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walters drugs Flashcards

1
Q

alkylating agents MAO

A

alkylate DNA and proteins

form highly reactive intermediates

cell cycle nonspecific

1) ring opening
2) depurinization
3) miscoding: GC substitutes for AT
4) crosslinking interrupts DNA replication

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2
Q

Mechlorethamine

A

1st gen nitrogen mustard

unstable, spontaneously cyclizes on injection

part of MOPP

powerful vesicant - avoid extravasation (risk tissue necrosis)

1) side chain cyclizes
2) form ethyleniminium ion
3) form carbonium ion
4) reactive species reacts w/DNA
5) transfer alkyl group
6) form covalent bond

SE: nausea, vomiting, phlebitis, alopecia, myelosuppression

teratogen
carcinogen

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3
Q

cyclophosphamide

A

wide spectrum nitrogen mustard

not a vesicant

activated by liver

1) creates 4OH-cyclophosphamide
2) creates aldophosphamide
3) liver makes carboxyphosphamide, blood makes phosphoramide mustard and acrolein
4) phosphoramide becomes normitrogen mustard, acrolein is responsible for hemorrhagic cystitis

SE: leukopenia - tx w/Filgrastim (recombinant G-CSF) or sargramostim (GM-CSF), hemorrhagic cystitis - tx w/Mesna (nucleophilic thiol), SIADH, nasuea, vomiting, alopecia, amenorrhea, apsermia, pulmonary toxicity, cardiotoxicity, carcinogenic, mutagenic, teratogenic

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4
Q

Melphan

A

nitrogen mustard

erratic oral absorption

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5
Q

Chlorambucil

A

nitrogen mustard

myelosuppresive activity

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6
Q

Bendamustine

A

nitrogen mustard

repairable crosslinks

no cross-resistance w/other alkylating agents

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7
Q

Nitrosureas MOS

A

alkylate DNA and carbamoylate proteins

attacks #6 O of G

not phase specific

lipophilic - crosses blood-brain barrier

not a vesicant

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8
Q

Carmustine

A

1st gen nitrosureas

SE: nasuea, vomiting, meylosuppression, PULMONARY FIBROSIS, nephrotoxicity, hepatotoxicity

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9
Q

Lomustine

A

nitrosureas

no pulmonary fibrosis

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10
Q

Busulfan

A

bifunctional alkyl sulfonate alkylating agent

myelosuppresion

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11
Q

Methotrexate

A

folic acid analog

inhibits DHFR, can’t synthesize DNA

SE: neurotoxicity w/motor deficits

Leucovorin rescue - rescue healthy cells that uptake folate

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12
Q

Pralatrexate

A

folic acid analog

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13
Q

Cytarabine

A

pyrimidine analog

incorporates into DNA, improper stacking of bp, fragmentation of double helix

give w/Danorubicine

SE: myelosuppression

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14
Q

6-mercaptopurine

A

purine analog

suppress BM

analog of hypoxanthine

1) substrate for HGPRT
2) becomes 6-T-IMP
3) incorporate into DNA
4) inhibit txn/tln

give w/allopurinol inhibit metabolism to uric acid

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15
Q

6-thiogruanine

A

purine analog

suppress BM

analog of G

1) activated by HGPR
2) incorporates into DNA
3) strand breaks

allopurinol has no effect

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16
Q

fludarabine

A

purine analog

resists deamination by guanase

inhibits DNA polymerase

SE: peripheral neuropathy

**fatal pulmonary toxicity if given w/pentostatin

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17
Q

pentostatin

A

purine analog

1) inhibits ADA
2) block DNA synthesis

**fatal if given w/fludarabine

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18
Q

cladribine

A

purine analog

1) incorporates into DNA
2) strand breaks
3) deplete NAD and ATP
4) disrupts cell metabolism

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19
Q

clofarabine

A

purine analog

cladribine for children

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20
Q

vinka alkaloids MOA + resistance

A

from periwinkle plant

M phase metaplase

1) bind tubulin
2) dissolve MTs
3) metaphase arrest
4) neurotoxicity

resistance: P-glycoprotein (efflux)

excreted in bile

**intrathecal administration is deadly

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21
Q

vinchristine

A

vinca alkaloid

part of MOPP

SE: neurotoxicity, loss Achilles tendon reflex

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22
Q

vinblastine

A

vinca alkaloid

SE: leukopenia (tx w/Filgrastim), phlebitis

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23
Q

topoisomerase II inhibitors MOA

A

from mandrake plant

1) bind tubulin w/o interfering with MT structure/function
2) forms tenary complex w/DNA
3) prevents reannealing
4) ds breaks

