Metabolism of Drug (Part 3) = Phase 2 of Metabolism (General Pharmacology- Pharmacokinetics)

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Drug metabolism is the term used to describe the biotransformation of pharmaceutical substances in the body so that they can be eliminated more easily. The majority of metabolic processes that involve drugs occur in the liver, as the enzymes that facilitate the reactions are concentrated there.

The purpose of metabolism in the body is usually to change the chemical structure of the substance, to increase the ease with which it can be excreted from the body.

Drugs are metabolized through various reactions including:
(1) Oxidation
(2) Reduction
(3) Hydrolysis
(4) Hydration
(5) Conjugation
(6) Condensation
(7) Isomerization

There are often two phases of drug metabolism.
(1) Phase I: Non-synthetic reactions such as cleavage (e.g. oxidation, reduction, hydrolysis), formation or modification of a function group.
Phase I reactions convert a parent drug to more polar (water-soluble) active metabolites by unmasking or inserting a polar functional group (-OH, -SH, -NH2) geriatric patients have decreased phase I metabolism. Drugs metabolized via phase I reactions have longer half-lives.
(2) Phase II: Synthetic reactions such as conjugation with an endogenous substance (e.g. sulfate, glycine, glucuronic acid).

(1) Glucuronic acid (glucose metabolite) conjugation by UDP glucuronyl transferase
(2) Sulfate conjugation by sulfotransferases
(3) Glutathione conjugation with reactive metabolic products by glutathione S- transferases
(4) Amino acid conjugation by acyl-CoA synthetase and N-acetyltransferase
(5) Acetylation- attachment of an acetyl group by N-acetyl transferases
(6) Methylation- attachment of a methyl group by methyltransferases

The most common and important enzyme group involved in the Phase I metabolism of drugs is the cytochrome P450 (CYP450) superfamily of enzymes. This group of enzymes acts as a catalyst for the oxidation of many drugs. It can, in turn, also be induced or inhibited by many drugs and other substances. As a result, the metabolism of some drugs is affected by the presence of other substances. This is what is known as a drug interaction.

Some of the important enzymes in this family include:

CYP1A2
CYP2C9
CYP2C19
CYP2D6
CYP2E1
CYP3A4

Description Credit- https://www.news-medical.net/health/Drug-Metabolism.aspx

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