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PHAR 211 > Midterm > Flashcards

Midterm Flashcards

1
Q

What are the four Rights of personalized medicine?

A

right patient
right drug
right time
right dose

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2
Q

What are the pros of personalized medicine?

A

more accurate diagnosis, safer, faster, lower s/e, increase efficacy

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3
Q

What are some challenges of personalized medicine?

A

patient engagement, privacy, cost, data ownership

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4
Q

Explain personalized medicine of tamoxifen?

A

used for breast cancer but needs CYP 2D6 to be active. some people are deficient in this

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5
Q

What are the cell cycle stages?

A

G1: grows and prepares
S: DNA replication
G2: grow
M: Mitosis
G0: Leaves cell cycle

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6
Q

What are the 2 checkpoints in cell cycle?

A

G1:before DNA Synth
G2: Prep for mitosis

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7
Q

When is the restriction point in the cycle?

A

commits to division
happens before S stage

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8
Q

How many chromosomes?

A

23 pair

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9
Q

What histones in chromosomes?

A

2 of H2A, H2B, H3 and H4 and H1 which clips it

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10
Q

What is transcription?

A

gene-> RNA

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11
Q

What is translation?

A

RNA->protein

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12
Q

What are Promoters?

A

promote expression, upstream

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13
Q

How can we suppress promoters?

A

methylation

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14
Q

What is encoding for genomes?

A

annotation of the pairs to make reading easier= AATTCCGGG to AAT TCC GGG

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15
Q

What are SNP’s?

A

single change

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16
Q

Most common genetic variation?

A

SNP

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17
Q

What are Copy number variations? What causes them?

A

variations in the number of copies of a gene
caused by recombination

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18
Q

What are insertions and deletions?

A

deletion of one or more or insertion of one or more

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19
Q

What are large scale variations?

A

LARGE portion repeated or gone

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20
Q

What is a hot spot of structural variations?

A

short arm of chromosome 1

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21
Q

What is bioinformatics?

A

merge biology and computers

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22
Q

Genetics vs genomics

A

look at one gene vs look at all genes

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23
Q

What is transcriptomics?

A

study of RNA and their functions

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24
Q

What is an exon vs intron?

A

exon- encodes
intron- does not encode/ spliced out

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25
Q

What is constitutive splicing?

A

exons retained in order

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26
Q

What is proteomics

A

study of proteins and their functions

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27
Q

What is top down vs bottom up?

A

top down= analyze without being broken down
bottom up= digest them into peptides first

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28
Q

What is metabolomics?

A

study of metabolites and their function

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29
Q

What is glycomics?

A

structure and function of glycans

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30
Q

What is a biomarker?

A

sign of normal OR abnormal

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31
Q

What is conventional medicine?

A

empirical therapy with universal drugs

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32
Q

What is PCR? steps?

A

quick method to make lots of copies of DNA
1. denature
2. anneal
3. synthesize

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33
Q

What is different about qPCR?

A

add fluorescent reporter- taqMan probe

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34
Q

What test uses PCR?

A

Abbott HIV-1 targeting 2 spots

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35
Q

Which is more money whole genome or whole exons?

A

whole genome

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36
Q

How do you sequence RNA?

A

make cDNA and then shatter it

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37
Q

What is the biggest gene?

A

duchene muscular dystrophy-X linked

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38
Q

What is a biochip? Which molecule cant be used?

A

array of biomolecules immobilized on surface
No RNA because unstable

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39
Q

What is a microarray?

A

uses DNA chip to sequence and analyze **

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40
Q

What does 23 and me use for biochip?

A

gene profiling array (DNA chip) affymetrix

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41
Q

What does AmpliChip CYP450 do?

A

biochip to see deletions and insertions of ALL CYP 450

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42
Q

What is a bio-Rad

A

protein chip

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43
Q

What is SELDI?

A

probe to immobilize then lazer to ionize

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44
Q

What is a kinome array?

A

when kinase rxn occurs with binding

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45
Q

What is an issue with protein chips?

A

more cost cause less stable

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46
Q

What is microfluidics?