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24
Q

Etoposide

A

topoisomerase II inhibitor

SE: leukopenia, thrombocytopenia

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25
Teniposide
topoisomerase II inhibitor retained longer in cells
26
anthracyclines MOA
1) intercalates between 2 bps on opposite DNA strands | 2) local uncoiling of double helix
27
Doxorubicin
anthracycline from streptomyces fungus avoid extravasation! - local vesican action (Adriamycin flare) SE: turns urine red, leukopenia - tx w/Filgrastim, cardiotoxicity - quinones chelate Fe and form ROS (tx w/Dexrazoxane - iron chelator)
28
Danorubicin
anthracycline from streptomyces fungus SE: cardiotoxic
29
Idarubicin
anthracycline SE: cardiotoxic
30
Epirubicine
anthracycline
31
Mitoxantrone
anthracenedione derived from anthracyclines
32
Bleomycin
from streptomyces verticillus 1) chelates copper and iron 2) create O2 radicales 3) DNA scission SE: pulmonary toxicity >> pulmonary fibrosis, cutaneous toxicity no significant myelosuppression
33
L-asparaginase
derived from E coli 1) hydrolyzes asparagine 2) deprives cells of asparagine SE: hypersensitivity, hyperglycemia, bleeding
34
Pegasparaginase
conjugated to PEG
35
Azacitidine
1) incorporates into DNA 2) demethylation 3) apoptosis SE: nausea, vomiting, myelosuppresion, GI symptoms
36
Decitabine
induces ds breaks
37
Nelarabine
incorporates into DNA, inhibits synthesis
38
Alemtuzumab
monoclonal antibody targets CD52 lysis of leukemic cells (Ab-C' toxicity)
39
90Y-ibritumomab tiuxetan
monoclonal antibody binds CD20 Ag generates free radicals destroys from inside
40
ofatumumab
monoclonal antibody (IgG analog) targets CD20 Ag Ag-C' toxicity and apoptosis
41
rituximab
monoclonal antibody targets epitope on CD20 Ag-C' toxicity and apoptosis
42
tositumomab
monoclonal antibody ionizing radiation (beta particles) destroy cells from inside
43
interferon MOA
bind specific cell-surface receptors enzyme induction inhibition of proliferation enhanced immune activities BBW: neurpsychiatric, autoimmune, ischemic, infectious disorders
44
interferon alpha 2a
interferon antiviral w/antineoplastic activity inhibits synthesis of ornithin decarboxylase
45
peginterferon alpha 2a
interferon attached to PEG to extend t1/2
46
interferon alpha 2b
interferon
47
Aldesleukin
recombinant interleukin2 produce LAK cells from T blasts SE: capillary leak syndrome (tx w/leukapheresis)
48
Denileukin Deftitox
immunotoxin recombinant IL2 w/diptheria toxin fragment A SE: hypersensitivity, vascular leak syndrome
49
tyrosine kinase inhibitors SE
nausea, vomiting, diarrhea, headache, muscle cramps, joint/muscle pain, rash, edema, pulmonary fibrosis, thrombocytopenia, neutropenia
50
imatinib
Tyr kinase inhibitor binds closed conformation of enzyme
51
nilotinib
Tyr kinase inhibitor binds closed conformation of enzyme
52
dasatinib
Tyr kinase inhibitor binds open and closed states
53
Ponatinib
Tyr kinase inhibitor BBW: arterial thrombosis, hepatotoxicity SE: hypertension, abdominal pain, fever, constipation
54
Ibrutinib
Tyr kinase inhibitor prevents activation of B cell pathways inhibits proliferation/migration
55
Hydroxyurea
analog of urea inhibits ribonucleotide disphosphate reductase S phase specific
56
Tretinoin
1st gen retinoid 1) binds retinoic acid receptor 2) forms heterodime RAR-RXR 3) induce differentiation of APL cells pregnancy category X
57
bexarotene
retinoid targets RXR receptor, forms heterodimers
58
Arsenic Trioxide
DNA fragmentation and apoptosis
59
Bortezomib
binds proteosomes
60
Vorinoistate
1) inhibits HDACs 2) accumulation of acetylated histone 3) induces cell cycle arrest
61
Thalidomide
inhibits angiogenesis anti-inflammatory decrease TNFa synthesis inhibit leukocyte migration pregnancy category X
62
Lenalidomide
less teratogenic thalidomide
63
pomalidomide
thalidomide derivative pregnancy category X

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