1. DIURETICS akashmarathakam@gmail.com

2. Diuretics are drugs that promote the output of urine excreted by the kidneys. The increased excretion of water and electrolytes by the kidneys is dependent on three different processes, viz (a) glomerular filtration (b) selective tubular reabsorption, and (c)subsequent secretion. It has been duly observed that as the ‘glomerular filtrate’ gets across through the tubules, substances that are absolutely essential to the blood and tissues,such as: water, salts, glucose, and amino acids are reabsorbed eventually.

3. Every normal human being essentially bears a daily rhythm in the excretion of water and electrolytes, being minimum during night and maximum in the morning. Diuretics’ may enhance the rate of urine-formation by either of the two following phenomena, viz., (a) Increasing glomerular filtration, and (b) Depressing tubular reabsorption

4. Diuretics are very effective in the treatment of cardiac oedema, specifically the one related with congestive heart failure. They are employed extensively in various types of disorders, for example, nephrotic syndrome, diabetes insipidus, nutritional oedema, cirrhosis of the liver, hypertension, oedema of pregnancy and also to lower intraocular and cerebrospinal fluid pressure

5. Classification of diuretics

7. (4)Pottassium sparing Diuretics:- Amiloride,triamterene, Spironolactone. (5)Loop diuretics:- Furosemide, Bumetanide, Ethacrynic acid. (6)Miscellanouus:- Indapamide,Clopamie,Metolazone.

8. Chlorothiazide

9. It may be prepared by the chlorination of 3-chloroaniline with chlorosulphonic acid to yield 3-chloroaniline-4, 6-disulphonyl chloride, which is then amidated with ammonia to give the corresponding 4, 6- disulphonamide analogue. This on heating with formic acid affords cyclization through double condensation.

10. Chlorothiazide is used in the treatment of oedema associated with congestive heart failure and renal and hepatic disorders. It is also employed in hypertension, either alone or in conjunction with other antihypertensive agents. It is also used in oedema associated with corticosteroid therapy thereby increasing the potassium-depleting action of the latter. Dose : Antihypertensive, 250 to 500 mg ; usual, antihypertensive, 250 mg 3 times per day ;diuretic 500 mg to 1g ; usual, diuretic, 500 mg 1 or 2 times per day.

11. HYDROCHLORTHIAZIDE

12. Its diuretic actions are similar to those of chlorothiazide but it is ten times more potent than the latter. However, when the treatment is prolonged loss of K+ causes hypokalemia which may be prevented by supplementation with potassium salts. Dose : 25 to 200 mg per day ; usual, 50 mg 1 or 2 times daily.

13. TRIAMTERENE 2, 4, 7-Triamino-6-phenylpteridine

14. Reacting guanidine with malonodinitrile gives 2,4,6-triaminopyrimidine (21.5.11)This undergoes nitrosation by reacting it with nitric acid, which results in the formation of 5-nitroso-2,4,6-triaminopyrimidine (21.5.12), which upon condensation with benzyl cyanide in the presence of sodium methoxide cyclizes into triamterene (21.5.13)

15. MODE OF ACTION:- Triamterene is a pyrazine derivative that inhibits reabsorption of sodium ions without increasing excretion of potassium ions. Triamterene directly blocks the epithelial sodium channel (ENaC) on the lumen side of the kidney collecting tubule. INDICATIONS:- Oedema, potassium conservation with thiazide and loop diuretics SIDE EFFECTS:- Side-effects include gastro-intestinal disturbances,dry mouth, rashes; slight decrease in blood pressure,hyperkalaemia, hyponatraemia; photosensitivity and blood disorders also reported; triamterene found in kidney stones

16. DOSE Initially 150–250 mg daily, reducing to alternate days after 1 week; taken in divided doses after breakfast and lunch; lower initial dose when given with other diuretics. BRAND NAME Trade NameDitide Manufacturer Glaxo Smithkline Pharmaceuticals Ltd. Unit50mg/25mg TypeTablet Quantity10Tablet Price37.2

17. FRUSEMIDE

18. 2, 4-Dichloro-5-sulphamoyl benzoic acid may be prepared by reacting 2, 4-dichlorobenzoic acid with chlorosulphonic acid at an elevated temperature and then carrying out the amidation. This on treatment with furfuryl amine in the presence of sodium bicarbonate, affords nucleophilic aromatic displacement of the highly activated chlorine at C-2, thereby yielding furosemide. However, the protection of the chlorine atom at C-4 may be achieved by regulating the temperature of the furfurylamination

19. Dose : Oral, 40 to 600 mg per day ; usual, 40 to 80 mg per day ; i.m. or i.v., 20 to 40 mg.

20. INDAPAMIDE SAR of Indapamide. It apparently differs from the thiazides structurally. However, it may be viewed chemically as comprising of a polar sulphonamidolchlorobenzamide and a highly lipoidal methyl indolyl functional moiety.

21. Indapamide is synthesized from 2-methyl indoline, the nitrosation of which gives 2-methyl-1-nitrosoindoline (21.3.31). Reducing this with lithium aluminum hydride leads to formation of 1-amino-2- methyl indoline (21.3.32). Acylating this with 3-sulfonamido-4- chlorbenzoic acid chloride leads to (21.3.33) Indapamide.

22. Some diuretics can cause low levels of potassium. A delicate balance of potassium is needed to properly transmit electrical impulses in the heart. A low potassium level can disrupt the normal electrical impulses in the heart and lead to irregular heartbeats (arrhythmias). If potassium levels are low, a potassium supplement may be prescribed.diureticspotassiumheart Eplerenone is a potassium-sparing diuretic, meaning that it helps the body get rid of water but still keep potassium.potassium-sparing diuretic

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