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Robert G. Luke, M.D., MACP Panama City.

Diuretic Therapy. USE AND ABUSE. Robert G. Luke, M.D., MACP Panama City. Presented by:. In a careful metabolic controlled study which diuretic produces more DAILY sodium loss in normal subjects. Hydrochlorothiazide 50mg Furosemide 40mg. CASE STUDY 2.

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Robert G. Luke, M.D., MACP Panama City.

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  1. Diuretic Therapy USE AND ABUSE Robert G. Luke, M.D., MACP Panama City. Presented by:

  2. In a careful metabolic controlled study which diuretic produces more DAILY sodium loss in normal subjects. • Hydrochlorothiazide 50mg • Furosemide 40mg

  3. CASE STUDY 2 A patient with new onset Cardiomyopathy and Anasarca is admitted for diagnosis, treatment and diuresis. Loop Diuretics are given iv for several days with considerable diuresis. Initial renal profile was: Na K Cl HCO, BUN CREAT 137 3.8 100 24 25 1.0 Now it is: 130 2.8 75 37 50 1.4 She is still quite edematous. What to do?

  4. CASE STUDY 3 A compliant patient in your clinic has chronic biventricular failure, previously well managed on medication. She now c/o “lasix no longer works and her ankle swelling is worse and she is gaining weight”. What should you do?

  5. CASE STUDY 4 Your Chief Resident treats a 70 year old lady for isolate systolic hypertension (BP 170/90 mm Hg) with HCT2 25mg daily. Two weeks later she is admitted with a generalized seizure and confusion. Serum electrolytes are Na110 Cl 80 K 2.7 HCO328 BUN 18 Creat 1.4

  6. LOOP DIURETICS

  7. THIAZIDE DIURETICS

  8. Aldosterone antagonist and Amiloride

  9. therefor LOOP DIURETIC PLUS THIAZIDE PLUS SPIRONOLACTONE OR AMILORIDE IS THE MOST POWERFUL DIURETIC TREATMENT WE HAVE

  10. MOBILIZATION EXCRETION

  11. CASE STUDY 2 A patient with new onset Cardiomyopathy and Anasarca is admitted for diagnosis, treatment and diuresis. Loop Diuretics are given iv for several days with considerable diuresis. Initial renal profile was: 137 3.8 100 24 25 1.0 Now it is: 130 2.8 75 37 50 1.4 She is still quite edematous. What to do? KCl+ ACETAZOLAMIDE ?

  12. In a careful metabolic controlled study which diuretic produces more daily sodium loss? • Hydrochlorothiazide 50mg • Furosemide 40mg

  13. “BRAKING” PHENOMENON • (Early)(1) Neuro-Humoral Response(2)Reabsorption at Sites Distal to Action • Post duration of action during ingestion of NaCl • (Later) Hypertrophy of Segment downstream of site of diuretic action(hence enhanced effectiveness of Lasix +Thiazide and Thiazide + Amiloride)

  14. ANSWER: THIAZIDE BECAUSE OF SHORT HALF LIFE OF LOOP DIRETIC AND SUBSEQUENT INCREASED REABSORPTION OF DIETARY SALT. HENCE CHLORTHALIDONE IS THE BEST THIAZIDE.

  15. NOW TO TREATMENT. . . . . Make a diagnosis of the cause of the edema first!

  16. PITTING, SACRAL OR ANKLE EDEMA? | No – Lymphedema or Myxedema? |(Yes) Symmetrical ? — No — A.Venous obstruction B Inflammatory |(Yes) JVP  — No— Ascites Prominent, signs liver disease | (Yes) CHF (Bilateral or Right –sided) | (Yes) Cirrhosis |(No) 4+ Proteinuria? | (No) Acute G’N |(Yes) Nephrotic Syndrome |(No) Serumalb.  ? |(Yes) IBD or malnutrition

  17. GOAL OF THERAPY IN EDEMA • Urgent Only in Pulmonary Edema • It’s NOT necessarily to Eliminate Edema • It’s to Maximize Patient’s Well Being!! • Compromise Between “Swelling” and Organ/Tissue Perfusion/Cardiac Optimum Filling * CONCEPT OF “OPTIMUM DRY WEIGHT”

  18. ALL LOOP DIURETICS are NOT THE SAME: Furosemide Renal Metabolism (Lasix) Variable Absorption Torsemide Liver Metabolism (Demodex) 80% ABS’N Ethacrynic acid No Sulphamoiety (Edecrin)

  19. CASE STUDY 3 A compliant patient in your clinic has chronic biventricular failure, previously well managed on medication. She now c/o “lasix no longer works and her ankle swelling is worse and she is gaining weight”. What should you do?

