Lipid-soluble drugs cross the membrane at a rate that is a function of their concentration gradient across the membrane and the lipid: water partition coefficient of the drug? (AIPG 2009)
a. The absorption, distribution, and elimination of drugs require that they cross various cellular membranes.
b. The descriptions that are given in the question define the various transport mechanisms. The most common method by which ionic compounds of low molecular weight (100 to 200) enter cells is via membrane channels.
c. The degree to which such filtration occurs varies from cell type to cell type because their pore sizes differ.
d. Simple diffusion is another mechanism by which substances cross membranes without the active participation of components in the membranes. Generally, lipid-soluble substances employ this method to enter cells. Both simple diffusion and filtration are dominant factors in most drug absorption, distribution, and elimination.
e. Pinocytosis is responsible for the transport of large molecules such as proteins and colloids. Some cell types (e.g., endothelial cells) employ this transport mechanism extensively, but its importance in drug action is uncertain, at best. In the grander scheme of things, it is not particularly important.
f. Membrane carriers are proteinaceous components of the cell membrane that are capable of combining with a drug at one surface of the membrane.
g. The carrier-solute complex moves across the membrane, the solute is released, and the carrier then returns to the original surface where it can combine with another molecule of solute. There are two primary types of carrier-mediated transport:
h. Active transport and B. Facilitated diffusion. During active transport,
i. The drug crosses the membrane against a con centration gradient,
ii. The transport mechanism becomes saturated at high drug concentrations and thus shows a transport maximum, The process is selective for certain structural configurations of the drug.
i. Active transport is responsible for the movement of a number of organic acids and bases across membranes of renal tubules, choroid plexuses, and hepatic cells. With facilitated diffusion, the transport process is selective and saturable, but the drug is not transferred against a concentration gradient and does not require the expenditure of cellular energy Glucose transport into erythrocytes is a good example of this process.
j. In both situations, if two compounds are transported by the same mechanism, one will competitively inhibit the transport of the other, and the transport process can be inhibited non-competitively by substances that interfere with cellular metabolism.