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Therapeutics 4 Kappa Epsilon > Therapeutics Exam 1 (Wendt and Dykhous) PT. 2 > Flashcards

Therapeutics Exam 1 (Wendt and Dykhous) PT. 2 Flashcards

1
Q

Uridine Analogs:

FdUMP mimics _____ and will bind to the active site of _________

A

mimics dUMP (hint the F is the fluorouracil that is screws everything up for DNA)

active site of: thymidylate synthase

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2
Q

Uridine Analogs:

FdUMP will form a ternary complex with _____ and ______

A

enzyme (synthase) and reduced folate cofactor (aka the methyl donor!!)

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3
Q

Uridine Analogs:

when FdUMP is in the ternary complex – the reaction cannot go to completion because why?

A

the F present (is usually an H) prevents the reaction to completing and letting the enzyme detach – enzyme is trapped!

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4
Q

Uridine Analogs:

5-FU leads to _____ depletion and leads to the inhibition of DNA synthesis (via a “_______ death”)

A

TMP depletion

thymineless death

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5
Q

Uridine Analogs:

5-FU is also converted to F-UTP and will affect _______

A

RNA processin and function

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6
Q

5-FU resistance can occur by what 2 mechanisms?

A

downregulation of activating enzymes

upregulation of thymidylate synthase

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7
Q

Thymidine and 5-FU drug interaction:

5-FU THEN thymidine = “_____” cytotoxic effect

Thymidine then 5-FU = “______” cytotoxic effect

A

then thymidine: is rescuing

thymidine 1st = enhances effect (giving this first will cause the cell to down regulate thymidine synthase!!)

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8
Q

the drug _____ can be given with 5-FU and increase the efficacy by increasing the stability of the synthase complex

A

Leucovorate

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9
Q

Leucovorate is a stable _____ cofactor and gets converted to _______ intracellularly

A

folate; tetrahydrofolate

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10
Q

______ breaks down 5-FU (~5% of the population has a polymorphism and has a deficiency of this enzyme)

*deficiency of this enzyme can lead to a life threatening 5-FU

A

DPD (dihydropyrimidine dehydrogenase)

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11
Q

who is FUdR (fluroreoxyuridine) different than 5-FU

A

FUdR is the deoxyribonucleoSIDE of 5-FU (aka FUdR has a sugar)

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12
Q

Capecitabine is a orally active prodrug of _____

A

5-FU

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13
Q

benefit of Capectiabine being a prodrug of 5-FU

A

longer 1/2 life!/can build up in tissues more

prodrug strategy generates higher levels of 5-FU selectively w/in some tumors

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14
Q

Cytosine analogs:

primarily inhibit _______

A

DNA synthesis

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15
Q

what bases are pyrimidines?

A

C & T

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16
Q

what drugs are cytosine analogs?

A

Cytosine arabinoside…

Gemcitabine

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17
Q

Cytosine arabinoside

is so structurally similar to deoxycytidine but the _______ makes it wack

A

B-OH at sugar 2’ (sugar is inverted somewhere)

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18
Q

Cytosine arabinoside

gets converted to _____ intracellularly and then acts as a competitive inhibitor to _________

A

Ara-CTP

DNA polymerase alpha

(Ara-CTP will also get incorporated into DNA and make it wack)

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19
Q

_________ will convert cytosine arabinoside to non-toxic uracil arbinoside

A

cytidine deaminase

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20
Q

Cytosine arabinoside:

cytidine deaminase is low in the ______ therefore this drug is good to use for these types of cancer: ______ and ______

A

CNS!!!

meningeal leukemia and lymphoma (aka cancers in lining of brain and spinal cord)

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21
Q

resistance mechanisms to cytosine arabinoside?

