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## Angiotensin-Converting Enzyme (ACE) Inhibitors
### Overview
ACE inhibitors are a class of drugs primarily used to treat cardiovascular conditions. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity, resulting in lower blood pressure.
### Primary Indications
* Hypertension
* Heart failure (systolic dysfunction)
* Post-myocardial infarction (to improve survival)
* Diabetic nephropathy (proteinuric kidney disease)
### Adult Dosing
Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient factors. Titration is typically done to achieve target blood pressure or clinical goals.
* **Hypertension:** Initial doses vary significantly by agent. For example, lisinopril: 10 mg once daily, titrated up to 40 mg once daily. Max doses are agent-specific.
* **Heart Failure:** Initial doses are lower than for hypertension. For example, enalapril: 2.5 mg twice daily, titrated up to 10-20 mg twice daily.
* **Post-MI:** Usually initiated within 24 hours of MI if no contraindications. For example, captopril: 6.25 mg three times daily, titrated up to 50 mg three times daily.
* **Diabetic Nephropathy:** Similar to hypertension dosing, titrated to blood pressure goals and proteinuria reduction.
Specific target doses should be guided by clinical response and local protocols.
### Pediatric Dosing
* **Hypertension:** Dosing is weight-based and varies by agent.
* **Enalapril:** 0.07 to 0.1 mg/kg/dose orally every 12-24 hours. Maximum dose: 0.5 mg/kg/day (or 20 mg/day, whichever is less).
* **Lisinopril:** 0.07 mg/kg/dose orally once daily. Maximum dose: 20 mg/day.
* **Ramipril:** 0.05 mg/kg/day orally once daily. Maximum dose: 10 mg/day.
* Dosing in pediatric heart failure or post-MI is less well-established and generally requires specialist consultation.
### Dose Adjustments
* **Renal Impairment:** Dose reduction is often necessary, particularly in severe renal impairment. Monitor serum creatinine and potassium closely.
* **Hepatic Impairment:** Generally do not require dose adjustments, but caution may be warranted.
### Contraindications
* History of angioedema related to prior ACE inhibitor treatment
* Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment
* Pregnancy (especially second and third trimesters)
* Known hypersensitivity to ACE inhibitors
### Adverse Effects
* **Common:** Dry cough, dizziness, hypotension, hyperkalemia, fatigue.
* **Less Common/Serious:** Angioedema (can be life-threatening, including laryngeal edema), acute kidney injury (especially in susceptible individuals), rash, impaired taste.
### Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia.
* **NSAIDs (including aspirin):** May reduce antihypertensive effect and increase risk of kidney damage, especially in volume-depleted patients.
* **Diuretics:** Increased risk of symptomatic hypotension, especially with loop diuretics.
* **Lithium:** ACE inhibitors can decrease lithium clearance, increasing the risk of lithium toxicity.
* **mTOR inhibitors (e.g., everolimus, sirolimus):** Increased risk of angioedema.
* **ARBs or Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment.
### Monitoring
* **Baseline:** Blood pressure, renal function (serum creatinine, BUN), electrolytes (potassium).
* **During Therapy:** Blood pressure, renal function, electrolytes (especially potassium). Monitor closely after initiation or dose increase.
* **Specific indications:** Echocardiogram for heart failure, urinalysis for proteinuria.
### Clinical Pearls
* The characteristic dry cough is thought to be due to increased bradykinin levels. If cough is bothersome, consider switching to an angiotensin II receptor blocker (ARB).
* Angioedema is a medical emergency. Discontinue the ACE inhibitor immediately and manage airway.
* Initiate at a low dose and titrate slowly, especially in patients with heart failure, volume depletion, or renal impairment.
* Monitor potassium closely, especially in patients with renal insufficiency or those taking potassium-sparing agents.
* ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria.
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*This information is intended for educational purposes and does not substitute for current prescribing information. Always verify the latest drug information with official sources before prescribing or administering.*
