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Flashcards in Heme Onc Part III Deck (150):
1

Auer rods seen mostly in

APL (formerly M3 AML)

2

Other impt finding in AML

Increased myeloblasts on peripheral smear

3

APL subtype translocation

t(15;17)

4

effect of all-trans retinoid acid?

Induces differentiation of promyelocytes.

5

RF's for AML

1) alkylating therapy
2) radiation
3) myeloproliferative disorders
4) Down syndrome

6

median age at diagnosis in CML

64

7

Blast crisis

CML acceleration and transformation to AML or ALL.

8

How do you distinguish CML from leukemoid reaction?

Very low LAP in CML (low activity in malignant neutrophils) vs benign neutrophilic with leukemia in which LAP is increased.

9

Burkitt's translocation

8,14

10

What happens with chromosome 14 translocations?

The Ig heavy chain genes on chromosome 14 are normally constitutively expressed. When other genes (c-myc or BCL-2) translocate next to this gene, they become over expressed.

11

ALL translocation can rarely be...

9;22, BCR-ABL/philadelphia chromosome

12

Mantle cell activation

Cyclin D1

13

mantle cell translocation

11,14

14

Folicular lymphoma translocation

14,18

15

APL translocation

15,17

16

Langerhans presentation

lytic bone lesions in a child + skin rash or recurrent otitis media with a mass involving the mastoid bone.

17

Cell markers in langerhans

S-100 or CD1a

18

Chronic myeloproliferative disorder gene association

V617F JAK2 mutation

19

myeloproliferative disorders...

1) polycythemia vera
2) ET
3) myelofibrosis
4) CML

20

Causes of relative polycythemia

1) dehydration
2) burns

21

Relative polycythemia
1) plasma volume
2) RBC mass
3) O2 sat
4) EPO levels

1) decreased
2) no difference
3) no difference
4) no difference

22

Appropriate absolute
1) plasma volume
2) RBC mass
3) O2 sat
4) EPO levels

1) no difference
2) increased
3) decreased
4) increased

23

Causes of appropriate absolute polycythemia

1) lung disease
2) congenital heart disease
3) high altitude

24

INAppropriate absolute
1) plasma volume
2) RBC mass
3) O2 sat
4) EPO levels

1) no change
2) increased
3) no change
4) increased

25

Causes of inappropriate absolute

Due to ectopic EPO secretion
1) malignancy (eg, RCC, HCC)
2) hydronephrosis

26

Polycythemia vera
1) plasma volume
2) RBC mass
3) O2 sat
4) EPO levels

1) Increased
2) Very increased
3) No difference
4) Decreased

27

polycythemia vera etiology

Decreased EPO production due to negative feedback suppressing renal EPO production.

28

heparin mechanism

Lowers activity of thrombin and factor Xa

29

what do you need to monitor with heparin?

PTT

30

heparin AE's

Bleeding + thrombocytopenia + osteoporosis

31

Differences between LMWH and heparin

LMWH's act more on factor Xa + have better bioavailability + 2-4 times longer half-life.

32

HIT etiology

IgG antibodies against heparin-bound platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets leading to thrombosis and thrombocytopenia.

33

direct thrombin inhibitors

bivalirudin

34

bivalirudin uses

1) venous thromboembolism
2) afib

35

bivaluridin AE's

Bleeding.

36

How do you treat bleeding associated with bivalirudin?

Can try activated prothrombin complex concentrates (PCC) and/or fibrinolytic (eg, tranexamic acid).

37

Cause of gynecomastia in cirrhosis?

Failure of the liver to degrade estrogen.

38

What is warfarin metabolism affected by?

Polymorphisms in the gene for vitamin K epoxide reductase complex (VKORC1)

39

What do you need to monitor with warfarin?

PT + INR

40

Warfarin half-life

Long

41

warfarin pharmacokinetic point

Proteins C and S have shorter half-lives than clotting factors II, VII, IX, and X, resulting in early transient hyper coagulability.

42

heparin structure

Large, anionic, acidic polymer

43

warfarin structure

small, amphipathic molecule

44

Heparin site of action

blood

45

warfarin site of action

liver

46

heparin mechanism

activates antithrombin, which decreases the action of IIa (thrombin) and factor Xa.

47

Would heparin or warfarin inhibit coagulation in vitro?

heparin, but not warfarin.

48

PE prophylaxis drug

rivaroxaban

49

Stroke prophylaxis in patients with Afib?

Apixaban, rivaroxaban

50

direct factor Xa inhibitors

Apixaban, rivaroxaban

51

thrombolytics

Alteplase (tPA)
reteplase (rPA)
*streptokinase
tenecteplase (TNK-tPA)

52

thrombolytics labs

Increased PT + increased PTT.

