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PHAR 211 > Final > Flashcards

Final Flashcards

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1
Q

What does metabolomics exclude?

A

enzymes, genetic material, structure molecules

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2
Q

What is the closest link to phenotype?

A

metabolomics

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3
Q

How does capiliary. electrophoresis work?

A

separate based on charge and partition coefficient

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4
Q

What can we do to speed up/ increase flow rate for Liquid chromatography?

A

sacrifice resolution

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5
Q

How do you calculate resolution?

A

R= (V2-V1)/(W1+W2/2)

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6
Q

What does it mean if R is >1.5?

A

good separation/resolution

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7
Q

What does particle size do to resolution?

A

smaller= better resolution

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8
Q

What can happen if high flow rate? Why?

A

loss of resolution due to back pressure

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9
Q

What is particle size for HPLC? WHat about flow rate?

A

5 microns
r8= 1ml/min

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10
Q

If column in LC is polar what happens?

A

polar things take longer to go through

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11
Q

What indicates the phase is non polar?

A

lots of carbons

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12
Q

What is difference between normal phase and reverse phase HPLC?

A

normal= stationary is polar
reverse= stationary is non polar

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13
Q

What is particle size for UPLC?

A

1.7-1.8 microns

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14
Q

For gas chromatography, what is the mobile phase?

A

gas- usually helium, H or N

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15
Q

For carrier gas what is pros and cons of each?

A

helium= best sensitivity, pricy
H= alright sense, flammable
N= bad sense but cheap

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16
Q

What is considered an abundant metabolite?

A

> 1 micro M

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17
Q

What is the database for metabolites?

A

HMDB

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18
Q

What is different between a targeted study vs a targeted?

A

target= know whats in sample

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19
Q

If someone is doing a metabolic fingerprint what can we assume?

A

dont know whats in it

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20
Q

What does metabolic profiling mean?

A

all involved in a disease state/ pathway

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21
Q

What is definition of pharmacometabolomics?

A

how metabolits change from a drug

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22
Q

WHat is path of biomarker discovery?

A

fingerprinting
then see if targets have
validation
clinical utility
approval

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23
Q

Why look at metabolomics?

A

fast, changes happen first before symptoms

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24
Q

What are the different matrixes for metabolomic study? pros and cons?

A

blood- easy but complex
Urine- not invasive, but different between age, gender
saliva= low amount
CSF- invasive
breathe- low concentration
tissue

