Drug metabolism Flashcards
What does phase one metabolism involve
Functionalisation reaction that modify the chemical structure of drugs
What’s the primary goal of Phase 1 metabolism
To prepare the drug molecule for phase 2
How does phase 1 metabolism prepare for phase 2
By creating sites for conjugation with endogenous molecules
Define endogenous
Growing or originating from within a molecule
What enzymes are involved in Phase 1 metabolism
Cytochrome P450 enzymes such as CYP3A
What is the function of the phase one enzymes
To catalyse REDOX reactions and hydrolysis
What can phase 1 metabolism result in
Formation of active metabolites ,inactive metabolites or toxic intermediates
What is phase 1 metabolism results depend on
The nature of the drug
Specific reactions involved
What is Phase 2 metabolism also known as
Conjugation
What happens in phase 2 metabolism
Involves conjugation of drug molecules or phase 1 metabolites with endogenous molecules to increase their water solubility and facilitate excretion
What do conjugation reactions involve
the attachment of glucuronic acid , sulphate, glycine, or glutathione to the drug molecule
What two general types of of enzyme systems take place in phase 1 reactions
1- Microsomal mixed function oxidases
2- Non-cytochrome oxidising enzymes
Give 2 examples of a Microsomal mixed function oxidases
1- flavoprotein
2- Cytochrome P450
Give 2 examples of Non-cytochrome oxidising enzymes
1- xanthine oxidase
2- alcohol/aldehyde dehydrogenase
What is aromatic hydroxylation
Oxidation reaction in which carbon-hydrogen bond oxidises into carbon hydroxyl bond by cytochrome P450 enzymes
What is aliphatic hydroxylation
Oxidation reaction by PY450 enzymes
this adds an OH
What effect does adding an OH from aliphatic hydroxylation
solubility increases
Where can aliphatic hydroxylation occur
The ultimate or penultimate carbon atom in the structure
activated carbon next to an sp or sp2 carbon
What is epoxidation
alkenes converted to epoxides (oxiranes)
What are epoxides/oxiranes
Three membered cyclic ethers
What occurs in epoxidation
Addition of a single oxygen atom across a double bond
True or false:
Epoxides are extremely reactive and hence undergo further reactions such as hydrolysis with water
True
What is dealkylation
Chemical process in which an alkyl group is removed and replaced with an hydrogen group
What is oxidative deamination
amine group is removed usually with introduction of an oxygen atom resulting in corresponding carbonyl compound releasing NH3 gas
