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# ACE Inhibitors
## Overview
ACE inhibitors (Angiotensin-Converting Enzyme 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 reduced blood pressure.
## Primary Indications
* Hypertension
* Heart failure (systolic dysfunction)
* Post-myocardial infarction (to improve survival and reduce reinfarction)
* Diabetic nephropathy (in patients with type 1 diabetes and proteinuria)
* Chronic kidney disease (in certain patients with proteinuria)
## Adult Dosing
Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response.
* **Benazepril:** Hypertension: Start at 5-10 mg once daily. Max: 40 mg daily. Heart Failure: Start at 2.5-5 mg twice daily. Max: 40 mg daily.
* **Captopril:** Hypertension: Start at 25 mg twice daily. Max: 450 mg daily. Heart Failure: Start at 6.25 mg three times daily. Max: 450 mg daily. (Note: Requires more frequent dosing).
* **Enalapril:** Hypertension: Start at 5 mg once or twice daily. Max: 40 mg daily. Heart Failure: Start at 2.5 mg twice daily. Max: 40 mg daily.
* **Fosinopril:** Hypertension: Start at 10 mg once daily. Max: 80 mg daily. Heart Failure: Start at 5 mg once daily. Max: 40 mg daily.
* **Lisinopril:** Hypertension: Start at 10 mg once daily. Max: 40 mg daily. Heart Failure: Start at 5 mg once daily. Max: 40 mg daily. Post-MI: 5 mg once daily, then 10 mg once daily.
* **Moexipril:** Hypertension: Start at 7.5 mg once daily. Max: 30 mg daily.
* **Perindopril:** Hypertension: Start at 2.5-5 mg once daily. Max: 10 mg daily. Heart Failure: Start at 2.5 mg once daily. Max: 10 mg daily.
* **Quinapril:** Hypertension: Start at 5-10 mg twice daily. Max: 80 mg daily. Heart Failure: Start at 5 mg twice daily. Max: 80 mg daily.
* **Ramipril:** Hypertension: Start at 2.5-5 mg once daily. Max: 20 mg daily. Heart Failure: Start at 1.25-2.5 mg once daily. Max: 10 mg daily. Post-MI: 1.25-2.5 mg once daily.
* **Trandolapril:** Hypertension: Start at 1 mg once daily. Max: 4 mg daily. Heart Failure: Start at 1 mg once daily. Max: 4 mg daily.
Titration is typically done every 2-4 weeks based on blood pressure response and tolerability.
## Pediatric Dosing
Dosing in children is often based on weight and can vary significantly. Consult specific pediatric guidelines or drug monographs.
* **Enalapril:** Hypertension: 0.07-0.1 mg/kg/dose once daily (max 5 mg/day initially, then titrate up to 0.21 mg/kg/day or 20 mg/day).
* **Lisinopril:** Hypertension: 0.07-0.2 mg/kg/day once daily (max 10 mg/day initially, then titrate up to 0.61 mg/kg/day or 40 mg/day).
## Dose Adjustments
* **Renal Impairment:** Dose reductions are often necessary, especially with moderate to severe renal impairment. Captopril and enalapril are often preferred in renal impairment due to lower accumulation. Specific recommendations vary by agent and creatinine clearance.
* **Hepatic Impairment:** Generally do not require significant dose adjustments, but caution is advised.
## Contraindications
* History of angioedema related to previous ACE inhibitor treatment.
* Hereditary or idiopathic angioedema.
* Concomitant use with aliskiren in patients with diabetes or renal impairment.
* Pregnancy (especially second and third trimesters).
* Known hypersensitivity to the drug.
## Adverse Effects
* **Common:** Dry cough (most frequent), dizziness, headache, fatigue, hyperkalemia.
* **Serious:** Angioedema (can be life-threatening), hypotension, acute kidney injury, elevated liver enzymes, neutropenia/agranulocytosis (rare).
## Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, aliskiren, ARBs:** Increased risk of hyperkalemia.
* **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction.
* **Lithium:** Increased lithium levels and toxicity.
* **Diuretics (especially potassium-wasting):** Additive hypotensive effect; increased risk of severe hypotension and hyperkalemia with potassium-sparing agents.
* **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema.
* **ARBs:** Increased risk of hyperkalemia, hypotension, and renal dysfunction.
## Monitoring
* **Blood Pressure:** Regularly monitor BP response to guide titration.
* **Renal Function:** Monitor serum creatinine and BUN, especially at initiation and with dose changes or in patients with risk factors for renal impairment.
* **Electrolytes:** Monitor serum potassium, particularly in patients with renal impairment, diabetes, or those taking potassium supplements/sparing diuretics.
* **Angioedema:** Educate patients on signs and symptoms and to seek immediate medical attention if they occur.
* **Cough:** Assess for persistent cough.
## Clinical Pearls
* The dry cough associated with ACE inhibitors is thought to be due to bradykinin accumulation. It is generally reversible upon discontinuation.
* Angioedema is a rare but serious side effect that can occur at any time, even after long-term use. Symptoms include swelling of the face, lips, tongue, and throat. It is a medical emergency.
* ACE inhibitors should be initiated at low doses and titrated slowly, especially in patients who are volume-depleted, on diuretics, or have heart failure or renal impairment.
* First-dose hypotension can occur, particularly in patients taking diuretics. It is recommended to discontinue diuretics 2-3 days prior to starting an ACE inhibitor if possible, or initiate ACE inhibitor at a lower dose.
* ACE inhibitors should be discontinued if angioedema develops.
* Consider switching to an Angiotensin II Receptor Blocker (ARB) if cough is bothersome, though cross-reactivity for angioedema exists.
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*Disclaimer: This information is intended for healthcare professionals and should not be a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines for complete and up-to-date details before making any treatment decisions.*
