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Flashcards in Heme-Onc Drugs Deck (118)
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1
Q
A
2
Q

Heparin mechanism

A

cofactor for the activation of antithrombin leading to decreased thrombin and factor Xa

3
Q

Use of Heparin

A

immediate anticoagulation for PE, acute coronary syndrome, MI, DVT **Follow PTT

4
Q

Heparin can be used during pregnancy bc...

A

it does not cross the placenta. Warfarin cannot be used in pregnancy.

5
Q

Toxicity of Heparin

A

-bleeding -HIT -osteoporosis

6
Q

For rapid reversal of Heparin, use...

A

protamine sulfate (which is a positively charged molecule that binds negatively charged heparin).

7
Q

Low-molecular weight heparins (2)

A

1. Enoxaparin 2. Dalteparin

8
Q

Low-molecular weight heparins act more on...

A

factor Xa, have better bioavailablity and 2-4x longer half life.

9
Q

Heparin Induced Thrombocytopenia (HIT)

A

-development of IgG antibodies agaisnt heparin bound to platelet factor 4 (PF4) -Ab-heparin-PF4 complex activates platelets leading to thrombosis and thrombocytopenia

10
Q

Argatroban, Bivalirudin MOA

A

Inhibit thrombin directly

11
Q

Argatroban and Bivalirudin are used...

A

instead of heparin for anticoagulating pts with HIT.

12
Q

Warfarin MOA

A

-interferes with normal synthesis and gamma-carboxylation of vitamin-K dependent clotting factors II, VII, IX and X and proteins C and S

13
Q

Warfarin is metabolized by...

A

the CYP450s.

14
Q

In lab assays, Warfarin has an effect on the...

A

extrinsic pathways and increases PT.

15
Q

Use of Warfarin

A

-chronic anticoagulation (after STEMI, venous thromboembolism prophylaxis, stroke prevention) **Follow PT/INR values.

16
Q

Toxicity of Warfarin

A

-bleeding -teratogenic -skin/tissue necrosis

17
Q

For reversal of warfarin overdose

A

-give vitamin K -if rapid reversal is necessary, give FFP

18
Q

Apixaban and Rivaroxaban MOA

A

bind and directly inhibit activity of factor Xa

19
Q

Use of Apixaban and Rivaroxaban

A

-treatment and prophylaxis of DVT and PE (rivaroxaban) -stroke prophylaxis

20
Q

Thrombolytics (3)

A

1. Alteplase (tPA) 2. Reteplase (rPA) 3. Tenecteplase (TNK-tPA)

21
Q

MOA of thrombolytics (tPA, etc)

A

directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots -increases PT and PTT

22
Q

Use of thrombolytics

A

-MI -ischemic stroke -directy thrombolysis of severe PE

23
Q

Thrombolytics are contraindicated in...

A

pts with active bleeding, hx of intracranial bleed, recent surgery, known bleeding diathesis or HTN.

24
Q

Treat thrombolytic toxicity with...

A

aminocaproic acid (inhibitor of fibrinolysis).

25
Q

Aspirin MOA

A

irreversibly inhibits COX1 and COX2 by covalent acetylation; platelets cannot synthesize new enzyme so the effects last until new platelets are produced

26
Q

Aspirin effects

A

-increased bleeding time -decreased TXA2 and prostaglandins -no effect on PT or PTT

27
Q

Use of Aspirin

A

-antipyretic -analgesic -anti-inflammatory -antiplatelet (decreased aggregation)

28
Q

Toxicity of aspirin

A

-gastric ulceration -tinnitus -reye syndrome in children with viral infxn

29
Q

Chronic use of aspirin can lead to...

A

acute renal failure, interstitial nephritis and upper GI bleeding.

30
Q

Overdose of aspirin causes....

A

respiratory alkalosis initially which is then superimposed by metabolic acidosis.

31
Q

ADP receptor inhibitors (4)

A

1. Clopidogrel 2. Ticlopidine 3. Prasugrel 4. Ticagrelor

32
Q

MOA of ADP recpetor inhibitors

A

inhibit platelet aggregation by irreversibly blocking ADP receptors; inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa binding

33
Q

Use of ADP receptor inhibitors

A

-acute coronary syndrome -coronary stenting (decreased risk of thrombotic stroke)

34
Q

Toxicity of ADP receptor inhibitors

A

-Neutropenia (Ticlopidine) -may see TTP/HUS

35
Q

Cilostazol and Dipyridamole MOA

A

phosphodiesterase III inhibitors leading to increased cAMP in platelets, thus inhibiting platelet aggregation vasodilators

36
Q

Use of Cilostazol and Dipyridamole

A

-intermittent claduication -coronary vasodilation -prevention of stroke/TIA/angina

37
Q

GP IIb/IIIa inhibitors (3)

A

Abciximab Eptifibatide Tirofiban

38
Q

GpIIb/IIIa inhibitor MOA

A

bind to the glycoprotein receptor IIb/IIIa on activated platelets, inhibiting aggregation

39
Q

Abciximab is made from...

