Drug Distribution Flashcards
Lipid-soluble drugs
bind non-specifically
Weak acids
bind to a specific, saturable site
Hydrophilic drugs
are highly soluble in aqueous, polar media.
Lipophilic drugs
are soluble in fats and non-polar solutions.
Many drugs are weak acids or bases
- Ionised:unionised ratio depends on pH
* Ionised drugs have low lipid solubility
Blood brain barrier
both a physical and functional barrier
Placenta
Tight endothelial cell junctions in maternal and fetal capillaries
Partially protective, except with:
– lipid soluble drugs
– unionised forms of weak acids and bases
Chronic abscesses
Avascular tissue compartments
Lung infection
Local low PO2 and high PCO2 cause vasoconstriction
Extracellular fluid
15 litres
plasma
3 litres
Interstitial fluids
12 litres
Intracellular fluids
27 litres
total body water (for a 70kg adult)
42 litres
large, water-soluble molecules (e.g. mannitol)
15 litres
Highly plasma- bound molecules
Highly charged molecules
Very large
molecules (e.g. heparin
3 litres
small, water-soluble molecules (e.g. ethanol)
42 litres
Plasma steady state conc. (Css)
The Css value reached depends on:
the rate of drug administered (K0)
divided by
volume of plasma cleared of drug per unit time (CL)
The time taken to reach Css depends on:
elimination half-life (t1/2)
The apparent volume of distribution (Vd) of a drug is
total amount of drug in the body
divided by
blood plasma concentration of drug
Vd varies with:
– Height –Weight –Age –Fluid accumulation • ascites • oedema • pleural effusion –Accumulation of fat
