PED2001 Metabolism Flashcards
What is drug metabolism?
The process by which animals detoxify foreign chemicals (xenobiotics), including drugs, carcinogens, and toxins.
What are the two types of reactions in drug metabolism?
Phase 1 and Phase 2 reactions.
What is the impact of chirality on drugs?
Chirality affects drug metabolism as different stereoisomers may have distinct metabolic pathways.
What is the primary function of Phase 1 reactions?
To introduce reactive groups into the molecule, a process known as ‘functionalisation.’
What types of reactions fall under Phase 1?
Oxidation, reduction, and hydrolysis.
Where do Phase 1 reactions primarily occur?
In the liver.
What are CYP enzymes?
Cytochrome P450 enzymes that are involved in drug metabolism.
How are CYP enzymes classified?
Based on amino acid sequence similarities.
Which CYP enzyme family mediates the majority of Phase 1 metabolism?
CYP families 1-3 mediate 70-80% of Phase 1 metabolism.
What is the main outcome of the P450 reaction mechanism?
The addition of one oxygen atom to the drug, forming a hydroxylated product.
What is hydrolysis in drug metabolism?
A reaction where water participates as a nucleophile, breaking a chemical bond.
What characterizes Phase 2 reactions?
They are synthetic (anabolic) and involve conjugation of a substituent group.
What are common chemical groups added in Phase 2 reactions?
Glucuronyl, sulphate, methyl, and acetyl.
What is stereoselectivity in drug metabolism?
The phenomenon where stereoisomers differ in their pharmacological effects and metabolism.
What is enzyme induction?
The process where certain drugs increase the activity of microsomal oxidase and conjugating systems.
What is the significance of pre-systemic metabolism?
It reduces the bioavailability of drugs after oral administration.
What are pro-drugs?
Drugs that are pharmacologically active only after metabolism.
What can enzyme inhibition lead to?
Slowed drug metabolism and increased action of other drugs metabolized by the inhibited enzyme.
What is the role of genetic polymorphisms in drug metabolism?
They are a major source of variation in P450 enzyme activity among individuals.
Fill in the blank: Phase 1 reactions are _______ and often precede Phase 2 reactions.
catabolic
True or False: All CYP enzymes are involved in drug metabolism.
False
What is the effect of grapefruit juice on P450 enzymes?
It is an inhibitor that can cause cardiac dysrhythmias.
What is the main route of warfarin inactivation?
Through oxidation by CYP2C9.
Name one environmental factor that can influence P450 enzyme activity.
Cigarette smoke.