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25
Which matrixes are bad for proteomics?
urine and breathe
26
What makes antibodies?
B cells
27
Explain humoral immunity?
b cells bind to foreign and make antibodies T cells bidn to antigen to kill T helper bind to antigen and release cytokines to activate B and T cells
28
What is the structure of antibodies?
heterotetramer with 2 identical light and heavy chains
29
What portion of antibody binds to antigen and which binds to other cells?
Fab binds to antigen Fc binds to cell
30
What do antibodies do?
neutralize, phagocytosis, lysis, NK
31
How are antibodies used in cancer?
stop angiogenesis= VEGFR and new interest in blocking checkpoints= nivolumab and iplimumab
32
Why can antibodies bind to many antigens?
diversity of CDR loops
33
How can we make a bunch of antibodies?
lots of immunoglobulin genes and recombination
34
What is the total diversity of antibodies in body?
>1 billions
35
How can we produce (scientifically) antibodies?
humanized through hybridoma, through mice bacteriophages transgenic mice human b cells
36
What has been a workhorse for protein engineering?
M13 bacteriophage
37
What is the success rate of MABs?
23% compared to 7% of small molecule drugs
38
How does bevacizumab work? How was it made?
stops VEGF= stop angiogenesis made by humanized
39
How does mutations to Fc change function?
increase or decrease binding affinity
40
What are some bispecific antibodies mechanisms?
bridge two cells, double receptor inhibition/activation, piggybacck
41
What is a quadroma?
fuse two different hydroma to get bispecific need advanced purification
42
What is knob-in holes tech?
mutate to get knob so that homodimerize doesnt happen so you get bispecific
43
What is cross mab tech?
knob to get proper bispecific but cross over happens on one of the heavy chain
44
What is the best success story of a bispecific antibody?
emicizumab for hemophilia
45
What is the most common site for bispecific antibodies?
PD1 and HER 2
46
How many approved bispecific antibodies?
3
47
Cons of antibodies?
high cost, poor penetration
48
Pros and cons of scaffolds?
Pros- low cost, better penetrate cons- immunogenicity and poor stability
49
What is RNA interference? WHat is a key requirment?
gene silencing requires dsRNA
50
What enzyme is needed to make silencing RNA from long dsRNA?
dicer
51
How do siRNA work?
promote degrade of mRNA
52
Where can dsRNA come from?
hairpin, complementary RNA
53
What is structure of siRNA?
21-23 nucleotide what a 2 nucleotide overhang on each 3 prime end
54
Where does siRNA act?
on RISC which cleaves the passenger strand and the guide strand stays on AGO part of RISC to bind to complementary mRNA to cleave
55
Which is another name for passenger and guide strands?
passenger= sense guide= antisense
56
What is miRNA
micro RNA= ds stem loop
57
WHat is process of miRNA
miRNA gene transcribed= ds cleaved by Drosha to get pre-miRNA exportin 5 sends it to cytoplasm dicer cuts off loop then it binds to RISC and loses passenger strand and same process
58
What is a key difference between miRNA and siRNA?
miRNA is not fully complimentary so it can bind to more sites and miRNA passenger strand is discarded not cleaved
59
WHat is a key pro of RNAi therapuetics?
act on gene target more of all classes of proteins and can go into cells
60
Cons of RNAi?
vulnerable to nucleases poor stability poor delivery because they cant permeate
61
What are a delivery system form for RNAi
viral vectors - Lentiviruses or AAV
62
Cons of viral vectors?
immunogenicity expensive mutagenesis
63
What are non viral delivery mechanisms?
polymer or lipid based
64
Which is more efficient Viral or non viral delivery?
viral
65
Where si the site of target for RNAi?
anywhere
66
What is CRISPR-cas9
genome editing
67
How many FDA approved CRISPAR?
1
68
How does CRISPR work?
cas 9 chops virus DNA/RNA, uses some of the pieces and inserts it to remember the virus when it cuts we can add or delete
69
What causes sickle cell?
mutation in hemoglobin-beta gene in chromosome 11
70
How can we use CRISPR in sickle cell?
edit gene that supresses fetal hemoglobin (gamma) which replaces beta unit
71
What is innate vs adaptive immunity?
