METABOLISM AND EXCRETION
The termination of drug effect is caused by biotransformation and excretion. All the substance in the circulatory system, including drugs, metabolites and nutrients will pass through the liver. A significant portion of the drug will be metabolized by hepatic enzymes to inactive chemical. The metabolic pathways are discussed in more details in Chapter 5.
Drugs and their metabolites can be excreted from the body by a number of routes such as via the lungs, the skin, the bile duct and the kidney. In general excretion by kidney is the most important route. Volatile and gaseous drugs can be excreted through the lungs. Such drugs pass out of the capillaries that supply the lungs then diffuse through cell membranes into the air sacs, from where they are exhaled. For example gaseous general anaesthetics are excreted in this way. A certain proportion of a drug can be excreted through sweat, saliva and breast milk. The kidneys are the principle route by which the drug and their metabolites are excreted. Blood is filtered under pressure to remove small molecule such as drugs and most of the water. However water is quickly reabsorbed, setting up a concentration gradient, which leads to hydrophobic molecules being reabsorbed in to the blood supply. Polar molecules remain in the nephron and are excreted in the urine. Drug metabolism makes a drug more polar, so that it is less likely to be reabsorbed from the nephrons.
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