Presented By: Ms. Kalaivani Sathish M. PharmAssistant Professor,

PIMS - Panipat

Diuretics is an agent which increase urine and solute.it may be classified as follows:

1. HIGH EFFICACY DIURETICS Furosemide,azosemide, bumetanide,piretanide,torsemide.

2.MODERATE EFFICACY DIURETICS THIAZIDES Benzothiadiazines –chlorothiazide,hydrochlorothiazide,

polythiazide

THIAZIDE RELATED AGENT Chlorthalidone,clopamide, indapamide,metolazone,xipamide. 3.LOW EFFICACY DIURETICS POTASSIUM SPARING DIURETICS Triamterene,amiloride,spironolactone. CARBONIC ANHYDRASE INHIBITOR Acetazolamide,methazolamide, dorzolamide

OSMOTIC DIURETICS Mannitol,urea,glycerol METHYLXANTHINE Theophylline 4.NEWER AGENT Vasopressin antagonist – conivaptan,tolvaptan,lixirvaptan.

Loop diuretics act on the ascending limb of the loop of henle.frusemide is the most commonly used diuretics.it is a sulphonamide derivative.it is a powerful diuretics.

Frusemide acts by inhibiting NaCL reabsorption in the thick ascending limb of the Henles loop.it blocks the Na K 2CL symporter in the loop.it greatly increase the excretion of Na and CL in the urine.as large amount of NaCL is absorbed in this segment. Diuretic response increases with dose and over treatment may cause dehydration.

In Loop of Henle

Frusemide inhibits Na Cl reabsorption

Increase the excretion of Na & Cl in urine

Leads to increased urinary output

Frusemide is also a weak carbonic enhydrase inhibitor hence it increase the excretion of HCO and phosphate.

PHARMACOKINETICS Frusemide is rapidly absorbed orally,

highly bound to plasma proteins,metabolized in the liver and excreted by kidneys.IV it acts in 2-5 minutes,oral it takes

20-40minutes.

BUMETANIDE Is a sulfonamide like Frusemide but it

is 40 times more potent than Frusemide.

TORSEMIDE Is longer acting and can be given

once a day. ETHACRYNIC ACID Is more likely to cause adverse effect

ototoxicity and is not commonly used.

Hyperkalemia and metabolic alkalosis

dehydration, hypotension Hyperuricemia,hypocalcemia, Hypomagnesemia,ototoxicity, Hyperglycemia,skinrashes, nausea,vomitting,hypotension, Weakness.

Edema Acute renal failure Acute pulmanary edema Cerebral edema Forced diuresis:in poisoning due to drug like barbiturates and salicylates, Frusemide is used with IV fluids.

Hypertension with renal impairment

Chlorthiazide was the first thiazide to be synthesized.

Mechanism of action Thiazide act on the early distal tubule.it

have a moderate efficacy 90% of the filtered sodium is already reabsorbed before reaching the distal tubule.they also inhibit carbonic anhydrase activity and increase bicarbonate loss.it also enhance excretion of Mg and K .But they inhibit urinary excretion of Ca and uric acid resulting in hypercalcemia and hyperuricemia.

In early distal tubule

inhibit carbonic anhydrase activity and increase bicarbonate loss

Enhance excretion of Mg and K and Inhibit urinary excretion of Ca and uric acid

Leads to increased urinary output

Thiazides are well absorbed orally and are rapid acting.they are excreted by kidney.

Hyperkalemia,hyperuricemia,hypotension,hyperglycemia,

GIT disturbance,allergic reaction.

HypertensionCongestive heart failureEdemaRenal stonesDiabetes insipidus

Example of potassium sparing diuretics is Spironolactone it is an aldosterone antagonist,

It may act two ways .they may be aldosterone antagonist or directly inhibition of channels in distal tubes and collecting duct.

Major amount of Na is reabsorbed is proximal parts. It also reduces K loss

Potassium sparing diuretics

Na is already Reabsorbed in proximal parts. Reduces K Loss.

Enhances the Ca excretion

Increases the Urinary Excretion

Ald0steroneAntagonist

Inhibition of channels in Distal Tubules &

Collecting Duct

Mannitol is an osmotic diuretics. Given in IV (Orally Not Absorbed), it gets

filtered by the glomerulus but not reabsorbed.

It causes water to be retained in proximal tubule and descending loop of Henle, by osmotic effect resulting in water diuresis.

There is also some loss of sodium.

Increased Osmotic Pressure in Proximal Tubule

Decreased Water reabsorption

Increased Urine Excretion

To maintain urine volume and prevent oliguria (Decreased Urine Output)

To reduce ICP and IOP following head injury and Glaucoma respectively.