Variability Due to Genetic Differences Flashcards
What is one of the main ways people vary in how they respond to drugs?
Genetic variations in pharmacokinetics
What are inherited variations to drug response?
Inherited differences can occur in any of the proteins involved in ADME, drug receptors and targets
What is the focus of this lecture?
Inherited variation in drug metabolism (phase one) particularly CYP 450
what is CYP450?
A family of proteins with many subgroups, isoforms etc that metabolize many endo and exogenous compounds.
What is phenotypic expression
Expression of genes, also influenced by environment
Though we just focus on variation in inherited genes for this lecture.
What is polymorhpism?
When two or more phenotype exist for that gene in a population
What is the poor metaboliser trait?
Inherited loss of function in a drug metabolizing enzyme
thus increased prolonged drug in system and risks…
What is extensive metabolizers?
Normal enzyme activity
How is the poor metabolizer (PM) inherited?
Autosomal recessive mendalian manner
What may PM lead to?
Elevated drug levels in blood, thus increased risk of toxicity especially for those with a small therapautic window
What are the genetic polymorphisms phenotype for enzyme function?
PM = null action, homozygous for deleterious allele IM = intermediate metabloizer, heterozygote carrier of a deleterious allele EM = extensive metabolizer, normal function (homozygous wild type allele)
What is omeprazol?
a proton pump inhibitor, (H/K ATPase), prevents stomach acid secretion (parietal cells). treats peptic ulcers.
What is metabolic ratio?
Drug / metabolite
High = poor metabolizer low = extensive
