Metabolism of Analgesics- 9 Flashcards
What is the first pass Metabolism
The fraction of the initial dose appearing in the portal vein is the fraction absorbed, and the fraction reaching the blood circulation after the first pass through the liver defines the bioavalability of the drug.
What are the two phases of analgesic drug metabolism
Phase 1- Activation by Oxidation, reduction and hydrolysis, introduce or expose a functional handle for phase 2
Phase II- Conjugation to make more polar molecules
What are some ways of paracetamol metabolism
CYP450 2E1 to liver protein binding
Sulfation
Glucoronidation
Arachadonic acid coupling
Ways of codeine metabolism
CYP450 2D6
CYP450 3A4
Glucuronidation
What is the cytochrome P450 system
Found in mitochondria or endoplasmic reticulum of cells
Most important Phase-I enzyme metabolic pathway
Family of Isoenzymes
Polymorphism and mechanism cause for cautious prescription
What does the polymorphism of CYP450 enzymes mean
They have different forms by which each is encoded in a specific gene and each will catalyse different classes of drug.
Why do interactions occur in the cytochrome p450 system
Most drugs undergo deactivation by CYP’s either directly or by facilitated excretion from the body.
Drugs which effect CYP activity be they inducers or inhibitors have an effect on the metabolic rate as well as plasma concentrations.
Factors affecting CYP metabolism
Polymorphism
Concomitant Medication
Genetic Variation of Population
Age difference
What is a cocomitant medications
What happens when on more than one drug?
Some medications and foods are not suitable together.
What medications can’t grapefruit juice be had with.
Nifedipine because it inhibits CYP4503A4 which metabolises the drug.
Why cant NSAID’s and ACE inhibitors be taken together.
Hypertension effects are antagonised when used together with associated renal toxicity due to CYP3A4 metabolite interactions.
Why can paracetamol and Codeine be taken together
Paracetamol is CYP4502E1 at phase I
Codeine is CYP450 3A4 at phase 1
So fine to use together.
How does genetic variation effect drug metabolism
People have different genes including genes that metabolise, some patients are deficient in genes which encode and produce various CYP metabolising enzymes.
How does age difference affect drug metabolism
As we get older we are less efficient at metabolising drugs, which may cause build-up of drugs and thus toxic side effects.
