ACE inhibitors

Mechanism of Action - RAAS Wrecking Crew

• Primary Target: Competitively inhibits Angiotensin-Converting Enzyme (ACE / Kininase II).
• RAAS Inhibition:
  • Blocks conversion of Angiotensin I → Angiotensin II.
  • Leads to ↓ vasoconstriction (↓ afterload) and ↓ aldosterone secretion.
  • Result: ↓ sodium/water retention & ↑ potassium.
• Bradykinin Potentiation:
  • ACE is also responsible for breaking down bradykinin.
  • Inhibition ↑ bradykinin levels, causing vasodilation.
  • This is also linked to the side effects of dry cough and angioedema.

⭐ By reducing angiotensin II-mediated efferent arteriole vasoconstriction, ACE inhibitors decrease intraglomerular pressure. This is renoprotective in diabetic nephropathy but can cause acute kidney injury in bilateral renal artery stenosis.

Indications & Drug Types - The Pressure Police

• Primary Indications

  • Hypertension: First-line, especially in compelling co-morbidities.
  • Heart Failure (systolic): ↓ mortality & morbidity by reducing preload/afterload.
  • Post-Myocardial Infarction: Limits adverse ventricular remodeling.
  • Diabetic Nephropathy & Proteinuria: Slows progression of kidney disease.

• Drug Classification (The "-prils")

  • Most are prodrugs (e.g., enalapril, ramipril) requiring hepatic activation.
  • Active Drugs: Captopril & Lisinopril.
    • 📌 Mnemonic: Capable Lads (Captopril, Lisinopril) are ready for action; preferred in severe liver disease.

⭐ ACE inhibitors are uniquely protective in diabetes, offering both blood pressure control and direct renal-protective effects by decreasing efferent arteriole pressure, thus reducing intraglomerular filtration pressure.

Adverse Effects - The 'PRIL' Perils

📌 Mnemonic: C A P T O P R I L

• Cough: Persistent, dry, non-productive cough from ↑ bradykinin and substance P. The most common reason for discontinuation.
• Angioedema: Swelling of tongue, lips, face. Life-threatening airway obstruction. Linked to ↑ bradykinin. Higher risk in Black patients.
• Potassium ↑ (Hyperkalemia): Inhibits aldosterone, reducing K⁺ excretion. Risk ↑ with renal failure, K⁺-sparing diuretics, NSAIDs.
• Taste changes (dysgeusia) or rash.
• Orthostatic hypotension: Significant first-dose hypotension, especially in salt- or volume-depleted patients.
• Pregnancy: ⚠️ BLACK BOX WARNING. Contraindicated in 2nd/3rd trimesters. Causes fetal hypotension, anuria, renal failure.
• Renal artery stenosis: Contraindicated in bilateral stenosis; can precipitate acute renal failure.
• Leukopenia/neutropenia: Rare; monitor WBC in high-risk patients.

⭐ ACE inhibitors block bradykinin breakdown. This accumulation mediates the classic dry cough and the rare but life-threatening angioedema.

Clinical Monitoring & Interactions - DDI Danger Zone

• Routine Monitoring:

  • BP, serum creatinine (SCr), and potassium.
  • ⚠️ Watch for ↑ SCr >30% from baseline post-initiation.
  • Monitor for hyperkalemia (K+ > 5.5 mEq/L).

• Key Drug Interactions:

  • K+ supplements/K+-sparing diuretics: Additive hyperkalemia risk.
  • NSAIDs: Impair antihypertensive effect; ↑ risk of nephrotoxicity.
  • Lithium: ACEIs reduce lithium clearance, ↑ toxicity risk.
  • ARBs/Aliskiren: Contraindicated due to severe hypotension & renal risk.

⭐ Triple Whammy Effect: The combination of an ACE inhibitor, a diuretic, and an NSAID carries a high risk of inducing acute kidney injury (AKI).

High‑Yield Points - ⚡ Biggest Takeaways

• ACE inhibitors (-prils) block the conversion of angiotensin I to II, leading to vasodilation and decreased aldosterone.
• They are first-line for hypertension, especially in heart failure and diabetic nephropathy.
• The most common side effect is a dry, hacking cough, due to increased bradykinin.
• Angioedema is a rare but life-threatening side effect.
• Monitor for hyperkalemia, especially with potassium-sparing diuretics or renal insufficiency.
• Absolutely contraindicated in pregnancy (teratogenic) and bilateral renal artery stenosis.