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 IV - How Do I Use Them
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IV - How Do I Use Them

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  • 1. DIURETICS How do they work? What do they do? When do I use them? HOW DO I USE THEM?
  • 2. CONCEPT OF CEILING DOSE Ceiling [Diuretic] TL Ceiling Effect Log [Diuretic] TL Fractional Excretion of Sodium (%)
  • 3. CONCEPT OF CEILING DOSE Dose of Diuretic that Achieves a Ceiling [Diuretic] in the Tubular Lumen. Said Differently Dose of Diuretic that Yields a Near-Maximal Diuretic Response.
  • 4. CONCEPT OF CEILING DOSE EFFECT < Ceiling Effect Ceiling Effect Ceiling Effect ACTUAL DOSE < Ceiling Dose Ceiling Dose > Ceiling Dose
  • 5. CONCEPT OF CEILING DOSE Exceeding Ceiling Dose Yields: Pointless, and possibly harmful, to exceed ceiling dose of diuretic!! No Additional Effect Possible Adverse Effects
  • 6. DETERMINANTS OF CEILING DOSE VARIABLE
    • Ceiling Dose Depends on:
      • Diuretic
      • Disease
    Increased Potency Decrease CEILING DOSE Decreased Tubular Transport (e.g., ARF/CRF) Increase Increased Binding to Urinary Proteins (e.g., Nephrotic Syndrome) Increase
  • 7. CEILING DOSES FOR I.V. LOOP DIURETICS (in mgs) CIRRHOSIS HEART FAILURE 40 to 80 1 to 2 10 to 20 NEPHROTIC SYNDROME AFR/CRF Moderate AFR/CRF Severe 160 to 200 8 to 10 50 to 100 80 to 160 4 to 8 20 to 50 80 to 120 2 to 3 20 to 50 40 to 80 1 to 2 10 to 20 Furosemide Bumetanide Torsemide Protein Binding Increases Ceiling Dose Impaired Delivery Increases Ceiling Dose
  • 8. CONVERTING I.V. DOSING TO ORAL DOSING BIOAVAILABILITY CONVERSION FACTOR ~ 50% (highly variable) ~ 100% ~ 100% 2 or higher 1 1 Furosemide Bumetanide Torsemide
  • 9. DETERMINANTS OF CEILING EFFECT VARIABLE
    • Ceiling Effect Depends on:
      • Diuretic
      • Disease
    Diuretic Loop > Thiazide > K-Sparing CEILING EFFECT Disease Diminished Nephron Response in Nephrotic Syndrome, Cirrhosis, & Heart Failure.
  • 10. MECHANISMS OF DIURETIC RESISTANCE MECHANISM Patient Counseling SOLUTION Patient Counseling Push to Ceiling Dose Noncompliance NSAIDS Decreased Tubular Transport (e.g., ARF & CRF) Bed Rest Decreased RBF
  • 11. MECHANISMS OF DIURETIC RESISTANCE (Continued) MECHANISM SOLUTION Bed Rest More Frequent Dosing or Continuous Infusion Combination Therapy (Sequential Blockade) Changes in “Volume Hormones” (SNS, RAS, ADH & ANF) Compensation by Distal Nephron Diminished Nephron Response (CHF, Cirrhosis, Nephrotic Syndrome)
  • 12. MECHANISMS OF DIURETIC RESISTANCE Proximal Distal Na Na Proximal Distal Na Proximal Distal Na Na Na Proximal Distal Na Na Acute Loop Chronic Loop Chronic Loop + Thiazide
  • 13. MECHANISMS OF DIURETIC RESISTANCE (Continued) MECHANISM SOLUTION Bed Rest More Frequent Dosing or Continuous Infusion Combination Therapy (Sequential Blockade) Changes in “Volume Hormones” (SNS, RAS, ADH & ANF) Compensation by Distal Nephron Diminished Nephron Response (CHF, Cirrhosis, Nephrotic Syndrome)
  • 14. RATIONALE FOR MORE FREQUENT DOSING OR CONTINUOUS I.V. INFUSION [Diuretic] TL Ceiling [Diuretic] TL [Diuretic] TL Ceiling Ceiling
  • 15. CEILING DOSES FOR CONTINUOUS I.V. INFUSION OF LOOP DIURETICS (in mgs per hour) LOADING DOSE (in mgs) CrCl < 25 10 0.5 5 10 to 20 0.5 to 1 5 to 10 20 to 40 1 to 2 10 to 20 40 1 20 Furosemide Bumetanide Torsemide CrCl: 25 to 75 CrCl > 75
  • 16. WHAT HAPPENS WHEN [DIURETIC] IN TUBULAR LUMEN IS LESS THAN CEILING?? Postdiuresis Sodium Retention!!
  • 17. RATIONALE FOR LOW SODIUM DIET A low sodium diet attenuates postdiuretic sodium retention, thereby lowering diuretic requirements!! Major Problem is Compliance
  • 18. IMPORTANT DRUG INTERACTIONS NSAIDS Salt Decongestants Probenecid Hyperkalemia- Induced by K-Sparing Diuretics Enhanced Ototoxicity of Loop Diuretic Diminished Diuretic Response ACE Inhibitors Beta-Blockers K Supplements K-Sparing Diuretics Heparin Ototoxic Drugs
  • 19. ARF/CRF Nephrotic Syndrome Cirrhosis Mild CHF Severe/Moderate CHF
    • DROP Thiazide &ADD Loop Diuretic:
      • 1) Titrate Single Daily Dose to Ceiling
      • 2) Optimize Frequency of Ceiling Dose
        • Furosemide: up to 4X daily
        • Bumetanide: up to 6X daily
        • Torsemide: up to 3X daily
    • ADD Thiazide Diuretic:
      • CrCl > 50, use 25 to 50 mg/d HCTZ
      • CrCl 20 to 50, use 50 to 100 mg/d HCTZ
      • CrCl < 20, use 100 to 200 mg/d HCTZ
    • ADD K-Sparing Diuretic:
      • If CrCl > 75
      • If Urinary [Na]:[K] ratio is < 1
    • (Note: May add K-Sparing Diuretic to Loop
    • and/or Thiazide Diuretic at Any Point in Algorithm
    • for K Homeostasis.)
    While Maintaining Other Diuretics, Switch Loop Agent to Continuous Infusion Spironolactone Titrated to 400 mg Daily.
    • ADD Thiazide:
    • If CrCl > 50
    • 50 to 100 mg/d HCTZ
  • 20.  

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