Personalized Medicine Flashcards Preview

Pharmacology > Personalized Medicine > Flashcards

Flashcards in Personalized Medicine Deck (54):
1

what are different responses to a single dose

1. hyperractive
2. hyporeactive

2

pharmacokinetic

changes in the disposition of the drug that influence the relative concentration of the drug in the body

3

pharmacodynamic

changes in cellular sensitivity
change in receptor # or function

4

name examples of pharmacodynamics

-desensitization (down regulation or refractoriness)
-supersensitivity
-malfunction
-changes in other components of the cellular response ("downstream") from the drug-receptor interaction

5

changes in the [ ] of an endogenous ligand may affect response to

antagonists

6

what is tolerance

a condition in which increasing disease of a drug are required to generate the same effect

7

see diagrams: slide 5 &6

see diagrams: slide 5 &6

8

what is pharmacogenomics

the study of how inherited genetic differences in humans influence individual response to drugs

9

genetic factors are the major determinants of what

normal variability of drug effects and are responsible for a # of striking quantitative and qualitative differences in pharmacological activity

10

the phenotype is influenced by what other factors

-age
-sex
-disease state
-smoking
-alcohol
-diet

11

if the mutation is relatively common (more than 1%) it creates a

polymorphism

12

what are the objectives of pharmacogenomics

1. identify variation in human drug response
2. elucidate the molecular mechanisms
3. evaluate the clinical significance
4. develop genetic screening test
5. individualize treatment and drug therapy

13

what are the major categories of variant responses

-drug metabolism
-drug transporters
-direct targets (receptors)
-indirect targets (other components affecting response or adverse reactions)

14

how many nucleotide bases does the human genome contain

~3 billion chemical nucleotide

15

the average gene consists of how many bases

3000 bases but sizes vary greatly with the largest known human gene being dystophin at 2.4 million bases

16

the total number of genes is estimated at

30,000

17

--% nucleotide bases are exactly the same in all people

99.9%

18

the function of over --% of discoveredgenes is unknown

50

19

what is polymorphism

-a variation in which one in every 1000 bases is different in any 2 humans

20

polymorphism is a result of

several types of mutations

21

polymorphism in specific genes can lead to

difference in response to drugs

22

what is an allele

an alternative form at a genetic locus on a single chromosome

23

for loci in most of the genome, a human has -- chromosomes which carry --

2
carry the same alleles or 2 different alleles

24

what is a genotype

alleles present in an individual

25

cystic fibrosis genotype

deletion of nucleotides encoding phenylalanine in CFTR gene

26

what is a phenotype

physical manifestation of the genotype

27

cystic fibrosis phenotype

chronic respiratory infection, mucus build-up, fat maldigestion

28

what are potential uses of genomics for therapy

-Individualized gene therapy for preventive/treatment measures (future)
-Identify genes conveying risk for development of chronic disease; implement preventive measures (future)
-Understand disease pathophysiology; identify new diagnostic or therapeutic targets (ongoing)
-Improve the drug development process (ongoing)
-Improve the clinical risk/benefit profile of therapeutic agents (here and now)
-Direct drug therapy and dose (here and now)

29

genetically polymorphic P450s are associated with what

changes in drug effects

30

59% of commonly prescribed drugs are metabolized by enzymes with

polymorphic alleles

31

metabolizer classifications

1. poor metabolizer
2. intermediate metabolizer
3. extensive metabolizer
4. ultra-rapid metabolizer

32

poor metabolizer

has 2 defective alleles and lacks functional enzyme

33

intermediate metabolizer

-heterozygous for one functional and one deficient allele
-has 2 partially defective alleles that cause reduced metabolism

34

extensive metabolizer

-2 normal alleles
-often majority of population
-"normal" metabolizers

35

ultra-rapid metabolizer

-duplicated or multiduplicated functional alleles with extremely high metabolic capacity

36

conversion of codeine to morphine is partially dependent on

CYP2D6

37

function if CYP2D6

genotype partially determines analgesic effect of codeine

38

poor metabolizers (PM) have low

CYP2D6 activity and do not efficiently convert codeine into morphine

39

ultra-rapid metabolizers (UM) have high

CYP2D6 activity and rapidly convert codeine into morphine

40

what is warfarin

inhibits synthesis of vit K dependent clotting factors

41

what are the polymorphic genes affecting warfarin metabolism

CYP2C9
VKORC1

42

allelic frequencies are usually associated with

ethnicity

43

see diagrams: slide 22-23

see diagram: slide 22-23

44

>50% of the variability in the warfarin dose may be explained by

polymorphism in CYP2C9 and VKORC1

45

the maintenance warfarin dose can estimated from

clinical and pharmacogenetic factors that can be obtained at the the time of warfarin initiation

46

what are carbamazepine ADRs

dangerous or even fatal skin reactions caused by carbamazepine therapy

47

carbamazepine ADRs are more common in patients with

a particular human leukocyte antigen (HLA) allele, HLA-B*1502

48

allele HLA-B*1502 occurs mostly in patents with ancestry across broad areas of

Asia, including South Asian Indians

49

see slides 26-27

see slides 26-27

50

examples of pharmacogenomic information supplied and test recommended

-mercaptopurine (TPMT deficiency)
-irinotecan (UGT1A1*28 allele)
-atomoxetine (CYP2D6 variants)
-tamoxifen (CYP2D6 variants)

51

tumor tissue tested for

somatic mutation before prescribing selected drugs

52

tumor therapy: pharmacogenomic information supplied and test recommended examples

cetuximab (EGFR expression)
trastuzumab (Her2/neu overexpression)

53

see slide 30

see slide 30

54

FDA list of approved biomarkers

-drug exposure and clinical response variability
-risk for adverse events
-genotype-specific dosing
-mechanisms of drug action
-polymorphic drug target and disposition genes