53

thrombolytics contraindications

1) bleeding
2) history of intracranial bleeding
3) recent surgery
4) known bleeding diathesis
5) severe HTN

54

thrombolytics bleeding managment

aminocaproic acid. Can also use fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.

55

What are the ADP receptor inhibitors?

clopidogrel
prasugrel
ticagrelor (reversible)
ticlopidine

56

ADP receptor inhibitor mechanism

1) inhibit platelet aggregation by irreversibly blocking ADP receptors
2) *prevent expression of glycoproteins IIb/IIIa on platelet surface.

57

Drug used for coronary stunting?

ADP receptor inhibitors

58

other uses for ADP receptor inhibitors?

1) ACS
2) decrease incidence or recurrence of thrombotic stroke

59

ticlopidine AE

neutropenia

60

Other AE possible with ADP receptor inhibitors?

TTP

61

PDE-III inhibitors?

Cilostazol
Diypridamole

62

PDE-III mechanism?

Increases cAMP in platelets, resulting in inhibition of platelet aggregation. Vasodilators

63

What do you use for angina prophylaxis?

cilostazol, dipyridamole

64

Other uses for PDE-III inhibitors?

1) claudication
2) coronary vasodilation
3) prevention of stroke or TIAs

65

PDE-III inhibitors AEs

Nausea + headache + facial flushing + hypotension + abdominal pain.

66

GP IIb/IIIa inhibitors?

abciximab, eptifibatide, tirofiban

67

GP IIb/IIIa inhibitor MOA?

Prevent aggregation.

68

Abciximab composition

monoclonal antibody Fab fragments

69

GP IIb/IIIa use..

1) unstable angina
2) percutaneous transluminal coronary angioplasty

70

GP IIb/IIIa AE's

bleeding + thrombocytopenia

71

cell cycle-independent cancer drugs?

1) Platinum agents
2) alkylating agents

72

hydroxyurea MOA

Inhibits ribonucleotide reductase

73

cisplatin MOA?

cross-links DNA

74

how do alkylating agents work?

cross-link DNA

75

Bleomycin MOA

Induces free radical formation --> DNA strand breakage

76

Dactinomycin, doxorubicin MOA

intercalators

77

etoposide MOA

inhibits topoisomerase *II

78

irinotecan MOA

inhibits topoisomerase *I

79

vinca alkaloid mechanism

inhibit microtubule formation

80

What activates azathioprine, 6-MP?

HGPRT

81

azathioprine relationship to 6-MP

Azathioprine is metabolized into 6-MP.

82

What do you use to wean patients off steroids in chronic disease?

Azathioprine, 6-MP

83

Other use for azathioprine, 6-MP

steroid-refractory chronic disease

84

azathioprine, 6-MP AE's

myelosuppresion, GI, liver

85

cladribine MOA

purine analog --> multiple mechanisms (inhibition of DNA polymerase, DNA strand breaks)

86

cladribine AE's

myelosuppression + nephrotoxicity + neurotoxicity

87

Cytarabine MOA

pyrimidine analog --> inhibition of DNA polymerase

88

cytarabine also known as...

arabinofuranosyl cytidine

89

Cytarabine AE's

myelosuppression with megaloblastic anemia. pancytopenia.

90

5-FU MOA

pyrimidine analog bioactivated to 5-FdUMP, which covalently complexes folic acid --> inhibition of thymidylate synthase --> decreased dTMP --> decreased DNA synthesis.

91

5-FU uses

1) colon cancer
2) pancreatic cancer
3) basal cell carcinoma (topical)

92

5-FU commonly combined with...

leucovorin (enhances effects but also worsens myelosuppression)

93

methotrexate mechanism

Folic acid analog that competitively inhibits dihydrofolate reductase leading to decreased dTMP and decreased DNA synthesis

94

cancers methotrexate is used for

1) ALL
2) lymphomas
3) choriocarcinoma
40 Sarcomas

95

How do you prevent myelosuppression with methotrexate?

leucovorin

96

methotrexate AE's

1) myelosuppresion
2) hepatotoxic
3) mucositis (mouth ulcers)
4) pulmonary fibrosis

97

Bleomycin uses

1) testicular cancer
2) Hodgkin lymphoma

98

bleomycin AE's

1) PF
2) skin hyper pigmentation
3) *minimal myelosuppression

99

dactinomycin (actinomycin D) uses

1) Wilms tumor
2) Ewing sarcoma
3) Rhabdomyosarcoma
* childhood cancers

100

Doxorubicin, daunorubicin MOA

1) generate free radicals
2) intercalate in DNA --> breaks in DNA and decreased replication.

