Pharmacogenetics and Personalized Medicine - IN

Question 1

what accounts for adverse drug reactions?

Answer 1

human DNA is all 99.5% identical, but its the 0.5% difference that is responsible for variety. ADRs are the 4th leading cause of death among adults in the US

Question 2

define pharmacogenetics

Answer 2

relates heritable variation to inter-individual variation for the purpose of optimal drug response

Question 3

define pharmacogenomics

Answer 3

field of new drug development studying how genes influence a patient’s response to medications
pharmacogenomics = pharmacogenetics for profit

Question 4

recognize these core prefixes - all genes involved in drug metabolism

Answer 4

CYP, ABC, SLC, NAT, UGT2B

Question 5

how does warfarin/coumadin work?

Answer 5

strong anticoagulant; inhibits enzyme epoxide reductase, resulting in inhibition of vitamin K metabolism

Question 6

what are side effects of warfarin?

Answer 6

it reacts with NSAIDs and to increases bleeding risk
its effectiveness is decreased in a high Vitamin K diet
it reacts poorly with alcohol consumption

Question 7

what are some current applications of next generation sequencing? (4)

Answer 7

mutations specific to one category of cancer
microdeletion syndromes
birth defect associated genes
ADME core markers for drug metabolism

Question 8

What is GINA

Answer 8

genetic information nondiscrimination act - prohibits discrimination in health coverage and employment based on genetic information

Question 9

what are loopholes in GINA

Answer 9

does not apply to small businesses (<15 employees) or protect someone from health care eligibility if they have an obvious disease.

Question 10

define screening

Answer 10

testing a population basis to identify individuals at risk of having or transmitting a specific disorder

Question 11

define MSAFP

Answer 11

prenatal screening - maternal serum quad/integreated test, Amniotic fluid a-Fetoprotein

Question 12

what are newborn screening tests used for

Answer 12

defined set of genetic diseases and usually mandatory, also large scale population tests that are rapid and inexpensive, with low false positives and no false negatives

Question 13

what is the purpose of carrier screening

Answer 13

looks at individuals who are phenotypically normal but may be at risk of having an affected child if their partner is also a mutation carrier for that disease - basically all ashkenazi jews are carriers for all diseases

Question 14

what are key factors for screening patients

Answer 14

high frequency of mutation in population
test is suitable for mass screening
genetic counseling available
prenatal testing available

Question 15

what was the most important outcome of the human genome project?

Answer 15

to generate a sequence for most human DNA, then next step to determine what it all means - information is centrally collected and available to all

Question 16

define pharmacokinetics

Answer 16

study of mechanisms of absorption and distribution of an administered drug, the rate at which a drug action begins and the duration of the effect

Question 17

what is the most well studied family of genes?

Answer 17

Cytochrome P450 - CYP - variety of enzymes involved in drug metabolism, specifically CYP2D6

Question 18

what are the classes of function of CYP2D6

Answer 18

Ultra - duplicate copies of two functional alleles
Extensive (normal) - two functional alleles
Intermediate - heterozygotes with one functional and one mutant allele
poor - no functional alleles, womp womp

Question 19

what is the warfarin mechanism

Answer 19

inhibits the enzyme epoxide reductase, resulting in inhibition of vitamin K metabolism, limiting the presence of functional cofactors, resulting in loss of ability to coagulate blood

Question 20

how do you diagnose UPD

Answer 20

DNA Microarray - comparing patient samples to ones from the parents
UPD - “region of homozygosity” or “long continuous stretches of homozygosity”

Question 21

define incest and consanguinity

Answer 21

incest is criminal version of consanguinity

Question 22

what diseases do ashkenazi jews typically carry

Answer 22

Tay Sachs, Cystic Fibrosis, Gauchers, Canavan, Niemann Pick

Question 23

what genetic predisposition is common of people of mediterranean descent

Answer 23

B-thalassemia

Question 24

what genetic predisposition is common of people of african descent

Answer 24

sickle cell anemia