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# ACE Inhibitors
## Overview
ACE (angiotensin-converting enzyme) 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
* Congestive Heart Failure (CHF)
* Post-myocardial infarction (MI) to improve survival
* Diabetic nephropathy
## Adult Dosing
Dosing is highly individualized based on the specific ACE inhibitor, indication, and patient response. Titration is common.
* **Hypertension:** Starting doses vary by agent. For example:
* Lisinopril: 10 mg orally once daily. Maximum: 40 mg daily.
* Enalapril: 5 mg orally once or twice daily. Maximum: 40 mg daily.
* Ramipril: 2.5 mg orally once daily. Maximum: 20 mg daily.
* **Heart Failure:**
* Lisinopril: Starting at 2.5-5 mg orally once daily, titrated up to a target of 20 mg daily.
* Enalapril: Starting at 2.5 mg orally twice daily, titrated up to a target of 10 mg twice daily.
* Ramipril: Starting at 1.25-2.5 mg orally twice daily, titrated up to a target of 10 mg daily.
* **Post-MI:**
* Lisinopril: Started within 24 hours of MI, 5 mg orally once daily, followed by 5 mg after 24 hours, then 10 mg daily. Continued for at least 6 weeks.
* Captopril: 6.25 mg orally three times daily, increased to 12.5 mg three times daily, then 25 mg three times daily.
* Ramipril: 2.5 mg orally twice daily, increased to 5 mg twice daily.
## Pediatric Dosing
* **Hypertension:** Dosing varies by agent and age. Generally initiated at lower doses and titrated based on response.
* Enalapril: 0.07 mg/kg/day orally once daily (range 0.07-0.2 mg/kg/day). Maximum: 40 mg/day.
* Lisinopril: 0.07 mg/kg/day orally once daily (range 0.07-0.2 mg/kg/day). Maximum: 40 mg/day.
* Captopril: 0.3 mg/kg/dose orally three times daily. Maximum: 4.5 mg/kg/day or 150 mg/day.
## Dose Adjustments
* **Renal Impairment:** Reduce starting dose and titrate cautiously. Monitor serum creatinine and potassium.
* Lisinopril: If CrCl < 30 mL/min, start at 5 mg daily.
* Enalapril: If CrCl < 30 mL/min, start at 2.5 mg daily.
* **Hepatic Impairment:** Use with caution; no specific dosing guidelines due to variable metabolism.
## Contraindications
* History of angioedema related to previous ACE inhibitor treatment.
* Hereditary or idiopathic angioedema.
* Concomitant use with aliskiren in patients with diabetes.
* Pregnancy (especially second and third trimesters).
## Adverse Effects
* Cough (dry, persistent)
* Hypotension
* Dizziness
* Hyperkalemia
* Angioedema (face, lips, tongue, throat, intestines)
* Renal impairment (especially in those with bilateral renal artery stenosis)
* Fatigue
* Rash
## Key Drug Interactions
* **Potassium-sparing diuretics (e.g., spironolactone), potassium supplements, salt substitutes:** Increased risk of hyperkalemia.
* **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment.
* **Diuretics:** Additive hypotensive effect; increased risk of dehydration and hypotension, especially with the first dose of ACE inhibitor.
* **Lithium:** ACE inhibitors can reduce lithium clearance, leading to lithium toxicity.
* **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., sitagliptin):** Increased risk of angioedema.
* **Sacubitril/Valsartan:** Avoid concurrent use; increased risk of angioedema. Separate administration by at least 36 hours.
## Monitoring
* Blood pressure (before and during treatment)
* Serum creatinine and BUN (baseline and periodically)
* Serum potassium (baseline and periodically)
* Renal function, especially in patients with pre-existing renal disease or at risk.
* Signs and symptoms of angioedema.
* Cough.
## Clinical Pearls
* Cough is a common side effect and may necessitate discontinuation and switching to an angiotensin II receptor blocker (ARB).
* First-dose hypotension can occur, particularly in volume-depleted patients or those on diuretics. Consider withholding diuretics or starting with a lower dose.
* Angioedema is a rare but potentially life-threatening side effect. Discontinue immediately if suspected.
* ACE inhibitors are generally safe and effective in patients with diabetes, as they can provide renal protection.
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This information is intended for clinical use and does not replace the need to consult the most current prescribing information or specific institutional protocols. Always verify current drug information before prescribing.
