Metabolism of drugs involves many important enzymes and pathways. Based on the type of reaction catalysed by them, they can be categorised as:

1. Enzymes involved in Phase I Metabolism include:
   i) In Oxidation: Cytochrome P-450 monooxygenase system, flavincontaining monooxygenase system, alcohol dehydrogenase, aldehyde dehydrogenase, monoamine oxidase, and co-oxidation by peroxidase.
   ii) In Reduction: NADPH-cytochrome P-450 reductase and reduced (ferrous) cytochrome P-450. It is important to note that a chemical can enter substrate cycle during reduction reactions. In this cycle, a freeradical electron is gained by the chemical which is also quickly lost towards oxygen to form a superoxide anion.
   iii) In Hydrolysis: Esterase, amidase, and epoxide hydrolase.
2. Enzymes involved in Phase II Metabolism include:
   i) In Methylation: Methyltransferase?
   ii) In Sulphation: Glutathione S-transferases and sulfotransferases.
   iii) In Acetylation: -N-acetyltransferases and amino acid N-acyl transferases.
   iv) In Glucuronidation: UDP-glucuronosyltransferases.

Factors Affecting Drug Metabolism

The following factors affect the biotransformation of a drug:

Inhibitors: Certain drugs, e.g., cimetidine, omeprazole, and ciprofloxacin, can inhibit enzymes that metabolise a drug. Since the metabolising enzymes are inhibited, metabolism of the administered drug decreases, which in turn leads to an increase in the duration of its action.

Stimulators: Certain drugs like phenobarbitone and rifampicin can increase the activity of enzymes that metabolise a drug. Hence, it proves advantageous when drugs like phenytoin and warfarin are administered, as it increases their metabolism.

Age: Young Children show poor drug metabolism as metabolic enzyme systems are not developed completely. For example, grey baby syndrome is seen in infants on administration of chloramphenicol as they lack glucuronyl transferase required for the inactivation of chloramphenicol.

Sex: In comparison to males, the females possess lesser ability for drug metabolism.

Species: Some enzymes may be species-specific. For example, rabbits possess atropinase enzyme and hence are able to metabolise atropine (therefore, atropine is non-toxic for rabbits); however, atropinase enzyme is absent in humans and hence, atropine proves toxic for humans.

Genetics: Drug metabolising enzymes show hereditary patterns; deficiencies of either of the enzymes belonging to the enzyme system can be inherited from one generation to the other. For example, an individual in whom Glucose-6-Phosphate Dehydrogenase (G-6-PD) enzyme is genetically deficient shows haemolysis when primaquine is administered to them.

Body Temperature: Temperature of the body is directly proportional to drug metabolism. Drug metabolism has been found to increase with an increase in body temperature and vice versa.