101

Doxorubicin, daunorubicin AE's

1) cardiotoxic (dilated cardiomyopathy)
2) myelosuppression
3) alopecia

102

Busulifan uses

1) CML
2) ablating bone marrow before bone marrow transplantation

103

busulfan AE's

1) severe myelosuppression
2) PF
3) hyperpigmentation

104

Cyclophosphamide, ifosfamide MOA and caveat

- Cross-link DNA at guanine N-7.
- require bioactivation by liver

105

What else can you use to prevent hemorrhagic cystitis with cyclophosphamide/ifosfamide?

N-acetylcysteine

106

Cyclophosphamide, ifosfamide AE's

1) myelosuppression
2) hemorrhagic cystitis

107

nitrosoureas AE's

CNS toxicity (convulsions, dizziness, ataxia)

108

paclitaxol uses

Ovarian + breast carcinomas

109

paclitaxol AE's

1) myelosuppression
2) neuropathy
3) hypersensitivity

110

what are the vinca alkaloids?

vincristine, vinblastine

111

vincristine, vinblastine MOA

Bind beta-tubulin and inhibit its polymerization into microtubules --> preventing mitotic spindle formation (M-phase arrest)

112

vinca alkaloid used for Hodgkin's

vinblastine

113

vinca alkaloid used for non-Hodgkin's

vincristine

114

Vincristine AE's

1) neurotoxicity (areflexia, peripheral neuritis)
2) constipation (including paralytic ileus)

115

cisplatin, carboplatin uses

Testicular + bladder + ovary + lung carcinomas

116

cisplatin AE's

1) nephrotoxicity
2) peripheral neuropathy
3) ototoxicity

117

How do you prevent nephrotoxicity with cisplatin, carboplatin?

Amifostine + chloride (saline) diuresis

118

etoposide, teniposide uses

testicular + small cell + leukemias/lymphomas

119

etoposide, teniposide AE's

myelosuppression + alopecia

120

irinotecan, topotecan MOA

inhibit topoisomerase I, preventing DNA unwinding and replication.

121

irinotecan uses

colon cancer

122

topotecan uses

ovarian + small cell lung cancers

123

irinotecan, topotecan AE's

severe myelosuppression + diarrhea

124

hydroxyurea MOA

Inhibits ribonucleotide reductase, leading to decreased DNA synthesis (S-phase specific).

125

hydroxyurea uses

1) melanoma
2) CML
3) sickle cell disease

126

Hydroxyurea AE's

severe myelosuppression

127

How is prednisone/prednisolone used in chemo MOA?

Various/bind intracytoplasmic steroid receptor; altering gene transcription.

128

prednisone/prednisolone uses

1) CLL
2) non-Hodgkin lymphoma

129

bevacizumab uses

Colorectal cancer
RCC

130

bevacizumab AE's

Hemorrhage + blood clots + impaired wound healing

131

Erlotinib MOA

EGFR tyrosine kinase inhibitor

132

Erlotinib uses

non-small cell lung carcinoma

133

erlotinib AE

rash

134

Cetuximab MOA

monoclonal antibody against EGFR

135

cetuximab uses

Stage IV colorectal cancer (wild-type KRAS), head and neck cancer.

136

cetuximab AE's

Rash + elevated LFTs + diarrhea

137

Imatinib uses

Tyrosine kinase inhibitor of BCR-ABL + c-kit

138

imatinib uses

1) CML
2) GI stromal tumors

139

rituximab MOA

monoclonal antibody against CD20

140

rituximab uses

1) non-Hodgkin lymphoma
2) CLL
3) ITP
4) RA

141

rituximab AE

Increased risk of progressive multifocal leukoencephalopathy.

142

Tamoxifen and endometrium

partial agonist in endometrium, which increases risk of endometrial cancer.

143

raloxifene AE's

Increased risk of thromboembolic events

144

herceptin uses

1) HER-2 positive breast cancer
2) gastric cancer

145

perception AE's

cardiotoxic

146

Paraganglioma

/rare neuroendocrine neoplasm. /can occur at various body sites (including head, neck, thorax, and abdomen). /usually either asymptomatic or present as a painless mass.

147

blood serum

plasma without clotting factors

148

plasma

extra cellular matrix of blood cells

149

Which ADP receptor inhibitor is reversible?

ticagrelor

150

ribonucleotide reductase

Enzyme that catalyzes the formation of deoxyribonucletoides from ribonucleotides, which are in turn used in the synthesis of DNA.