A

downregulation of deoxycytidine kinase (? - apparently an activating enzyme..)
upregulation of cytidine deaminase
downregulation of transport to move drug into cells

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22
Q

Gemcitabine:
gets phosphorylated to ____ and ____ intracellularly

______ will inhibit ribonucleotide reductase (inhibits DNA synthesis)

___ gets incorporated in DNA and halts further chain elongation

A

dFdCDP; dFdCTP

dFdCDP

dFdCTP

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23
Q

what drugs are used to stop purine biosynthesis

A

6-mercaptopurine

6-thioguanine

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24
Q

what drugs are used to stop DNA and RNA incorporation of purine analogs

A

fludarabine
Nelarabine
Cladribine

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25
Q

6-Mercaptopurine: (6-MP)

is a thio analog of _____

A

adenine

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26
Q

6-Mercaptopurine: (6-MP)

will inhibit MULTIPLE enzymes in the de novo ________ pathyway

A

purine biosynthesis (aka blocks synthesis of purine nucleotides – all of them not just Adenine)

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27
Q

6-Mercaptopurine: (6-MP)

gets converted to _____ (the active metabolite) by _____

A

converted to: TIMP (thiosine monophosphate)

by: HGPRT

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28
Q

6-Mercaptopurine: (6-MP)

is inactivated by ______

A

TPMT!!!

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29
Q

6-Mercaptopurine: (6-MP)
TPMT polymorphism occur in about ~10% of kids — these can result in _____ toxicity

heterozygotes need about _____ of standard dose
homozygotes need about _____ of standard dose

A

hematologic;

65%

10%

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30
Q

6-Mercaptopurine: (6-MP)

is also broken down by ________ (not just TPMT)

A

xanthine oxidase

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31
Q

what drug can increase the risk of 6-Mercaptopurine: (6-MP) toxicity

A

allopurinol (xanthine oxidase inhibitor)

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32
Q

6-Thioguanine: (6-TG)

is very similar to 6-MP but the main difference is _________

A

allopurinol (canthine oxidase inihibitor) DOES NOT block breakdown of 6-TG

*6-TG and 6-MP both get activated by HGPRT and get inactivated by TPMT

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33
Q

Arabino adenosine analogs will interfere with _____ and _______ aka inhibit DNA replication and transcription
*what drugs are arabino adenosine analogs

A

interfere with DNA polymerase and ribnucleotide reductase

fludarabine; Nelarabine; (Cladribine - has an extra MOA but still an adenosine analog..)

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34
Q

which Arabino adenosine analogs is used to treat blood cancers because phosphorylation keeps it in the bloodstream

A

fludarabine (it has sugar and phosphate!! - charge)

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35
Q

Cladribine will inhibit __________ and for some reason that enzyme is critical for ___ cells

A

inhibit adenosine deaminase (converts adenosine to inosine…?)

critical for B cells! – aka useful for leukemias

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36
Q

Folate is vitamin B___

A

9

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37
Q

Folate enters “folate pool” as ______ which is (active or inactive)

A

FH2 (dihydrofolate) — inactive

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38
Q

Dihydroflate (FH2) gets converted to tetrahydrofolate by ______

A

DHFR (dihyrdofolate reductase)

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39
Q

Folate Cycle:
inhibit _____ will reduce FH4 pools and folate pools accumulate as the inactive dihydrofolate —–>
____ and _____ synthesis decreases

A

DHFR;

TMP and purine nucleotide synthesis decreases!!

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40
Q

What compounds will bind and inhibit DHFR

A

Methotrexate
Pralatrexate
Pemetrexed

(they all similar structures to folic acid)

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41
Q

resistance to MTX (methotrexate) can happen how?

A

DHFR gene is amplified or mutation in DHFR gene leads to resistance
decrease polyglutamylation = decreased intracellular MTX accumulation

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42
Q

MTX can have increased accumulation in cells if ______ occurs

A

polyglutamylation

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43
Q

what is the “extra benefit” of pralatrexate

*compared to MTX just inhibiting DHFR

A

it is designed to accumulate in tumor cells — selectively enters tumor cells that are expressing RFC-1 (reduced folate carrier type)

RFC-1 is typically overexpressed on tumor cells over normal cells

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44
Q

what is the “extra benefit” of Pemetrexed

*compared to MTX just inhibiting DHFR

A

also inhibits thymidylate synthase

glycinamide ribonucloetide formyltransferase
aka less susceptible to drug resistance

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45
Q

how is Leucovorin used when in conjuction with MTX?