Innate= first line rapid Acquired- second line, memory
72
What are the cells of innate immunity and what they do?
NK dendritic mast- histmaine neutrophils- most basophil- parasites macrophages
73
How can innate recog pathogens?
PRR-recog toxins DAMP-see molecules released by damaged cells detecting missing self- recog healthy
74
Which cells have MCH 1 and 2
1= all nucleated cells 2- macrophages, dendritic and B cells
75
What are the two divisions of adaptive immuntiy?
cell mediated- cytotoxic t cells humoral-b cells
76
What is path of t cell maturation?
made in marrow m,ature in thymus
77
What is CD4+ and CD8+ t cells?
4= t helper 8= cytotoxic
78
How do you activate cytotoxic t cells?
APC stims proliferation activate by bond between cytotoxic t cell and MHC 1 and need secondary signal from CD28 CD80 and CD86 are co stim
79
WHat are T regs?
suppress immune response
80
How can B cells be activated?
binds to antigen, T cell, memory or dendritic
81
What do each Ig do?
IgA= stop bacteria and viruses, in gi and resp IgD= activate B cells and basophils in mucosa IgE=hypersensitivity IgG= viruses and bacetria IgM= for humoral response
82
Which Ig is most predominant?
IgG
83
Which Ig is biggest?
IgM
84
Which Ig gets released first for humoral immunity?
IgM
85
What are the opioid receptors?
mu kappa delta NOP
86
What are our endogenous opioids?
enkephalin dynorphin Sub P endorphin
87
How does acetaminophen work? What enzyme for metabolism
COX inhibitor in CNS, boosts endocannabinoid levels metabolized by CYP 2E1- can make toxic
88
How is NSAIDs metabolized?
CYP 2C9 and 2D6
89
How do cannabinoids work?
trick brain into thinking less pain stops inflammation
90
What distinguished enogenous opiods from exongenous?
endogenous are peptides
91
What do opioids and cannabinoids both do the same thing to limit pain?
block neurotransmitter release from presynaptic
92
What polymorphisms at each opioid receptors?
mu= 118 A to G= less analgesia kappa= 36 Gto T= addiction delta= none
93
What polymoprhisms for NSAIDs?
GG= rofecoxib better than ibu GC or CC= ibu better
94
WHat polymoprhisms for cannabinoids?
none for effect G1359A= T2DM AAT= more abuse
95
WHat are the three general; gene polymorphisms?
Poor= loss of at least 2 alleles Normal Ultra= at least 3 coppies of alleles
96
What polymorphisms for tylenol?
more CYP 2E1= more hepatotoxicity through NAPQI
97
What enzyme metabolizes codeine?
CYP 2D6
98
WHat are the only actionable polymorphisms?
2D6- for codeine and tramadol and OPRM1-morphine
99
What can polymorphisms of opioids look like?
drug seeking behaviour
100
What type of cancer is CAR-T for?
liquid tumours
101
What do helper t cells do?
differentiation of b cells
102
What is the TCR-CD3 complex?
TCR binds to CD3epsilon gama to alpha unit, epsilon delta to beta unti and CD3 theta
103
How do cytotoxic T cells perform funtion?
perforin to make pores on target granzyme for apop granulysin for pores in microbes
104
How can cancer evade cytotoxic t cells?
downreg of MCH 1 downreg CD80 over express CD47
105
How do you do CAR T therapy?
collect T cells and add chimeric gene, grow t cells and infuse
106
What is CAR core (first generation)?*******
scFv binds cancer antigen and CD3 theta to bind ZAP70 and activate t cell Hinge, transmembrane domain
107
WHat is scFv?
like antibody but only the variable region to bind antigens
108
What are added to future generations of CAR T?
co stimulators of CD28, 4-1BB, NFAT, JAK-STAT
109
WHat is second gen CAR T?***
CD28 also
110
What is 3rd gen CAR T?****
CD28 + 4-1BB
111
What is 4th gen CAR T?
also NFAT
112
What is 5th gen CAR T?
JAK-STAT
113
What does addition of CD28 do for CAR T?
cytotox and proliferation
114
What does core CAR T actually do?
cytotoxic
115
WHat does 3rd gen actually do for CAR T?
cytotox, proliferation and survival
116
WHat are cons of CAR T?
long time, pricey, t cell exhaustion
117
Do we use core CAR T at all?
FUCK NO
118
How many CAR T therapies are approved?
6
119
EXplain B lymphocyte antigen CD19?
biomarker for lymphoma and leukemia
120
What does BCMA tell us?
biomarker for myelomas
121
WHat is Kymriah for/What costimulator?
targets CD19 for has 4-1BB
122
What is Yescarta for/What costimulator?
