PA1-_Antihypertensive_therapy

Diuretics Overview

  • Definition: Diuretics are medications that increase renal sodium excretion, primarily used to manage hypertension through their natriuretic effect.

  • Key Classes of Diuretics:

    • Thiazides: First choice for hypertension.

    • Loop Diuretics: Less effective for hypertension and may increase the risk of hyponatremia.

    • Potassium-Sparing Diuretics: Used mainly in combination therapy to prevent hypokalemia.

General Advice on Diuretics

  • Use the lowest effective dosage to minimize adverse effects and protect renal function.

  • High salt intake can reduce the efficacy of diuretics.

Thiazide Diuretics

  • Indications:

    • Arterial hypertension (first-line therapy).

    • Sequential nephron blockage (when loop diuretics are ineffective).

    • Edema related to cardiac or renal issues.

    • Urolithiasis due to hypercalcuria.

    • Nephrogenic diabetes insipidus.

  • Examples:

    • Hydrochlorothiazide (thiazide).

    • Indapamide, Metolazone, Chlorthalidone, Xipamid (thiazide-like).

Mechanism of Action

  • Blocks Na+/Cl- symporter in the distal convoluted tubule.

  • Results in increased excretion of water, sodium, chloride, and potassium.

  • The effect stabilizes after about 3 weeks.

Effects of Thiazides

  • Reduces blood volume and lower blood pressure.

  • Long-term effects include reduction of sodium in vascular smooth muscle cells, leading to lower contractility and peripheral vascular resistance.

  • Serum changes: ↓Na, ↓K, ↑Ca. Higher doses beyond therapeutic range yield no additional effects.

Adverse Effects

  • Electrolyte Imbalances:

    • Hypokalemia, hyponatremia, and hypercalcemia.

  • Metabolic Effects:

    • Hyperglycemia (due to reduced insulin sensitivity).

    • Elevated lipid levels and hyperuricemia (risk of gout).

  • Interactions:

    • Can increase the effects of loop diuretics.

    • Efficacy is affected by GFR < 50 ml/min.

Loop Diuretics

  • Examples: Furosemide, Torasemide, Bumetanide, Piretanid.

  • Indications:

    • Requires intensive diuresis (e.g., peripheral and pulmonary edema).

    • Hypertension when thiazides are contraindicated.

    • Renal failure scenarios, volume overload, and forced diuresis for toxins.

Mechanism of Action

  • Inhibits Na+/K+/2Cl- cotransporter in the ascending limb of the loop of Henle.

  • Reduces osmotic pressure in the medulla, achieving diuresis even in poor renal function patients.

Effects of Loop Diuretics

  • Rapid and strong; the most potent diuretics available.

  • Serum changes: ↓Na+, ↓K+, ↓Ca+.

Adverse Effects

  • Electrolyte imbalances: hypokalemia, hyponatremia, hypermagnesemia.

  • Ototoxicity risk at high doses, especially with renal impairment.

  • Contraindications include electrolyte imbalances, hypovolemia, and sulfonamide allergy.

Potassium-Sparing Diuretics

  • Types:

    • Na+ Channel Blockers (e.g., Amiloride, Triamterene).

    • Aldosterone Receptor Antagonists (e.g., Spironolactone, Eplerenone).

  • Indications:

    • Treating hyperaldosteronism or hypokalemia caused by thiazides or loop diuretics.

Mechanism of Action

  • Both types prevent sodium reabsorption and potassium secretion in distal tubules and collecting ducts.

Adverse Effects

  • Hyperkalemia (rare, often with ACE inhibitors or renal dysfunction).

  • Specific side effects of Spironolactone: gynecomastia, impotence, amenorrhea.

Summary of Diuretic Use

  • Thiazides for arterial hypertension; cautious use below GFR <50 ml/min.

  • Loop diuretics for heart failure and situations of poor renal function; avoid evening doses to prevent nocturia.

  • Potassium-sparing diuretics added for patients developing hypokalemia under therapy.

  • Monitor renal function closely as all diuretics can cause electrolyte imbalances and potentially reduce renal function if not managed properly.