drug disposition Flashcards
what is distribution?
reversible transfer of drug between the blood and other tissues within the body.
Drug is in blood, delivers drugs to different organs which is important so you know it will deliver drug to the relevant organ that is needed at that time as a target.
what does rate of distribution depend on?
- delivery of drug to tissue by perfusion - via the blood supply, this is the main factor for most drugs
- permeability of the tissue membranes
- physiological properties of the drug (lipo/hydrophilic)
- binding of drug to plasma proteins
- binding to acidic phospholipids in tissue membranes
when is is likely that perfusion will limit distribution?
Small and lipophilic molecules distributing across thin permeable membranes, rapid equilibrium. The only thing that would affect distribution in this case is blood flow
what is tissue perfusion?
NOT the same across tissues
- rapid eqm acheieved in highly perfused tissyes and small lipopholic molecules will reach is rapidly
- slow eqm for poorly perfused and polar
what are the highly perfused organs?
lungs
kidneys
liver
brain
reach eqm fast
what are the poorly perfused organs?
muscle
skin
adipose
reach eqm slow
what is perfusion rate?
ml/min/ml of tissue
what does entry of drug in cerebrospinal fluid shiw?
Differences in the rate of distribution linked to lipophilicity and degree of ionization of drugs
For the same tissue, distribution is slower for more polar drugs
what type of the drug crosses the membrane?
unbound is what we need to cross and unionised
what does location of distribution barrier do?
blood brain barrier
- very small pores
- tight junctions
- barrier at a capillary level
- polar molecules may struggle to cross
muscle
- capillaries porous to small molecules
- barrier at cellular level
- more leaky so polar may cross
