Kinetics in renal disease

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giddyupp
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45880
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Kinetics in renal disease
Updated:
2011-01-13 13:02:20
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Kinetics renal disease PHPR521
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Kinetics in renal disease
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  1. What is rate of excretion?
    rate of filtration + rate of secretion - rate of reabsorption
  2. What is secretion?
    • facilitates extraction of drug in addition to filtration
    • capacity limited
    • active process (requires energy)
    • kicks in when clearance exceeds filtration
  3. What is reabsorption?
    • generally a passive process
    • no competition for absorption
    • nonpolar, lipophilic, low MW can be reabsorbed (why drugs are usually polar and hydrophilic)
  4. What characteristics must substances used to estimate GFR have?
    • freely filtered by the glomerulus
    • no renal secretion or reabsorption
    • constant concentration during the period of measurement (in blood)
  5. What substances are commonly used to estimate GFR?
    • inulin
    • Cr-EDTA
    • Tc-DTPA
    • Na iothalamate I
    • creatinine (the only one ideal for clinical use - it's endogenous)
  6. Where is creatine produced?
    in the liver
  7. Where is creatine converted to creatinine?
    in skeletal muscle
  8. What are the characteristics of creatinine?
    • freely filtered
    • limited secretion (causes over-estimation of filtration)
    • no reabsorption
  9. What is normal creatinine clearance?
    • male - 125mL/min/1.73m2
    • female - 115mL/min/1.73m2
    • by 60yo = 70% of young adults
  10. What equations are used to estimate CrCl?
    • Jelliffe
    • Cockcroft-Gault
    • Schwartz
    • Shull
  11. What equations are used to estimate GFR?
    • MDRD
    • CKD-EPI
  12. What disease states influence estimates of CrCl?
    • spinal cord injuries (low muscle mass)
    • amputations (low muscle mass)
    • Cushing's syndrome (low muscle mass)
    • muscular dystrophy (low muscle mass)
    • Guillain-Barre syndrome (low muscle mass)
    • rheumatoid arthritis (low muscle mass)
    • liver disease
    • glomerulopathic disease (damage to filter)
  13. What diet factors influence estimation of CrCl?
    • high meat protein diets (high creatinine values)
    • vegetarians (low creatinine values)
    • protein-calorie malnutrition (low creatinine values)
  14. What drugs/endogenous substances influence estimation of CrCl?
    • non-creatinine chromogens (false elevations)
    • cephalosporins (false elevations)
    • acetoacetate (false elevations)
    • IDMS-traceable assays (decreases values by 0.1-0.2mg/dL)
    • trimethoprim (increase values)
    • cimetidine (increase values)
    • fibric acid derivatives - other than gemfibrozil (increase values)
    • tronederone (increase values)
  15. What are the breakpoints to consider dosage adjustment in renal disease?
    • 60 mL/min/72kg = modest decrease (first decrease)
    • 30 mL/min/72kg = moderate decrease (second decrease)
    • 15 mL/min/72kg = significant decrease (third decrease)
  16. What drug pharmacokinetic characteristics call for adjustment in renal disease?
    • <50% renal drug elimination - adjust at 60 mL/min/72kg or less
    • 50-74% renal drug elimination - adjust at 30-45 mL/min/72kg
    • >75% renal drug elimination - adjust at 15 mL/min/72kg
  17. What plasma protein do acidic drugs compete for?
    albumin
  18. What plasma protein do basic drugs compete for?
    alpha-1 acid glycoprotein and lipoproteins
  19. What are the causes of hypoalbuminemia?
    • urinary loss
    • leakage into interstitial fluid
    • decrease in hepatic synthesis
    • altered intestinal absorption of dietary amino acids
  20. What endogenous substances can compete and displace drugs from binding sites?
    • urea
    • uric acid
    • hippuric acid
    • creatinine
    • free fatty acids
    • various furan carboxylic acids

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