Chapter 17

Metabolism

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Student Objectives for this Chapter

After completing the material in this chapter each student should:-

The body has another way of removing drugs in the body. This method of elimination is metabolism or biotransformation. Metabolic processes, in general, have the overall effect of converting drug molecules into more polar compounds. Again, in general, the effect of this should be to decrease tubular re-absorption in the kidney and thus increase overall drug elimination. Generally, it also means an immediate loss of pharmacological activity because transport into the site of action is hindered (less lipid soluble) or the molecule no longer fits into the receptor site. There are exceptions however, and a number of 'new' drugs have been discovered as active metabolites, 'pro-drugs'.

Metabolism takes place by enzymatic catalysis (by reducing the activation energy of the reaction). Most metabolism occurs in the liver although other sites have been described, such as intestinal wall, kidney, skin, blood. An individual's enzyme activity and concentration in an organ and tissue is can be quite variable, controlled by factors such as age, disease, sex, diet, co-administration of other drugs and genetics. Drugs that are extensively metabolized, where metabolism is a major route of elimination, usually have considerable between individual variability. With these drugs therapeutic drug monitoring and pharmacogenomics become important considerations.


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