Drug metabolism Flashcards
How does metabolism tend to chemically alter drugs?
Converts lipophilic, pharmacologically active compounds to polar, non-active derivatives that can be easily excreted
What 3 reactions are classed as phase 1 metabolic reactions?
Reduction
Oxidation
Hydrolysis
What is the purpose of phase 1 metabolism?
To create or unmask functional groups to use as a point of attachment for phase 2 metabolism
What enzyme is responsible for most phase 1 metabolic reactions?
Cytochrome p450
How many isoenzymes of CYP450 are there in humans?
57
What reaction does CYP450 most commonly catalyse?
oxidation
What are the general reactants and products in a CYP450 reaction?
Reactants: drug, NADPH, oxygen, H+
Products: drug-OH, NADP, H2O
What enzyme is responsible for nitrogen-oxidation reactions?
FNO (flavine-containing nitrogen oxidase)
Recall the mechanism of the metabolism of a drug by FNO, and the disorder that results from dysfunction of this system
nitrogen forms dative bond to oxygen: nitrogen = delta neg, oxygen = delta pos –> very polar and very water-soluble amine
Dysfunction –> fish odour syndrome
Describe the kinetics of alcohol metabolism
Reversible oxidation with 0 order kinetics
What is the main purpose of phase II metabolism?
Add large polar group to the molecule to make drug water soluble for excretion
What similarities exist between phase II metabolic enzymes?
- All called “transferase”
2. Apart from glucathione, all pretty much act on same functional groups
Recall the 6 possible reactions of phase 2 metabolism
- Glucuronidation
- Methylation
- Acetylation
- Glucathione
- Sulphation
- Amino acid conjugation
What is the conjugating factor in glucuronidation?
UDPGA
What is the conjugating factor in methylation?
S-adenosyl methionine