A

used to rescue normal tissues bc it is a stable folate cofactor

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46
Q

hydroxyurea MOA?

A

decreases production of deoxyribonucleotides BY inhibiting ribonucleotide reductase

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47
Q

hydroxyurea MOA?

DNA synthesis is inhibited in the ___ Phase

A

S

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48
Q

MOA of Actinomycin?

A

binds DNA and inhibits transcription by RNA polymerase

Aromatic drugs — slips into DNA and intercolates stuff

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49
Q

MOA of Actinomycin?

DNA synthesis is inhibited in the ___ Phase

A

any phase! non cell cycle specific (unlike other antimetabolites)

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50
Q

most antimetabolites affect the _____ phase in the cell cycle

A

S

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51
Q

Topoisomerases provide a mechanism to reduce ______ and provide access to _________

A

reduce: localized supercoiling
access: to double stranded DNA

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52
Q

Topoisomerase I:

will cut ______ DNA and relax the remaining strand and ______

A

cut ONE strand of double stranded DNA;

and reanneal

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53
Q

Topoisomerase I inhibitors:

mechanism?

A

the inhibitor has a strong nucleophile spot – will bind to topo I when it is attached to DNA

prevents Topo I from religating the cut DNA

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54
Q

most cells in ____ phase are sensitive to Topo I inhibitors

A

S

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55
Q

most topoisomeraise inhibitors will have a polycyclic _____ motif for intercalation — these will preferentially stack with _____

A

aromatic; guanine

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56
Q

Drug resistance possibilities with Topo I inhibitors

A

PGP overexpression
MRP overexpression (multidrug resistant protein)
GLUTATHIONE S-TRANSFERASE overexpression\
Topo downregulation or mutation to inhibit binding

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57
Q

what drugs are Topo I inhibitors

A

topotecan
irontecan

(the camptothecins)

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58
Q

Topo I inhibitors:
Camptothecin - natural product: low solubility/unpredictable toxicity

Topotecan: water soluble analog of camptothecin

Irinotecan: is a prodrug made into _____

A

Sn-38 *** related to genetic testing!!!

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59
Q

why do genes affected irinotecan?

A

active metab of irinotecan = SN-38;

SN38 is metabolized by UGT1A1

toxicity of irinotecan can happen if low expression of UGT1A1

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60
Q

Topo II is able to relieve ______ and ______

A

torsional strain; untangle DNA

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61
Q

two forms of Topo II:

Top2A and Top2B: which is most targeted? and why?

A

Top2A:

is required for decatenation of cells during mitosis

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62
Q

Anthracyclines: inhibit ______

A

Topo II

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63
Q

what drugs are Anthracyclines:

A

Doxorubicin
Dauomycin
Epirubicin
Idarubicin

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64
Q

how do Anthracyclines work?

A

multiple mechanisms:
intercalator
FREE RADICAL causes DNA damage
Inhibit Topo II***

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65
Q

issue with Anthracyclines?

A

free radical damage –> cardiotoxicity

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66
Q

Topo II inhibitors - Anthracyclines:

which one is most widely used?

A

doxorubicin

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67
Q

Topo II inhibitors - Anthracyclines:

which one has a dark red color/known as red death/red devil

A

doxorubicin

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68
Q

Topo II inhibitors - Anthracyclines:

which one has less cardiotoxicity than doxorubicin and faster elimination

A

epirubicin

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69
Q

Topo II inhibitors - Anthracyclines:

which one has increased fat solubility and cellular uptake

A

Idarubicin

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70
Q

which drug can be given with anthracyclines to decrease cardiotoxicity and how does it work

A

Dexrazoxane;

binds to iron/blocks iron-oxygen toxicities;

cardiotoxicity of doxorubicin and daunomycin believed to be caused by iron catalyzed free radical formation!!!

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71
Q

Mitoxantrone works how?

A

similar to anthracyclines but NOT an anthracycline — will intercalate and inhibit topo II buuut NO FREE RADICAL TOXICITY = less cardiotoxicity!!!!!

