Drug Interacting Substances

Xenobiotics, whether they are drugs or not, can influence the activity of drug-metabolizing enzymes in a variety of ways.

Inducers: are xenobiotics that cause an increase in the drug-metabolizing activity of a target enzyme, usually by increasing the concentration of the enzyme in the liver or other tissue. Several CYP450 enzymes and glucuronosyltransferases are known to be inducible. 

In the case of drug–drug interactions, the compound causing the induction is called the precipitant drug, whereas the drug that is being affected is called the object drug. The consequence of induction is dependent on the extent of induction by the precipitant drug and the pharmacological characteristics of the object drug. For example, if the object drug is metabolized to a toxic metabolite, then induction by the precipitant drug may result in greater toxicity as a result of the increased drug-metabolizing activity.

Inhibitors: are opposite of inducers in that they decrease the metabolizing activity of a target enzyme, usually by competing with the object drug for the enzyme and preventing its metabolism.

The extent of inhibition is dependent on the affinity of the inhibitor, the availability of alternate metabolic pathways of the object, and the pharmacologic characteristics of the object drug. For example, if the object drug has a narrow margin of safety and one metabolic route of elimination, the addition of an inhibitor to that pathway could result in accumulation of the object drug and ultimately toxicity.

The extent of protein binding: can be altered by the administration of another compound that is also highly protein bound. Two drugs that compete for similar binding sites on plasma proteins can result in the displacement of (usually) the agent with the lower affinity. As a result, there is an increase in the free fraction of one or both drugs that can lead to increased receptor interactions, metabolism, or toxicity of the displaced drug.

Antibiotic therapy: may also influence the metabolic rate of a drug that is dependent on the gut microflora for its metabolism or enterohepatic circulation.

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