1 / 32

DIURETICS (1 of 2)

DIURETICS (1 of 2). Dr R. P. Nerurkar Dept. of Pharmacology T. N. Medical College & BYL Nair Ch. Hospital, Mumbai. DECEMBER 5, 2005. Learning Objectives At the end of my 2 lectures you should be able to. List 5 major types of diuretics and their mechanism and site of action

iolana
Download Presentation

DIURETICS (1 of 2)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. DIURETICS (1 of 2) Dr R. P. Nerurkar Dept. of Pharmacology T. N. Medical College & BYL Nair Ch. Hospital, Mumbai DECEMBER 5, 2005

  2. Learning ObjectivesAt the end of my 2 lectures you should be able to • List 5 major typesof diuretics and their mechanism and site of action • List the major applications and toxicities of them • Describe the measures that reduce K+ loss during natriuresis • List the Rx of hypercalcimia and hypercalciuria • manage refractory edema cases • List Rx of nephrogenic diabetes insipidus

  3. Overview of Diuretic lectures • Definition • Physiology of Urine formation and drugs modifying it • Classification and Mechanism of action • Pharmacology of Individual class of diuretics • Group discussion and Exercises on • Prescription writing, • Patient oriented problem solving • Identification of drugs acting according • ADR and drug interactions

  4. Physiology of Urine Formation • Nephron • Glomerular filtration, Reabsorption, Secretion • GFR 120 ml/min • 99 % reabsorbed • Urine formation 1ml/min  60ml/hr 1.5L/day • Most diuretics prevent reabsorption of Na & H2O

  5. Diuretic - Definition • Diuretic = drug which increase urine formation • Increase urine volume (Diuresis) • Increase excretion of Na and H2O (Natriuresis) • Mechanisms of diuresis • Extrarenal • By increasing Cardiac output : Digoxin, Dopamine in CHF • By Inhibiting ADH : H2O, alcohol • On the kidney (Nephron) – Most diuretics • Inhibit Na and H2O reabsorption Q. What will be the uses of diuretics in therapuetics?

  6. Diuretics- Classification • High efficacy(upto 25% NaCl excretion)Loop diuretics • Frusemide, Torsemide, Bumetanide (SO2NH2 group) • Ethacrynic acid (No SO2NH2 group) • Organic mercurials: Mersalyl (Now obsolete) • Medium efficacy(5 –10 % NaCl excretion) • Thiazides : Hydrochlorothiazide, ChloroTh, BenzTh, HydroflumeTh, Clopamide, PolyTh • Thiazide like : Chlorthalidone, Metolazone, Xipamide, Indapamide

  7. Diuretics- Classification • Carbonic Anhydrase Inhibitors(5%NaCl excretion ) • Acetazolamide, Methazolamide, Dichlorphenamide • Potassium Sparing Diuretics(3% NaCl excretion) • Aldosterone Antagonists Spironolactone, eplerenone • Directly acting: Amiloride, Triamterene • Osmotic Diuretics(upto 20% NaCl excretion) • Mannitol, Glycerol, Isosorbide • Misc:Theophylline

  8. Diuretics - Sites of Action

  9. Loop Diuretics- Frusemide MOA • Acts on thick ascending part of Loop of Henle • Inhibit Na+-K+-2Cl-cotransport and reabsorption • Increase NaCl excretion (upto 25% High efficacy) • Na exchanges with K+ in the DT  K+ loss • Effective in very low GFR of < 30ml/min • Other actions • Increase Ca++, Mg ++ excretion • Induce renal PG synthesis (blocked by NSAIDs) • Direct vasodilatation (IV route) imp. In pulm edema, LVF

  10. Loop Diuretics-Preparations, dosage Which is the most potent loop diuretic? Bumetanide

  11. Loop Diuretics- USES • Edema : Cardiac (CHF), Hepatic (cirrhotic Ascites), Renal (Nephrotic syndrome) • Acute pulmonary edema • Cerebral edema (Mannitol preferred) • Acute hypercalcemia • Acute Renal failure • Forced diuresis in drug poisoning (Barbiturate)

  12. Loop Diuretics- USES contd • Hypertension (Thiazides preferred) • Hyperkalemia mild • Along with massive blood transfusion • Anion overdose (Iodide, Bromide, Flouride)

  13. Loop Diuretics-Adverse Effects • Hypokalemia • Clinical Features : may Increase digoxin toxicity, arrhythmia Muscle weakness, fatigue, cramps • To prevent Hypokalemia • Use low dose • Give KCl supplement (oral solution or IV infusion) • Combine with K sparing diuretic • Advice: More intake of K containing food: coconut water, fruit juice • Hypochloremic Alkalosis • Dehydration • Hyponatremia • Ototoxicity: more likely with IV use, in RF, other ototoxic drugs

  14. Loop Diuretics-Adverse Effects • Hyperuricemia • Hyperglycemia • Hyperlipidemia • Allergic reaction (SO2NH2 group) • Hypomagnesemia • Overzealous use may precipitate volume depletion • Hepatic encephalopathy in hepatic coma • Renal failure • Cardiac failure

  15. Carbonic Anhydrase Inhibitors

  16. Acetazolamide - Site of Action

  17. Carbonic Anhydrase (CA) Enzyme Cytoplasm of Proximal tubule C.A. H2O + CO2 H2CO3 H+ + HCO3- C.A. Renal brush border (Luminal) • CA is also present in • Ciliary body of eye (Aquous humor formation) • Choroid plexus (CSF formation)

  18. C.A. Inhibitor – Acetazolamide CA CO2 + H2O H2CO3 H+ + HCO-3 Cytoplasmic (PT) NaHCO3 Na+ CO2 + H2O H2CO3 HCO3 + H+ Na+ CA Luminal • Net effect of Acetazolamide • Loss of HCO3, Na, K, Cl • Retention of H+ Met. Acidosis

  19. Effects of Acetazolamide • Inhibits CA in the proximal tubule • Loss of HCO3, Na, Cl in urine • Hypokalemia • Urine becomes alkaline and acidosis develops • Acidosis limits the diuretic action within 2 weeks Rarely used as diuretics

  20. Acetazolamide • USES • Glaucoma Oral Acetazolamideor topical dorzolamide • Acute mountain sickness • To alkalinize the urine • Periodic paralysis • Epilepsy • Rarely as a diuretic ADVERSE EFFECTS • Hypokalemia, Fatigue • Acidosis • Sedation • Paresthesias • Abdominal discomfort • Allergic reactions • C/I in liver disease

  21. Exercises on 1st Lecture

  22. Question Fastest Finger First Q . Starting with lower to higher efficacy arrange the following diuretics according their efficacy (ability to cause maximum % excretion of the filtered Na+) A.AmilorideB. Furosemide C.HydrochlorothaizideD.Mannitol Answer: A C D B

  23. MCQ – Case Study type A 70 year old man is admitted with a history of heart failure and acute left ventricular myocardial infarction. He has severe pulmonary edema. Which of the following drugs is LEAST likely to prove useful in the treatment of acute pulmonary edema. A.Bumetanide B.Ethacrynic acid C.FurosemideD.Hydrochlorothiazide Answer D

  24. True or False • NSAIDs may reduce the efficacy of loop diuretics • Acetazolamide does not lower intraocular tension • Frusemide overdose may cause alkalosis • Bumetanide is more potent than frusemide • Frusemide is useful in the Rx of hypercalciuria Answer T F T T F

  25. To be continued in the next class

  26. Title • Text

  27. Title • Text

  28. Table1:(Comparsion of Loop diuretic with Thiazides) All values are Mean + S.E (n=6)

More Related