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hem/onc Flashcards

1
Q

heparin MOA?

A

activates antithrombin –> decreased thrombin and Xa

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2
Q

LMWH vs heparin?

A

LMWH (enoxaparin, dalteparin) and fondaparinux = FXa inhib

  • more Xa action
  • better bioavail
  • longer T1/2
  • don’t need monitoring
  • less easily reversible
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3
Q

how to reverse heparin?

A

protamine sulfate ( + charge –> binds heparin)

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4
Q

HIT?

A

IgG against heparin-bound platelet factor 4 (PF4)

Ab-heparin-PF4 complex –> platelet activation –> thrombosis and TCP

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5
Q

direct thrombin inhibitors?

A

argatroban
bivalirudin
dabigatran

** alternatives to heparin in pts with HIT

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6
Q

warfarin MOA?

A

blocks gamma-carboxylation of vit K dependent factors
metabolism affected by polymorphisms in VKORC1 gene (vit K epoxide reductase complex)

** affects extrinsic pathway, PT/INR

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7
Q

mechanism of warfarin-induced tissue necrosis?

A

small vessel microthromboses

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8
Q

direct F Xa inhibitors?

A

apixaban, rivaroxaban

uses: tx and ppx for DVT/PE, stroke ppx in afib

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9
Q

how to tx thrombolytic tox?

A

aminocaproic acid (inhibits fibrinolysis)

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10
Q

aspirin MOA?

A

irreversible COX1/2 inhib via acetylation
increases bleeding time, decreases TXA2 and PGs

** no effect on PT or PTT

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11
Q

ADP receptor inhibitors/

A

clopidogrel, prasugrel, ticagrelor, ticlopidine
irreversible block of ADP receptor –> prevent expression of GPIIb/IIIa –> inhibit platelet agg

    • ticagrelor = reversible
    • ticlopidine –> neutropenia
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12
Q

cilostazol, dipyramidole?

A

PDEIII inhib –> increased cAMP in platelets –> inhib of aggregation; vasodilation

    • used in intermittent claudication, coronary syndromes
    • tox: nausea, HA, flushing, hypoT, abd pain
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13
Q

GP IIb/IIIa inhibs?

A

abciximab, eptifibatide, tirofiban
used for unstable angina, PTCA

** tox: bleeding, TCP

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14
Q

antimetabolites that are purine analogs?

A

6MP
azathioprine
cladribine

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15
Q

azathioprine/6MP MOA?

A

purine analogs, activated by HGPRT

inhibit de novo purine synth

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16
Q

azathioprine/6MP uses?

A

rejection ppx, RA, IBD, SLE

weaning pts off steroids in chronic dz

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17
Q

azathioprine/6MP toxicity?

A

myelosuppression
GI
liver

** increased toxicity with allopurinol and febuxostat (metab by XO)

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18
Q

cladribine MOA?

A

purine analog

multiple mechanisms: DNA pol inhib, DNA breaks

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19
Q

cladribine uses?

A

hairy cell leukemia

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20
Q

cladribine toxicity?

A

myelosuppresssion
nephrotoxicity
neurotoxicity

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21
Q

antimetabolites that inhibit pyrimidine synthesis?

A

cytarabine
5FU
methotrexate

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22
Q

cytarabine MOA?

A

pyrimidine analog

inhibit DNA pol

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23
Q

cytarabine uses?

A

leukemia - AML

lymphomas

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24
Q

cytarabine toxicity?

A

pancytopenia, megaloblastic anemia

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25
Q

5FU MOA?

A

pyrimidine analog, activated to 5F-dUMP –> covalently complexes folate
complex inhibits thymidylate synthase –> decreased dTMP –> decreased DNA synthesis

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26
Q

5FU uses?

A

colon cancer
pancreatic cancer
topical –> basal cell carcinoma

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27
Q

5FU toxicity?

A

myelosuppresion

** NOT reversible with leucovorin (folinic acid)

28
Q

MTX MOA?

A

folic acid analog

competitive inhibition of DHFR –> decreased dTMP –> decreased DNA synthesis

29
Q

MTX uses?

A

cancer: ALL, lymphoma, choriocarcinoma, sarcoma

non-cancer: ectopic preg/abortion, RA, psoriasis, IBD, vasculitis

30
Q

MTX toxicity?

A

myelosuppression
hepatotoxicity
mucositis
pulmonary fibrosis

** myelosuppresion REVERSIBLE with leucovorin (folinic acid) - contrast to 5FU

31
Q

bleomycin MOA?

A

free radical formation –> DNA strand breaks

32
Q

bleomycin uses?

