Antihypertensive Agents

Overview & Diuretics - Water Pills Power

• Hypertension (HTN): BP > 140/90 mmHg. Goal: ↓ target organ damage.
• Lifestyle: DASH diet, exercise, ↓Na+, ↓alcohol, smoking cessation.
• Diuretics: ↑Na+ & H2O excretion → ↓ blood volume → ↓ cardiac output → ↓ BP.
  • Thiazides (e.g., Hydrochlorothiazide/HCTZ, Chlorthalidone):
    • Site: Distal Convoluted Tubule (DCT).
    • Uses: Mild-moderate HTN, edema, nephrogenic DI.
    • SE: ↓K+, ↓Na+, ↑uric acid, ↑glucose, ↑lipids, ↑Ca2+ (hypercalcemia).

    ⭐ Thiazide diuretics can cause hypercalcemia (beneficial in osteoporosis) and are associated with hyperglycemia and hyperlipidemia.

  • Loop Diuretics (e.g., Furosemide, Torsemide):
    • Site: Thick Ascending Limb (TAL), Loop of Henle.
    • Uses: Severe HTN, CHF, pulmonary edema. Most potent.
    • SE: ↓K+, ↓Ca2+, ototoxicity, hyperuricemia. 📌 OH DANG (Ototoxicity, Hypokalemia, Dehydration, Allergy, Nephritis, Gout).
  • K+-sparing Diuretics:
    • Site: Collecting Duct (CD).
    • Types: Aldosterone antagonists (Spironolactone, Eplerenone); ENaC blockers (Amiloride, Triamterene).
    • Uses: HTN (with other diuretics), hyperaldosteronism.
    • SE: ↑K+. Spironolactone: gynecomastia.

RAAS Inhibitors - Ace the Pressure

• Classes: ACE Inhibitors (ACEIs), Angiotensin II Receptor Blockers (ARBs), Direct Renin Inhibitors (DRIs).
• ACEIs ("-pril" e.g., Ramipril, Lisinopril):
  • MoA: Inhibit ACE → ↓ Angiotensin II, ↑ Bradykinin.
  • Side Effects: Dry cough, angioedema (bradykinin-mediated), hyperkalemia, teratogenic, first-dose hypotension. 📌 PRIL: Potassium ↑, Rash, Increased cough, Low BP.
• ARBs ("-sartan" e.g., Losartan, Telmisartan):
  • MoA: Block AT1 receptors for Angiotensin II.
  • Side Effects: Hyperkalemia, teratogenic; less cough & angioedema vs ACEIs.
• DRIs (Aliskiren):
  • MoA: Directly inhibits renin activity.
  • Side Effects: Diarrhea, hyperkalemia, teratogenic.
• Key Uses: Hypertension, Heart Failure, Diabetic Nephropathy, Post-MI.

⭐ ACE inhibitors are contraindicated in patients with bilateral renal artery stenosis due to the risk of acute renal failure.

Calcium Channel Blockers - Smooth Muscle Relaxers

• Mechanism: Block L-type Ca²⁺ channels → ↓ intracellular Ca²⁺ → vascular smooth muscle relaxation (vasodilation) & ↓ myocardial contractility/conduction.
• Types:
  • Dihydropyridines (DHPs): e.g., Amlodipine, Nifedipine. Primarily potent vasodilators.
    • Uses: Hypertension, angina.
    • SE: Peripheral edema, flushing, headache, reflex tachycardia.
  • Non-Dihydropyridines (Non-DHPs):
    • Verapamil (cardioselective), Diltiazem (intermediate).
    • Uses: Hypertension, angina, supraventricular tachyarrhythmias (SVTs).
    • SE: Bradycardia, AV block, constipation (esp. Verapamil), gingival hyperplasia.

⭐ Verapamil and Diltiazem (non-DHP CCBs) can cause constipation and gingival hyperplasia, and should be used cautiously with beta-blockers due to risk of heart block.

• Other Uses: Prinzmetal's angina, Raynaud's phenomenon.

Sympatholytics & Vasodilators - Nerve & Vessel Agents

• Centrally Acting ($α_2$ Agonists)
  • Clonidine: ↓ Sympathetic outflow. AE: Rebound HTN, sedation.
  • Methyldopa: Prodrug. AE: Coombs +ve hemolytic anemia.
• $α_1$ Blockers (Selective)
  • Prazosin, Doxazosin: Vasodilation. AE: First-dose hypotension.
• $α$ & $β$ Blockers
  • Labetalol, Carvedilol: Vasodilation + ↓ HR.
• Direct Arterial Vasodilators
  • Hydralazine: ↑ cGMP. AE: Drug-induced lupus, reflex tachycardia.
  • Minoxidil: K+ channel opener. AE: Hypertrichosis (📌 Minoxidil for MAX hair), reflex tachycardia.
• Arterial & Venous Vasodilator
  • Sodium Nitroprusside: Releases NO. AE: ⚠️ Cyanide toxicity.

⭐ Labetalol and Methyldopa are preferred antihypertensives during pregnancy; Sodium Nitroprusside is used in hypertensive emergencies but carries a risk of cyanide toxicity with prolonged use.

High‑Yield Points - ⚡ Biggest Takeaways

• Thiazides: First-line; cause hypokalemia, hyperuricemia, hyperglycemia.
• ACEIs/ARBs: Preferred in DM, CKD; cause cough (ACEI), hyperkalemia; contraindicated in pregnancy.
• CCBs (Dihydropyridines) like Amlodipine: Cause pedal edema, gingival hyperplasia, reflex tachycardia.
• Beta-blockers: Post-MI, HF; avoid in asthma, heart block; mask hypoglycemia symptoms.
• Hydralazine can cause drug-induced lupus; Minoxidil can cause hirsutism.
• Sodium Nitroprusside: For hypertensive emergencies; risk of cyanide toxicity with prolonged use.