Uploaded byTONY SCARIA
Diuretics REVISION NOTES
The document provides a comprehensive overview of various diuretics, including their mechanisms of action, side effects, and clinical uses. It covers categories such as carbonic anhydrase inhibitors, loop diuretics, thiazide diuretics, osmotic diuretics, and potassium-sparing diuretics, detailing their impact on renal function and electrolyte balance. Additionally, it discusses the role of diuretics in treating conditions like hypertension, heart failure, and edema, alongside potential adverse effects and contraindications.
More Related Content
Similar to Diuretics REVISION NOTES
More from TONY SCARIA
Diuretics REVISION NOTES
- 1.
- 7. Basics of diuretic Diuretics can act only when they are secreted in to lumen by tubular secretion Except aldosterone which is lipophilic
- 8. Basics of diuretics Highly plasma protein bound drugs are excreted by tubular secretion Uric acid NSAIDS Diuretics Penicillin Tubular secretion follows a saturable kinetics Only one drug can be eliminated at a time When NSAID are given along with diuretic activity of diuretic is reduced by NSAID as they are not secreted in to lumen Diuretics compete with uric acid for excretion hyperuricemia GOUT
- 10. Drugs acting onPCT 65 -70 % SODIUM ABSORPTION IN PCT
- 11.
- 12. CARBONIC ANHYDRASE PRESENTIN GASTRIC MUCOSA RBC PCT EYE CILIARY BODY (CARBONIC ANHYDRASE TYPE II) BRAIN EXOCRINE PANCREAS
- 15. CARBONIC ANHYDRASE INHIBITORS NON COMPETITIVE REVERSIBLE
- 16. CARBONIC ANHYDRASE INHIBITORS REDOMINANTLY ACT IN : PCT INHIBIT ABSORPTION OF NaHCO3 HCO3 is excreted along with Na + urinary alkalisation
- 17. Inhibitors ofthis enzyme (acetazolamide, dichlorphenamide and methazolamide) result in the excretion of sodium and bicarbonate in the urine. Due to urinary excretion of bicarbonate, metabolic acidosis (and urinary alkalosis) ensues that result in reduced fIltration of HCO3 – at the glomerulus. Therefore, action of these diuretics is self limiting
- 18. Metabolic acidosisUrinary alkalinisation •Renal calculi formation • Aggravate hepatic encephalopathy • Alkaline urine increase reabsorption of NH3
- 19. KALIURESIS (EXCRETION OFK+) At equally natriuretic doses, K+ excretion is maximum with CA inhibitors because Na+ delivered to the distal tubules is exchanged only with K+ (excretion of H+ is inhibited by these drugs) HYPOKALEMIA
- 20. OTHER USES CAinhibitors also decrease aqueous humor formation (therefore used in glaucoma) Dorzolamide and brinzolamide are topically acting CA inhibitors for use in glaucoma as eye drops BRINZOLZMIDE IS SPECIFIC FOR CARBONIC ANAHYDRASE TYPE II OF EYE DECREASES CSF pH Raise seizure threshold (basis of their use in absence seizures). acute mountain sickness alkalinize urine (for excretion of acidic drugs). Prevents formation of cysteine stones But causes formation of ca2+ stones
- 21. Other uses ofCAI Epilepsy glaucoma alkalinise urine mountain sickness Raise seizure threshold (basis of their use in absence seizures) also decrease aqueous humor formation • for excretion of acidic drugs • Prevents formation of cysteine stones • DECREASES CSF pH increase rate of ventilation • Decrease CSF formation
- 23. A/E HYPOKALEMIA METABOLICACIDOSIS HYPERSENSITIVITY IN PATIENTS WITH ALLERGY TO SULFA DRUGS Aplastic anemia Increase hair growth RENAL STONES IN ALKALINE URINE CA2+ SALTS ARE INSOLUBLE CA2+ STONE FORMATION
- 24. C/I HEPATIC CIRRHOSIS PRECIPITATE HEPATIC COMA BY INTERFERING WITH ELIMINATION OF NH3 COPD ALTERATION OF CO2 TRANSPORT IN LUNGS & TISSUES Metabolic acidosis
- 25.
- 26. Loop diuretic Siteof action LOOP OF HENLE Where they inhibit Na+K+Cl- Secreted in proximal tubule by organic anion transport & reaches ascending LOH act on lumional side Induce PG synthesis cause vasodilation Weak carbonic anhydrase effect except ethacrynic acid High ceiling diuretic maximum natriuretic action
- 27.
