Transcript Distribution & Fate

Distribution
& Fate
Lesson 5
Distribution
Drug disperses throughout system
 does not reach target
 silent receptors
 Distributes in
 Blood & extracellular fluid
 organs & tissues ~

Redistribution
Drug releases re-enters circulatory
system from
 Depot binding
 Protein binding
 Ion trapping
 Bound / unbound drug
 Ratio maintained
 Prolongs drug effects ~

Depot Binding
Unable to cross membranes
 Slow drug effects
 or prevent
 Prolong drug effects
 not metabolized
 Termination of drug effects
 Redistribution ~

Protein
Binding
Depot
Binding
Organs
&
Tissues
Blood
T
Brain
A
C
T
Z
Protein Binding
Large blood proteins
 albumin most abundant
 Nonselective binding
 Prevents drug from reaching target
 multiple drugs  compete

higher
effective dose for 1
Seldom clinical implications
Valium 99% bound, 1% free
 Redistribution ~

Drug Fate
Immediate & long-term drug disposal
 Determines duration of drug effects
 drug in system  drug effects
 Terminates drug effects ~

Half-life - t½
After complete absorption
 Plasma half-life
 time blood levels drop by half
 distribution half-life
 elimination half-life

metabolism
& excretion ~
Biotransformation
Metabolism
 structure altered  metabolite
 By enzymes
 site of action
 blood plasma
 liver
 Inactivation
 Some metabolites active
 e.g., valium, codeine ~

Liver
Main site of metabolism
 nutrients
 detoxification
 1st pass metabolism
 GI tract  liver ~

Cytochrome P-450

Main detoxification enzyme
 liver and intestine
 enzyme induction


contributes to tolerance
Inhibited by…
 grapefruit juice


6',7'-dihydroxybergamottin?
red wine to lesser extent ~
Excretion: Kidneys
Filtration of blood
 Excretion in urine
 Ionization required
 ion-trapping
 Active & inactive form
 Koryak tribesmen (Siberia)
 Amanita muscaria ~

Excretion: Kidneys
Smoking cessation
 diet  alkalinity of urine
 stress  excretion
 Antidiuretic Hormone (ADH)
 regulation of water
 alcohol, caffeine inhibit
 dehydration ~

Excretion: Other routes
Lungs
 alcohol breath
 Breast milk
 acidic  ion traps alkaloids
 alcohol: same concentration as blood
 antibiotics
 Also bile, skin, saliva ~~
