Lecture on Diuretics

Introduction

• Discussion on diuretics and their classification
• Importance of diuretics in eliminating sodium, chloride, water, etc. from the body
• Familiarity with nephron anatomy is essential for understanding diuretics' mechanisms
• Encouragement to use supplementary resources like website notes and illustrations

Nephron Anatomy and Physiology

• Bowman's Capsule: Initial part, no specific diuretics act here
• Proximal Convoluted Tubule (PCT): ~65% sodium reabsorption
  • Diuretic: Carbonic Anhydrase Inhibitors (e.g., acetazolamide)
• Loop of Henle
  • Descending limb: Water reabsorption, Mannitol acts here
  • Ascending limb: ~25% sodium reabsorption, Loop Diuretics act here (e.g., furosemide, bumetanide)
• Distal Convoluted Tubule (DCT): Sodium and water reabsorption
  • Early DCT: Thiazide Diuretics (e.g., hydrochlorothiazide)
  • Late DCT: Potassium Sparing Diuretics
    • Aldosterone Antagonists (e.g., spironolactone)
    • Epithelial Sodium Channel Blockers (e.g., amiloride)
• Collecting Duct: Dependent on ADH and aldosterone

Diuretic Mechanisms

• Carbonic Anhydrase Inhibitors: Inhibit bicarbonate reabsorption, mild sodium/water loss, primarily used for specific conditions like glaucoma, altitude sickness
• Loop Diuretics: Block Na-K-2Cl cotransporter, significant sodium, chloride, and water loss
• Thiazide Diuretics: Block Na-Cl cotransporter, moderate sodium and water loss, also increase calcium reabsorption
• Potassium Sparing Diuretics: Inhibit Na reabsorption and K excretion, reduce potassium loss
  • Aldosterone antagonists: spironolactone, eplerenone
  • Epithelial Sodium Channel blockers: amiloride, triamterene
• Osmotic Diuretics: Increase urine osmolality, pull water into urine, used for specific conditions like increased ICP

Clinical Uses and Complications

• Fluid Diuresis
  • Initial treatment with Loop Diuretics
  • Addition of Thiazide Diuretics for increased diuretic effect or hypernatremia
  • Combating hypokalemia and metabolic alkalosis with Carbonic Anhydrase Inhibitors and Potassium Sparing Diuretics
  • Monitoring and adjustment based on patient's response
• Specific Conditions
  • Acute Pulmonary Edema: Loop Diuretics
  • Hypertension: Thiazide Diuretics
  • Cerebral Edema/Increased ICP: Osmotic Diuretics (e.g., Mannitol)
  • Hepatic Cirrhosis: Aldosterone Antagonists (e.g., spironolactone)
  • Hypercalciuria and Osteoporosis: Thiazide Diuretics
• Adverse Effects
  • Loop Diuretics: Hypernatremia, hypovolemia, hypocalcemia, hypomagnesemia, hypokalemia, metabolic alkalosis, hyperuricemia, hyperglycemia, ototoxicity
  • Thiazide Diuretics: Hyponatremia, hypercalcemia, hypomagnesemia, hypokalemia, metabolic alkalosis, hyperuricemia, hyperglycemia, hyperlipidemia
  • Potassium Sparing Diuretics: Hyperkalemia, metabolic acidosis, gynecomastia (with spironolactone)
  • Carbonic Anhydrase Inhibitors: Metabolic acidosis, increased risk of kidney stones, hyperammonemia
• Special Considerations
  • Patients with renal failure: Careful monitoring with osmotic diuretics to avoid pulmonary edema
  • Combined use of diuretics for synergistic effects in severe cases

Summary: Key Points

• Diuretics play a critical role in managing fluid balance and treating specific medical conditions
• Understanding the nephron physiology is crucial for grasping how different diuretics work
• Choice of diuretic depends on the condition being treated and the patient's response
• Monitoring and managing potential adverse effects is important to ensure safe and effective treatment