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# ACE Inhibitors
## Overview
ACE inhibitors (e.g., lisinopril, enalapril, ramipril) 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 aldosterone secretion.
## Primary Indications
* Hypertension
* Heart failure (systolic dysfunction)
* Post-myocardial infarction (left ventricular dysfunction)
* Diabetic nephropathy (in select patients)
## Adult Dosing
Dosing is highly individualized and titrated based on blood pressure response and tolerability. Starting doses are typically low, with gradual increases.
* **Hypertension:** Usual starting doses vary by agent (e.g., lisinopril 5-10 mg once daily, enalapril 5 mg once or twice daily, ramipril 2.5 mg once daily). Maintenance doses commonly range from 10-40 mg daily for lisinopril, 10-40 mg daily for enalapril, and 5-10 mg daily for ramipril. Maximum doses depend on the specific agent and indication.
* **Heart Failure:** Usual starting doses are low (e.g., lisinopril 2.5-5 mg once daily, enalapril 2.5 mg twice daily, ramipril 1.25-2.5 mg twice daily). Doses are titrated upwards as tolerated, often to target doses like lisinopril 10 mg daily, enalapril 20 mg daily, or ramipril 5 mg twice daily, depending on the specific agent and clinical trial data.
## Pediatric Dosing
Established pediatric dosing is available for some ACE inhibitors, often for hypertension. Dosing is based on weight and requires careful titration. Consult specific pediatric guidelines for precise dosing (e.g., enalapril: 0.07-0.1 mg/kg/dose every 8-24 hours).
## Dose Adjustments
* **Renal Impairment:** Dose reduction is necessary, especially in severe renal impairment. Specific recommendations vary by agent and creatinine clearance.
* **Hepatic Impairment:** Caution is advised; dose adjustments may be needed, though less common than with renal impairment.
## Contraindications
* History of angioedema related to previous ACE inhibitor therapy.
* Concomitant use with aliskiren in patients with diabetes.
* Pregnancy (Category D in 2nd and 3rd trimesters, Category X in 1st trimester).
## Adverse Effects
* **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, headache, fatigue.
* **Less Common/Serious:** Angioedema (can be life-threatening), renal dysfunction (especially in those with bilateral renal artery stenosis), rash, elevated liver enzymes.
## Key Drug Interactions
* **Potassium-Sparing Diuretics, Potassium Supplements, Aldosterone Antagonists:** Increased risk of hyperkalemia.
* **NSAIDs, COX-2 Inhibitors:** May blunt antihypertensive effect and increase risk of renal dysfunction.
* **Diuretics (Thiazide/Loop):** Increased risk of hypotension, especially with initiating therapy.
* **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk.
* **mTOR Inhibitors (e.g., everolimus, sirolimus):** Increased risk of angioedema.
* **ARBs and Aliskiren:** Increased risk of hyperkalemia, renal dysfunction, and hypotension. Avoid combination in diabetics.
## Monitoring
* Blood pressure (regularly).
* Serum potassium (especially at initiation, dose increase, or in renal impairment).
* Renal function (BUN, creatinine) at baseline and periodically.
* Signs/symptoms of angioedema or hypersensitivity.
## Clinical Pearls
* The characteristic dry cough is thought to be due to bradykinin accumulation and typically resolves upon discontinuation.
* Angioedema is a rare but serious side effect that can occur at any time during therapy and requires immediate discontinuation and emergency management.
* Initiate at low doses and titrate slowly to minimize hypotension and other adverse effects, particularly in volume-depleted patients or those with heart failure.
* Avoid in pregnancy due to risk of fetal harm.
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**Disclaimer:** This information is intended for clinical use and does not replace comprehensive drug information resources. Always consult the most current prescribing information, institutional protocols, and expert consultation before making clinical decisions.
