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Similar to DIURETICS 15-09-23.pptx diuretics classification, mechanism of action, uses and adverse effects
DIURETICS 15-09-23.pptx diuretics classification, mechanism of action, uses and adverse effects
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- 2. Site 0f Actionsof Diuretics
- 3. DIURETICS • Drugs thatcause net loss of sodium and water in urine
- 4. CLASSIFICATION • High efficacydiuretics • Medium efficacy diuretics • Weak diuretics
- 5. CLASSIFICATION HIGH EFFICACY DIURETICS (a)Sulphamoyl derivatives: Furosemide, Torsemide, Bumetanide, piretanide, Azosemide,Tripamide (b) Phenoxyacetic acid derivative: Ethacrynic acid
- 6. CLASSIFICATION… MEDIUM EFFICACY DIURETICS (a)Benzothiadiazines (thiazides): Hydrochlorothiazide, Benzthiazide, Hydroflumethiazide, polythiazide, Clopamide (b) Thiazide like: Chlorthalidone, Metolazone, Xipamide, Indapamide.
- 7. CLASSIFICATION… WEAK OR ADJUNCTIVEDIURETICS (a) Carbonic anhydrase inhibitors: Acetazolamide,methazolamide, dichlorophenamide (b) Potassium sparing diuretics (i) Aldosterone antagonist: Spironolactone, Canrenone, Eplerenone, Pot. canreonate (ii) Directly acting (Inhibitors of renal epithelial Na⁺ channel): Triamterene, Amiloride. (c) Osmotic diuretics: Mannitol, Isosorbide, Glycerol
- 8. USES : • GLAUCOMA •ALKALINIZE URINE IN ACIDIC DRUG POISONING • ACUTE MOUNTAIN SICKNESS • ADVERSE EFFECTS : • HYPOKALEMIA • RENAL STONES • ACIDOSIS • CONTRA INDICATIONS : • LIVER DISEASE : HEPATIC COMA precipitated in patients with cirrhosis due to excretion of NH3 in alkaline urine • COPD :Worsening of acidosis is seen in patients with COPD
- 9. OSMOTIC DIURESIS • MANNITOL •Intravenously • Metabolised in the body • Freely filtered at glomerulus • MOA:Draws water from tissues by osmotic action.Results in increased excretion of water and electrolytes • Site of action : loop of henle and proximal tubule
- 10. Loop diuretics • Chemistry Sulfonamidederivatives: Egs Furosemide,Torsemide, Bumetanide Phenoxy acetic acid derivative: Eg Ethacrynic acid • Site of action – Thick ascending limb of loop of Henle • MOA – Inhibition of Na+ -K+ -2Cl- symporter
- 11. • Uses • Intracranialpressure following head injury or tumour • Acute congestive glaucoma • Mannitol used to maintain osmolality of ECF after dialysis • Adverse effects : • Too rapid quantity pulmonary oedema • Headache nausea vomiting
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- 13. • MOA : •SITE OF ACTION : Thick ascending loop of henle • USES: Initial stages of renal and cardiac odema loop diuretics preferred • Iv frusemide along with isotonic saline is used in hypercalcemia as it promotes excretion of calcium in urine • Acute pulmonary edema ,cerebral odema • HTN With CCF /RENAL FAILURE ,HTN EMERGENCY. • Blood transfusion
- 14. • Side effects:electrolyte disturbances • Hypokalemia • Hyponatremia • Hypocalcemia • Hypomagnesemia • Metabolic disturbances like • Hyper glycemia, hyper uricemia,Hyper lipidemia • Ototoxicity • hypersensitivity
- 15. Thiazides • Medium efficacydiuretics
- 16. PHARMACOKINETICS: Absorption orally Excrerted urine Uses: Hypertensionodema Hypercalciuria Diabetes insipidus Side effects : hypokalemia hyponatremia
- 17. Loop diuretics • Highefficacy • High ceiling diuretic Efficacy increases with dose L o o p d i u r e ti c s