A

testicular cancer

Hodgkin lymphoma

33
Q

bleomycin toxicity?

A

pulmonary fibrosis
skin pigmentation
mucositis

34
Q

dactinomycin MOA?

A

intercalates in DNA

35
Q

dactinomycin uses?

A

childhood tumors!

Wilms, Ewing, rhabdomyo

36
Q

dactinomycin toxicity?

A

myelosuppression

37
Q

doxo/daunorubicin MOA?

A

free radicals, intercalates in DNA

DNA breaks –> decreased replication

38
Q

doxo/daunorubicin uses?

A

solid tumors
leukemias
lymphomas

39
Q

doxo/daunorubicin toxicity?

A

dilated cardiomyopathy
myelosuppression
alopecia

** DEXRAZOXANE prevents cardiomyopathy

40
Q

busulfan MOA?

A

DNA crosslinking

41
Q

busulfan uses?

A

CML

BM ablation prior to txp

42
Q

busulfan toxicity?

A

SEVERE myelosuppression
pulmonary fibrosis
skin pigmentation

43
Q

cyclophosphamide, ifosfamide MOA?

A

cross link DNA at guanine-N7

need bioactivation in liver

44
Q

cyclophosphamide/ifosfamide uses?

A

solid tumors
leukemia
lymphomas

45
Q

cyclophos/ifos toxicity?

A

myelosuppression
hemorrhagic cystitis

** MESNA partially prevents hemorrhagic cystitis

46
Q

nitrosureas MOA?

A

(carmustine, lomustin, semustine, streptoxocin)
need bioactivation
cross BBB –> CNS
cross link DNA

47
Q

nitrosureas use?

A

brain tumors - GBM, etc

48
Q

nitrosureas toxicity?

A

CNS - convulsions, dizziness, ataxias

49
Q

taxol MOA?

A

hyperstabilize microtubules in M phase –> prevent progression to anaphase

50
Q

taxol uses?

A

ovarian and breast ca

51
Q

taxol toxicity?

A

myelosuppression
alopecia
hypersensitivity

52
Q

vincristine/blastine MOA?

A

bind beta-tubulin –> inhibit polymerization into micrtubules –> prevent spindle formation - M phase arrest

53
Q

vincristine/blastine uses?

A

solid tumors
leukemias
Hodgkin - vinblastine
non-Hodgkin - vincristine

54
Q

vincristine toxicity?

A

neurotoxicity - areflexia, peripheral neuritis, paralytic ileus

55
Q

vinblastine toxicity?

A

myelosuppression

56
Q

cisplatin/carboplatin?

A

cross link DNA
used in testicular, bladder, ovary, lung carcinomas
tox: nephro, oto

** AMIFOSTINE and saline diuresis prevent nephrotoxicity

57
Q

Etoposide/teniposide?

A

inhibit topo II –> increased DNA degradation
used in solid tumors (esp testicular and SCLC), leuk, lymph
tox: myelosuppression, GI, alopecia

58
Q

irinotecan/topotecan?

A

inhibit topo I –> prevent DNA unwinding/replication
irinotecan –> colon cancer
topotecan –> ovarian and SCLC
tox: SEVERE myelosuppression, diarrhea

59
Q

hydroxyurea?

A

inhibits ribonucleotide reductase –> decreased DNA synth
used in melanoma, CML, sickle cell
tox: SEVERE myelosuppression, diarrhea

60
Q

prednisone used in which cancers?

A

CLL

non-Hodgkin

61
Q

bevacizumab?

A

VEGF monoclonal Ab

use: CRC, RCC
tox: hemorrhage, clots, impaired wound healing

62
Q

erlotinib?

A

EGFR tyr kinase inhib

used: non small cell lung ca
tox: rash

63
Q

imatinib?

A

tyr kinase inhibition of BCR-ABL and c-kit
used in CML, GI stromal tumors
tox: fluid retention

64
Q

rituximab?

A

anti-CD20 monoclonal Ab
used in Non-Hodgkin, CLL, IBD, RA
tox: increased risk of PML

65
Q

tamoxifen/raloxifene?

A

SERMS

tamoxifen: brca tx
raloxifene: osteoporosis ppx

tamoxifen tox: increased risk of endo ca, hot flashes
raloxifene: no increase in endo ca

66
Q

trastuzumab?

A

HER2 monoclonal Ab (tyr kinase)
used in br ca and gastric ca
tox: CARDIAC

67
Q

vemurafenib?

A

small molecule inhib of BRAF oncogene + melanoma

used in metastatic melanoma

step 1 - pharm (13 decks)

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