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72
Q

how do Topo II inhibitors - Epipodophyllotoxins work?

A

inhibit religation of double stranded breaks induced by Topo II but DO NOT INTERCALATE

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73
Q

what drugs are Topo II inhibitors - Epipodophyllotoxins

A

Etoposide and Teniposide

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74
Q

what cell phase are they effective?
Anthracyclines:

Epipodophyllotoxins:

A

Anthra: non cell cycle specific

Epipop: G2 block

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75
Q

drug resistance problems with Topo II inhibitors?

A

PGP overexpression
MRP overexpression (multidrug resistant protein)
GLUTATHIONE S-TRANSFERASE overexpression - ONLY anthracyclines
increased DNA damage repair
Topo II downregulation or mutation to inhibit binding

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76
Q

how does bleomycin work?

A

has charged side chain and will intercalate with DNA and then imidazole part does Fe+/O2 species generate DNA free radical

radical leads to DNA single strand/double strand breaks

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77
Q

bleomycin:
______ is dose limiting and cumulative

and myleosuppression is minimal!!

A

pulmonary toxicity

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78
Q

bleomycin:

gets inactivated by _________ which is in high concentrations for everywhere but _______

A

by aminohydrolase

skin and lungs (why pulmonary toxicity and rash ADEs)

*resistant cancers will have elevated aminohydrolase

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79
Q

what are the two major general microtubule inhibitor drug classes

A

Microtubule destabilizer
and
microtubule stabilizer

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80
Q

microtubule stabilizers will make microtubules “_____”
and
microtubule destabilizers will _______

A

stabilzers “frozen”

destabilizers “won’t form”

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81
Q

Vinca alkaloids prevent _______

microtubule assembly or microtubule disassembly

A

microtubule assembly

82
Q

Taxanes prevent _____

microtubule assembly or microtubule disassembly

A

disassembly

83
Q

Vinca alkaloids- microtubule inhibitors:
bind to _____ and leads to inhibition of microtubule _______

ADE is ________

A

tubulin; ASSEMBLY;

peripheral neuropathy (b/c microtubules are critical to nerve cell axon function)

84
Q

Vinca alkaloids- microtubule inhibitors:

are (small or large) molecules

85
Q

Vinca alkaloids- microtubule inhibitors:

main drug resistance issue?

A

PgP transporter

86
Q

microtubule inhibitors work in the _____ cell cycle phase

A

M (because duh thats when the chromosomes separate and need microtubules)

87
Q

Spindle Assembly Checkpoint:
_______ need to be attached to spindle microtubules;
there needs to be _______

A

kinetochores

kinetochore tension

88
Q

what drugs are vinca alkaloids

A

vincristine
vinblastine
vinorelbine

(neurotoxicity and myleosuppression is prevalent with these)

89
Q

what does Erubulin do?

A

prevents elongation of microtubules!! so prevents microtubule assembly (sorta)

and has LOW RATE OF NEUROTOXICITY compared to the the vinca alkaloids

90
Q

what drugs are taxanes

A

paclitaxel
docetaxel
cabazitaxel

91
Q

how do taxane drugs work?

A

promote microtubule assembly into STABLE bundles (leads to less free tubulin and prevent microtubule formation at spindle – since stable the microtubules do not depolymerize –> mitotic arrest/sister chromatids cannot separate)

92
Q

Taxane drugs:

drug resistance problem?

A

great substrates for PGP transporter (except Cabazitaxel!!)

and tubulin mutations

93
Q

what are epothilones

A

Ixabepilone

similar action to taxanes but more potent and are poor PGP substrates

94
Q

taxanes:

ADE?

A

neurotoxicity

95
Q

Misc Agents:

Aflibercept MOA?

A

fusion protein: VEGF parts and Fc portion of IgG

96
Q

Types of posttranslational modification?

A

phosphorylation and acetylation and methylation…

97
Q

Misc Agents:

Romidepsin MOA?

