Ace%2525252525252525252525252525252525252525252520inhibitors

## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications used primarily for cardiovascular conditions. 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 (reduced ejection fraction) * Myocardial infarction (post-MI management) * Diabetic nephropathy * Chronic kidney disease (proteinuric) ## Adult Dosing Dosing varies significantly by agent and indication. Initiation is typically at a low dose, titrated upwards based on patient response and tolerance. * **Hypertension:** * **Benazepril:** 10-40 mg once daily. Max: 80 mg/day. * **Captopril:** 25 mg BID to TID. Max: 450 mg/day. * **Enalapril:** 5-40 mg once or BID. Max: 40 mg/day. * **Fosinopril:** 10-40 mg once daily. Max: 80 mg/day. * **Lisinopril:** 10-40 mg once daily. Max: 80 mg/day. * **Moexipril:** 7.5-30 mg once daily. Max: 60 mg/day. * **Perindopril:** 2.5-10 mg once daily. Max: 10 mg/day. * **Quinapril:** 10-40 mg BID. Max: 80 mg/day. * **Ramipril:** 2.5-10 mg once daily. Max: 10 mg/day. * **Trandolapril:** 1-4 mg once daily. Max: 4 mg/day. * **Heart Failure:** Dosing often starts lower and is titrated more slowly than for hypertension. Consult specific agent guidelines and local protocols for initiation and titration. * **Enalapril:** Typically 2.5 mg BID, titrating to 10-20 mg BID. Max: 40 mg/day. * **Lisinopril:** Typically 5 mg QD, titrating to 10-40 mg QD. Max: 40 mg/day. * **Ramipril:** Typically 1.25-2.5 mg BID, titrating to 5-10 mg BID. Max: 10 mg/day. * **Post-MI:** Usually initiated within 24 hours in patients with evidence of LV dysfunction or heart failure. * **Captopril:** 6.25 mg TID, titrating to 50 mg TID. * **Enalapril:** 2.5 mg BID, titrating to 5 mg BID. * **Lisinopril:** 5 mg QD, titrating to 10 mg QD. * **Diabetic Nephropathy/CKD:** Doses typically align with hypertension guidelines, aiming for BP control and proteinuria reduction. ## Pediatric Dosing Dosing is weight-based and varies by agent. Refer to specific pediatric formularies and guidelines. * **Hypertension:** * **Enalapril:** 0.07-0.1 mg/kg/dose, usually BID. Max: 0.61 mg/kg/day (or 40 mg/day). * **Lisinopril:** 0.07-0.2 mg/kg/dose, usually QD. Max: 20 mg/day. * **Ramipril:** 0.07-0.14 mg/kg/dose, usually QD. Max: 10 mg/day. ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate cautiously. Captopril and moexipril are renally eliminated. Monitor potassium. * *Example:* For Lisinopril, in CrCl < 30 mL/min, start with 5 mg QD. * **Hepatic Impairment:** Use with caution, especially prodrugs like enalapril, benazepril, fosinopril, moexipril, quinapril, and ramipril, as they are metabolized by the liver. Captopril has less hepatic metabolism. ## Contraindications * History of angioedema related to ACE inhibitor therapy. * Concomitant use with aliskiren in patients with diabetes mellitus. * Pregnancy (risk of fetal injury or death). * Known hypersensitivity to the specific ACE inhibitor. * Conditions where the RAAS system is critically important for maintaining renal perfusion (e.g., bilateral renal artery stenosis, severe heart failure with low ejection fraction and renal dysfunction). ## Adverse Effects * **Angioedema:** Life-threatening swelling of the face, lips, tongue, throat, and intestines. Higher risk in Black patients. * **Cough:** Dry, persistent, non-productive cough (most common). * **Hyperkalemia:** Especially in patients with renal impairment or taking potassium-sparing diuretics/supplements. * **Hypotension/Dizziness:** Particularly with initial doses or in volume-depleted patients. * **Acute Kidney Injury (AKI):** Can occur, especially in patients with bilateral renal artery stenosis. * **Neutropenia/Agranulocytosis:** Rare. * **Rash, dysgeusia (altered taste).** ## Key Drug Interactions * **Potassium-Sparing Diuretics, Potassium Supplements, Salt Substitutes:** Increased risk of hyperkalemia. * **NSAIDs/COX-2 Inhibitors:** May blunt antihypertensive effect and increase risk of renal impairment. * **Diuretics:** Additive hypotensive effect. Hypovolemia from diuretics can increase risk of AKI. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing risk of lithium toxicity. * **mTOR Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs (Angiotensin II Receptor Blockers):** Increased risk of adverse events (hypotension, hyperkalemia, AKI) compared to monotherapy. Avoid concurrent use. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Contraindicated in patients with diabetes. ## Monitoring * **Blood Pressure:** Regularly, especially after initiation or dose changes. * **Serum Creatinine and Potassium:** Baseline and periodically, especially in patients with renal impairment, heart failure, or taking other drugs affecting potassium. * **Renal Function:** Monitor for signs of AKI. * **Angioedema:** Educate patients to report immediately. ## Clinical Pearls * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. * Initiate at low doses and titrate slowly, especially in patients who are elderly, volume-depleted, or have heart failure or renal impairment. * Discontinue immediately if angioedema occurs and do not rechallenge. * If cough is bothersome and persistent, consider switching to an ARB. * ACE inhibitors are contraindicated in pregnancy. *** **Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines for complete details and to ensure patient safety. Local protocols may influence prescribing decisions.