Drug Metabolism Flashcards
What 3 reactions does phase 1 metabolism involve (HOR)
- Hydrolysis
- Oxidation
- Reduction
What 2 things does phase 1 do?
- Increases the polarity
- Provides an active site for phase 2
What enzymes carry out phase 1 metabolism mainly?
Cytochrome P450’s
Where is CYP3A4 found in the body?
Liver
What 3 drugs does CYP3A4 metabolise?
- Diazepam
- Methadone
- Simvastatin
What does CYP2D6 metabolise?
- Antidepressants
- Antipsychotics
- Codeine
What does CYP2D6 do to codeine?
Converts it to morphine
What percentage of the population don’t express the gene for CYP2D6?
5-10%
What can induce the effects of CYP2D6 and CYP1A2?
Smoking
What does CYP1A2 metabolise?
Theophylline
What process does phase 2 metabolism involve?
Conjugation
What does conjugation involve?
Attachment of something to the compound
What 4 compounds can be attached during conjugation
- Glucaronic acid
- Gluthianone
- Sulphate
- Acetate
What are the 4 compounds in conjugation (phase 2) attached to?
The metabolite from phase 1
What does conjugation do to a drug (referring to activity)
Inactivates most drugs, some may stay active
What 7 factors may inhibit or induce drug metabolism?
- Other drugs/substances
- Genetics
- Hepatic blood flow
- Liver disease
- Age
- Sex
- Ethnicity
How does enzyme induction affect drug metabolism?
- Drug metabolic enzymes can be induced by other substances
- This decreases the drugs efficacy
What common inducers of enzymes are there that will reduce a drugs efficacy?
- Smoking
- Alcohol
What common drugs are there that will cause enzyme induction?
- Phenytoin
- Carbamazepine
What is a drug that can cause enzyme inhibition?
- Erythromycin
- Cimetidine
- Clarithromycin
How do genetic mutations result in reduces/induced drug metabolism?
- May alter coding genes which can lead to absences/deficiencies of an enzyme
What can genetic mutations in the enzymes gene result in when a drug is taken?
Toxicity
What is a result of difference in individual gene expression
Different forms of metabolising enzymes
What can enhanced expression lead to?
- Increased metabolism
- Reduced efficacy
