Diuretics Overview

Diuretics

• Carbonic anhydrase inhibitor: Acetazolamide used in proximal convoluted tubule.
• MOA: Inhibits carbonic anhydrase, reducing H+ formation and Na-H exchange, leading to sodium excretion with bicarbonate and water.
• Therapeutic uses: High altitude sickness, glaucoma, urinary alkalinization.
• Osmotic diuretics: Mannitol and glycerol increase plasma osmolarity for fluid shifts.
• Therapeutic uses: Cerebral edema, acute congestive glaucoma, oliguria, hemodialysis.
• Loop diuretics (Furosemide, Bumetanide) act on the thick ascending limb, inhibiting Na/K/2Cl cotransporter.
• Therapeutic uses: CHF, hypertensive emergencies, pulmonary edema.
• Adverse effects: Hyperuricemia, ototoxicity, hypokalemia, metabolic alkalosis.
• Thiazide diuretics (Hydrochlorothiazide, Chlorthalidone, Indapamide) inhibit Na/Cl symport in early distal tubule.
• Therapeutic uses: Mild hypertension, nephrolithiasis.
• Adverse effects: Impaired carbohydrate tolerance, hyperlipidemia.
• Potassium-sparing diuretics include aldosterone antagonists (Spironolactone, Eplerenone) and direct Na-channel inhibitors (Amiloride, Triamterene).
• Promote potassium retention and are often combined with thiazides/loops to prevent potassium loss.
• Adverse effects: Hyperkalemia, hyperchloremic metabolic acidosis.

Antiasthmatics

• Short-acting beta-agonist (SABA): Salbutamol provides quick relief.
• Long-acting beta-agonist (LABA): Salmeterol for prolonged bronchodilation.
• MOA for beta-agonists: Activates B2 receptors increasing cAMP leading to bronchodilation.
• Adverse effects: Tremors, tachycardia, hyperglycemia, hypokalemia.
• Muscarinic antagonist (Ipratropium) is preferred for COPD.
• Phosphodiesterase III inhibitors: Aminophylline, Theophylline have a narrow therapeutic index.
• Inhalational corticosteroids (Budesonide, Fluticasone, Beclomethasone) may cause oropharyngeal candidiasis.

Antitussives and Antihistamines

• Antitussives for non-productive cough include: Codeine, Dextromethorphan, Benzonatate.
• Mucolytics (Bromhexine, Acetylcysteine) thin mucus for easier expulsion.
• H1 antihistamines:
  • 1st generation: Diphenhydramine, Doxylamine, Promethazine (cross BBB, sedating).
  • 2nd generation: Fexofenadine, Loratadine (less sedating, longer duration).

Antitubercular Agents

• First-line drugs:
  • Isoniazid with Pyridoxine to prevent peripheral neuritis.
  • Rifampin causes red-orange urine and flu-like symptoms.
  • Pyrazinamide and Ethambutol may lead to hepatotoxicity and optic neuritis.
• Chemoprophylaxis with Streptomycin.
• Treatment phases: Intensive phase with 4 drugs for 2 months, continuation phase with 2 drugs for 4 months.

Anticoagulants

• Parenteral agents:
  • Heparins (LMWH: Enoxaparin), fondaparinux, thrombin inhibitors (Lepirudin).
• Oral agents:
  • Warfarin, direct oral anticoagulants (Dabigatran, Rivaroxaban).
• Expected adverse effects: Hematuria, heparin-induced thrombocytopenia, osteoporosis.
• Antidotes: Protamine sulfate for heparin, Vitamin K1 for warfarin.

Antiplatelet Drugs

• Inhibit TXA2 synthesis: Aspirin irreversibly inhibits COX1.
• Other agents: Cilostazol and Clopidogrel (ADP receptor antagonist).
• Glycoprotein IIb/IIIa receptor antagonists include Abciximab.

Antianginals

• Acute relief: Sublingual nitroglycerin, isosorbide dinitrate.
• Chronic treatment: Oral isosorbide mononitrate, beta-blockers (Propranolol), calcium channel blockers.
• MOA: Increased cGMP from nitric oxide leads to vasodilation.
• Adverse effects: Tolerance, extensive vasodilation.