Intro to PM Flashcards
Give 4 examples of a personalised approach to medicine.
Allomap – blood test of 20 genes expressions to predict if a heart transplant will be rejected instead of invasive biopsy. 2) Plavix (clopidogrel) – genotyping for CYP2C9T enzyme, 3) Warfarin – genotype for CYP2C9T + VKORC needed (3* and AA = slow), familial 4) hypercholesterolemia – drugs to test this (high cholesterol In young people) need genotyping.
How would you tailor clopidogrel (Plavix) therapy?
Genotyping for CYP2C9T
What is the enzyme called involved in the metabolism of clopidogrel?
CYP2C9T
CYP2C9T stabalises clopidogrel to it’s inactive form.
FALSE – destablises i.e. metabolises it to it’s active form. People with various SNPs in this enzyme don’t metabolise it to its active form effectively as reduced CYP2C9T activity = less metabilsed drug = less active metabolite = inactive drug.
What important information should be known before taking clopidogrel?
Genotype of CYP2C9 that metabolises it to its active form, and other medications being taken e.g. Omeprazole.
Why may genotyping for the CYP2C9T polymorphism before Plavix (clopidogrel) therapy not be effective?
Not everyone has the same polymorphism variation e.g. if testing for the ‘correct’ SNP you could be counted as someone who doesn’t metabolise Plavix to active form, when you just have a different SNP that doesn’t affect metabolism or actually increases it.
What are the things that affect drug concentrations (not the main ones apart from 1)?
Polymorphims (Genes - also a main) Inter-individual variation (specific dose may lead to different intensities in different people). Pharmkokinetics (variations in how the drug is absorbed lead to different druc concentrations in different regions of the body) Pharmakodynamics variation (individualised response to drug look at pharmacodynamic behaviour of physiological endpoints e.g. how platelets are behaving i.e. aggregation, blood pressure). Can then adjust care based on these endpoints.
Why are bar graphs not as good as individual data graphs?
Masks inter-individual variation. I.e. extremes are masked and also opposite reactions i.e. one patient decreases but masked by all the increases, or one much higher but average of group is lower so masked.
OR no significant difference when there is lots but group average is similar. Could be due to age/ethnicity/genetics etc.
What are the main factors that cause variation in drug effectiveness?
Age, ethnicity, genetics (SNPs), immunological factors, concomitant disease, drug interactions (e.g. omazeprole in clopidogrel therapy).
The response to a drug is more effective in newborns than elderly people.
FALSE – half life of digoxin is 200hr vs 80 hr for elderly (and 40 for adult). This is because their organs aren’t fully developed, and drug metabolising enzymes are altered in newborns, and body composition changes with age.
Why are drugs often not as effective in elderly patients?
Body composition changes with age, polypharmacy so other drug interactions e.g. omazeprole with Plavix, drug metabolising enzymes may be altered? (like in newborns).
Hydralazine is more effective in white people.
FALSE – more effective in black people (when used with nitrates for lowering BP).
Give an example of a gene which an SNP increases the ability to form clots (thrombosis).
Clotting factor 5 (CFV) – her pal had this on plane and had to take Warfarin afterwards.
Give examples of concomitant diseases which influence a drug concentration.
Kidney or liver disease, gastric stasis e.g. migranes, diseases that influence RECEPTORS e.g. familial hypercholesterolemia i.e. lack of LDL reeceptors.
What can be used as an alternative to statins to lower cholesterol?
PCSK9 inhibitors.
