Liver Flashcards
What does Phase I metabolism do to a drug?
Provides a functional group (e.g. OH or NH2) to increase polarity and provide a site for Phase II reactions
What are the most important enzymes involved in Phase I reactions?
Cytochrome P450
When are drugs susceptible to Phase II reactions?
If they have a suitable site that was already present or present as a result of a Phase I reaction
What do Phase II reactions involve?
Conjugation: the attachment of a large chemical group to a functional group on the molecule (almost always becomes pharmacologically inactive)
Why are the conjugates from Phase II reactions easier to excrete from the body?
More hydrophilic
What does Phase III involve?
Transport: into circulation for Renal elimination (main route) or into bile for elimination in faeces (for larger molecules)
What is the general aim of drug metabolism in the liver?
To make drugs less active and more hydrophilic
Which phase can produce toxic metabolites?
Phase I (e.g. Paracetamol)
Which 4 factors affect Drug Metabolism?
Age
Genetic Constitution
Drug Interactions / Environmental Influence
Liver Disease
What is drug metabolism like in neonates?
Worse: hepatic enzyme systems are immature and renal clearance is inefficient, so LOWER doses of all drugs needed
What is drug metabolism like in Children?
Can be QUICKER: CYPs are mature and relative liver mass and blood flow are higher
Judge doses by age and body surface area
What is drug metabolism like for the Elderly?
Overall, but particularly Phase I, capacity is reduced (relative liver mass and blood flow are lower)
Start treatment with smallest effective dose, and minimise number of drugs prescribed
What does CYP2D6 do?
Converts pro-drug Codeine into active form Morphine
What proportion of Whites have no CYP2D6 activity?
6-10%
What is the impact of having no CYP2D6 activity when taking codeine?
Cannot convert Codeine to Morphine, so no pain relief, and also experience exaggerated side effects (dose often increased in futile attempt to relieve pain)
