Metabolism of analgesics Flashcards
what is the fraction of the initial dose appearing in the portal vein called?
fraction absorbed
what does the fraction reaching blood circulation after first pass metabolism define?
bioavailability of the drug
What must a drug be in to have its desired pain killing action?
in a therapeutic window
What are the levels above and below the therapeutic window?
Above - can be toxic (adverse response)
Below - Sub therapeutic (no effect on pain relief)
What is the basics of analgesic drug metabolism?
- the body processes the concentration of the drug by metabolism using the liver followed by excretion
- break down all the chemical entities in blood “xenobiotics” using a range of enzyme systems
- as drug conc is reduced over time it eventually loses its effect so more drug is required
- too much drug however can lead to toxic side effects
What is the overall of of analgesic drug metabolism?
To breakdown drug into metabolites which can be excreted more easily
Increase water solubility to aid excretion in two ways
- Phase I: Activation by oxidation, reduction and hydrolysis, introduce or expose a functional handle for phase II
- Phase II: conjugation to make more polar molecules
what is 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 polymorphism of CYP450 mean?
There are many different forms, each encoded by a specific gene
Each will catalyse different classes of drug
How do most drugs undergo deactivation by CYPs?
Either directly or by facilitated excretion from the body
What happens if substances are bio activated by CYPs?
they form their active compounds (prodrugs etc)
What does drugs which effect CYP activity having an effect on?
Metabolic rate as well as plasma concentrations and there for therapeutic effects of any co-administered drugs
What are factors affecting CYP metabolism?
Polymorphism
Concomitant medication
Genetic variation of population
Age difference
Why do pharmacists need to be aware of polymorphism?
causes drug-drug interactions (CYP450 phase-1 metabolism is the main cause of these interactions)
Why can some drugs not be taken with grapefruit juice?
inhibits CYPs which metabolise the drug
Why are paracetamol and codeine fine to take together?
They have different routes of metabolism so there are no drug-drug interactions
why is genetic variation of population a problem with CYP450 metabolism?
People have different genes
Some people are deficient in genes which encode and produce various CYP metabolising enzymes
Why is age difference a problem in CYP450 metabolism?
As we get older we are less efficient at metabolising drugs and less efficient at eliminating them
- may lead to build up of drug and thus toxic side effects
