Distribution

Absorbed drugs are distributed throughout bodily tissues. Most of even the psychoac-tive drugs will linger in areas other than the brain, and this contributes to unwanted side effects. Nevertheless, the total amount of the drug absorbed determines the size and the duration of its effects because there is a balance between drug concentrations in the brain, blood, and other tissues. Factors influencing distribution, that is, how much of the absorbed drug is taken up by a particular organ or tissue, and how fast the drug gets there, depend upon the chemical characteristics of the drug, vascularization of the tissue, and the existence of specific barriers.

An important factor to consider is the degree to which unspecific binding to blood plasma proteins occurs. Many drug molecules bind to blood-borne proteins such as albumin, and an equilibrium develops between bound and free fractions of the drug in the blood. Protein-bound drug cannot leave the blood vessels and thus is neither eliciting any action nor being cleared from the body. Protein-bound drug thus constitutes a reservoir from which the drug is released dependent upon the speed with which the free drug leaves the bloodstream by entering into tissues. Some psychoactive drugs have very high proportions of the bound fraction. For example, approximately 19 out of 20 molecules of diazepam in the blood are bound to plasma proteins at a given time.

Drugs must pass cell membranes in order to be absorbed or to enter tissues. Cell membranes consist of complex lipid molecules, called phospholipids, that form a bilayer with their hydrophilic parts forming the surfaces of the membrane. This phospholipid bilayer contains protein molecules of varying size. Some of these form channels, others can act as transporters through the cell membrane. Because of the lipid nature of cell membranes, drugs that are well soluble in lipids penetrate these membranes easily by simple diffusion and distribute in accordance with the concentration gradient, that is, toward tissues and body parts where the concentration of the drug is lower.

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