C-CAI DRUG

Carbonic Anhydrase Inhibitors

  • MOA: Inhibit carbonic anhydrase, the enzyme that catalyzes the reaction of CO2 and H2O, leading to H+ and HCO3- production. This inhibition can result in the spillage of Na+, causing diuresis.

  • Action Site: Primarily acts on the proximal convoluted tubule (PCT).

Types of Carbonic Anhydrase Inhibitors

  • Acetazolamide - Diamox(MOSTLY USED)

  • Brinzolamide

  • Dorzolamide

Carbonic Anhydrase Inhibitors - Side Effects

  • Limited Diuretic Effect: Generally lasts 2 to 3 days.

  • Side Effects:

    • Metabolic acidosis

    • Bone marrow depression (similar to sulfonamide toxicity)

    • Allergic reactions (e.g., Stevens-Johnson syndrome)

Loop Diuretics

  • Also known as High Ceiling Diuretics: Most efficacious compared to other diuretics.

  • Action Site: Acts on the thick ascending Loop of Henle.

Mechanism of Action for Loop Diuretics

  • MOA: Inhibit the Cl-Na-K cotransporter in the thick ascending limb of the loop of Henle.

  • Examples:

    • Furosemide - Lasix(MOSTLY USED)

    • Bumetanide

    • Torsemide

    • Ethacrynic acid

Loop Diuretics - Common Indications

  • Appropriate for patients who cannot tolerate thiazides, have renal impairment, or show inefficacy with thiazides.

  • Side Effects:

    • Hypovolemia

    • Ototoxicity

    • Increase in serum creatinine

  • Drug Interaction (DI): Efficacy may be reduced by NSAIDs (Nonsteroidal anti-inflammatory drugs)

Loop Diuretics - Detailed Side Effects

  • Hypokalemia

  • Loss of bicarbonate in urine

  • Increased calcium excretion leading to hypocalcemia

  • Ototoxicity due to electrolyte imbalances

Thiazide Diuretics

  • MOA: Inhibit Na-Cl cotransporter at the distal convoluted tubule.

  • Examples:

    • Chlorothiazide

    • Hydrochlorothiazide

    • Chlorthalidone

    • Indapamide

Thiazide Diuretics - Uses

  • First-line drug for uncomplicated hypertension as recommended by JNC 7.

  • Effective initial therapy combined with beta-blockers.

  • Usage in Nephrogenic Diabetes Insipidus(NDI)

Thiazide Diuretics - Side Effects

  • Common Side Effects:

    • Hypokalemia

    • Hyponatremia

    • Hyperuricemia

    • Hyperglycemia

    • Hyperlipidemia

  • DI: Efficacy can be decreased by NSAIDs.

Thiazide - Specific Side Effects

  • Hypokalemia

  • Decreased calcium excretion leading to hypercalcemia

  • Decreased uric acid secretion leading to hyperuricemia

  • Hyperglycemia

Potassium-Sparing Diuretics

  • MOA: Act in the collecting tubule by inhibiting Na+ reabsorption and K+ secretion.

  • Examples:

    • Spironolactone

    • Eplerenone

    • Amiloride

    • Triamterene

Potassium-Sparing Diuretics - Indications

  • Used for patients where potassium loss is significant and supplementation isn't feasible.

  • Often combined with thiazides (e.g., Amiloride, Spironolactone, Triamterene).

  • Precautions: Avoid in patients with acute renal failure; use caution in those with impaired renal function.

Potassium-Rich Foods( T,O,P,P N,B,B,S)

  • T: Tomatoes

  • O: Oranges

  • P: Peaches

  • P: Potatoes

  • P: Prunes

  • N: Nuts

  • B: Bananas

  • B: Broccoli

  • S: Spinach

Potassium-Sparing Diuretics - Side Effects

  • Not associated with hypokalemia.

  • Can be combined with other diuretics to minimize hypokalemia risk.

  • Side Effects: Hyperkalemia, gynecomastia, impotence, and potential sterility.

Osmotic Diuretics

  • MOA: Increase osmotic pressure at the proximal convoluted tubule and Loop of Henle, preventing water reabsorption.

  • Examples:

    • Mannitol

    • Sorbitol

    • Urea

Osmotic Diuretics - Uses

  • Typically used to induce forced diuresis, especially to reduce intracranial pressure.

  • Side Effects: Hypernatremia, hypovolemia.

Diuretics Comparison

  • Diuretic Class:

    1. Carbonic Anhydrase Inhibitor

      • Action Site: Proximal Tubule

      • Special Side Effect: Acidosis

    2. Thiazide and Thiazide-like

      • Action Site: Distal Tubule

      • Special Side Effects: Hyperuricemia, Hypokalemia

    3. Loop Diuretics

      • Action Site: Thick Ascending Loop of Henle

      • Special Side Effects: Hypokalemia, Ototoxicity

    4. Potassium-Sparing

      • Action Site: Distal Tubule

      • Special Side Effect: Hyperkalemia

    5. Osmotic Diuretic

      • Action Site: Glomerulus

      • Special Side Effects: Hypovolemia & Hypotension

Diuretics Comparison - Special Uses

  • Diuretic Class:

    1. Carbonic Anhydrase Inhibitor

      • Special Uses: Mountain sickness, Meniere's disease

    2. Thiazide and Thiazide-like

      • Special Uses: Nephrolithiasis due to calcium stones, Hypocalcemia

    3. Loop Diuretics

      • Special Uses: Hypercalcemia

    4. Potassium-Sparing

      • Special Uses: CHF patients on digoxin

    5. Osmotic Diuretics

      • Special Uses: Increased Intracranial Pressure and Lithium toxicity