A

use small amounts for biochips

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47
Q

What is FISH?

A

fluorescent prob

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48
Q

What biomolecules are you looking at for gene expression profiling?

A

RNA and protein

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49
Q

What are some gene expression tech?

A

DEG, SEG, SAGE, biopsy, rna splicing

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50
Q

What is a PET scan?

A

positron, use fluorodeoxyglucose as tracer

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51
Q

What is a drug?

A

substance with physiological effect

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52
Q

what is an aptamer?

A

chemical antibody

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53
Q

What makes a good drug?

A

potent and specific

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54
Q

What are the steps of drug development?

A

target selection-find stuff that binds to target- good ones are put through
then preclinical: Phase 1-2–3, approval, post marketing

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55
Q

How long to make a drug and how much money?

A

15 years, 1.5 billion

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56
Q

What is the most expensive part of discovery?

A

clinical

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57
Q

What is the data mining approach to identification?

A

identify important proteins in disease- look at databases

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58
Q

What is the genetic approach to identification?

A

identify genes that cause by comparing

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59
Q

What is the in vitro approach to identification?

A

identify targets

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60
Q

What is target validation?

A

does knock out of target give right effect

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61
Q

What is difference between knock out and knock down?

A

down= decreased, reversible
out= all and permanent

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62
Q

What is a choke point?

A

no other alternative pathways

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63
Q

Two methods to chemogenomic screen?

A
  1. have a chemical what does it effect
  2. I have a target what binds
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64
Q

What are the most successful targets?

A

enzymes and GPCRs

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65
Q

All targets are druggable?

A

NO

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66
Q

What makes a protein druggable?

A

binding site size

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67
Q

How can you predict druggability?

A

sequence based
structure based(pockets)
does it bind endogenous
high affinity drug(ligand based)
established target (precedence based)

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68
Q

Why has antibiotic research fallen off?

A

cant put high price on them
liability for side effects
rapid resistance

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69
Q

What is the pasteur act?

A

pay the company the value it is rather than the amount prescribed

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70
Q

What are the properties of targets in bacteria?

A

essential to survival, and only in bacteria

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71
Q

Explain CCR5 and HIV?

A

if you get the delta 32 version it is shorter so then the HIV cell cannot kill T cell

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72
Q

What is the K value paradox?

A

complexity does not correlate with number of chromosomes

73
Q

What is the c value paradox?

A

complexity is not correlated with genome size

74
Q

What is the n value paradox?

A

complexity is not correlated with gene number

75
Q

Why are mice good models?

A

share a lot of same genes

76
Q

What are common variations in CYP?

A

CYP2D6
CYP 2C9-warfarin
CYP 4F2- lowers vitamin K

77
Q

What does VKORC1 do?

A

recycles Vit K

78
Q

What is the function of CFTR and what does variation cause?

A

chloride channel in lung
variation= no transport or not enough, this will cause cystic fibrosis

79
Q

How does Ataluren work?

A

overcome nonsense mutation(premature stop codon), so it reads through

80
Q

What is the G551D mutation of CFTR? What drug fixes?

A

channels dont open correcly
kalydeco

81
Q

What medication fixed CFTR mutations that lower the amount and helps them open correctly?

A

TRIKAFTA

82
Q

What is an antisense oligonucleotide?

A

single stranded NA that hybridize with mRNA= inhibit expression

83
Q

What name shows its an ASO?

A

rsen
fomivirsen

84
Q

What are the mutations in the DMD gene (muscle dystrophy)?

A

large deletions and SNPs

85
Q

Which gender does DMD affect?

A

male b/c x linked

86
Q

If woman are carriers, how do they present?

A

some muscle weakness

87
Q

How can Eteplirsen help with DMD?

A

skip exon 51(nonsense mutation)

88
Q

What other med can help with DMD?

A

Ataluren-supressor tRNA that makes it place an AA instead of stopping

89
Q

How does SMA happen?

A

neurodegenerative disease of spinal neurons due to SMN1 and SMN2

90
Q

Which one has more function, SMN1 or 2? why?

