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Kinetics in renal disease
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What is rate of excretion?
rate of filtration + rate of secretion - rate of reabsorption
What is secretion?
facilitates extraction of drug in addition to filtration
capacity limited
active process (requires energy)
kicks in when clearance exceeds filtration
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)
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)
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)
Where is creatine produced?
in the liver
Where is creatine converted to creatinine?
in skeletal muscle
What are the characteristics of creatinine?
freely filtered
limited secretion (causes over-estimation of filtration)
no reabsorption
What is normal creatinine clearance?
male - 125mL/min/1.73m
2
female - 115mL/min/1.73m
2
by 60yo = 70% of young adults
What equations are used to estimate CrCl?
Jelliffe
Cockcroft-Gault
Schwartz
Shull
What equations are used to estimate GFR?
MDRD
CKD-EPI
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)
What diet factors influence estimation of CrCl?
high meat protein diets (high creatinine values)
vegetarians (low creatinine values)
protein-calorie malnutrition (low creatinine values)
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
)
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)
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
What plasma protein do acidic drugs compete for?
albumin
What plasma protein do basic drugs compete for?
alpha-1 acid glycoprotein and lipoproteins
What are the causes of hypoalbuminemia?
urinary loss
leakage into interstitial fluid
decrease in hepatic synthesis
altered intestinal absorption of dietary amino acids
What endogenous substances can compete and displace drugs from binding sites?
urea
uric acid
hippuric acid
creatinine
free fatty acids
various furan carboxylic acids
Author
giddyupp
ID
45880
Card Set
Kinetics in renal disease
Description
Kinetics in renal disease
Updated
2011-01-13T18:02:20Z
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