Pharmacodynamics At the Drug Target

TABLE 3.9 Properties of oral drugs marketed from 1983 to 200218 

The term blood-brain barrier (BBB) refers to the special obstacle that drugs encounter when trying to enter the brain from the circulatory system. The difference between the brain and other tissues and organs is that the capillaries in the brain do not have pores for the free flow of small molecules in the interstitial fluid of the brain. To enter the interstitial fluid, all molecules must cross a membrane. This design is a protective measure to defend the brain from unwanted and potentially hazardous xenobiotics. Traditionally, drugs that target the brain or central nervous system (CNS) cross the BBB by passive diffusion. Transport by carrier proteins across the BBB is becoming better understood but remains an area of active research. 

Drugs typically do not travel only to the site of their intended target. Drugs instead are distributed throughout the body to the location of many possible targets. 

While drugs are designed to interact primarily with just one target, they often interact weakly with multiple targets. With access to multiple targets, drugs frequently show side effects. Not all side effects occur because of undesired, off-target interactions, but many do. 

The discovery and design of drugs in a form that is well absorbed, distributes effectively, and shows sufficient activity falls under the areas of lead discovery and optimization, the topics of Chapters 10 through 12. 

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