A

SMNI has more cause more stable

91
Q

What drug helps with SMA?

A

nusinersen that helps SMN2 the copy of SMN1

92
Q

WHat does SMN2 lack?

A

exon 7

93
Q

What are molecular glues? What are the uses?

A

encourage 2 proteins to come together
used if no druggable active site and need less levels

94
Q

What is PROTAC?

A

glue that forces target to be ubiquitinylated and degraded in proteasome

95
Q

What are the characteristics of cancer cells?

A

Proliferative
evade growth suppress
evade cell death
angiogenesis
immortal
metastasis

96
Q

Benefits of small molecules

A

easier to cross membranes
act in or outside cells

97
Q

What is the first drug for tyrosine kinase?

A

imatinib

98
Q

How many small molecules interact with TK?

A

LOTS

99
Q

What makes BCR ABL gene and what does this do?

A

translocation of piece of Chromosome 22 and 9
makes always on TK

100
Q

How does imatinib work?

A

blocks ATP from donating to enzyme

101
Q

What is BCR ABl mutations that are dependent and independent resisitance?

A

dependent= change imatinib binding site= p loop and T3151
Independent= change transport that imports drug = stops import

102
Q

What is the only effective TRK inhibitor that can bypass BBB?

A

entrectinib

103
Q

What is the front end of an antibody? What is back?

A

front=binds targets
Back= bind other immune cells

104
Q

What are bispecific antibodies?

A

bind two usually bind to bad then bind to CD3 of t cell

105
Q

Mechanism of antibody drugs.

A

can flag it for NK destruction
or deliver toxin to the cell

106
Q

What drug is used for Her2?

A

trastuzumab= flags for killing

107
Q

What role does pertuzumab have?

A

also blocks dimerization

108
Q

What happens if EGFR1 inhibitor is used with a tumour with KRAS?

A

NO effect

109
Q

How does bevacizumab work?

A

stops angiogenesis

110
Q

What do MMP’s do for tumour?

A

dissolve ECM and build vessels

111
Q

What happens if a tumour is very turgid?

A

reisstant to drugs

112
Q

What does VEGF do?

A

vessel survive, increase permeability and angiogenesis

113
Q

What CYP is a major player in metabolism and has alot of genetic variability?

A

CYP 2D6

114
Q

What is the concept of tumour heterogenicity?

A

surface make up of cells are not constant neither in time as well

115
Q

How can tumour heterogenicity effect personalized medicine?

A

make take sample from part of the tumour that doesnt have the target. The drug will not kill it all

116
Q

How does antigen shedding work?

A

shedding the antigen can dodge the drug, by modulating.

117
Q

How does antigen modulation work?

A

endocytosis the antigen back inside cell

118
Q

IN relation to general cancer what is cancer stem cells?

A

more resistant
more metastasis
infinite proliferative

119
Q

WHat are the issue with cancer vaccine development?

A

suppress immune system
look normal
large or advanced
each tumour is unique
people who are sick already have weakened immune system

120
Q

What cancers have vaccines?

A

viral ones- HPV, HBV,

121
Q

How does BCG vaccine work?

A

uses weakened bacteria to help boost bladder cancer

122
Q

How does Sipuleucel-T vaccine work?

A

patients own dendritic cells that are stimulated to boost immune response to prostate cancer

123
Q

What does MCH-1 tell us?

A

I am infected

124
Q

What bacteria is involved in BCG vaccine?

A

mycobacterium bovis- TB

125
Q

What does MCH-2 tell us?

A

i am immune cell

126
Q

What is overproduced in prostate cancer?

A

PAP and PSA

127
Q

How can we boost cytotoxic t cells?

A

modify to release perforins and granzyme to break down
CAR-T

128
Q

What is CAR-T for usually?

A

liquid cancer

129
Q

Side effects of CAR-T?

A

CRS= massive release of cytokines that results in fever and drop in BP
Mass die off of B cells= aplasia

130
Q

Issues with CAR-T?

A

expensive, time consuming
tumour heterogeneity is bad

131
Q

What happens if PD-L1 or PD-L2 bind to PD-1?

