DISTRIBUTION OF DRUG
Once the drug has been absorbed into the blood, it is distributed around the body. It gets distributed throughout the blood supply, within a minute. Although drug is evenly distributed throughout the blood supply, this does not mean the drug is evenly distributed around the body, since the blood supply is rich in some areas of the body than the other. The drug in the blood system freely and rapidly distributes into the aqueous fluid surrounding the various tissue and organs.
The entry of the drug into the cell depends upon many mechanisms. Very small water molecules and ions diffuse (eg. K, CT) through the aqueous channels. Lipid soluble drugs of any size diffuses freely through the cell membrane. Water soluble molecule and ions of moderate size including the ionic form of most of the drugs, cannot enter cell readily, except by special technique. Drug that is too large to pass through any pores and practically insoluble in the membrane can form a lipid soluble complex at the membrane surface. The complex then move by diffusion within the cell membranes. Some drugs bind to the protein in the plasma and cannot reach its target site. After reaching the tissue, the drugs exert its effect, if target receptor site is situated in a cell membrane. To cross the cell membrane the drug must be sufficiently hydrophobic.
The concentration of a drug in blood supply rapidly drops after administration due to distribution, but there are other factors that reduce the amount of drug in the blood, drugs that are excessively hydrophobic are often absorbed into fatty tissue and removed from the blood supply, drugs that are charged may bound to various macromolecules and also removed from the blood supply, the drugs that reversibly binds to plasma protein, lowers the level of free drug. Therefore only a small percentage of the administered drug will actually reach the desired target.
The blood capillaries feeding the brains are lined with tight fitting cells that do not contain pores (unlike capillaries). More over, the capillaries are covered on the outside by a fatty barrier formed from nearby cells. Therefore, drugs entering the brain have to dissolve through the cell membrane of the capillaries and also through the fatty acid coating the capillaries. As a result polar drugs cannot enter blood brain barrier easily eg. Penicillins. Drugs intended to act on other site in the body can be made sufficiently polar that they do not enter the brain, thus minimizing the changes of CNS side effect.
The placental membrane separates the mother's blood from that of her fetus, Drugs can cross the placental barrier into the fetus and have unpredictable effect on development. When fetus is born, it lacks the ability to detoxify drugs and drug level in the new born may prove fatal.
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