients.
* **Hyperkalemia:** Risk increased with renal impairment or concomitant potassium-sparing diuretics/supplements.
* **Angioedema:** Rare but life-threatening swelling of the face, lips, tongue, or throat.
* **Renal dysfunction:** Worsening of renal function, particularly in patients with bilateral renal artery stenosis.
* **Dizziness, fatigue, headache.**
## Key Drug Interactions
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride), potassium supplements, heparin:** Increased risk of hyperkalemia.
* **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction.
* **Aliskiren:** Increased risk of hypotension, hyperkalemia, and renal dysfunction. Avoid coadministration in patients with diabetes or renal impairment.
* **Lithium:** ACE inhibitors can decrease lithium clearance, leading to lithium toxicity. Monitor lithium levels closely.
* **Antidiabetic agents:** May enhance the blood-glucose-lowering effect of insulin and oral antidiabetic agents.
## Monitoring
* **Blood Pressure:** Regularly monitor for therapeutic effect and hypotension.
* **Renal Function:** Monitor serum creatinine and BUN, especially at initiation and during dose adjustments or in high-risk patients.
* **Potassium Levels:** Monitor serum potassium, particularly in patients with renal impairment or taking other medications that affect potassium.
* **Angioedema:** Educate patients to report any signs or symptoms immediately.
## Clinical Pearls
* The characteristic dry cough is a class effect and usually resolves upon discontinuation.
* Initiate at low doses and titrate slowly, especially in elderly patients, volume-depleted individuals, or those with renal impairment.
* Consider switching to an Angiotensin II Receptor Blocker (ARB) if cough is intolerable.
* ACE inhibitors are generally considered safe and effective in patients with diabetes, offering renal protection.
* Avoid use in pregnancy due to potential fetal harm.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details before making any treatment decisions.*
