P4: pharmacokinetic journey Flashcards
Why can’t some people get pain relief from codeine?
Lack of certain CYP (can’t convert to morphine) or High levels of UDP-GA/UDP transferase (quickly converted from morphine to be excreted).
What is the mechanism of glutathione conjugation?
R-CH2-X —(GST)(GSH (Glu-cys-gly)) —> R-CH2-S-Cys-(^Gly \/Glu)
Where does a drug makes its first pass?
Liver - oral drugs absorbed through stomach and small intestines, arrive at the liver where they are modified (biotransformation). Less active drug available after first pass.
Where is ethanol metabolised?
Liver
What is ethanol metabolised into?
Acetaldehyde
Is acetaldehyde safe?
It is toxic.
Build up causes red skin, nausea and vomitting
What enzyme catalyses the reaction from ethanol to acetaldehyde?
Alcohol dehydrogenase (ADH)
What is acetaldehyde metabolised to?
Acetate
What enzyme catalyses the acetaldehyde to acetate reaction?
Aldehyde dehydrogenase (ALDH)
What causes Asian flush syndrome?
Deficiency of ALDH - so cant convert Acetaldehyde to acetate.
What is acetate synthesised to?
Acetyl CoA
What factors affect drug metabolism?
Pharmacogenetics - study of genetic variation and the effect it has on drug action.
Drug-Drug interaction
Gender
Age
Circadian rhythms - rate of drug absorption, hepatic clearance, 1/2-life and duration of action, show to differ depending when a drug was administered.
What can polymorphisms cause?
Result in AA changes that alter activity of the protein. eg can increase (extensive metabolisers), decreased/absent (poor metabolisers), altered substrate specificity of enzyme.
What does St John’s Wort do?
Induces production of cyt p450 CYP3A4.
- Increased metabolism of cyclosporine.
- Decreased bioavailability.
- Transplant rejection
- CYP3A4 metabolises 50% of all prescription drugs.
What phase metabolism do young children not have?
Phase II –> chloramphenicol toxicity due to poor glucuronidation (Gray baby syndrome).
