Renal Diuretics Overview

Renal Diuretics

• Diuretics accelerate urine formation, resulting in sodium and water removal.
• Sodium loss leads to water loss.
• 20-25% of sodium is reabsorbed in the loop of Henle, 5-10% in distal tubules, and 3% in collecting ducts.
• Classes of diuretics include osmotic, loop, thiazide, carbonic anhydrase inhibitors, aldosterone antagonists, and sodium channel blockers.

Diuretic Agents

• Drugs that accelerate urine formation, leading to sodium and water removal.

Classes of Diuretics, Their Mechanisms of Action, and Tubular Sites of Action

• Osmotic diuretics (mannitol): Inhibit water and solute reabsorption by increasing tubular fluid osmolarity. Act primarily in proximal tubules.
• Loop diuretics (furosemide, bumetanide): Inhibit sodium-potassium-chloride co-transport in the ascending loop of Henle. Also increase renal prostaglandins, causing vasodilation.
• Thiazide diuretics (hydrochlorothiazide, chlorthalidone): Inhibit sodium-chloride co-transport in the early distal tubules. Also excrete potassium, but to a lesser extent.
• Carbonic anhydrase inhibitors (acetazolamide): Inhibit hydrogen secretion and bicarbonate reabsorption, reducing sodium reabsorption. Act primarily in proximal tubules.
• Aldosterone antagonists (spironolactone, eplerenone): Inhibit aldosterone's action on receptors in collecting tubules, and thus decrease sodium reabsorption and potassium secretion.
• Sodium channel blockers (triamterene, amiloride): Block sodium entry into channels in the luminal membrane of collecting tubules, decrease sodium reabsorption and potassium secretion.

Carbonic Anhydrase Inhibitors (CAIs)

• Specific examples: acetazolamide (Diamox), methazolamide, dichlorphenamide.
• Mechanism of Action: Carbonic anhydrase helps create hydrogen ions, which are exchanged for sodium and water in proximal tubules. CAIs block this process, reducing sodium and water reabsorption.
• Therapeutic Uses: Glaucoma, edema, epilepsy, high-altitude sickness.
• Uses specifically related to CHF: Acetazolamide can be used to address edema associated with congestive heart failure (CHF) when other diuretics are ineffective.
• Less potent diuretics compared to loop diuretics or thiazides: Metabolic acidosis induced by CAIs reduces their diuretic effectiveness within 2-4 days of use.
• Side Effects: Metabolic acidosis, drowsiness, anorexia, paresthesias, hematuria, urticaria, photosensitivity, melena.

Loop Diuretics

• Specific examples: bumetanide (Bumex), ethacrynic acid (Edecrin), furosemide (Lasix).
• Mechanism of Action: Act directly on the ascending limb of the loop of Henle to inhibit sodium and chloride resorption; increase renal prostaglandins, leading to vasodilation.
• Drug Effects: potent diuresis and subsequent fluid loss, decreased blood pressure, reduced pulmonary and systemic vascular resistance, decreased central venous pressure and left ventricular end-diastolic pressure, potassium depletion.
• Therapeutic Uses: edema associated with heart failure or liver or kidney disease, hypertension.
• Side Effects: dizziness, headache, tinnitus, blurred vision, nausea, vomiting, diarrhea; agranulocytosis, neutropenia, thrombocytopenia, hypokalemia, hyperglycemia, hyperuricemia.

Osmotic Diuretics

• Specific example: mannitol (Resectisol, Osmitrol).
• Mechanism of Action: Work in the proximal tubule; non-absorbable, creating an osmotic effect; pulling water into blood vessels and nephrons from surrounding tissues.
• Drug Effects: reduced cellular edema, rapid excretion of water, sodium, electrolytes, and toxic substances from the kidney; reduced intraocular pressure.
• Therapeutic Uses: treatment of patients in the early, oliguric phase of acute kidney injury (ARF), to promote excretion of toxic substances, reduction of intracranial pressure, and treatment of cerebral edema.
• Side Effects: convulsions, thrombophlebitis, pulmonary congestion, headaches, chest pains, tachycardia, blurred vision, chills, fever.

Potassium-Sparing Diuretics

• Specific examples: amiloride (Midamor), spironolactone (Aldactone), triamterene (Dyrenium).
• Mechanism of Action: Work in collecting ducts and distal convoluted tubules; interfere with sodium-potassium exchange; competitively bind to aldosterone receptors; block sodium and water reabsorption usually induced by aldosterone.
• Drug Effects: prevent potassium from being pumped into the tubule, thus preventing secretion; competitively block aldosterone receptors and inhibit its action; promote sodium and water excretion.
• Therapeutic Uses: hyperaldosteronism, hypertension, reversing potassium loss from potassium-losing drugs, treatment of congestive heart failure (CHF).
• Side Effects: dizziness, headache, cramps, nausea, vomiting, diarrhea, urinary frequency, weakness, hyperkalemia; gynecomastia, amenorrhea, irregular menses (spironolactone).

Thiazide and Thiazide-Like Diuretics

• Specific examples: hydrochlorothiazide (Esidrix, HydroDIURIL), chlorothiazide (Diuril), trichlormethiazide (Metahydrin), chlorthalidone (Hygroton), metolazone (Mykrox, Zaroxolyn).
• Mechanism of Action: Inhibit tubular resorption of sodium and chloride ions, primarily in the ascending loop of Henle. Dilate arterioles by direct relaxation.
• Drug Effects: lowered peripheral vascular resistance, sodium and water depletion.
• Therapeutic Uses: hypertension, edematous states, idiopathic hypercalciuria, diabetes insipidus, CHF, hepatic cirrhosis (as an adjunct).
• Side effects: dizziness, headache, blurred vision, paresthesias, decreased libido, anorexia, nausea, vomiting, diarrhea, impotence, urticaria, photosensitivity, hypokalemia, glycosuria, hyperglycemia.

Clinical Notes for Diuretic Agents

• Thorough patient history and physical exam.
• Baseline fluid volume status (intake and output), serum electrolytes, weight, and vital signs.
• Assess for contraindications or the need for cautious use.
• Instruct patients to take medication in the morning to avoid sleep interference.
• Monitor serum potassium levels closely; potassium supplements usually not recommended if levels exceed 3.0 mEq/L.
• Teach patients about proper nutritional and fluid intake, dietary potassium, and the importance of reporting weight changes, illness symptoms, and syncope.
• Monitor for adverse effects such as metabolic alkalosis, drowsiness, lethargy, hypokalemia, tachycardia, hypotension, leg cramps, and decreased mental alertness.
• Monitor for therapeutic effects including reduced edema, fluid volume overload (CHF), and hypertension and return to normal intraocular pressure.

This quiz explores the various classes of renal diuretics, their mechanisms of action, and the tubular sites where they act. Understand how diuretics facilitate sodium and water removal and learn about their clinical applications. Perfect for students studying pharmacology or renal physiology.