A

monoclonal antibody Fab fragments.

40
Q

Use of GP IIb/IIIa inhibitors

A

-unstable angina -percutaneous transluminal coronary angioplasty

41
Q

Antimetabolites (6)

A

1. Metotrexate 2. 5-Fluorouracil 3. Cytarabine 4. Azathioprine 5. 6-Mercaptopurine 6. 6-Thioguanine *all are S-phase specific

42
Q

Methotrexate MOA

A

folic acid analog that inhibits dihydrofolate reductase leading to decreased dTMP, DNA and protein synthesis.

43
Q

Cancer uses of methotrexate

A

-leukemias/lymphomas -choriocarcinoma -sarcomas

44
Q

Non-neoplastic uses of methotrexate

A

-abortion/ectopic pregnancy -RA -psoriasis -IBD

45
Q

Toxicity of Methotrexate

A

-Myelosuppression -Macrovesicular fatty change in liver -mucositis -teratogenic

46
Q

Myelosuppression from methotrexate is reversible with...

A

leucovorin.

47
Q

5-FU MOA

A

pyrimidine analog bioactivated to 5F-dUMP which covalently complexes folic acid; this complex inhibits thymidylate synthase leading to decreased dTMP, DNA and protein synthesis

48
Q

Clinical uses of 5-FU

A

-colon cancer -pancreatic cancer -basal cell carcinoma

49
Q

Toxicity of 5-FU

A

-myelosuppression (not reversible w/ leucovorin; use uridine) -photosensitivity

50
Q

Cytarabine MOA

A

-pyrimidine analog leading to inhibition of DNA polymerase

51
Q

Clinical use of Cytarabine

A

-leukemias -lymphomas

52
Q

Cytarabine toxicity

A

Pancytopenia (thrombocytopenia, leukopenia, megaloblastic anemia)

53
Q

Azathioprine, 6-MP and 6-TG MOA

A

purine analogs that decrease de novo synthesis of purines; activated by HGPRT

54
Q

Clinical uses of azathioprine, 6-MP and 6-TG

A

-preventing organ rejection -RA -SLE (azathioprine) -Leukemia/IBD (6-MP, 6-TG)

55
Q

Toxicity of Azathioprine, 6-MP and 6-TG

A

-bone marrow, GI and liver

56
Q

Azathioprine and 6-MP are metabolized by...

A

xanthine oxidase and thus both have increased toxicity with allopurinol.

57
Q

Antitumor antibiotics (3)

A

1. Dactinomycin 2. Doxorubicin, Daunorubicin 3. Bleomycin

58
Q

Dactinomycin MOA

A

intercalates in DNA

59
Q

Use of Dactinomycin

A

-Wilms tumor -Ewing sarcoma -Rhabdomyosarcoma

60
Q

Toxicity of Dactinomycin

A

myelosuppression

61
Q

Doxorubicin, Daunorubicin MOA

A

generate free radicals; intercalate DNA decreasing replication

62
Q

Clinical use of Doxorubicin

A

solid tumors lymphomas/leukemias

63
Q

Toxciity of Doxorubicin

A

-Cardiotoxicity (DCM) -myelosuppression -alopecia

64
Q

When giving Doxorubicin, cardiotoxicity can be prevented with...

A

Dexrazoxane.

65
Q

Bleomycin MOA

A

induces free radical formation which causes breaks in DNA

66
Q

Uses of Bleomycin

A

-testicular cancer -Hodgkin lymphoma

67
Q

Toxicity of Bleomycin

A

-pulmonary fibrosis -skin changes -mucositis

68
Q

Alkylating Agents

A

1. Cyclophosphamide, Ifosfamide 2. Nitrosoureas (Carmustine, Lomustine, Semustine, Streptozocin) 3. Busulfan

69
Q

Cyclophosphamide and Ifosfamide MOA

A

covalently X-link (interstrand) DNA at guanine N-7; requires activation by liver

70
Q

Clinical uses of cyclophosphamide/Ifosfamide

A

-solid tumors -leukemia/lymphomas -some brain tumors

71
Q

Toxicity of Cyclophosphamide/Ifosfamide

A

-myelosuppression -hemorrhagic cystitis

72
Q

Hemorrhagic cystitis from cyclophosphamide and Ifosfamide can be partiall prevented with...

A

mensa which binds toxic metabolites.

