DIURETICS AGENT CARBONIC ANHYDRASE INHIBITORS (ACETAZOLAMIDE) well absorbed after oral admin increase in urine pH from HCO3

O3 block carbonic anhydrase and block NaHCO3 reabsorption dieresis K SPARING DIURETICS (SPIRONOLACTONE, AMILORIDE, TRIAMTERENE) spironolactone - activation occur in liver - slow onset - competitive antagonist to aldosterone amiloride & triamterene - direct inhibitors of + Na influx in the CCT + reduce Na absorption in the collecting ducts spironolacone bind to aldosterone receptor amiloride & trismterene directly + interfere with Na entry
+

AGENTS

LOOP DIURETICS (FUROSEMIDE) rapidly absorbed eliminated by the kidney by glomerular filtration & tubular secretion half life depends on renal function

THIAZIDES (CHLOROTHIAZIDE) can be admin orally may blunt uric acid secretion & elevate serum uric acid level

OSMOTIC DIURETICS given parentarally oral- causes osmotic diarrhea

PHARMACOKINETICS

PHARMACODYNAMICS

overall effect = 45% bcoz some HCO3 can still be absorbed at other nephron sites by carbonic anhydraseindependent mechanisms causes significant losses & hyperchloremic metabolic acidosis

CLINICAL INDICATION

glaucoma - reduction of aqueous humor production urinary alkalinization - excretion of weak acids metabolic alkalosis acute mountain sickness - increase ventilation & diminish

inhibit luminal + + Na /K /2Cl transporter in TAL reabsorption of NaCl & diminish the lumen +ve potential that + comes from K recycling 2+ 2+ Mg & Ca excretion pulmonary congestion & left ventricular filling pressure in heart failure hyperkalaemia - enhanced urinary + excretion of K acute renal failure - - rate of urine flow & enhanced urinary + excretion of K anion overdose

inhibit NaCl reabsorption from luminal side of epithelial cells in the DCT by + blocking Na /Cl transporter 2+ enhanced Ca reabsorption

oppose action of ADH in CT urine volume + Na as well as H2O reabsorption lead to excessive water loss & hypernatremia

hypertension heart failure nephrolitis due to idiopathic hypercalciuria nephrogenic DI

mineralcorticoid excess/ hyperaldosteronism

to increase urine volume reduction of intracranial & intraocular pressure

TOXICITY

symptoms hyperchloremic metabolic acidosis renal stone - phospaturia & hyperccalciuria renal potassium wasting hyperammonemia hepatic encephalopathy

CONTRAINDICATION

hypokalaemic metabolic alkalosis + + - secretion of K & H ototoxicity hyperuricemia hypomagnesemia allergic & other reactions exhibit allergic crossreactivity may be dangerous in hepatic cirrhosis, borderline renal failure/ heart failure

hypokalaemia metabolic alkalosis & hyperuricemia impaired CHO tolerance hyperlipidemia hyponatremia allergic reaction dangerous in hepatic cirrhosis, boerderline renal failure, heart fsilure

mild. moderate, severe hyperkalaemia hyperchloremic metabolic acidosis gynecomastia acute renal failure kidney stones severe even fatal hyperkalaemia in susceptible patients

extracellular volume expansion dehydration, hyperkalaemia, hypernatremia