Class diuretics
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This document provides information on diuretic drugs, including their mechanisms and sites of action, indications for use, and adverse effects. It discusses loop diuretics like furosemide and bumetanide that act in the thick ascending loop of Henle, thiazide diuretics like hydrochlorothiazide that act in the distal tubule, and potassium-sparing diuretics like amiloride and spironolactone that act in the collecting ducts. It also covers carbonic anhydrase inhibitors and osmotic diuretics. Non-diuretic uses and combinations with other drugs are mentioned. Resistance, interactions, and specific adverse effects are summarized for each drug class.
![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 Na+/H+ exchange
increased lumen Na+, increased
H2O retention](https://image.slidesharecdn.com/classdiuretics-140805005429-phpapp01/85/Class-diuretics-24-320.jpg)
![ 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](https://image.slidesharecdn.com/classdiuretics-140805005429-phpapp01/85/Class-diuretics-25-320.jpg)
Class diuretics
- 1. Dr. RAGHU PRASADA M S MBBS,MD ASSISTANT PROFESSOR DEPT. OF PHARMACOLOGY SSIMS & RC. 1
- 2. 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, THIAZIDE like-CHLORTHALIDONE, METOLAZONE INDAPAMIDE, ZIPAMIDE
- 3. C) Those acting on collecting ducts and tubules AMILORIDE, TRIAMTERINE Aldosterone antagonist- SPIRONOLACTONE, EPLERENONE INDIRECTLY ACTING Osmotic diuretics- MANNITOL, GLYCEROL Carbonic anhydrase inhibitors- ACETAZOLAMIDE, DORZOLAMIDE, ETHOXZOLAMIDE, METHAZOLAMIDE, DICHLORPHENAMIDE
- 4. 70% 20% 5% 4.5% 0.5% Volume 1.5 L/day Urine Na 100 mEq/L Na Excretion 155 mEq/day 100% GFR 180 L/day Plasma Na 145 mEq/L Filtered Load 26,100 mEq/day Collecting duct Thick Ascending Limb
- 6. Ethacrynic acid-ototoxicity, hepatotoxicity, hypochloremic alkalosis Furosemide Bumetanide – 40 times potent Torsemide – three times potent and long acting Indacrinone –gout patients
- 8. RENAL TUBULAR INTERSTITIUM LUMEN Na+ K+ Cl- TPC Na+ H+ Na+ K+ PARACELLULAR DIFFUSION Na+ K+ Mg++ Ca++ Cl- +8 mV
- 9. RENAL TUBULAR INTERSTITIUM LUMEN Na+ K+ Cl- TPC Na+ H+ Na+ K+ PARACELLULAR DIFFUSION Na+ K+ Mg++ Ca++ Cl- +8 mV THICK ASCENDING LOOP LOOP DIURETICS
- 10. Edematous conditions associated with CCF, Cirrhosis of liver, renal disease including nephrotic syndrome Hypertension Acute renal failure Toxicity of ions Mild hyperkalemia Non-diuretic use-moderate hypercalcaemia
- 11. Hyperuricemia Hypercalciurea and hypomagnesaemia Hypokalemia Ototoxicity Hyperglycemia Hypersensitivity reactions RESISTANCE TO LOOP DIURETICS Renal insufficiency Nephrotic syndrome Cirrhosis of liver Congestive heart failure
- 12. Digitalis toxicity—due to hypokalemia Elevated serum lithium levels Aminoglycosides – increased ototoxicity NSAIDs diminish the action Probenacid competitive inhibition Cotrimoxazole –thrombocytopenia
- 13. 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
- 14. Early DCT Late DCT Na+ Cl- LUMEN K+ Na+ Cl- THIAZIDES
- 15. Hypertension Congestive heart failure Hypercalciurea: prevent excess ca2+ excretion to form stones in ducts Osteoporosis Nephrogenic diabetes insipidus Treatment of li+ toxicity
- 16. Hypokalemia—digitalis toxicity Hyponatremia, hyperglycemia Hypochloremic alkalosis Diminished insulin secretion Elevated plasma lipids, hyperuricemia Hypercalcaemia Hypersensitivity reactions-sulfonamide derivative
- 17. 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.
- 18. Prevent K loss caused by other diuretics in: Hypertension Refractory edema Primary aldosteronism- caused by increased production of aldosterone Hirsutism due to P C O D. Cirrhotic Edema
- 19. Collecting Duct Na Na Na Na Amiloride and Triamterene directly block the ENaC channel(Epithelial sodium channels) 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 KK
- 20. Collecting Duct Li Li Li Li Li Amiloride blocks Li+ resorption through Na+ Channelsreduces lithium induced polyuria They can be used to treat edematous conditions including liver cirrhosis, as they cause hyperkalemia Combined with thiazides to treat refractory oedema
- 21. 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.
- 22. Acetazolamide prototype carbonic anhydrase inhibitor developed from sulfanilamide (causes metabolic acidosis and alkaline urine) limited uses as diuretic It is well absorbed orally and excreted unchanged in urine Action lasts for 8-12hrs
- 24. 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 Na+/H+ exchange increased lumen Na+, increased H2O retention
- 25. 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
- 26. Rapid tolerance Increased HCO3- excretion causes metabolic acidosis Drowsiness, fatigue, CNS depression Paresthesia (pins and needles under skin) Nephrolithiasis (renal stones), K+ wasting
- 27. Mannitol (prototype), Glycerol, Mannitol is a nonelectrolyte of low molecular weight and is pharmacologically inert freely filtered at glomerulus 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 expands Extracellular volume Inhibits transport processes in thick ascending LH Prevents passive reabsorption of H2o It increases urinary volume, excretion of all cations(Na, K,Mg, Ca) and anions(Cl, HCO3, PO4)
- 28. Uses To treat oliguria state in shock Cerebral edema and glaucoma To maintain GFR and urine flow in acute renal failure Adverse effects Osmotic diarrhea- mannitol May worsen cardiac failure and pulmonary edema C/I- acute tubular necrosis, anuria, pulmonary edema, CHF, cerebral hemorrhage, left ventricular failure
- 29. Loop diuretics can be used to treat mild to moderate hypercalcaemia Thiazides reduce volume of urine in diabetes insipidus more water reabsorption from collecting ducts Thiazides are helpful in idiopathic hypercalciurea Potassium sparing diuretics can reduce lithium induced polyuria Amiloride can be used to treat cystic fibrosis by increasing the fluidity in respiratory secretions
- 30. Spironolactone in congestive heart failure retards the disease progression and reduces mortality Carbonic anhydrase inhibitors and osmotic diuretics in glaucoma Osmotic diuretic in cerebral oedema CAs can be used in metabolic alkalosis-as they produce hyperchloremic acidosis CAs can be used to treat petitmal epilepsy Acute mountain sickness