A

T cell apoptosis, downregulation, suppress anti tumour response

132
Q

What is an example of PD-1 blockers?

A

nivolumab or pembrolizumab

133
Q

How does CTLA-4 work and what drug blocks it?

A

CTLA inhibits T cell activation
drug- iplimumab

134
Q

What are the 4 types of biomarkers?

A

Molecular
Radiographic
histological
Physiological

135
Q

What are radiographic biomarkers?

A

from medical images so like CT scan or x ray

136
Q

What is a histological biomarkers?

A

reflects molecular changes such as cancer grading

137
Q

What is a physiological biomarker?

A

measures body processes such as BP

138
Q

How long to develop biomarker?

A

3-4 years

139
Q

Which stage of biomarker development is the most expensive?

A

clinical validation

140
Q

What is multiomics?

A

combo of genomics etc

141
Q

What is a susceptibility biomarker?

A

indicates potential of disease
ex BRCA gene

142
Q

What is a diagnostic biomarker?

A

detect or confirm disease
Ex GFR, B amyloid

143
Q

What type of biomarker is GFR?

A

diagnostic for CKD

144
Q

What is a monitoring biomarker?

A

assess status of disease

145
Q

What is an example of a monitoring biomarker?

A

level of CA-125 or PSA

146
Q

What is a prognostic biomarker?

A

likelihood of health outcome

147
Q

True or False: Prognostic biomarker predicts response to treatment

A

FALSE

148
Q

What is a predictive biomarker? Ex?

A

identify those likely to respond
ex- HER2 gene= use HER2 therapy

149
Q

Where does trastuzumab and pertuzumab work?

A

4
2

150
Q

What is a pharmacodynamic/response biomarker?

A

drug interacts with target
ex BP

151
Q

What is a safety biomarker?

A

presence of toxicity
ex albumin or S cr from nephrotoxic drug

152
Q

What is a pharmacogenomic biomarker?

A

genetic differences
ex CYP P450

153
Q

What is proteomics?

A

total set of [proteins and how they function and interact

154
Q

What is primary protein structure?

A

AA sequence

155
Q

What is secondary structure?

A

how it folds

156
Q

Why study proteomics?

A

change in gene or RNA does not always translate into protein, post translational mods

157
Q

What is functional, expression and structural proteomics?

A

F= how it functions
E= expression
S= structure

158
Q

Why use electrophoresis?

A

separate based on charge and size

159
Q

Pros of using X ray crystallography and cons?

A

pros- high resolution, see structure
Cons- time consuming, expensive

160
Q

What does a protein microarray do?

A

purify, function and quanitfy

161
Q

What is P4?

A

predictive
personalized
preventive
participatory

162
Q

What is benefits of P4 mentality?

A

cost effective, lower rates of illness,

163
Q

True or false P4 is curative

A

False- more preventative

164
Q

What is systems medicine?

A

uses studys of the levels of life to integrate good care

165
Q

What does omics mean?

A

interactions and functions of biomolecules

166
Q

What does pharmacoproteomics?

A

deals with the changes of proteins due to drugs

167
Q

Why is it better to look at proteins than DNA?

A

1 gene makes multiple proteins and Post TM

168
Q

What is purpose of electrophoresis?

A

isolate crude identification and quantification

169
Q

What is purpose of chromatography?

A

isolate crude identification and quantification

170
Q

What do you need to do before mass spectrometry?

A

chromatography

171
Q

What is purpose of immunoassay and mass spectrometry?

A

identify and quantify

172
Q

What is a western blot?

A

gel put on paper to visualize

173
Q

What moves slower in chromatography?

A

whatever is close to what stationary phase is

174
Q

What is mass spectrometry?

A

see gas ions and sort based on charge and size

175
Q

What is toxicoproteomics?

A

how chemical exposure modifies protein or expression

176
Q

The Philadelphia chromosome is formed between chromosome 9 and chromosome 22 due to:

A

Translocation

177
Q

In general, how many coding SNPs are present in a gene?

A

5

178
Q
A

PHAR 211 (2 decks)

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