Flashcards in Pharmacogenics Deck (57)
the study of differences in drug response due to allelic variation in genes affecting drug metabolism, efficacy, and toxicity
variable response to individual gene
the genomic approach to the pharmacogenetics, is concerned with the assessment of common genetic variants in the aggregate for their impact on the outcome of drug therapy.
Variable response due to multiple loci across the genome
pharamcogenetics is the study or
clinical testing of genetic variation that gives rise to differing response to drugs
require CYP2D6 gene to activate.
More copies makes you metabolize more
normally metabolize ____% of codeine to morphine
once a drug is taken, the drug must:
1. reach its target
2. exert its effect
3. do the above before being inactivated/eliminated
describes absorption, distribution, metabolism and excretion of drugs (commonly referred to as ADME)
cytochrom p450, glyconyltransferase, thiopureine methyltransferase
describes the relationship between the concentration of a drug at its site of action and observed biological effects
most major drugs are only effective in ___% of patients
the CYP450 complex is
1. the gene products active in liver and intestinal epithelium
2. 3 main families: (CYP1, CYP2, CYP3)
the CYP1, CYP2, CYP3 have 6 main genes:
and phase I for ___% of common drugs
CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4
what gene accounts for 40% of all common drugs
There is less genetic variation on CYP3A4 than other CYPs
Most CYP's function to _____ drugs
But rarely they are needed to activate
example of gene needed to activate a drug
which converts codeine to morphine
4. grapefruit juice
codeine, this is needed to activate
CYP2c9 + VKORC1
6-mercaptopurine/6-thiguanine and childhood
hemolytic anemia after sulfa drugs
• Genetic Examples:
Cytochrome P450, glucuronyltransferase, thiopurine methyltransferase
• Genetic Examples:
Glucose-6-phosphate dehydrogenase, vitamin K epoxide complex
Pharmacokinestics is broken down farther into
two basic ways that drugs are metabolized through biotransformers
phase 1 metabolism
attach a polar group onto the compound to make it more soluble; usually a hydroxylation step
phase 2 metabolism
attach a sugar/acetyl group to detoxify the drug and make it easier to excrete
alter reading frame --> NO ACTIVITY
skip exons and/or alter reading frame--> no activity
alter protein function--> usually REDUCED ACTIVITY
copy number alleles -->
increased gene copy alleles --> INCREASED (ULTRAFAST)
based on the combinations (since individuals have 2 alleles in their genotypes), have 3 major phenotypes
2. poor (includes null alleles)
A single 8 oz glass of grapefruit juice can inhibit _______ activity for 24-48 hours.
(largely through intestinal inhibition of CYP3A).
drinking grapefruit juice while taking felodipine for hypertension can lead to ________
significant hypotension due to potentiation of the felodipine effect since CYP3A activity is reduced and metabolism/elimination of felodipine is similarly slowed.
Dosage of the immunosuppressive drug _______ (used in kidney transplants for instance) must be reduced by _____% to avoid toxicity when the _________ is added to treat a fungal infection.
Mechanism- ketoconazole temporarily inhibits _____ metabolism which leads to raised levels of _______ which can be neprotoxic.
Renal transplant patient who is exposed to tuberculosis and requires________:
the dose of cyclosporine must be ______ since rifampin is a _____ inducer and leads to more ______.
rapid metabolism and elimination of cyclosporine.
If you fail to take this into account, the cyclosporine levels will decrease and organ rejection will become a problem.
2. grapefruit juice
what gene effects cyclosporin?
1. tricyclic antidepressants
what gene is involved with tricyclic antidepressants?
isoniazid for tuberculosis
isoniazid for tuberculosis gene involved is?
-Often presented as the classic example of a pharmacogenetic mechanism that can be fatal if ignored
what gene is involved in 6-mercaptopurine?
mechanism of G6PD drugs
G6PD deficient individuals are susceptible ______
to hemolytic anemia after drug exposures
gene affected by sulfonamide
gene for dapsone?
gene for warfarin
Warfarin is a
blood thinner that is most commonly prescribed medicines, given to >200,000 patients/yr
one of the most commonly prescribed drugs