k5- kuliah drug excretion 2010
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DRUG EXCRETION
Prof Dr dr Jazanul Anwar SpFK
Dept Farmakologi dan TerapetikFK USU
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Overview - ADMEA
are biotransformed perhaps to several different compounds by
enzymes evolved to cope with natural materials - this may
increase, decrease or change drug actions
Most drugs:
enter the body (by mouth or injection or) - must cross barriersto entry (skin, gut wall, alviolar membrane..)
are distributed by the blood to the site of action- intra- or extra-
cellular - cross barriers to distribution (capillaries, cell wall.)
- distribution affects concentration at site of action and sitesof excretion and biotransformation
are excreted (by kidney or .) which removes them and/or their
metabolites from the body
Pharmacokinetics is the quantification of these processes
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Drug Absorption
disintegration
disintegration
dissolution
dissolution
absorption
intestinal
metabolism
absorption
hepatic
metabolism
gastric emptying rate
intestinal transit rate
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Drug excretion
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Renal Function
1. Glomerular filtration2. Active tubular
secretion
3. Passive tubularreabsorption
4. Excretion
Drug Excretion
-most drugs are excreted in urine either as unchanged or
drug metabolites
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Elimination by the Kidney
Excretion - major
1) glomerular filtration
glomerular structure, size constraints,protein binding
2) tubular reabsorption/secretion
- acidification/alkalinization,
- active transport, competitive/saturable,
organic acids/bases- protein binding
Metabolism - minor
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Glomerular Filtration- 1ststep in renal drug excretion
Drug enters renal tubule as a dissolved solute
Drug filtration rate= Free drug Plasma conc.X Glomerular filtration
rate (GFR)
For Penicilin G- 40% unbound in plasma;
pKa= 2.8; Plasma conc.=3 mg/mL; Free drug conc.= ?
Drug excretion rate-1200 mg/min
Glomerular filtration rate- 100 mL/min
Excreted drug = (Filtered+ secreted) - reabsobed
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Routes of excretion
1 Renal Excretion:It is the result of three processes:Passive glomerular filtration, active tubular secretion in proximal
tubules and passive tubular re-absorption.
Factors affecting renal excretion:
1-Glomerular filtration rate. Only free unbound water soluble
drugs with low molecular weight are filtered.
2-Change in urinary pH affect excretion of weak acid and base
drugs. Thus: -Alkalinization of urine by NaHCO3increases
of acidic drugs e.g. aspirin.
-Acidification of urine by NH4CL or vitamin C increasesexcretion of base drugs e.g., amphetamine.
3-Active tubular secretion e.g., probenecid, penicillin, uric acid...
Excretion of drugs
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Passive Reabsorption
-most substances are reabsorbed across renal tubular cells
if unionized and lipid soluble
Can manipulate urine pH to ensure drugs are not reabsorbed in overdose situations
5.8 = 5.8 + log A-/HA= 1= 1:1
Rate of reabsorbtion = 1.2 g/mL x 1/2 = 0.6 g/mL
increase urine pH to 7.0
7.0 = 5.8 + log A-/HA= 1.2 = 15.8:1= 1.2 g/mL x 1/16.8 = 0.071 g/mL
Renal Clearance= excretion rate/plasma drug concentration (units: L/h)
For penicilin: 1200 ug/min/ 3ug/mL= 400 mL/minx60 min/h=24000mL/h=
24000mL/hX 1L/1000mL= 24L/h
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Excretion of drugs
2-Gastrointestinal Tract:
a. Salivary glands: e.g., iodides, rifampicin andacidic drugs as salicylates.
b. Stomach: e.g., morphine (free and conjugated).
c. Large intestine: e.g., tetracycline, streptomycin.
d. Liver through bile, e.g.
-Ampicillin and rifampicin are excreted in active
form so can be used in biliary infection and
ampicillin in typhoid carriers.
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Other routes of excretion:
Biliary excretion- drugs with mwts >300 excreted in to bile
Enterohepatic cycling-
Sweat, Saliva-
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3-Sweat:e.g., rifampicin, vitamin B1.
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http://www.google.co.id/imglanding?q=cross+section+mammary+gland&hl=en&sa=G&biw=949&bih=461&tbs=isch:1&tbnid=FJMctpK9xk9d1M:&imgrefurl=http://en.wikivisual.com/index.php/Mammary_gland&imgurl=http://en.wikivisual.com/images/6/64/Illu_breast_anatomy.jpg&zoom=1&w=274&h=349&iact=hc&ei=kdSxTI7dJY7yvQPxpJzGBQ&oei=kdSxTI7dJY7yvQPxpJzGBQ&esq=1&page=1&tbnh=148&tbnw=116&start=0&ndsp=8&ved=1t:429,r:3,s:0&gbv=1 -
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.
5-Milk:basic drugs are trapped and excreted in acidic
milk, e.g., morphine, ampheta.Also chloramphenicol and oral anticoagulants can be
excreted in milk.
http://www.google.co.id/imglanding?q=cross+section+mammary+gland&hl=en&sa=G&biw=949&bih=461&tbs=isch:1&tbnid=FJMctpK9xk9d1M:&imgrefurl=http://en.wikivisual.com/index.php/Mammary_gland&imgurl=http://en.wikivisual.com/images/6/64/Illu_breast_anatomy.jpg&zoom=1&w=274&h=349&iact=hc&ei=kdSxTI7dJY7yvQPxpJzGBQ&oei=kdSxTI7dJY7yvQPxpJzGBQ&esq=1&page=1&tbnh=148&tbnw=116&start=0&ndsp=8&ved=1t:429,r:3,s:0&gbv=1 -
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IV. OTHER ROUTES
A.Hair
drugsheavy metals
B. Tears
http://www.hair-drug-tests.com/?portalid=LOOHDT
Rifampin + =
Soft contact
lens
http://www.hair-drug-tests.com/?portalid=LOOHDT