73
Q

Nitrosureas (carmustine, lomustine, semustine, streptozocin) MOA

A

cross BBB and cross-links DNA; requires activation

74
Q

Use of Nitrosurease (carmustine, lomustine, semustine, streptozocin)

A

brain tumors (including glioblastoma multiforme)

75
Q

Toxicity of Nitrosureas

A

CNS toxicity

76
Q

Busulfan MOA

A

cross-links DNA

77
Q

Clinical use of Busulfan

A

CML -and to ablate pts bone marrow before BMT

78
Q

Toxicity of Busulfan

A

-severe myelosuppression -pulmonary fibrosis -hyperpigmentation

79
Q

Microtubule Inhibitors

A

1. Vincristine/Vinblastine 2. Paclitaxel (-taxols)

80
Q

MOA of Vincristine/Vinblastine

A

vinca alkaloids that bind beta-tubulin and inhibits its polymerization into microtubules, thereby preventing mitotic spindle formation (m-phase arrest)

81
Q

Clinical use of Vincristine/Vinblastine

A

-solid tumors -leukemias/lymphomas

82
Q

Toxicity of Vincristine/Vinblastine

A

-myelosuppression (vinblastine) -neuotoxicty, pralytic ileus (vincristine)

83
Q

Paclitaxel MOA

A

hyperstabilizes polymerized microtubules in M-phase so that mitotic spindle cannot break down preventing anaphase

84
Q

Use of Paclitaxel

A

-ovarian cancer -breast cancer

85
Q

Toxicity of Paclitaxel

A

-myelosuppression -alopecia -hypersensitivity

86
Q

Cisplatin and Carboplatin MOA

A

cross-link DNA

87
Q

Cisplatin and Carboplatin Use

A

testicular, bladder, ovary and lung carcinomas

88
Q

Cisplatin and Carboplatin toxicity

A

-nephrotoxicity -acoustic nerve damage

89
Q

Nephrotoxicity from cisplatin and carboplatin can be prevented with...

A

amifostine and chloride diuresis.

90
Q

Etoposide and Teniposide MOA

A

inhibits topoisomerase II leading to increased DNA degradation

91
Q

Clinical use of Etoposide and Teniposide

A

-solid tumors (esp. testicular, small cell lung) -leukemias/lymphomas

92
Q

Toxicity of Etoposide/Teniposide

A

-myelosuppression -GI irritation -alopecia

93
Q

Irinotecan and Topotecan MOA

A

inhibit topoisomerase I and prevent DNA unwinding and replication

94
Q

Use of Irinotecan and Topotecan

A

-colon cancer (irinotecan) -ovarian and small cell lung (topotecan)

95
Q

Toxicity of Irinotecan and Topotecan

A

-severe myelosuppression -diarrhea

96
Q

Hydroxyurea MOA

A

inhibits ribonucleotide reductase leading to decreased DNA synthesis

97
Q

Use of Hydroxyurea

A

-melanoma -CML -sickle cell

98
Q

Toxicity of Hydroxyurea

A

-myelosuppression -GI upset

99
Q

MOA of Prednisone and Prednisolone

A

may trigger apoptosis

100
Q

Use of Prednisone and Prednisolone

A

-most commonly used glucocorticoids in cancer chemo -used in CLL, non-Hodgkins -also as immunosuppressants

101
Q

Toxicity of Prenisone and Prednisolone

A

-Cushing-like symptoms

102
Q

Tamoxifen and Raloxifene MOA

A

selective estrogen reuptake modulators (SERMs) - receptor antagonists in breast and agonists in bone

103
Q

Use of tamoxifen and raloxifene

A

-breast cancer treatment (tamoxifen) -osteoporosis prevention (raloxifene)

104
Q

Tamoxifen toxicity

A

partial agonist in endometrium which increases risk of endometrial cancer

105
Q

Trastuzumab MOA

A

monoclonal Ab against HER-2, a tyrosine kinase receptor; helps kill breast cancer cells through inhibition of HER2 cellular signaling and Ab-dependent cytotoxicity

106
Q

Use of Trastuzumab

A

HER2 + breast and gastric cancer

107
Q

Toxicity of Trastuzumab

A

Cardiotoxicity

108
Q

Imatinib MOA

A

tyrosine kinase inhibitor of bcr-abl and c-Kit

109
Q

Imatinib Use

A

-CML (bcr-abl) -GI stromal tumors (c-Kit)

110
Q

Imatinib toxicity

A

fluid retention

111
Q

Rituximab MOA

A

monoclonal antibody agaisnt CD20 which is found on most B-cell neoplasms

112
Q

Use of Rituximab

A

-Non-hodgkins -RA -ITP

113
Q

Toxicity of Rituximab

A

-incrneased risk of progressive multifocal leukoencephalopathy

114
Q

Vemurafenib MOA

A

inhibitor of forms of B-Raf kinase with V600E mutation

115
Q

Use of Vemurafenib

A

metastatic melanoma

116
Q

Bevacizumab MOA

A

monoclonal Ab against VEGF; inhibits angiogenesis

117
Q

Use of Bevacizumab

A

solid tumors (colorectal, RCC)

118
Q

Toxicity of Bevacizumab

A

-hemorrhage -impaired wound healing