A

inhibits HDAC

98
Q

if a histone is acetylated that means the gene will or will not have transcriptional activity

99
Q

if a histone is deacetylated — that promotes _______ and prevents ________

A

promotes heterochromatin

prevents transcription
issue when tumor suppressor genes are deacetylated and then not being transcribed

100
Q

ADE of Romidepsin

A

activation of infections (parts of DNA that we don’t normally use can have come from viruses —- evolution stuff — and then now they are activated)

101
Q

Misc Agents:

Vorinostat MOA?

A

HDAC inhibitor

102
Q

Misc Agents:

Belinostat MOA?

A

HDAC inhibitor

103
Q

methylation usually happens in the _____ area of genes and will turn the gene (on or off)

methylation happens because of the _____ enzyme

A

promoter; off

DNMT (DNA methylation transferase)

104
Q

Misc Agents:

Azacytidine MOA?

A

DNMT inhibitor

105
Q

Misc Agents:

decitabine mOA?

A

DNMT inhibitor

106
Q

why would trentinoin be used?

A

retinoids promote differentiation and inhibit proliferation

107
Q

Retinoids:

_____ converts ______ into a transcriptional activator and induces differentiation of leukemic cells

A

ATRA (all trans retinoic acid receptor); PML-RAR (promyeloctyic leukemia - retinoic acid receptors)

108
Q

APL (acute promyelocytic leukemia) is characteried by the fusion of what two things?

A

RAR and PML

promyeloctyic leukemia - retinoic acid receptors

109
Q

Misc Agents:

Bexarotene MOA?

A

3rd gen retinoid that acts as agonist for RXR (rentinoids receptors)

110
Q

RXRs tend to form heterodimers with what types of receptors?? and then go act as transcription factors that increase cellular differentiation/inhibit proliferation and induce apoptosis!!

A

RARs or vit. d receptor or thyroid receptor, or PPAR

111
Q

Misc Agents:

MOA of tazemetostat?

A

inhibits methyltransferase activity of EZH2

112
Q

EZH2 will do the the trimethylation of lysine 27 of H3 histones…. aka will lead to the ________ of ______ genes

A

repression; tumor suppressor

113
Q

Misc Agents:
Thalidomide:
strong anti-_____ activity - wil block effects of ____ and ____

A

anti-angiogenic activity!

blocks VEGF!!! and bFGF

114
Q

Misc Agents:
Thalidomide and its analog _______
is a potent ______ aka why it has a REMS program

A

Pomalidomide or Lenalidomide

teratogen — must prevent pregnancy

115
Q

what drugs are proteosome inhibitors

A

bortezomib, carfilzomib, and ixazomib

the -zomibs!!!

116
Q

what are proteosome inhibitors helpful?

A

so proteosomes break down misfolded proteins…
normally a molecule called Ik-Ba will get phosphorylated and then ubiquinated — once that happens Nf-kB can go to the nucleus and drive transcription of pro-inflammatory and proliferation genes…

long story short if the Ik-Ba cannot get degraded then Nf-Kb cant get to the nucleus

(then hella misfolded protein in cell leads to apoptosis)

117
Q

Misc Agents:

what drugs are used for basal cell carcinoma

A

Vismodegib
and
sonidegib

they will bind to and inhibit smoothened from activating GLI1
(hedgehog signaling??)

118
Q

Components of Hedgehog signaling:

Hedgehog binds to ______ and release the inhibition on ______ this leads to nuclear translocation of ______

A

binds to patched; smoothened; GLI1

119
Q

how do vismodegib and sonidegib work?

A

they will bind to and inhibit smoothened from activating GLI1

120
Q

_____ overexpression allows cancer cells to evade apoptosis by sequestering pro-apoptotic proteins

121
Q

what drug selectively binds to BCL-2 which leads to apoptosis

A

venclexta/venetoclax

122
Q

how does venclexta work?

A

BCL-2 inhibitor

selectively binds to BCL-2 –> will free pro-apoptotic proteins –> lead to apoptosis

123
Q

what kind of molecule is venclexta the first of?

A

small molecule that inhibits a protein-protein interaction

124
Q

Misc Agents:

MOA of Omacetaxine?

