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# ACE Inhibitors
## Overview
Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used primarily 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 (MI) for individuals with evidence of left ventricular dysfunction or heart failure symptoms
* Diabetic nephropathy (proteinuria reduction)
## Adult Dosing
Dosing is highly individualized and depends on the specific agent, indication, and patient response. Titration is typically required.
* **Hypertension:** Common starting doses vary by agent (e.g., lisinopril 10 mg daily, enalapril 5 mg twice daily, ramipril 2.5 mg daily). Maximum daily doses also vary (e.g., lisinopril 40 mg daily, enalapril 20 mg twice daily, ramipril 10 mg daily).
* **Heart Failure:** Often initiated at lower doses than for hypertension and titrated upwards as tolerated (e.g., lisinopril 2.5-5 mg daily, enalapril 2.5-5 mg twice daily, ramipril 1.25-2.5 mg daily). Doses are then titrated to target doses or maximally tolerated doses (e.g., lisinopril up to 40 mg daily, enalapril up to 20 mg twice daily, ramipril up to 10 mg daily).
* **Post-MI:** Dosing similar to heart failure, initiated within 24 hours of MI in eligible patients and titrated.
* **Diabetic Nephropathy:** Dosing typically targets maximally tolerated doses to achieve blood pressure goals and reduce proteinuria.
## Pediatric Dosing
Dosing in pediatric patients is less established and often based on weight.
* **Hypertension:** Dosing varies by agent and age group. For example, enalapril: 6 months to <16 years, 0.08-0.3 mg/kg/day divided twice daily; maximum 0.6 mg/kg/day or 40 mg/day. Specific recommendations should be consulted for each agent and age group.
## Dose Adjustments
* **Renal Impairment:** Dose reduction is often necessary, especially in severe renal impairment. Specific adjustments depend on the agent and creatinine clearance.
* **Hepatic Impairment:** Caution is advised; dose adjustments may be needed, though data is limited.
## Contraindications
* History of angioedema related to prior ACE inhibitor treatment.
* Hereditary or idiopathic angioedema.
* Concomitant use with aliskiren in patients with diabetes mellitus.
* Second or third trimester of pregnancy.
## Adverse Effects
* **Common:** Dry, persistent cough (non-productive), dizziness, hypotension, hyperkalemia, fatigue, headache, nausea.
* **Serious:** Angioedema (facial, lip, tongue, throat, limbs, intestines), acute kidney injury (especially in patients with bilateral renal artery stenosis or severe heart failure), severe hypotension, hyperkalemia, hepatotoxicity (rare).
## Key Drug Interactions
* **Potassium-Sparing Diuretics & Potassium Supplements:** Increased risk of hyperkalemia.
* **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction, particularly in elderly patients or those with pre-existing renal disease.
* **Diuretics (Thiazide, Loop):** Increased risk of hypotension, especially with initial doses.
* **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment; contraindicated in diabetic patients.
* **ARBs:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid concomitant use.
* **mTOR Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema.
* **Sacubitril/Valsartan:** Avoid initiating ACE inhibitor within 36 hours of the last dose of sacubitril/valsartan due to increased angioedema risk.
## Monitoring
* **Baseline:** Renal function (serum creatinine, BUN), electrolytes (potassium).
* **During Therapy:**
* Renal function and electrolytes (especially within 1-4 weeks of initiation or dose increase, and periodically thereafter).
* Blood pressure.
* Signs and symptoms of angioedema.
## Clinical Pearls
* The characteristic dry cough is thought to be related to bradykinin accumulation and typically resolves after discontinuation.
* First-dose hypotension can occur, especially in volume-depleted patients or those on diuretics. Consider lower starting doses or a test dose with close monitoring.
* Hyperkalemia is a significant risk, especially in patients with renal impairment or those taking potassium supplements or potassium-sparing diuretics.
* ACE inhibitors are generally safe and effective in patients with diabetes, offering renal protective benefits.
* In patients with bilateral renal artery stenosis, ACE inhibitors can precipitate acute renal failure.
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*This information is intended for healthcare professionals and does not substitute for current prescribing information, which should be consulted before making any clinical decisions.*
