ACE Inhibitors

# ACE INHIBITORS ## Overview - **Classification**: Angiotensin-Converting Enzyme (ACE) Inhibitor, Antihypertensive. - **Mechanism**: Blocks conversion of Angiotensin I to Angiotensin II, reducing vasoconstriction and aldosterone release. Also increases bradykinin, leading to vasodilation. ## Primary Indications 1. **Hypertension**: Management of essential and renovascular hypertension. 2. **Heart Failure**: Reduces morbidity and mortality in symptomatic HF and asymptomatic left ventricular dysfunction. 3. **Post-Myocardial Infarction**: Improves survival and prevents heart failure progression. 4. **Diabetic Nephropathy**: Slows progression of kidney disease in patients with diabetes and microalbuminuria/proteinuria. ## Adult Dosing *(Doses vary by specific ACEI. Examples below use Lisinopril as a common prototype.)* ### Standard Dosing **Hypertension (Lisinopril)** - **Dose**: **10 mg** orally initially. - **Frequency**: Once daily. - **Route**: Oral. - **Maximum Dose**: **40 mg/day**. **Heart Failure (Lisinopril)** - **Dose**: **2.5-5 mg** orally initially. - **Frequency**: Once daily. - **Route**: Oral. - **Maximum Dose**: **20-40 mg/day**. - **Special Considerations**: Start lower in patients on diuretics or with renal impairment. **Post-Myocardial Infarction (Lisinopril)** - **Dose**: **5 mg** orally within 24 hours of MI, then **5 mg** after 24 hours. - **Frequency**: Once daily. - **Route**: Oral. - **Maximum Dose**: **10 mg/day** for maintenance. - **Duration**: Continued for 6 weeks, then reassess. **Diabetic Nephropathy (Lisinopril)** - **Dose**: **10-20 mg** orally. - **Frequency**: Once daily. - **Route**: Oral. ### Dose Adjustments - **Renal Impairment**: - CrCl 30-80 mL/min: Reduce initial dose by 50%. - CrCl <30 mL/min: Reduce initial dose by 75-80% (e.g., Lisinopril **2.5 mg** initially). - Monitor closely for hyperkalemia and acute kidney injury. - **Hepatic Impairment**: Generally no specific dose adjustment; monitor closely as some are prodrugs. - **Elderly Patients**: Start at lower doses (e.g., **2.5-5 mg** daily for Lisinopril) due to potential reduced renal function and increased sensitivity. ## Pediatric Dosing *(Use in pediatric patients should be initiated under specialist supervision. Dosing below uses Enalapril as a common example.)* ### Neonates (0-28 days) - **Special Notes**: **Not generally recommended** unless absolutely necessary for severe hypertension, and only under specialist care. - **Dose**: **0.05-0.1 mg/kg** orally. - **Frequency**: Once daily. - **Maximum**: **0.1 mg/kg/day**. - **Special Notes**: Monitor closely for hypotension, renal failure, and hyperkalemia. ### Infants (1-12 months) - **Dose**: **0.1 mg/kg** orally initially. - **Frequency**: Once daily. - **Maximum**: **0.5 mg/kg/day** (up to **20 mg/day**). - **Special Notes**: Oral solution (1 mg/mL) often preferred for accurate dosing. ### Children (1-12 years) - **Dose**: **0.08 mg/kg** orally once daily initially. - **Frequency**: Once daily. - **Maximum**: **0.5 mg/kg/day** (up to **40 mg/day**). - **Special Notes**: Titrate based on blood pressure response and tolerability. ### Adolescents (13-18 years) - **Dose**: Approach adult dosing, starting with **5 mg** orally once daily (Enalapril) or **2.5-5 mg** (Lisinopril). - **Maximum**: Adult maximum dose for the specific indication. ## Safety Information ### Contraindications - **Absolute**: Pregnancy (second and third trimesters - **fetal toxicity/death**). - **Absolute**: History of angioedema related to previous ACE inhibitor use. - **Absolute**: Hereditary or idiopathic angioedema. - **Absolute**: Concomitant use with aliskiren in patients with diabetes or renal impairment (CrCl < 60 mL/min). - **Absolute**: Concomitant use with sacubitril/valsartan (Entresto) due to angioedema risk (must wait 36 hours after discontinuing ACEI). ### Common Adverse Effects - **Very Common (>10%)**: Dry, persistent cough, Headache. - **Common (1-10%)**: Dizziness, Fatigue, Hypotension (especially first-dose), Hyperkalemia, Renal dysfunction (initial increase in Cr), Nausea, Diarrhea, Rash. - **Serious but Rare**: Angioedema (potentially fatal swelling of face, lips, tongue, larynx), Acute renal failure, Agranulocytosis, Hepatic failure. ### Key Drug Interactions - **Potassium-sparing diuretics/K+ supplements/ARBs/Aliskiren**: Increased risk of **hyperkalemia**. Avoid concurrent use or monitor K+ closely. - **NSAIDs**: May reduce antihypertensive effect; increased risk of **acute kidney injury**, especially in dehydrated or elderly patients. - **Lithium**: Increased lithium levels and toxicity. Monitor lithium levels closely. - **Sacubitril/Valsartan**: **Contraindicated** due to significantly increased angioedema risk. Allow 36 hours washout. - **mTOR inhibitors (e.g., sirolimus, everolimus)**: Increased risk of angioedema. ## Monitoring & Follow-up - **Before Treatment**: - Blood pressure. - Serum electrolytes (K+, Na+). - Renal function (BUN, creatinine, eGFR). - **During Treatment**: - Blood pressure: Regularly, especially after initiation or dose increase. - Serum electrolytes (K+): 1-2 weeks after initiation/dose change, then periodically (e.g., every 3-6 months). - Renal function (BUN, creatinine): 1-2 weeks after initiation/dose change, then periodically. - Monitor for signs of angioedema or persistent cough. - **Clinical Signs**: Watch for dizziness/fainting (hypotension), swelling of face/lips/tongue/throat (angioedema), persistent dry cough, muscle weakness/palpitations (hyperkalemia). ## Clinical Pearls - 💡 **First-dose hypotension**: Start with a low dose, especially in volume-depleted patients or those on diuretics. - 💡 **Persistent dry cough**: A common side effect; often resolves upon discontinuation. Consider an ARB if intolerable. - 💡 **Angioedema is a medical emergency**: Educate patients on symptoms and to seek immediate medical attention. - 💡 **Avoid in pregnancy**: Counsel all women of childbearing potential about severe fetal risk and advise contraception. - 💡 **Hyperkalemia risk**: Caution with potassium-rich foods, supplements, or other medications affecting potassium levels. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.