5)Drug metabolism

Question 1

Process of drug metabolism

Answer 1

• Transforms lipophilic drugs into more polar, readily excretable drugs
• Liver ⇢ major site of drug metabolism
• Specific drugs ⇢ May undergo bio transformation in other tissues: eg kidney/intestines
• Metabolic transformation of drugs is catalysed by ⇢ enzymes + most reactions obey Micheaelis-Menten kinetics

Question 2

Factors affecting drug metabolism

Answer 2

• Age
• Diet
• Diseases
• Genetic factors

Question 3

Lipid-soluble agents

Answer 3

Must be metabolised in liver BEFORE being secreted by kidney

For this to occur 2 sets of reactions must occur in liver:

1. Phase I - Oxidation/reduction/hydrolysis
2. Phase II - Conjugation

Question 4

Phase I - oxidation/reduction/hydrolysis

Answer 4

• Conversion of lipophilic molecules into ⇢ more polar molecules via introducing a polar functional group
• Increases/decreases a drug’s pharmacologic activity

Cytochrome P450 system ⇢ carries out majority of phase I reactions

• Found on liver + intestines
• Responsible for addition of an O2 atom to form a hydroxyl group

Question 5

Phase II - Conjugation

Answer 5

• If after phase I a metabolite is sufficiently polar ⇢ it can be excreted by kidneys
• Forms an inactive product that can be excreted in urine/bile
• Many phase I metabolites are too lipophilic to be retained in kidney tubules ⇢ Further transformation required

Conjugation reaction occurs w/endogenous structure (sulphuric acid, acetic acid, amino acid)

• Results in polar compound that is therapeutically inactive