Shake it off
The four factors influencing drug concentration after oral medication administration.
What are absorption, distribution, metabolism, and elimination?
This is how often CPIC guidelines are updated
Every 2 years
Three groups with clinical guideline annotations on PharmGKB
What are (any of):
CPIC: Clinical Pharmacogenetics Implementation Consortium
DPWG: Dutch Pharmacogenetics Working Group
CPNDS: Canadian Pharmacogenomics Network for Drug Safety
RNPGx: French National Network of Pharmacogenetics
The '*2' of CYP2C19 *1/*2
What is a haplotype or star-allele?
(or a no-function allele)
What you call an idiosyncratic or bizarre reaction unrelated to a drug's pharmacological action
What is a Type B adverse drug reaction (ADR)?
(a Type A ADR is a predictable and exaggerated reaction aligned with a drug's pharmacological action)
This pharmacokinetic property is known to be most affected by interindividual pharmacogenetic variation.
What is metabolism?
Something that CPIC guidelines CANNOT tell you.
What are either of these statements:
'When or in whom to perform PGx testing'
or
'If a drug will work/have adverse effects for a person'
The definition of a Tier 1 Very Important Pharmacogene (VIP).
Genes with substantial evidence to support their importance in pharmacogenomics. New genes will be added to Tier 1 as and when they are linked to recommendations from CPIC clinical guidelines.
What is a Genome Wide Association Study (GWAS)?
A gene that could not reach consensus in the term standardization process conducted by the CPIC?
What is VKORC1?
These three categories are used in the Flockhart table to identify the different ways medications can interact with cytochrome P450 enzymes.
What are substrates, inducers, and inhibitors?
Of the following list, one of these gene/drug pairs does not have a CPIC guideline at this time:
a) CYP2D6/atomoxetine,
b) CYP2D6/metoprolol,
c) TPMT/azathioprine, or
d) SLCO1B1/atorvastatin
What is the pair CYP2D6/metoprolol?
The definition of an 'actionable PGx' drug label
What is a drug label that may contain information about changes in efficacy, dosage, metabolism, toxicity, or contraindication with certain variants/genotypes/phenotypes.
What is a 'phenocopy'?
The group that is the primary source for star-allele definitions.
What is the Pharmacogenes Variation Consortium (PharmVar)?
Pharmacodynamic processes can be divided into these three categories.
What are receptor binding, signal transduction, and physiologic effect?
These are the three strengths of recommendations used in CPIC guidelines
The study design is given the most weight in PharmGKB variant annotation scoring.
What are hypothesis-driven association studies? (Weighted more than GWAS, meta-analyses, and in-vitro studies.)
The activity score of a CYP2D6 *1/*4 genotype.
(bonus: the predicted phenotype)
What allele combination gives a CYP2D6 activity score of 1.0?
(Intermediate metabolizer)
The terminology for a high-risk HLA-B*57:01 genotype?
What is a "positive" HLA-B*57:01 genotype?
This is the expected change in codeine efficacy in a person on bupropion, compared to someone on no other medications.
What is decreased efficacy.
The CPIC guideline recommendation for tacrolimus dosing in a person with CYP3A5 *3/*3 genotype.
What is:
Initiate therapy with standard recommended dose. Use therapeutic drug monitoring to guide dose adjustments.
The level of evidence (LOE) assigned to the association between variant rs6295 for the serotonin 1A receptor gene (HTR1A) and sertraline efficacy.
Bonus - what is the LOE score and why?
What is a Level 3 LOE?
LOE score = 5.75
There are 5 positive association studies and 3 negative association studies. There are no dosing guidelines or drug labels for the class-gene pair.
This is what happens if a laboratory does not test for the variants in a CYP2C19 *3 allele in a person who has the true genotype of CYP2C19 *1/*3.
What is a false negative call to a CYP2C19 *1/*1 genotype, and a phenotype misclassification to 'normal metabolizer' instead of an 'intermediate metabolizer.'
There was a higher incidence of haemolytic anemia in African American soldiers exposed to antimalarial drugs in WWII due to variations in this gene.
What is G6PD?