Ace%252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520inhibitors

# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, decreased aldosterone secretion, and reduced sodium and water retention. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (proteinuric) * Chronic kidney disease (proteinuric) ## Adult Dosing Dosing is highly individualized and depends on the specific agent and indication. Titration is typically based on blood pressure response, tolerability, and clinical improvement. * **Hypertension:** * Benazepril: Start 10 mg once daily, usual range 20-40 mg/day. Max 80 mg/day. * Captopril: Start 25 mg BID-TID, usual range 25-150 mg/day divided BID-TID. Max 450 mg/day. * Enalapril: Start 5 mg once daily, usual range 10-40 mg/day. Max 40 mg/day. * Fosinopril: Start 10 mg once daily, usual range 20-40 mg/day. Max 80 mg/day. * Lisinopril: Start 10 mg once daily, usual range 10-40 mg/day. Max 80 mg/day. * Moexipril: Start 7.5 mg once daily, usual range 7.5-30 mg/day. Max 30 mg/day. * Perindopril: Start 2.5-5 mg once daily, usual range 5-10 mg/day. Max 10 mg/day. * Quinapril: Start 10 mg once daily, usual range 20-40 mg/day divided BID. Max 80 mg/day. * Ramipril: Start 2.5 mg once daily, usual range 5-10 mg/day. Max 10 mg/day. * Trandolapril: Start 0.5-1 mg once daily, usual range 2-4 mg/day. Max 8 mg/day. * **Heart Failure:** Dosing typically starts low and is titrated up slowly to target doses based on clinical response and tolerability. For example, enalapril typically starts at 2.5 mg BID and titrated to 10 mg BID. * **Post-MI:** Similar titration as heart failure, starting at low doses and titrating to target doses. ## Pediatric Dosing ACE inhibitors are used in pediatric hypertension. Dosing varies significantly by age, weight, and the specific agent. * **Enalapril:** 0.07-0.1 mg/kg/dose every 12-24 hours. Max 0.5 mg/kg/day. * **Lisinopril:** 0.07-0.2 mg/kg/dose once daily. Max 20 mg/day. * **Ramipril:** 0.03-0.06 mg/kg/dose once daily. Max 5 mg/day. Dosing in pediatric patients with heart failure or renal disease may require further adjustments. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary. Specific recommendations vary by agent and the degree of renal impairment (e.g., creatinine clearance). Generally, start at a lower dose and titrate cautiously. * **Hepatic Impairment:** Caution is advised. Some agents (e.g., enalapril, lisinopril) are renally excreted and may not require significant adjustment. Others (e.g., benazepril, quinapril) undergo hepatic metabolism and may require lower doses. * **Volume Depletion:** Initiate with lower doses due to risk of symptomatic hypotension. Correct volume depletion before initiating therapy. ## Contraindications * History of angioedema related to ACE inhibitor therapy. * Concomitant use of aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (teratogenic risk). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hypotension. * **Serious:** Angioedema (can be life-threatening), hyperkalemia, acute kidney injury (especially in patients with bilateral renal artery stenosis), neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone:** Increased risk of hyperkalemia. * **NSAIDs, aspirin:** May reduce antihypertensive effect and increase risk of kidney damage, especially in elderly or volume-depleted patients. * **Lithium:** Increased lithium levels and toxicity. * **Allopurinol, procainamide:** Increased risk of severe hypersensitivity reactions. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Avoid concomitant use due to increased risk of angioedema. If switching from ACE inhibitor to sacubitril/valsartan, allow at least a 36-hour washout period. ## Monitoring * Blood pressure regularly. * Serum potassium and renal function (BUN, creatinine) at baseline, within 1-2 weeks of initiation or dose increase, and periodically thereafter. * Signs and symptoms of angioedema. ## Clinical Pearls * Cough is a common side effect, often occurring weeks to months after initiation. If bothersome, consider switching to an ARB. * First-dose hypotension can occur, especially in volume-depleted patients or those on diuretics. Monitor closely after the first dose and initial dose titrations. * Avoid in patients with bilateral renal artery stenosis due to risk of severe renal failure. * Angioedema can occur at any time, even after prolonged use. It is a medical emergency. * Discontinue immediately if pregnancy is detected. *** *This information is intended for healthcare professionals. Always consult the most current prescribing information and clinical guidelines for definitive recommendations. Local protocols may dictate specific dosing strategies.*