diuretics are the drugs which cause a net loss of sodium and water in urine. However, sodium balance is soon restored even with continuing diuretics action by compensatory homeostatic mechanism of the body.
Application of the diuretic in the management of hypertension, has outstriped their use in edema. Diuretics has also helped in understanding renal pharmacology.
1.HIGH EFFICACY DIURETICS: furosemide, bumetamide, torsemide
- MEDIUM EFFICACY DIURETICS:
a. thiazide: hydrochlorothiazide, benzthiazide, chlorothiazide ,hydroflumethiazide
b. thiazide related drugs: chlorthalidone, metolazone,indapamide, clopamide.
- WEAK OR ADJUNCTIVE DIURETICS:
a. carbonic anhydrase inhibitor: acetazolamide
b. potassium sparing diuretics: spironolactone, eplerenone, amiloride, triamterene
c. osmotic diuretics: mannintol, glycerol, isosorbid
- HIGH CEILING DIURETICS:
furosemide: the diuretics response gets on increasing with increasing dose upto 10l of urine may be produced in a day. it is active even in patients with relatively severe renal failure.
major site of action is thick ascending loop of henle where furosemide inhibits sodium-potassium-2chlorine transport.
furosemide has weak carbonic anhydrase inhibiting action ,increased HCO3 excretion, as well urinary pH may rise but the predominant urinary action is chlorine.therefore acidosis does not develop . the diuretics action is independent of acid-base balance of the body.
furosemide increase calcium excretion as well as magnesium excretion by abolishing transepithelial potential difference in the thick ascending loop of henle which drives reabsorption of the divalent cations.
bumetamide: similar to furosemide but 40 times more potent. hyperuricaemia ,k+ loss, glucose intolerance and toxicity are less marked but it rarely cause myopathy.
- during the inital stages of renal, hepatic and cardiac odema loop duretics are preferred.
- intravenous furosemide is used in hypercalcaemia as it promotes the excretion of calcium in urine.
- acute pulmonary oedema
- loop diuretic may be used in cerebral oedema, but i.v. mannintol is the preferred drug, in hypertensive emergencies. furosemide is not preferred in uncomplicated primary hypertension because of short duration of action.
5.loop diuretics can be used in mild hyperkalaemia.
1.electrolyte disturbance: hypokalaemia, hyponatraemia, hypokalaemic metabolic alkalosis, hypocalcaemia and hypomagnesia
- metabolic disturbances: hyperglycaemia, hyperlipidaemia, hyperuricaemia.
- ototoxicity manifests deafness, vertigo, and tinnitus. the symptoms are usually reversible on stoppage of therapy.
- furosemide with digoxin: these diuretic cause hypokalaemia which increase the binding of digoxin to sodium and potassium ATPase leading to digoxin toxicity.
- furosemide with aminoglycoside: both are ototoxic drugs and cause enhanced toxicity when use together.
- furosemide with nonsteroidal antiinflammatory: non seroidal antiinflammatory drugs inhibit PG synthesis and block postaglandin mediated haaemodynamic changes of loop diuretics.
- furosemide with amiloride; furosemide cause hypokalaemia whereas amiloride conserve potassium.
2.MEDIUM EFFICACY DIURETICS:
thiazides and related diuretics:
chlorothiazide was synthesized a carbonic anhydrase inhibitor variant which produces urine that was rich in chloride and diuresis ocurred in alkalosis aw well as acidosis.
the medium efficacy diuretics with primary site if action in the cortical diluting segment or the early distal tubes. here they inhibit sodium and chloride symport at the luminal membrane. they donot effect the corticomedullary osmotic gradient indicating lack of action at the medullary thick ascending loop of henle.
by their action to reduce blood volume as well as intrarenal haemodynamic change they tend to reduce glomerular filtration rate.
chlorthalidone: long acting compound.
metolaone: common with loop diuretics. it is able to evoke a clinically usefusl
1.hypertension: thiazides are used in the treatment of essential hypertension
- heart failure : thiazides are used for mild to moderate case of heart failure
- hypercalciuria: thiazides are used in calcium nephrolithiasis as they reduce the urinary excretion of calcium.
- diabetes insipidus:
- WEAK OR ADJUNCTIVE DIURESIS;
it is a aldosterone antagonist . aldosterone bind to specific mineralocorticoid receptor in the cytoplasm of the late distal tubule and collecting duct cells. spironolactone is most effective when circulating aldosterone levels are high. it also increase calcium excretion.
- odematous conditions associated with secondary hyperaldosteronism.
- spironolactone is often used with thiazides to compensate potassium loss.
ACE inhibitors with spironolactone : dangerous hyperkalemia can occur.
AMILORIDE AND TRIAMTERENE:
they directly block the sodium channels in the luminal membrane of the cells of the late DCT and CD cells.
- treatment of hypertension
- treatment of lithium induced nephrogenic diabetes insipidus
- amiloride improves mucociliary clerance in patients with cystic fibrosis.
B. CARBONIC ANHYDRASE INHIBITOR:
it function in co2 and HCO3 transport and H + ion secretion. the enzyme is present in renal tubular cell, gastric mucosa etc.
2.alkalinize urine in acidic drug poisoning
- acute mountain sickness
hypersensitivity reactions, drowsiness, paraesthesia, hypokaemia, metabolic acidosis , headache etc.
CONTRADICTIONS: liver diseae and chronic obstructive pulmonary disease
C. OSMOTIC DIURETICS:
MANNINTOL: adminstered i.v. . it is neither metabolized in the body nor reabsorbed from the renal tubules.
- shock, renal shutdown, cardiovascular surgery, haemolytic transfusion
- reduce elevated intracranial tension
3.acute congestive glaucoma.