GE 13: DIURETIC DRUGS

Definition: drugs that induce a state of increased urine flow Classes of diuretics Example of drugs Mechanism of action - Inhibits the enzyme carbonic anhydrase in proximal tubular epithelial cells - the enzyme catalyses the reaction between CO2 and H2O to produce H+ and HCO3Inihibits the Na+/K+/Clcarrier in the luminal membrane Site of action Proximal tubule Therapeutics uses - treatment of chronic glaucoma - prophylaxis of acute mountain sickness Pharmacokinetics Adverse effects

Carbonic Acetazolamide anhydrase inhibitor

Loop/high-ceiling diuretics

Bumetanide Furosemide

Ascending loop of Henle

- reduce acute pulmonary edema due to congestive heart failure - stimulate tubular Ca2+ secretion in hypercalcemia condition - reduce intracranial pressure in patients with severe traumatic brain injury

- administered orally or parentally - duration of action about 1 6 hours - the most effective diuretic

- potassium depletion (hypokalaemia), high concentration of Na+ in distal tubule results in increase exchange of Na+ for K+ - acute hypovolemia (decrease in volume of blood plasma) - hyperuricaemia, blocking of uric acid secretion causing attacks of gouts - ototoxicity,

permanent hearing damage with continued treatment (worse with aminoglycoside antibiotics) Thiazides and related agents Chlorothiazide - decrease the Na+ Hydrochlorothiazide reabsorption by binding Chlorthalidone to the Cl- site of Na+/Clcontransporter on luminal membrane & inhibiting its action Chlorothiazide actions: - increase excretion of Na+ and Cl- loss of K+ - decrease urinary calcium excretion - reduced peripheral vascular resistance with continued use Distal tubule

Distal tubule

Potassium-sparing diuretics

Spironolactone - a synthetic aldosterone antagonist

- competes with aldosterone for intracellular receptors prevent translocation of receptor complex to

- reduce systolic and diastolic bp for extended periods in the treatment of hypertension - reduce extracellular volume in mild/moderate congestive HF - prevent recurrent kidney stone formation in idiopathic calciuria - distal tubule - diuretic - collecting - treatment of tubule secondary hyperaldosteronism

- administered orally - taken 1 -3 weeks for stable reduction in bp

- potassium depletion - hyperuricaemia - volume depletion which can cause dizziness - hypercalcemia - hyperglycaemia - hypersensistivity

- completely absorbed orally - rapidly converted to active metabolite

- disturbance in hormonal activity, may induce gynaecomastia in male and irregular

- amiloride - triamterene

Osmotic diuretics

- mannitol - urea

the nucleus prevent transcription and translation of mediator protein - these mediators normally stimulate Na+/K+ exchanger - prevent Na+ reabsorption and secretion of K+ and H+ - blocks Na+ luminal channels (act independently of aldosterone) - inhibit reabsorption of Na+ - reduce secretion of K+ and H+ - act indirectly by modifying the content of filtrate by increasing the osmolarity

menstruation in female - hyperkalaemia, nausea, lethargy, confusion

- distal tubule - collecting tubule

- glomerulus

- reduce intracranial pressure - treatment of acute renal failure