A

inhibitor of protein translation/inhibits elongation step of protein synthesis

125
Q

why is the drug asparaginase useful in cancer cells?

A

normal cells make asparagine with the asparagine synthase enzyme….

malignant cells do not have this enzyme:

if you use this drug (it decrease asparagine levels)
normal cells can adapt and increase the synthase enzyme

cancer cells cant adjust and dieeee

126
Q

Bone metastasis:

bisphosphonates good why?

A

bisphosphonates stop osteoclasts/stop breakdown of bone

when bone is broken down the remnants will actually feed tumor cells — booooo

127
Q

Misc Agents:

Denosumab?

A

inhibitor of RANKL!

RANKL binds to RANK on osteoclasts and lead to the bone resorption process

128
Q

_______ is a natural binder of RANKL

A

OPG (osteoprotegerin)

129
Q

explain TLS

A

TLS = tumor lysis syndrome

aka massive raise in uric acid in the blood because of high DNA content being released

130
Q

TLS leads to renal issues how?

A

uric acid can precipitate in renal tubules —- worse kidney function = worsening hyperkalemia and hyperphosphatemia and Ca2+ and this all precipiates in the kidneys too

(the hyperkalemia leads to cardiac rhythms and arrhythmias)

131
Q

what drugs can be given for helping with TLS

A

Allopurinol (duh uric acid is a problem in TLS) - use prophylactically

Rasburicase - a recombinant urate oxidase — breaks down uric acid (humans do not express this endogenously)

132
Q

Tisagenlecleucel:

MOA?

A

aka Kymriah
t cells are isolated from patient —- they are grown with CAR stably expressed;
then cells grown are put back in patient

aka pt essentially gets immunized against CD-19 and

133
Q

Kymriah leads to all ______ cells being eliminated

A

immature B cells

134
Q

Provenge (Sipuleucel) is approved for _______ cancer

A

metastatic prostate

135
Q

Provenge (Sipuleucel) — how does it work

A

they stimulate pts own immune system to attack the cancer

take APCs from pt — give the APCs the “drug” (PAP-GM-CSF) – PAP = a phosphotase and GM-CSF macrophage colony stimulating factor

136
Q

the ____ virus is associated with liver cancer

A

HBV (hepatitis B) virus

137
Q

why is it hard to vaccinate against tumor proteins??

A

well tumors come from us..therefore it is hard to target self proteins

138
Q

HPV cancer happens because HPV is a _____ virus that produces proteins (___ and ___) that will increase proliferation and allow for accumulation of DNA mutations

139
Q

which HPV types are the major causative agents for cervical cancer and therefore can be vaccinated against as means to prevent HPV infection

A

HPV 16 and 18

140
Q

HPV vaccines can help prevent against what kinds of cancer?

A

most notably cervical (but also vulvular, vaginal, anal, and penile cancers)

141
Q

Gardaisl vs Ceravarix:

which one is quadrivalent

A

gardasil (has 16, 18, and types 11 and 6 covered)

142
Q

Gardaisl vs Ceravarix:

which one is bivalent

A

ceravarix (just 16 and 18 HPV types)

143
Q

MOA of Aldesleukin?

A

it is a recombinant protein of Interleukin 2 and will activate T cells
(very pro-inflammatory cytokine - enhances lymphocyte mitogenesis and cytotoxicity)

VERY non specific!!

144
Q

MOA of Interferon Alpha:

A

recombinant protein – but has direct antiproliferative effect
and enhanced host immune response

145
Q

ADE Comparisons:
Anthracyclines causes cardiotoxicity —-
rank order of toxicity issues of daunorubicin, doxorubicin, and epirubicin (lowest to highest cardiotoxicity)

A

epirub –> doxo –> danu

*danu is the worst one

146
Q

ADE Comparisons:

Mitxoantrone or Doxorubicin has worst cardiotoxicity?

