Pharmacogenomics Flashcards
What are the 4 different types of responses a patient group can have?
- drug is toxic but beneficial
- drug is toxic and not beneficial
- drug is not toxic and not beneficial (non responders)
- drug is not toxic and is beneficial (responding well)
OR ESSENTIALLY
- no drug response
- therapeutic response
- drug toxicity
What are ADRs?
Adverse Drug Reactions- these are negative and undesirable effects from drug treatments. They can influence many body systems and have potentially fatal outcomes.
THIS IS A SERIOUS HEALTHCARE ISSUE AND ONE OF THE MAJOR LEADING CAUSES OF DEATH
What are some pharmacogenetic factors that contribute to how a patient responds to medication?
Pharmacokinetic variation (movement of drugs throughout body) Pharmacodynamic variation (body's biological response to drugs)
What are some demographic factors (characteristics of populations) that contribute to how a patient responds to medication?
Age- Drug metabolism and elimination are less efficient in newborns and elderly. Glomerular Filtration Rate (GFR) are lower in neonates and declines after the age of 20. This results in longer time for drug excretion. There are also a change in enzyme expression levels like CYPs and phase 2 conjugating enzymes for example.
Weight- BMI and fat
Sex/Gender/ Pregnancy
Ethnicity/ Genetic Ancestry - some ethnicities are more susceptible to harmful effect of a drug than other ethnicities.
What are some clinical factors that contribute to how a patient responds to medication?
Liver function (Drug metabolism) Kidney function (Since severe renal disease causes a reduction in the plasma protein binding of many drugs, the metabolic clearance of such drugs will be increased) Concomitant medications (others drugs that are also being taken)
What are some dosing factors that contribute to how a patient responds to medication?
- Formulation
- Route ( how drug is taken)
- Regimen ( how often drug is taken)
What are some other factors that contribute to how a patient responds to medication?
- If they adhere to the drug schedule
- Their food intake ( sometimes drug can irritate GI tract and stomach depending when its taken with regards to food)
What are 3 types of genetic variation a gene could have that causes an altered enzyme activity?
-regulatory variation (increased/decreased expression)
-coding variation (SNPs, deletion, insertion, frameshift, start/stop codon lost, stop codon gained)
-splice-site variation (the introns or parts of the introns are spliced in different ways- splicing defects)
RECALL THAT INTRONS ARE CUT OUT TO MAKE A FUNCTIONAL PROTEIN
What are expression quantitative trait loci (eQTL)?
cis vs trans?
eQTL change the expression level of a gene
cis eQTL- act on local genes
trans eQTL- act on genes on distant/ different chromosomes
What is pharmacogenomics (PGx)?
-how genetic variations can impact responses to treatments
What is precision health?
Precision health takes into account both genetic and not-genetic factors. Used to prevent adverse effects. It’s a personalized treatment.
What is the CYP2D6 pharmacogene?
It codes for the CYP2D6 enzyme that is important for drug metabolism. It is also regarded as polymorphic (genetic variations) in PGx
What is the risk of metabolizing drugs too slowly?
Can result in drug toxicity is drug concentration is too high
What is the risk of metabolising drugs too quickly?
Could result in a lack of drug efficacy
What risks could happen when an ultrarapid metabolizer takes codeine?
A lot of the codeine will be converted to its active form morphine by CYP2D6 than usual. This can be a toxic risk for this person.
