Diuretics

1. Presented by
Nabeel Malik
B.Pharm 3rd year
Under the guidance of
Ms.Gurvinder Kaur
Departement of Pharmaceutical chemistry

2. INTRODUCTION
Diuretics are used in the management of edema associated
with cardiovascular, renal, and endocrine abnormalities, as
well as in the treatment of hypertension, glaucoma, and
several other clinical disorders. The drugs act
at various sites in the nephron to cause diuresis (an increase
in urine production). Most diuretics inhibit the reabsorption
of sodium from the nephron into the circulation and thereby
increase natriuresis (the excretion of sodium in the urine).

3. ClASSIFICATION
Thiazide Diuretics
 Chlorthiazide
 Hydrochlorthiazide
Loop Diuretics
 Furosemide
 Ethacrynic acid
Potassium sparing Diuretics
 Spirinolactone
 Amiloride
 Triamterene
Carbonic Anhydrase Inhibitors
 Acetazolamide
 Dorzolamide

4. STRUCTURES
Thiazide Diuretics
Chlorthiazide Hydrochlothiazide

5. Loop Diuretics
Furosemide Ethacrynic acid

6. Potassium sparing diuretics
Triamterene Spirinolacton
e

7. Osmotic diuretic
Mannitol Glycerine

8. Carbonic Anhydrase Inhibitors
Acetazolamide

9. MECHANISM OF ACTION
Loop diuretics inhibit the Na+,K+,2Cl− symporter in the
ascending limb of the loop of Henle and thereby exert a
powerful natriuretic effect. In comparison with other diuretics,
loop diuretics can inhibit the reabsorption of a greater
percentage of filtered sodium. Loop diuretics are sometimes
called high-ceiling diuretics because they produce a
dose-dependent diuresis throughout their clinical dosage
range.

10. In addition to their natriuretic effect, the loop diuretics
produce kaliuresis by increasing the exchange of sodium and
potassium in the late distal tubule and collecting duct via the
same mechanisms as those described for the thiazide diuretics.
Loop diuretics also increase magnesium and calcium
excretion by reducing the reabsorption of these ions in the
ascending limb

12. ADVERSE EFFECTS
 Loop diuretics can produce a variety of electrolyte
abnormalities, including
 hypokalemia
 hypocalcemia
 hypomagnesemia
 metabolic alkalosis.
 Also increase blood glucose and uric acid levels in the
same manner as the thiazide diuretics.
 use of loop diuretics causes ototoxicity with
manifestations such as tinnitus, ear pain, vertigo,
and hearing deficits. In most cases the hearing loss is
reversible.

13. SAR OF LOOP DIURETICS
 They are either 5-sulphamoyl-2-amino benzoic acid or 5-
sulphamoyl-3-amino benzoic acid derivatives.
 The carbonyl group at C-1 provides optimal diuretic activity.
The substitution of activating group (X) in the position 4 by
Cl, alkoxy, aniline, benzyl, or benzoyl group at 4th position
increases the diuretic activity.
The presence of sulphamoyl group in the 5th position is
essential for activity.
The two series of 5-sulphamoyl benzoic acid differ in the
nature of the functional group that substi- tuted in 2nd and
3rd position.

14. The presence of furfuryl, phenyl, and thienyl methyl group at
2nd amino group of 5-sulphomoyl
 -2-amino benzoic acid gives maximum diuretic activity.
The wide range of alkyl group can be substituted at 3rd
amino group of 5-sulfamoyl-3-amino ben- zoic acid without
modifying the optimal diuretic activity.
A molecule with a weakly acidic group to direct the drug to
the kidney and an alkylating moiety to react with sulphydryl
groups and lipophilic groups seemed to provide the best
combination of a diuretic in the class.

15. USES
Diuretic actions of Loop Diuretics:
 Oedema due to cardiac failure, hepatic disease, nephrotic
syndrome.
 Acute pulmonary edema & cerebral edema, pregnancy &
idiopathic edema.
 Acute chronic renal failure.
 Barbiturate poisoning, salicylate poisoning.

16. Nondiuretic action of Loop Diuretics:
 As an antihypertensive.
 Idiopathic calcium urolithiasis.
 In Hypocalcaemia.
 Diabetes insipidus.

17. Several types of diuretics also increase kaliuresis (the excretion
of potassium in the urine) and affect the excretion of
magnesium, calcium, chloride, and bicarbonate ions.

18. SYNTHESIS
Furosemide

20. REFERENCES
 Wilson & Gisvold’s Text book of Organic Medicinal &
Pharmaceutical chemistry 11th edition pg. no:596-621.
 Bertram G.Katzung –Basic & Clinical pharmacology 12th
edition pg.no:251-269.