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Potassium -sparing diuretics

Collecting tubule
2-5% of NaCl reabsorption principal cells ; Na+, K+, H2O transport; Na+ reabsoption, K+ secretion ; aldosterone intercalated cell ; proton secretion antidiuretic hormone (ADH) : reabsorption of water

Potassium -sparing diuretics

Pharmacodynamics
reduce Na+ absorption in the collecting tubules and ducts aldosterone antagonists direct interfere with Na+ entry through the sodium-selective ion channels

Clinical indication
hyperaldosteroidosm ; primary hypersecretion, secondary aldosteronism conjunction with a thiazide or loop diuretics

Toxicity
hyperkalemia, gynecomastia, hyperchloremic metabolic acidosis acute renal failure, kidney stone

Thiazide
Distal convoluted tubule
Only 10 % filtered NaCl reabsorbed impermeable to water Na/Cl cotransporter Ca++ actively reabsorbed; parathyroid hormone thiazide diuretics

Thiazide
Chemistry & pharmacokinetics
can be administered orally

Mechanism of action
inhibit NaCl reabsorption from the luminal side of epithelial cell in the distal convoluted tubule by blocking the Na+/Cl- transporter enhance Ca2+ reabsorption Loss of K+

Clinical indication
hypertension heart failure nephrolithiasis due to idiopathic hypercalciuria nephrogenic diabetes insipidus

Toxicity
Hypokalemic metabolic alkaloisis Hyperuricemia Impaired carbohydrate tolerance Hyperlipidemia, Hyponatremia Allergic reaction

Loop diuretics
Loop of Henle
descending loop of Henle : water extraction by osmotic forces created in the hypertonic medullary interstitium Thick ascending limb ; actively reabsorbed NaCl (35%) ; impermeable to water : diluting segment Na+/K+/2Cl- cotransporter reabsorption of cations; Mg2+, Ca 2+ loop diuretics

Loop diuretics
administered orally or parenterally rapid onset inhibit the luminal NA+/K+/Cltransporter in the thick ascending limb of Henles Loop induce renal prostaglandin synthesis

Loop diuretics
Clinical indication
drug of choice for acute pulmonary edema acute hypercalcemia hyperkalemia, acute renal failure, anion overdose

Toxicity
hypokalemic metabolic alkalosis ototoxicity hyperuricemia hypomagnesemia allergic reactions

Proximal tubule
sodium bicarbonate (85%), sodium chloride (40%), glucose, amino acid and other organic solute are reabsorbed ; water (60%) osmotic agent, carbonic anhydrase inhibitor organic acid secretion ; S 2 segment ; uric acid , NSAIDs, diuretics, antibiotics

Carbonic anhydrase inhibitor

acetazolamide well absorbed after oral administration renal insufficiency depress bicarbonate reabsorption in the proximal tubule hyperchloremic metabolic acidosis, decrease diuretic efficacy following several days of therapy Clinical indication
glaucoma urinary alkalinization metabolic alkalosis acute mountain sickness

Toxicity
hyperchloremic metabolic acidosis renal stone renal potassium wasting

Agent that alter water excretion

Osmotic diuretics
proximal tubule, descending limb of loop of Henle ; major action oppose the action of ADH in the collecting tubule mannitol ; nonreabsorbable solute Clinical indication
to increase urine volume reduction of intracranial and intraocular pressure

ADH antagonists
inhibit effects of ADH in collecting tubule lithium, demeclocycline ; reduce cAMP

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