  20. DIURETIC RESISTANCE *** • High Salt Intake • Nsaids • Failure of GI Absorption • “BRAKING” • Minoxidil • Failure of Delivery to PT • Fall in GFR;Renovascular Renal Failure

  21. USE 1. THE PREVIOUS CHECK LIST 2. YOU NEED PREVIOUSLY DETERMINED “OPTIMAL DRY WEIGHT”AND HOME WEIGHING SCALES!

  22. HYPERTENSION • Diuretic should be First or Second CHOICE!(ALLHAT ;Diab. Mell., Proteinuric Renal Dis.) • Affordable • HCTZ 6 — 50 mg MAXCHLORTHAL*** 6 — 25 mg MAX • Enhances Hypotensive Effectiveness • Routine K Supplementation Unnecessary • Best with Modest Salt Restriction, Dash Diet

  23. CASE STUDY 4 Your Chief Resident treats a 70 year old lady for isolate systolic hypertension (BP 170/90 mm Hg) with HCT2 25mg daily. Two weeks later she is admitted with a generalized seizure and confusion. Serum electrolytes are Na110 Cl 80 K 2.7 HCO328 BUN 18 Creat 1.4

  24. PREVENTION OF THIAZIDE-INDUCED HYPONATREMIA *** • Danger in Elderly • Thiazides Account for 25% of all Cases • Avoid High Fluid Intake and Nsaids • One Hyponatremic Episode Contraindicates Thiazides—YES ! Value of Testing early ? CH20 ADH PgE2 (ANN IM 110,24, 1989)

  25. DIURETIC TREATMENT: CAUTION WHEN • Cirrhosis with ascites but not peripheral edema • Diastolic cardiac failure • Severe nephrotic syndrome • K-wasting – GI losses, high salt diet • Amiloride combinations – CRF, Type 4 renal tubular acidosis (Diabetes mellitus)

  26. DON’T. . . • Treat edema without making a diagnosis • Use expensive antihypertensive agents when a cheaper one will do at least as well • Repeat the same non-diuretic dose twice daily in edematous states • Over treat to “dryness” or plasma vol. contraction.

  27. DO. . . • Remember the negative effects of too high a salt intake and of Nsaids • Check renal profile before and 7-10 days after initiating thiazides for hypertension • Treat anasarca in hospital with daily weights and renal electrolyte measurements • Remember diamox for Metabolic Alkalosis • Potency of Loop + DCT + CD inhibition • Use “Optimum Dry Weight”

  28. THANK YOU FOR YOUR ATTENTION. QUESTIONS?

  29. OTHER USES (cont’d) • Hyponatremic Encephalopathy Loop Diuretics [UNa] = 80 mEq/L • Acute Mountain Sickness Prophylaxis - Diamox • ? NOT in Myeloma Kidney • ? NOT in Malignant Hyp./Eclampsia

  30. OTHER USES • Recurrent Renal Calcium stones : Idiopathic Hypercalcemia (Thiazides Only) • Treatment of Acute Hypercalcemia (Loop/D’s/Only) • Nephrogenic Diabetes Insipidus (Thiazides)

  31. SIDE EFFECTS PROX LOOP D. C. TUB. CD ALL SITES GOUT, HYPERCALCEMIA HYPOKALEMIA, MET.ALKALOSIS, HYPOMAGNESEMIA HYPONATREMIA, HYPOKALEMIA, MET.ALKALOSIS HYPERKALEMIA ,MET ACIDOSIS HYPOTENSION, PRE-RENAL FAILURE, HEPATIC ENCEPHALOPATHY

  32. MANAGEMENT OF HYPERKALEMIA WHEN ACEI, ARB OR SPL INDICATED (Measure Urine K) • Dietary K • Loop diuretic • Treat low HCO3 • Remove other relevant med’s if possible • Β-blocker, NSAIDS

  33. BARTTER’S SYNDROME = “CONGENITAL LASIXEMIA” • GITELMAN’S SYNDROME = “CONGENITAL THIAZIDEMIA”

  34. DIURETIC HISTORY • Calomel (HgCl2) • Organic Mercurials 1919 (“Southey’s Tubes”) • Suphonamides  Thiazide (1960)  Loop Diuretics •  ION Transporters  Molecular Genetics  Genetic Diseases (e.g. Gitelman)  Molecular Structure & Basis of ION Selection  • New Diuretics?? • Genetic Basis of E.H.

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