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# ACE Inhibitors
## Overview
Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily 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 decreased blood pressure.
## Primary Indications
* Hypertension
* Congestive heart failure (CHF)
* Post-myocardial infarction (MI)
* Diabetic nephropathy
* Proteinuric chronic kidney disease
## Adult Dosing
Dosing is highly individualized and depends on the specific ACE inhibitor and indication. Common starting doses for **hypertension** are typically low and titrated upwards. For example:
* **Lisinopril:** Start at 5 mg to 10 mg orally once daily. Maximum dose: 40 mg once daily.
* **Enalapril:** Start at 2.5 mg to 5 mg orally once or twice daily. Maximum dose: 20 mg to 40 mg daily (divided).
* **Ramipril:** Start at 2.5 mg orally once daily. Maximum dose: 10 mg once daily.
For **heart failure**, starting doses are usually lower to avoid hypotension and worsening renal function, and doses are titrated more slowly.
## Pediatric Dosing
Dosing in pediatric patients is less established and often based on weight. Specific protocols or specialist guidance is recommended.
* **Captopril:** 0.1 mg/kg to 0.5 mg/kg orally every 8 to 12 hours. Maximum dose: 3 mg/kg/day or 50 mg/day.
* **Enalapril:** 0.08 mg/kg to 0.4 mg/kg orally once daily. Maximum dose: 0.6 mg/kg/day or 40 mg/day.
## Dose Adjustments
* **Renal Impairment:** Dose reduction is generally required for patients with significantly impaired renal function (e.g., creatinine clearance <30 mL/min). Specific recommendations vary by agent and baseline renal function.
* **Hepatic Impairment:** Caution is advised, though dose adjustments are not always necessary.
## Contraindications
* History of angioedema related to prior ACE inhibitor treatment.
* Concomitant use with aliskiren in patients with diabetes.
* Pregnancy (particularly in the second and third trimesters).
* Known hypersensitivity to ACE inhibitors.
## Adverse Effects
* **Dry, persistent cough** (most common)
* Hypotension
* Hyperkalemia
* Angioedema (rare but potentially life-threatening)
* Dizziness
* Renal dysfunction, especially in patients with pre-existing renal artery stenosis
* Fatigue, headache
## Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia.
* **NSAIDs:** May reduce the antihypertensive effect and increase the risk of renal dysfunction.
* **Diuretics:** Increased risk of hypotension, especially with thiazide diuretics.
* **Lithium:** ACE inhibitors can increase serum lithium levels, leading to toxicity.
* **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema.
* **Sacubitril/Valsartan:** Concomitant use is contraindicated due to increased risk of angioedema. A washout period is required when switching between these agents.
## Monitoring
* **Blood pressure:** Regularly, especially after initiation or dose changes.
* **Serum creatinine and potassium:** Within a few weeks of initiation and periodically thereafter, particularly in patients with renal impairment or risk factors for hyperkalemia.
* **Renal function:** Monitor for signs of worsening renal function.
* **Angioedema:** Educate patients to report any swelling, particularly of the face, lips, tongue, or throat.
## Clinical Pearls
* Initiate at a low dose and titrate slowly, especially in the elderly, volume-depleted, or renally impaired patients, to minimize the risk of symptomatic hypotension.
* The characteristic dry cough may develop months after starting therapy and usually resolves upon discontinuation.
* ACE inhibitors are renoprotective in patients with diabetes and proteinuria.
* Patients of African ancestry may have a less pronounced blood pressure response to ACE inhibitors compared to other antihypertensives.
* Monitor closely for signs of angioedema; discontinue ACE inhibitor immediately if suspected.
**Disclaimer:** This information is intended for clinical use and does not substitute for professional medical advice. Always verify the most current prescribing information and local protocols before administering any medication.