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- 19. Furosemide- actions Renal Diuresis –high efficacy, high ceiling On electrolytes Hyponatraemia Hypokalaemia Hypomagnesemia Hypocalcemia Hypochloraemia Alkalosis Hyperuricemia ↑ PGE₂, PGI₂ syn → ↑RBF Extrarenal Dilatation of peripheral blood vessels – subdiuretic doses Change in electrolyte composition of endolymph ↑ TGL, LDL; ↓ HDL Hyperglycemia Relative potency Bumetanide (40) >>>>>Torsemide (3) >> Frusemide (1)
- 20. Pharmacokinetics • Routes –oral, I/V, I/M • Secreted into tubules competes with uric acid • All undergo metabolism Torsemide –active metabolite Bioavail ility Onset t ½ Frusemide 60% 20- 40 min (oral) 10-20 min (I/M) 2-4 min (I/V) 1.5 hours Bumetanide 80% 0.8 hours Torsemide 80% 3.5 hours
- 21. USES • Edema CCF- diuresis→ rapid mobilisation of edema fluid → relief of symptoms Acute LVF - vasodilatation → ↓ preload & improve ventricular efficiency Redistributes blood from pulmonary to systemic circulation Nephrotic syndrome- controls pl. volume dependent rise in BP • Hypertensive emergencies
- 22. Furosemide-Uses… • Cerebral edema(combi with osmotic diuretics) • Acute renal failure (oliguric → non-oliguric) • Anemia (blood transfusion) • Hyperkalemia • Hypercalcemia • Anion overdose
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- 24. ADR Hearing loss (dueto changes in electrolyte conc. In endolymph) Allergic manifestations (Less with Ethacrynic acid) Hyperuricemia Hyperglycemia Hyperlipidimia
- 25. THIAZIDES Classification Thiazides -Sulfonamide derivatives Thiazidelike • Site of action – Early Distal convoluted tubule (cortical diluting segment) • MOA – Inhibition of Na+ -Cl- symporter
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- 27. Thiazides - actions Renal Diuresis– moderate efficacy, low ceiling Decreases blood volume & GFR(except metolazone) Increses Ca reabsorption thiazide induced vol depletion ↑ Na⁺ & Ca²⁺ reabsorption Hypomagnesemia Hyperuricemia Extrarenal Antihypertensive action ↓ TPR, vessel wall stiffness → ↓ BP ↑ TGL, LDL; ↓ HDL Hyperglycemia
- 28. THIAZIDES… PK Well absorbed orally→ PPB → less metabolised → mainly excreted unchanged in urine 100% oral BA – polythiazide PREPARATION Only oral (chlorthalidone – parenteral) DOSE Hydrochlorthiazide – 12.5-100 mg/ day Indapamide – 2.5- 5 mg/ day
- 29. Kinetics t ½ (hours) Potency Chlorothiazide 1.50.1 Hydrochlorothiazide 2.5 1 Polythiazide 25 25 Chlorthalidone 47 1 Indapamide 14 20 Metolazone - 10
- 30. THIAZIDES-USES • Edema- mainlyfor maintenance therapy • Hypertension (indapamide, chlorthalidone) diuresis → ↓ ECF volume → ↓ CO ↓ TPR ↓ intracellular Na → ↓ vessel wall stiffness ↑ compliance ↓ responsiveness to AT II, NA • Hypercalciuria Renal stones • Diabetes insipidus Enhanced Na & water reabsorption at PCT due to volume depletion
- 31. THIAZIDES - ADR… Electrolyteimbalance Metabolic - Hyperglycaemia, hyperuricaemia & hyperlipidaemia Allergic reaction Impotence
- 32. POTASSIUM SPARING DIURETICS •Chemistry Synthetic steroid : spironolactone Pyrazinoylguanidine derivative: amiloride Pteridine : triamterene • Site of action – Late distal convoluted tubule & collecting duct • MOA – Inhibits Na channels • Direct inhibition Eg triamterene, Amiloride • Via mineralocorticoid receptor Eg. Spironolactone,Eplerenone
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- 34. Amiloride & Triamterene •Direct inhibitors of sodium channels • Retention of K and H ions Hyperkalaemia &acidosis
- 35. Inh of renalepithelial Na+ channel-USES • Cirrhotic edema • Combi with thiazides, loop DA to prevent hypokalemia • Cystic fibrosis - ↑ fluidity of resp. secretion • Li⁺ induced DI – blocks Li reabsorption
