PHARMACOLOGY

 Cell- membrane and various transport mechanism ::

When the drug is in the soluble state absorption occurs through the cell- membrane The cell - membrane is a bimolecular lipid sheath bound on either side by protein layers 

        The membrane is about 80.A thick On the membrane there are numerous pores In general pores are of 4.A However in endothelial membrane (membrane of veins ) they are of 4.A 

        The absorption through the membrane may occur by three different mechanisms :: (1) Passive diffusion (2) Facilitated diffusion and (3) Active transport 

1.passive diffusion ::

It is unsaturable non selective and energy independent Such diffusion is proportionate to the conce tration gradient Most of the drugs (non-ionized forms) are absorbed by this me hanism The diffusion occurs from higher concentration to lower concentration 

ion-pair transport ::

While non-ionized drugs can be absorbed by simple passive diffusion the zwitterionic drugs which are too large can also pass through the lipoidal membrane by process of ion pair transport in this method the drugs form ion-pair with endogenous ions of the gastrointestinal tract and the resulting molecule gets partitioned into the lipoidal membrane Smaller ionic drugs can be transported through water filled pores in the membrane Absorption of ampicillin may take place by this mechanism 

2.Facilitated diffusion ::

It is saturable non -selective and energy independent phenomenon This diffusion is proportionate to the concentration gradient glucose and aminoacids are absorbed by this mechanism Drugs are also absorbed by this mechanism it has been found that there are number of carriers (membrane transporter proteins) involved in facilitated diffusion 5-fluorourocil is absorbed by this mechanism using pyrimidine transporter 

3. Active transport ::

This phenomenon is saturable selective and energy dependent The diffusion is not propontionate to the concentration gradient and this type of transport is carrier mediated very few drugs are absorbed through this route Alpha-methyldopa is an analogue of endogenous substance phenylalanine therefore it is absorbed by this mechanism other substances like steroids amino acids and glucose may also be absorbed by the active transport the drugs (e.g. cardiac glycosides ) that interfere with the active transport may affect absorption and distribution of drugs Recently various transporters (membrane proteins) have been identified which are involved in transport of drugs and other endogenous substances most common transporters are ATP- binding casselte (ABC) and solute carrier (SLC)