The extent of distribution of a drug depends on its-
> lipid solubility
> ionization at physiological pH
> extent of binding to plasma and tissue proteins
> presence of tissue-specific transporters
> differences in regional blood flow
Drugs which easily pass through cell membrane achieve wide distribution and drugs which do not pass through cell membrane are limited in their distribution.
Distribution of drug proceeds until an equilibrium of unbound drug in plasma and tissue fluids is established.
Factors that affects the volume of drug distribution are,
-Lipid : water portion coefficient of the drug
-pKa value of drug
-Degree of plasma protein binding
-Affinity for different tissues
-Fat : lean body mass ratio, which can vary with age, sex, obesity etc.
-Diseases like CHF, uremia, cirrhosis
Penetration or entry into brain and CSF(Cerebrospinal fluid) or central nervous system :-
Entry of drug into central nervous system is controlled by blood brain barrier.
It is a hypothetical barrier which exists between plasma and extracellular surface of brain.
This barrier is constituted by glial cells and capillary endothelium in the brain.
Only lipid soluble, non ionized drugs readily passed through this barrier.
Passage across placenta or fetal circulation :-
Entry of drugs into fetal circulation is controlled by blood placental barrier.
It is also a hypothetical barrier which exists between maternal and fetal circulation.
It permits the entry of only lipid soluble and non ionized forms of drugs.
Accumulation :-
A drug can accumulate at different areas of the body. Slow release of the drug from these areas can produce prolonged effects. The drugs can be mostly accumulate in following storage sites,
> Cells like liver cells E.g. Quinacrine an antimalarial drug.
> Plasma proteins like albumin E.g. Phenylbutazone and sulfonamides.
> Connective tissues like bone E.g. Heavy metals and tetracyclines.
> Fat, if the drug is highly lipid soluble E.g. Thiopental, a lipid soluble barbiturate.
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