Ace%252525252525252525252525252525252525252525252525252520inhibitors

### Overview ACE inhibitors (ACEIs) are a class of medications that block the conversion of angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor and also stimulates aldosterone release, which promotes sodium and water retention. By inhibiting this conversion, ACEIs lead to vasodilation, reduced aldosterone secretion, and decreased sodium and water reabsorption, resulting in lower blood pressure. ### Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Diabetic nephropathy * Post-myocardial infarction (for certain agents) * Secondary prevention of cardiovascular events (in select populations) ### Adult Dosing Dosing is highly individualized and depends on the specific ACEI, indication, and patient response. Titration is typically guided by blood pressure and tolerability. * **Hypertension:** Common starting doses for agents like lisinopril are 10 mg once daily. Usual effective range is 10-40 mg daily. Maximum daily dose for lisinopril is 40 mg. Other agents have different dosing ranges. * **Heart Failure:** Common starting doses for agents like enalapril are 2.5-5 mg twice daily. Doses are titrated upwards based on tolerance and efficacy, with typical target doses of 10-20 mg twice daily. Maximum daily dose for enalapril is 40 mg. * **Post-MI:** Often initiated at low doses (e.g., captopril 6.25 mg TID, enalapril 2.5 mg BID) within 24 hours of MI in stable patients, with titration upwards if tolerated. ### Pediatric Dosing Established pediatric dosing varies by agent and indication. Always consult specific pediatric guidelines. * **Hypertension:** * Enalapril: 0.08 mg/kg/day to 0.58 mg/kg/day (max 40 mg/day) divided BID. * Lisinopril: 0.07 mg/kg/day to 0.61 mg/kg/day (max 40 mg/day) once daily. * Ramipril: 0.03 mg/kg/day to 0.06 mg/kg/day (max 10 mg/day) once daily. ### Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, particularly in moderate to severe renal impairment (CrCl < 30 mL/min). Initial doses should be lowered and titration guided by renal function and potassium levels. * **Hepatic Impairment:** Some ACEIs are prodrugs and require hepatic activation (e.g., enalapril, ramipril). Caution and potential dose reduction may be needed in severe hepatic impairment. ### Contraindications * History of angioedema related to prior ACEI therapy. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment. * Pregnancy (especially second and third trimesters) due to risk of fetal injury or death. * Known hypersensitivity to the specific ACEI. ### Adverse Effects * **Common:** Dry cough (most frequent), dizziness, headache, fatigue, hyperkalemia, hypotension. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury (especially in bilateral renal artery stenosis or volume depletion), severe hypotension, rash, hepatotoxicity. ### Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, losartan, ARBs, aliskiren:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, especially in elderly or volume-depleted patients. * **Diuretics (especially thiazides or loop diuretics):** Increased risk of hypotension, particularly with initial doses. * **Lithium:** ACEIs can decrease lithium clearance, leading to increased lithium toxicity. Monitor lithium levels closely. * **mTOR inhibitors (e.g., sirolimus, everolimus, temsirolimus):** Increased risk of angioedema. ### Monitoring * **Blood Pressure:** Regularly monitor BP, especially after initiation or dose changes. * **Renal Function:** Monitor serum creatinine and BUN, particularly in patients with pre-existing renal disease, heart failure, or volume depletion. * **Potassium:** Monitor serum potassium, especially in patients with renal impairment, diabetes, or those taking potassium-sparing agents. * **Angioedema:** Educate patients to report any swelling, especially of the face, lips, tongue, or throat, immediately. ### Clinical Pearls * Dry cough is a common and often dose-limiting side effect, typically reversible upon discontinuation. * ACEIs are generally renoprotective in diabetic patients with proteinuria. * The risk of angioedema is higher in Black patients and those with a history of angioedema. * Initiate at a low dose and titrate slowly, especially in the elderly, volume-depleted, or renally impaired patients, to minimize hypotension. * Discontinue ACEI therapy promptly if angioedema occurs. * Consider switching to an Angiotensin II Receptor Blocker (ARB) for patients who develop a cough or angioedema on an ACEI, although cross-reactivity exists. *** **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 clinical guidelines before making any treatment decisions.