Study notes on ACE inhibitors (ACEIs) and Angiotensin II Receptor Blockers (ARBs):

1. Physiology Recap: RAAS

• Trigger: ↓ renal perfusion → JG cells (kidney) release renin.

• Renin: Converts angiotensinogen (liver) → angiotensin I.

• ACE (lungs): Converts angiotensin I → angiotensin II.

• Angiotensin II effects:

  • Vasoconstriction → ↑ TPR → ↑ BP.

  • Posterior pituitary → ↑ ADH → ↑ water reabsorption (collecting duct).

  • Adrenal cortex (zona glomerulosa) → ↑ aldosterone → ↑ Na⁺ & water reabsorption, ↑ K⁺ excretion → ↑ blood volume.

2. Mechanism of Action

• ACE inhibitors ("-pril") → block ACE enzyme → ↓ angiotensin II formation.

• ARBs ("-sartan") → block AT₁ receptors on target tissues → prevent angiotensin II effects.

Both lead to:

• Vasodilation (↓ afterload, ↓ TPR)

• ↓ ADH & aldosterone → ↓ Na⁺/water retention → ↓ preload

• Net effect = ↓ BP + ↓ stress on heart

3. Drug Names

• ACE inhibitors: Captopril, Enalapril, Lisinopril, Benazepril.

• ARBs: Losartan, Valsartan, Candesartan.

4. Indications

• Hypertension (esp. effective except in low-renin hypertension: elderly, African-American).

• Heart failure (systolic) → ↓ preload & afterload → ↓ cardiac remodeling.

• Post-MI / CAD → ↓ cardiac stress, ↓ remodeling.

• Diabetic nephropathy / proteinuric CKD → nephroprotective, ↓ proteinuria.

5. Side Effects

• Both ACEI & ARBs:

  • Hyperkalemia (↓ aldosterone → ↓ K⁺ excretion)

  • Hypotension

  • Acute kidney injury (esp. in renal artery stenosis)

• ACE inhibitors specific:

  • Dry cough (↑ bradykinin)

  • Angioedema (↑ bradykinin, rare but life-threatening)

6. Contraindications

• Pregnancy (teratogenic)

• History of ACEI-induced angioedema (absolute contraindication)

• Bilateral renal artery stenosis

• Severe chronic kidney disease (caution)

• C1 esterase inhibitor deficiency (↑ risk of angioedema)

7. Drug Interactions

• K⁺-sparing diuretics (spironolactone, eplerenone): ↑ risk of severe hyperkalemia

• NSAIDs: reduce effectiveness (Na⁺/water retention, ↓ renal perfusion)

• Lithium: ↓ clearance → lithium toxicity

8. Clinical Pearls

• ACE inhibitors = 1st line, ARBs if ACEI not tolerated (e.g., cough, angioedema).

• ↓ preload + ↓ afterload → ↓ stress on failing heart.

• Improve survival in HF, MI, CKD with proteinuria.

• Monitor K⁺, renal function, BP.

Key memory hooks:

• "PRILs stop the enzyme, SARTANs block the receptor."

• ACE = Angioedema, Cough, ↑ Electrolyte (K⁺).

• ARBs = no cough, no bradykinin buildup.