- 29. Bumetanide ismost potent
- 30. Loop diuretic inducePG synthesis Induce synthesis of PGE2 & PGI2 First effect in pulmonary edema d/t vasodilation Quick relief in LVF & pulmonary edema Increase renal blood flow increase GFR
- 31. Loop diuretic Abolishescorticomedullary osmotic gradient Blocks positive as wellas negative free water clearance
- 32. Uses Pulmonary edema Cerebral edema Along with blood transfusion n Hypercalcemia Renal calcium stone
- 33. S/E Hypokalemia most common Hyperureicemia Hypocalcemia Metabolic alkalosis Hearing loss ototoxicity maximum with ethacrynic acid Hyperglycemia Hypomagnsemia increased excretion of Mg2+
- 34.
- 35. Thiazide diuretics Thiazide Chlorthiazide Hydrochlorthiazide Benzthiazide Hydroflumethiazide Thiazide like diuretic Indapamide Metolazone Chlorthalidone
- 36. MOA SECRETED BYORGANIC ACID SECRETORS INTO PROXIMAL TUBULE AS THEY ACT ON LUMINAL MEMBRANE COMPETES WITH URIC ACID FOR EXCRETION HYPERURICEMIA inhibiting Na+-Cl– symporter at the luminal membrane of early DT Increased synthesis of PGE2 & PGI2 increase renal blood flow ALSO INHIBIT CARBONIC ANHYDRASE EXCEPT INDAPAMIDE
- 37. Because thesite of action of the thiazide derivatives is on the luminal membrane, these drugs must be excreted into the tubular lumen to be effective. Therefore, with decreased renal function, thiazide diuretics lose efficacy except metolazone
- 38. –Thiazide diuretics→initially ↓ BP by inhibit Na+/ Cl¯ & H2O re-absorption→ ↓ blood volume → ECF volume shrink ,so→ COP declines –After 6–8 weeks → COP returns toward normal while PVR declines – Thiazide diuretics → act primarily on the kidney but secondarily on Blood vessels Therefore → the initial antihypertensive effect seem to be mediated by ↓intravascular volume → ↓COP → ↓BP → ↓ preload -With chronic use → the plasma volume returns to nearly pre-treatment level after a few weeks due to development of tolerance after prolonged use
- 42. Thiazides causemild hypomagnesemia
- 43. Hypercalcemia is mediatedby PTH Decreased urinary calcium excretion: Thiazide diuretics decrease the Ca2+ content of urine by promoting the reabsorption of Ca2+. This effect contrasts with the loop diuretics, which increase the Ca2+ concentration of the urine.
- 45. Decreased absorptionof Na+ results in its greater delivery to late DT and CD that is responsible for hypokalemia (more than loop diuretics). Chlorthiazide has minimum potency and efficacy whereas other drugs differ only in potency (effcacy is similar). Thiazides are moderate efficacy diuretics with low ceiling effect (flat DRC, natriuretic effect does not increase appreciably with increase in dose). These drugs tend to reduce GFR, therefore are not indicated in renal failure patients.
- 46. Decrease insulinrelease hyperglycemia
- 48. S/E of thiazidediuretics Hyperglycemia Sulfonamide allergy Hyperlipidemia Thiazides causes impotence Greater incidence than other antihypertensives
- 49. Indapamide Metolazone •Excreted by bile (other thiazides by tubular secretion) • Donot have carbonic anhydrase inhibitory activity • Peripheral vasodilator action • Both are effective when GFR <30 (but other thiazides are ineffective
- 50. • Polythiazideand trichloromethiazide are most potent thiazides. 100 % bioavailability polythiazide & bendrofluromethiazide • Chlorthalidone is the longest acting thiazide. Chlorothiazide is shortest acting • Metolazone is useful even in severe renal failure. • Indapamide has no CA inhibitory action. It has vasodilatory property because of which, its antihypertensive effect precedes the natriuretic effect.
- 51. Uses Essential hypertension Heart failure Nephrolithiasis Nephrogenic diabetes insipidus d/t Li
- 52. A/E Erectile dysfunction Hypercalcemia Hyperuricemia Hyperglycemia Hypokalemia metabolic alkalosis s Hypokalemia increased risk of torsades pointes
- 53.
- 54. Osmotic diuretic •It should exert osmotic effect. • It should be pharmacologically inert. • It should be freely fltered at the glomerulus. • It should not be reabsorbed.
- 55. RAISES PLASMA OSMOLARITY FLUID SHIFT FROM ICF TO ECF RAISES BLOOD VISCOSITY
- 57. INCREASES RENALBLLOD FLOW (ESPECIALLY TO MEDULLA)MEDULLARY HYPERTONICITY DECREASES)CORTICOMEDULLARY OSMOTIC GRADIENT IS DISSIPITATED PASSIVE SALT REABSORPTION DECREASES
- 58. Mannitol, glycerol,urea and isosorbide are inert drugs that can cause osmotic diuresis
- 59. Mannitol USES i.v.for the treatment of glaucoma and cerebral edema. to maintain GFR in the impending renal failure. CONTRAINDICATIONS acute renal failure because ECF volume increases but it cannot be filtered. cerebral hemorrhage (active bleeding) because in this situation, mannitol can leak from ruptured cerebral blood vessels resulting in the increased ICT (more fluid retention due to its osmotic effect in the cells) If given orally, mannitol can result in osmotic diarrhea. Isosorbide and glycerol can be used orally for the treatment of glaucoma and cerebral edema
- 61.
