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 ~

T

A

Blood

Brain

CTZ

Organs &

Tissues

ProteinBinding

DepotBinding

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 ~~