targets CD19 for diffuse B cell lymphoma and follicular lymphoma co stim of CD28
123
WHat is Tecartus for/What costimulator?
targets CD19 for mantle lymphoma Co stim of CD28
124
WHat is breyanzi for/What costimulator?
targets CD19 for diffuse B cell lymphoma co stim of 4-1BB
125
WHat is abecma for/What costimulator?
Targets BCMA for multiple myeloma co stim of 4-1BB
126
In what stage of B cell development does CD19 expressed?
early
127
What is carvykti for/What costimulator?
targets BCMA for relapsed multiple myeloma 4-1BB
128
What costimulator is better for lymphoblastic leukemia?
4-1BB
129
Who made the first vaccine and what was it for?
Ed Jenner for small pox
130
What is a therapeutic vaccine?
stim immune response who is already infected
131
What is a tolerogenic vaccine?
against self antigens so auto immune
132
What are primary vs secondary lymph organs?
primary= marrow and thymus secondary= nodes, spleen
133
Explain the adaptive immune response?
dendritic present antigens to t helper, t helper mature and activate other t cells and b cells to make memory cells an d mount a better response
134
Does a protein antigen ellicit a good immune response?
NO- need adjuvant
135
How do Dendritic cells know self vs non self?
PAMPs on invaders and PRR on human cells
136
Pros of using adjuvants in vaccine?
increase immunogenicity, reduce amount of antigen or frquency of shots, improve efficacy
137
What delivery systems for vaccine?
MF59, PLG
138
What vaccines prevent cancer?
HPV, Hep b
139
WHat therapeutic vaccines do we have?
BCG and Sipuleucel T and stimuvax
140
Explain stimuvax vaccine.
targets 25 AA sequence of MUC-1 in cancer cells
141
Are we concerned about Covid vaccine changing our genome?
no stays in cytoplasm and RNA vaccine are very easily degraded
142
What are inhibitory immune checkpoint molecules?
CTLA-4 (CD152) and PD-1
143
What is CTLA-4?
binds CD80 and 86 or called B7, if blocked immune system will kill cancer cells
144
WHat other site competes with CTLA-4?
CD28
145
When is CTLA-4 highly present?
if cell exposed to antigen
146
What happens if PD-1 and PD-L1 bind?
stops immune response
147
How does iplimumab work?
CTLA-4
148
How does Tremelimumab work?
CTLA-4
149
WHat are the PD-1 drugs
Pembrolizumab Nivolumab Cemiplimab
150
WHat are the PD-L1 drugs?
Atezolizumab Avelumab Durvalumab
151
Most common ADRs of checkpoint inhibitors?
rash, diarrhea, fatigue skin, chest, liver, renal disease diabetes
152
What is pseudo progression?
response after intitial increase in volume of cancer
153
What is hyper progression?
acceleration of tumor growth during inhibition of checkpoints
154
How does relatlimab work?
LAG-3 or CD223
155
What is the most common form of cancer in women?
breast
156
What is treatment of stage 1 Breast cancer?
Surgery or radiation
157
What is treatment of stage 2 breast cancer?
Surgery radiation chemo= AC-T, T AC, CAF
158
WHat is treat of stage 3 breast cancer?
chemo, targeted, surgery
159
What is treat of stage 4 breast cancer?
hormonal, chemo, targeted
160
What causes the signalling of cancer from HER 2?
dimer with itself or EGFR
161
What is MOA of trastuzumab?
subdoamin 4 of HER 2
162
What is MOA of pertuzumab?
subdomain 2 blocks dimerization
163
What does margetuximab do?
igG antibody that binds to HER2
164
What is T-DM1?
trastuzumab with emastine
165
What is fam-trastuzumab deruxtecan?
deruxtecan is topoisomerase inhibitor to get death
166
What does lapatinib do?
TK inhibitor that REVERSIBLY binds to BOTH EGFR and HER2
167
What does Neratinib do?
irreversibly bind tk inhibitor
168
What does tucatinib do?
reversible inhibitor of HER2
169
WHat are the CDK4 inhibitors?
palbociclib ribociclib abemaciclib all stop cell going past R point
170
How does everolimus work?
mTOR inhibitor
171
How does Alpelisib work?
alpha specific PI3K inhibitor for patients with PIK3CA mutation
172
How do olaparib / parib drugs work?
block DNA repair in cancer cells - DOESNT TARGET NORMAL CELLS
173
Which is more efficient talazoparib or olaparib?
talazoparib
174
What is therapy for triple negative cancer and what does it target?
sacituzumab govitecan targets Trop-2

PHAR 211 (2 decks)

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