k5- kuliah drug excretion 2010

8/12/2019 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

k5- kuliah drug excretion 2010

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