A

doxorubicin:

mitoxantrone does not have free radical formation – has less cardiotox

147
Q

most microtubule drugs are critical to _____ function (as well as normal cell function) and lead to ________

A

nerve cell axon; peripheral neuropathy

148
Q

Vince Alkaloid ADE Comparisons:
Vincristine, Vinblastine, or Vinorelbine?

which one has really bad neurotoxicity

A

vincristine

149
Q

Vince Alkaloid ADE Comparisons:
Vincristine, Vinblastine, or Vinorelbine?

which one has dose limiting myleosuppression

A

vinblastine and vinorelbine

150
Q

Vince Alkaloid ADE Comparisons:
Vincristine, Vinblastine, or Vinorelbine?

which one can cause severeeee local inflammation because of extravasation

A

vincristine

151
Q

ADE Comparisons:

Erubulin or Vincristine has neurotoxicity worse?

A

vincristine

erubilin - low rate of neurotoxicity for a microtubule

152
Q

ADE Comparisons:

Taxanes get pumped out the cell —-except one does not – which one?

A

Cabazitaxel`

153
Q

ADE Comparisons:

cyclophosphamide or ifosphamide has increased CNS toxicity

A

ifosphamide

154
Q

ADE Comparisons:
Cisplatin, Carboplatin, or Oxaplatin?

has dose limiting neprhotoxicity

155
Q

ADE Comparisons:
Cisplatin, Carboplatin, or Oxaplatin?

has dose nephrotoxicity but low bone marrow toxicity

156
Q

ADE Comparisons:
Cisplatin, Carboplatin, or Oxaplatin?
has minimal nephrotoxicity

A

both carboplatin and oxaplatin

157
Q

ADE Comparisons:
Cisplatin, Carboplatin, or Oxaplatin?

has significant bone marrow toxicity

A

carboplatin

158
Q

ADE Comparisons:
Cisplatin, Carboplatin, or Oxaplatin?
has acute and chronic neuropathy

159
Q

Indications for Drugs:

the hedgehog signaling drugs (Vismodegib and Sonidegib)

A

basal cell carcinoma

160
Q

Indications for Drugs:

Tamoxifen

A

ER+ or PR+ breast cancer

(ok for prevention of breast cancer!!)

(also ok in pre or post menopausal women)

161
Q

Indications for Drugs:

Fulvestrant

A

ER+ breast cancer – POST menopausal women

162
Q

ADE Comparisons:

Aromotase inhibitors or SERMs hae increased risk for fractures

A

aromatase inhibitors because decrease estrogen in general (SERMs are agonists at the bones!! aka yay healthy bones)

163
Q

Indications for Drugs:

medroxyprogesterone

A

prevent endometrial cancer (post menopausal women!)

can be used in appetite stimulation/wt gain and antiemetic

164
Q

Indications for Drugs:

LHRH analogs

A

for women: premenopausal breast cancer (estrogen dependent..)

for men: prostate cancer

165
Q

Indications for Drugs:

abarelix

A

prostate cancer (LHRH antagonist)

166
Q

Indications for Drugs:

degarelix

A

prostate cancer (LHRH antagonist)

167
Q

Indications for Drugs:

exemestane

A

ER+ breast cancer in POST menopausal women

168
Q

Indications for Drugs:

Gefitinib

A

NSCLC – have mutations on exon 19 or 21 (L858R mutation!)

169
Q

Indications for Drugs:

Erlotinib

A

NSCLC – have mutations on exon 19 or 21 (L858R mutation!)

170
Q

Indications for Drugs:

Afatinib

A

NSCLC (covalent) and does L858R mutation (NOT T790M :( )

171
Q

Indications for Drugs:

Osimertinib

A

NSCLC that has T790M mutation!!!

172
Q

Indications for Drugs:

Lapatnib

A

tx HER2+ breast cancer

usually used if pts progressed when on trastuzumab therapy

173
Q

Indications for Drugs:

Nerabitinib

A

tx HER2+ breast cancer

usually used if pts progressed when on trastuzumab therapy

174
Q

Indications for Drugs:

Cabozantinib

A

it is a cMET inhibitor — cMET is amplified in some lung cancers
ALSO thyroid cancer!!
will target RET and VEGFR too
(good when ROS1 mutations have occurred with crizotinib)

175
Q

Indications for Drugs:

Crizotinib

A

it is a cMET inhibitor — cMET is amplified in some lung cancers

also a EML4-ALK inhibitor: 6% of NSCLC pts have this fusion gene (needs diagnostic for the fusion gene)

176
Q

BCR-Abl is seen in about 95% of what kinds of cancer?