- 62. Drugs acting oncollecting duct Cortical collecting tubule (CCT) K+-sparing Diuretics Medullary collecting duct Vasopressin antagonist
- 63.
- 64. Potassium sparing diuretic Aldosterone antagonist Spiironolactone Eplerenone Renal epithelial Na+ channel inhibitor Amiloride Triameterene
- 66.
- 67. aldosterone andproduce effects similar to amiloride. These drugs act from the interstitial site of tubular cell (all other diuretics act from luminal side). These agents have maximum effect when aldosterone levels are high (e.g. hepatic cirrhosis, CHF, nephrotic syndrome etc.) and are ineffective in its absence (e.g. Addison’s disease). Spironolactone increases Ca++ excretion whereas amiloride decreases it. Spironolactone is converted to canrenone and other active metabolites in the liver.
- 68. Uses: Theseare weak diuretics and are used only in combination with thiazides or loop diuretics to counteract K+ loss. CHF (decrease mortality), hypertension and Conns syndrome cirrhotic edema (diuretic of choice is spironolactone) the treatment of hirsutism because of its anti-androgenic action. (Its structure is similar to testosterone and thus it acts as a competitive antagonist at testosterone receptors.
- 69. Uses of spironolactone Antiandrogeniceffect Aldosterone blocking effect • PCOD • hirsutism • Conns syndrome • Cirrhosis of liver • CCF
- 70. S/E Hyperkalemia Gynaecomastia Impotence Menustral irregularities Metabolic acidosis d/t H+ retentionn
- 71. Renal ENaC inhibitors Inhibit luminal ENaC inhibitors Amiloride blocks entry of Li through ENaC Li induced diabetes insipidus Aerosol amiloride in cystic fibrosis increases fluidity of respiratory secretions Amiloride decreases excretion of ca2+ & mg2+ & increases excretion of uric acid
- 72. Li enters through ENaC ENaCis blocked by amiloride & triameterene
- 73. Free water clearance Vasopressin Increases free water absorption Decrease free water clearance
- 74. diuretics ↑ Na +excretion ↓ECF volume ↑ vasopressin Hyponatremia ↓ free water clearance
- 75. Main contributorto medullary interstitial osmotic gradient is Na+K+2 Cl- (blocked by furosemide) than NaCl- co transporter (blocked by thiazide) ADH can act only in presence of medullary interstitial osmotic gradient Therefore furosemide blocks main contributor of medullary osmotic gradient less medullary osmotic gradient less action of ADH more free water clearance less hyponatremia
- 76. Loop diuretic Thiazide ↑Na+ excretion ↓ AVP ↑ free water clearance less hyponatremia ↑Na + excretion ↑ AVP ↓free water clearance more hyponatremia
- 77. Carbonic anhydrase inhibitor Carbonic anhydrase inhibition ↑HCO3alkaliniseurine Metabolic acidosis Loop & thiazides Na + exchanged with H+ & K+ Metabolic alkalosis K+ sparing diuretic Block mineralocorticoid receptor block excretion of H+& K+ Metabolic alkalosis
- 78. Osmotic diuretic Loop& thiazide diuretic ↑ vascular volume Decrease renin Decreased vascular volume Increase renin
- 79. Na + Cl-K+ Ca2+ Mg2+ CAI ↑ ↑ ↑ Osmotic ↑ ↑ ↑ ↑ ↑ Loop ↑ ↑ ↑ ↑ ↑ Thiazides ↑ ↑ ↑ ↓ ↑ K + sparing diuretic ↑ ↑ ↓ ↓ ↓ Urinary excretion of ions
- 80.
- 85. Desmopressin • Major indicationis central DI • Longer acting than vasopressin • V2 selective no V1 mediated action
- 86. Terlipressin • DOC foresophageal varices
- 88.
- 89. Central DI NephrogenicDI Drugs causing • Li • Clozapine • Foscarnet • Demeclocycline Rx Chlorfibrate Carbamazepine Clofibrate Thiazide • Amiloride • Thiazide • Indomethacine
- 90. Drugs used inDI • Vasopressin (ADH) & its analogue only in central DI • Other antidiuretics • chlorpo
- 91.
- 93. Drugs causing SIADH Drugsstimulating ADH Direct renal • Nicotine • Phenothiazine • TCA • SSRI • Desmopressin • Oxytocin • Clofibrate • Chlorpropamid e • Cyclophosphamid e • Thiazide • Vincristine