- 36. Inh of renalepithelial Na+ channel-ADR • Hyperkalemia, acidosis Amiloride Skin rashes, diarrhoea Triamterene Glucose intolerence, photosensitivity, megaloblastic anemia, muscle cramps, renal stones
- 37. spironolactone MOA -Antagonist ofmineralocorticoid activty Anti androgenic effect gynaecomastia Eplerenone No anti androgenic action Less ADR PK • Not secreted into tubular lumen • Well absorbed orally → PPB → completely metabolised in liver→ CANRENONE ( active metabolite ) • T1/2 spironolactone – 2 hrs; canrenone- 18 hrs DOSE – 25-50 mg BD
- 38. POTASSIUM SPARING DIURETICS-USES Edema – esp in cirrhosis Hypertension Primary & secondary hyperaldosteronism Cystic fibrosis Lithium induced DI adjuvant to thiazides to prevent hypokalemia, To decrease resistance Amiloride
- 39. POTASSIUM SPARING DIURETICS-ADR • Hyperkalemia • Acidosis • Peptic ulcer • Abdominal upset, drowsiness, confusion • Hirsuitism, gynaecomastia, impotence, menstual irregularities (Spironolactone)
- 40. Eplerenone Selective aldosterone receptorantagonist(SARA) • No action on androgen, progesterone receptor • Interfere with fibrotic & inflammatory effects of aldosterone; ↓ progression of albuminuria in DM • ↓ myocardial perfusion defects after MI • ↓ mortality rate by 15% in pts with post-MI cardiac failure
- 41. D/I of Potassiumsparing diuretics Potassium supplements → hyperkalemia ARB,ACE-I ,NSAIDS, beta blockers → hyperkalemia ↑ digoxin levels Aspirin inhibits TS of Canrenone → blocks action Strong CYP3A inhibitors ↑ pl eplerenone
- 42. OSMOTIC DIURETICS MANNITOL • Nonelectrolyte of low MW • Pharmacologically inert • Filtered from glomerulus;mininal reabsorption SITE OF ACTION Proximal tubule &descending limb of loop of henle MOA 1.Retains water isoosmotically in PT → dilutes luminal fluid → ↓ NaCl absorption 2.Draws water from IC compartment → ↓ intracellular oedema
- 43. Mannitol PK Not absorbed orally IV10-20% solution USES 1. Raised ICT/IOT- 1-1.5g/kg over 1 hr 2. To maintain GFR in impending renal failure 3. To counteract low pl osmolality d/t rapid dialysis
- 44. Mannitol CI ATN, anuria, pulm.edema, CHF, cerebral haemorrhage ADR Head ache d/t hyponatremia, nausea, vomiting, hypersensitivity rn. ISOSORBIDE & GLYCEROL Orally active
- 45. CARBONIC ANHYDRASE INHIBITORS •Chemistry Sulfonamide derivatives • Site of action – Proximal convoluted tubule • MOA – Non competitive inhibition of carbonic anhydrase enzyme
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- 47. CARBONIC ANHYDRASE INHIBITORS-ACTIONS Renal • Inhibits H⁺ secretion in DCT,CD • Maximum kaliuresis • Self limiting action Extrarenal • ↓ secretion of HCO₃⁻ to aqueous humour • ↓ gastric acid , pancreatic HCO₃⁻ secretion • ↑ seizure threshold • Alters CO₂ transport in lungs
- 48. CARBONIC ANHYDRASE INHIBITORS-USES Glaucoma acetazolamide(oral) dorzolamide,brinzolamide(t opical) Alkalinisationof urine – UTI, poisoning, cystinuria, uric acid calculi Metabolic alkalosis Epilepsy Diuretic – less used Acute mountain sickness ↓ resp. work in pts weaned from respirator Hyperkalemic periodic paralysis Hyperphosphatemia
- 49. CARBONIC ANHYDRASE INHIBITORS… PK Wellabsorbed orally excreted unchanged in urine DOSE - 250 mg OD/BD ; oral preparation
- 50. CARBONIC ANHYDRASE INHIBITORS… ADR •Hypokalemia, acidosis • Hypesensitivity reactions, rashes • Drowsiness, paresthesia, fatigue • Crystalluria CI – liver disease; alkaline urine interferes with ammonia elimination
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