A

the Philadelphia chromosome (BCR-Abl) is found in CMLs!! (chronic myelocytic leukmeia)

177
Q

Indications for Drugs:

imatinib

A

the first kinase ever!
is indicated for CML (for the BCr-Abl fusion gene)

but also indicated for GIST because it targets c-kit as well!

178
Q

Indications for Drugs:

nilotinib

A

for CML (the BCR-Abl fusion gene) good for when there are mutations that imatinib cant take care of`

179
Q

Indications for Drugs:

Ponatinib

A

CML!
it is effective against all major mutant forms of the BCR-Abl fusion gene!

will inhibit the T3151 mutation! (aka the gatekeeper mutation?)

180
Q

Indications for Drugs:

Dasatinib

A 
for CML (the BCR-Abl fusion gene)
does NOT do the T3151 mutation though
181
Q

Indications for Drugs:

Bosutinib

A 
for CML (the BCR-Abl fusion gene)
does NOT do the T3151 mutation though
182
Q

Indications for Drugs:

Alectinib

A

for EML4-ALK fusion gene in NSCLC (will need genetic testing!!)

183
Q

Indications for Drugs:

Sorafenib

A

NOT melanoma because cant do the V600M mutation

can be used for renal carcinoma and hepatocellular carcinoma

184
Q

Indications for Drugs:

Vemurafenib

A

melanoma! can inhibit BRAF when V600 mutation is there

careful because can activate the wild type and lead to tumor growth :(

185
Q

Indications for Drugs:Dabrafenib

A

melanoma with V600 mutation!!!

careful because can activate the wild type and lead to tumor growth :(

186
Q

Indications for Drugs:

Trametinib

A

it is a MEK inhibitor: MEK is downstream from BRAF — therefore melanoma?

do NOT use if pt has previous BRAF therapy

187
Q

Indications for Drugs:

Cobimetinib

A

it is a MEK inhibitor: MEK is downstream from BRAF — therefore melanoma?

do NOT use if pt has wild type BRAF

188
Q

what kinase inhibitors are TYPE III

A

the MEK inhibitors

tramitenib and combimetinib

189
Q

what drug is notably a TYPE II kinase inhibitor

190
Q

Indications for Drugs:

Idelalisib

A

P13K inhibitor is for CLL (chronic lymphocytic leukemia)

191
Q

Indications for Drugs:

Ibrutnib

A

b cell leukemia

it is targeting BTK which is downstream from b cell receptors

192
Q

Indications for Drugs:

Acalabrutinib

A

b cell leukemia

it is targeting BTK which is downstream from b cell receptors

193
Q

Indications for Drugs:

Vandetanib

A

thyroid cancer!!
has multiple cancers (like cabozitinib)
targets VEGFR and RET, and EGFR

194
Q

Indications for Drugs:

Temsirolimus

A

renal cell carcinoma!

mTOR inhibitors/rapalogs are good renal cell carcinoma

195
Q

Indications for Drugs:

Everolimus

A

renal cell carcinoma

196
Q

Indications for Drugs:

the CDK inhibitors (-ciclibs)?

A

ER+ but HER- breast cancer — usually in combo with an anti-endocrine drug

197
Q

Indications for Drugs:

Trastuzumab

A

breast cancer that over expresses HER2

198
Q

Indications for Drugs:

Pertuzumab

A

breast cancer that over expresses HER2

199
Q

Indications for Drugs:

Cetuximab

A

colorectal, head and neck cancers (even though it targets EGFR… it is not for NSCLC because the lung cancer will have mutations)

200
Q

Indications for Drugs:

Panitumumab

A

colorectal cancer

need to check for KRAS mutational status

Therapeutics 4 Kappa Epsilon (16 decks)

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