Diuretics work by interfering with electrolyte reabsorption in the kidney to promote excretion of sodium and water. They are classified based on where in the nephron they act: carbonic anhydrase inhibitors act in the proximal convoluted tubule; loop diuretics act on the ascending loop of Henle; thiazide diuretics act in the distal convoluted tubule; and aldosterone inhibitors act on the collecting tubule. Common diuretics include acetazolamide, furosemide, hydrochlorothiazide, and spironolactone. They are used to treat conditions like hypertension, heart failure, and edema. Adverse effects can include electrolyte imbalances like hyp

1. DIURETICS
By D.Kokhila,
B.Pharm final year.

2. DIURETICS
DEFENITION
Diuretic is a drug , which increase the urine output of electrolyte and water from the kidney by
interfering with one (or) more reabsoprtive process occurring at different segment of nephrone which promote
excrete of sodium and water from body by an action of kidney.
CLASSIFICATION
1.During acting proximal convoluted tubule “Carbonic Anhydrase Inhibitors”
Acetazolamide, Dichlorphenamide,Methazolamide
2,3.During acting on ascending Loop of Henle “Loop diurectic”
Furosemide,Bumetanide,Torsemide,Piretanide and Etha-Cryni-C Acid, Indacrinone(uricosuric diurectic).
4.During acting Distal Convoluted tubule “Thiazide diurectic”.
Thrazide , Chlorthiazide , Benzthiazide , Hydrochlorthiazide.
5. During acting on collecting tubule and dust “Aldosterone Inhibitor”
Spiranolactone,Explerenone.
6. During acting Indiretly and modifying the content of urinary filtration “Osmotic Diurectic”
Mannitol , Potassium acetate, Glycerol.

5. Carbonic anhydrase Inhibitor:
Acetazolamide is the most common drug that inhibit the enzyme carbonic anhydrase in proximal
tubule.
Acetazolamide:
Mechanism of action: Acetazolamide inhibit carbonic anhydrase located in cytoplasm and atypical
membrane of Proximal tubule .Carbonic anhydrase catalyses the reaction of CO2 and H2O leading to H2CO3
which spontaneously ionise hydrogen and HCO3 the decrease ability to exchange sodium and hydrogen .In
presence of acetazolamide result mild diuretics .Additional HCO3 retain un lumen with marked elevation in
urinary ph lose of HCO3 causes hyperchloremic Metabolic acidosis.

6. Therapeutic uses:
Treatment of glaucoma,diuretics,acute mountain sickness,epilepsy.
ADME:
Acetazolamide given orally once four times daily.It secreated by proximal tubule.
Adverse reaction:
Metabolic acidosis,potassium depletion,renal stone formation,drowsiness.

7. Loop Diuertics
They act on ascending loop of Henle.Compare to other class of drugs this have highest efficacy in
mobilizing sodium and potassium from the body.
Eg:Furosemide,etharynic acid.
Furosemide:
It is a rapid acting diuretics.It increases upto 10L of urine may be produced in a day . It inhibit Na+/K-
/2Cl cotransporter.
Mechanism of action:
loop diuretis inhibit cotransport of Na+/K+/2Cl- .In luminal membrane ,in asending loop of
henle,therefore reabsorption of these ion decresed,this is most efficacious diuretic drug because the
ascending limb accounts for reabsorption of 25 to 30% of filtered Nacl.
Loop diuretic act promply in patients have poor renal function and those who not respond to
thiazide.Loop diuretics carises decreases renal vascular resistance and increases blood flow.
Therapeutics uses:
Reducing acute pulmonary edema,heart failure,treating hyper calcemia because it stimulate calcium
excreation,treatment of hyper kalemia.

8. ADME:
Loop diuretics administer oraly they secreted through urine.Duration of action 2-4hrs.
Adverse effect:
Ototoxicity,hyper uricemia,potassium depletion,hypomagnesemia.

9. Thiazide diuretics:
This are most widely used diuretics.They are sulphonamide diuretic.
Eg:Thiazide,chlorthiazide.
Thiazide
They act in distal tubule.
Mechanism of action:
Thiazide derivatives act in distal tubule to decreases reabsorption of Na+ by inhibiting Na+/cl-
cotransporter on luminal membrane of distal convoluted tubule result the increase concentration of Na+
and cl- tubular fluid,the acid-base balance not usually affected.

10. ADME
Drug affective oraly,most thiazide take 1 to 3 weeks to produce stable reduction in BP.
Pharmacological action:
a)Increased excretion of Na+ and cl-.In causes increase Na+ and cl- excretion .Which result excretion of
hyper osmolar urine.
b)Loss of K+:Because thiazide increase the Na+ in the filtrate arriving at the distal tubular more K+ is
also exchange for Na+ resulting in continual loss of K+ from the body with prolonged use of these drug.
c)Loss of Mg2+:Magnesium deficiency requiring supplementation.
d)Decrease urinary calcium excretion:Thiazide diuretic decrease Ca2+ content of urine by promoting
reabsorption of Ca2+.
e)Reduced peripheral vascular resistance:Initial reduction in BP result decrease blood volume and
decrease CO.
Therapeutic uses:
Hypertension,heart failure,hyper calciuria,diabetes insipidus.
Adverse effect:
Potassium depletion,hyponatremia,hyper uricemia,hyper calcemia,hyper glycemia.

11. Aldosterone inhibitor(potassium sparing diuretics)
Potassium sparing diuretics act in collecting tubule to inhibit Na+ reabsorption and K+ excretion.
Eg:spironolactone.
Spironolatone
Mechanism of action:
Spironolactone is synthetic steroid that antagonize aldosterone,Intracellular cytoplasm receptor.
It become inactive and prevent translocation of receptor complex in to nucleus of target cell.This result
failure to produce proteins normally synthesised in response to aldosterone. This mediator protein stimulate
Na+/K+ exchange site of collecting tubule and prevent Na+ reabsorption K+ and H+ secretion.
Pharmacological action:
This drug may less endocrine effect.
Therapeutic uses:
Diuertic,secondary hyperaldosteronium,heart failure.

12. ADME:
It adsorped orally,rapidly convert to active metabolite.
Adverse effect:
Peptic ulcer, nausea,lethargy,mental confusion.

13. Osmotic diuretics
Manitol
It is non electrolyte of low molecular weight.Large quantity required to raise osmolarity of plasma
and tubular fluid.It is not metabolised in body freely filtered in glomerules.
Administration:
Manitol is not absorbed orally has to given IV as 10-20% solution.It excreated with a t1/2 of 0.5-1.5hrs.
Therapeutic uses:
Treatment of congestive glaucoma,it is used in patient with renal failure,pulmonary edema,heart
failure.