Class diuretics

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CLASS DIURETICS Dr. RAGHU PRASADA M S MBBS,MD ASSISTANT PROFESSOR DEPT. OF PHARMACOLOGY SSIMS & RC. 1

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Diuretics in brief for undergraduates

Transcript of Class diuretics

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CLASS DIURETICS

Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.

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CLASSIFICATION

DIRECTLY ACTING A) Acting on thick ascending loop of henle-

FUROSEMIDE, BUMETANIDE, TORSEMIDE, PIRETANIDE,ETHACRYNIC ACID, INDACRINONE(uricosuric drug)

B) Acting on proximal part of distal tubule THIAZIDE group- HYDROCHLORTHIAZIDE,

CHLORTHIAZIDE, BENZTHIAZIDE, POLYTHIAZIDE, CHLORTHALIDONE, METOLAZONE

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CLASSIFICATION

C) Those acting on collecting ducts and tubules

AMILORIDE, TRIAMTERINEAldosterone antagonist-

SPIRONOLACTONE, EPLERENONEINDIRECTLY ACTINGOsmotic diuretics- MANNITOL,

GLYCEROLCarbonic anhydrase inhibitors-

ACETAZOLAMIDE, DORZOLAMIDE, ETHOXZOLAMIDE, METHAZOLAMIDE

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70%

20%

5%

4.5%

0.5%Volume 1.5 L/dayUrine Na 100 mEq/LNa Excretion 155 mEq/day

100%GFR 180 L/day Plasma Na 145 mEq/LFiltered Load 26,100 mEq/day

Collecting duct

Thick Ascending Limb

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Loop diuretics or High ceiling diuretic

Ethacrynic acid-ototoxicity, hepatotoxicity, hypochloremic alkylosis

Frusemide Bumetanide – 40 times potent Torsemide – three times potent and

long acting Indacrinone –gout patients

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RENAL TUBULAR INTERSTITIUM LUMEN

Na+K+Cl-

TPC

Na+

H+

Na+

K+

PARACELLULAR DIFFUSIONNa+ K+ Mg++ Ca++

Cl-

+8 mV

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RENAL TUBULAR INTERSTITIUM LUMEN

Na+K+Cl-

TPC

Na+

H+

Na+

K+

PARACELLULAR DIFFUSIONNa+ K+ Mg++ Ca++

Cl-

+8 mV

THICK ASCENDING LOOP

LOOP DIURETICS

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Therapeutic uses

Oedematous conditions associated with CCF,

Cirrhosis of liver, renal disease including nephrotic syndrome

Hypertension Acute renal failure Toxicity of ions Mild hyperkalemiaNon-diuretic use-moderate

hypercalcemia

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Adverse effects

Hyperuricemia Hypercalciuria and

hypomagnesaemia Hypokalemia Ototoxicity Hyperglycemia Hypersensitivity reactions

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Drug interactions

Digitalis toxicity Elevated serum lithium levels Aminogycosides – increased

ototoxicity NSAIDs diminish the action Probenacid competative inhibition Cotrimoxazole –thrombocytopenia

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THIAZIDES

MECHANISM OF ACTION Inhibit Na+ and Cl- transporter in distal

convoluted tubules Increased Na+ and Cl- excretion Weak inhibitors of carbonic anhydrase,

increased HCO3- excretion Increased K+/mg2+ excretion Decrease Ca2+ excretion

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D C T Early DCT Late DCT

Na+

Cl-

LUMEN

K+

Na+

Cl-

THIAZIDES

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THIAZIDES-Uses

Hypertension Congestive heart failure Hypercalciuria: prevent excess ca2+ excretion

to form stones in ducts Osteoperosis Nephrogenic diabetes insipidus Treatment of li+ toxicity

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THIAZIDES-adverse effects

Hypokalemia Hyponatremia, hyperglycemia Diminished insulin secretion Elevated plasma lipids, hyperuricemia Hypercalcemia

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K+ sparing diuretics

Spironolactone is a steroid compound, which is a competitive aldosterone antagonist.

It increases Na+ excretion and decreases K+ and urea excretion. Its diuretic action is weak and is achieved slowly.

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K+ sparing diuretic

Prevent K loss caused by other diuretics in: HypertensionRefractory edemaPrimary aldosteronism- caused by increased production of aldosteroneHirsutism due to P C O D.Cirrhotic Edema

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K-Sparing Diuretics

Collecting DuctNa Na

NaNa

Amiloride and Triamterene directly block the ENaC channel

Aldo

Spares potassium by decreasing the lumen-negative gradient that drives the expulsion of K/H into the lumen

Site of action: cortical collecting duct

Mechanism: Blocks E Na channels

Pharmacokinetics: Half-life = 3-5 hours

K K

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K-Sparing Diuretics

Collecting Duct

Li

Li

Li

Li

Li

Amiloride blocks Li+ resorption through Na+ Channelsreduces lithium induced polyuria

They can be used to treat oedematous conditions including liver cirrhosis, as they cause hyperkalemia

Combined with thiazides to treat refractory oedema

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K-Sparing Diuretics-side effects

Hyperkalemia-better to avoid K+ supplementation Drug interaction - do not use their combination,

since the potassium sparing effect is greater than additive

Caution with ACE inhibitors Reversible azotemia (triamterine) Triamterene nephrolithiasis.

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Carbonic anhydrase inhibitors limited uses as diureticAcetazolamide prototype carbonic anhydrase inhibitor developed from sulfanilamide (caused metabolic

acidosis and alkaline urine)

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Mechanism of CAIs

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Carbonic anhydrase inhibitors inhibits carbonic anhydrase in renal proximal tubule

cells carbonic anhydrase catalyzes formation of HCO3-

and H+ from H2O and CO2 inhibition of carbonic anhydrase decreases [H+] in

tubule lumen less H+ for for Na+/H+ exchange increased lumen Na+, increased H2O retention

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Carbonic anhydrase inhibitors-uses

Used to treat chronic open-angle glaucoma aqueous humor has high [HCO3-] Acute mountain sickness decrease CSF formation

and by decreasing pH Metabolic alkalosis they can produce

hyperchloremic acidosis Sometimes in epilepsy decreasing the pH Mostly used in combination with other diuretics in

resistant patients Alkalinisation of urine

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Carbonic anhydrase inhibitors-S/E

Rapid toleranceIncreased HCO3- excretion causes metabolic acidosisDrowsiness, fatigue, CNS depressionParesthesia (pins and needles under skin)Nephrolithiasis (renal stones), K+ wasting

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Osmotic diuretics

Mannitol (prototype), Urea, Glycerol, do not interact with receptors or directly block renal

transport activity dependent on development of osmotic

pressure Osmotic diuretics are not reabsorbed Increases osmotic pressure specifically in the

proximal tubule and loop of Henle Prevents passive reabsorption of H2o

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Osmotic diuretics

Osmotic force in lumen > osmotic force of reabsorbed Na+

Increased H2o and Na+ excretionUsesTo treat oliguria state in shockCerebral edema and gloucoma Adverse effects Osmotic diarrhea- mannitol May worsen cardiac failure and pulmonary edema

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