3/14 heme/onc Flashcards Preview

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Flashcards in 3/14 heme/onc Deck (120):
1

Myelodysplastic syndromes
-can progress to what cancer?

AML

2

Myelodysplastic syndromes
-cause?

-Caused by de novo mutations or environmental exposure (e.g., radiation, benzene, chemotherapy)

3

Myelodysplastic syndromes
-whats marrow look like?

Hypercellular bone marrow, but the cells are not
formed properly and dont get released into blood,
so pts have cytopenias.

4

Pseudo–Pelger-Huet anomaly
-seen in what disease?
-what is it?

Bilobed neutrophils seen in myelodysplastic syndromes following chemotherapy.

5

TDT
-what is it?
-which cells/disease is it found it?

-marker for lymphoblasts, so seen in ALL.
-TDT = DNA pol. Only present in lymphoblast nucleus, no other cells. Not in mature lymphoblasts or any other cell.
*TDT found in the nucleus.

6

Whats the marker for myeloblasts (AML)?

-myeloperoxidase => Auer rods
-AML only.

7

Age: <15
-which leukemia(s)?

ALL

8

Age: >60
-which leukemia(s)?

CLL

9

Age: 15-60
-which leukemia(s)?

AML

10

Age: 40-59
-which leukemia(s)?

CML

11

Mediastinal mass
-which leukemia?
-whats the mass?
-mnemonic?

-T-cell ALL
-leukemic infiltration of the thymus
*T cell, T-hymus

12

CD10+
-T or B cell marker?

pre-B cell marker.

13

Down Syndrome
-associated w/which leukemias?

ALL
AML

14

ALL
-most often spreads to where?
-is it responsive to chemo?

-CNS and testes.
-Yes it is.

15

Does normal chemo help CNS & testes?

-Normal chemo doesn't pass BBB or B-testicle-barrier. So give those two their own chemo.

16

Which ALL translocation has a better prognosis?

-t(12;21) = better prognosis

17

CLL
-neoplasm of which cell? T or B cells?
-markers?

-B cells
-CD20+, CD5+

*CD5 surprisingly.

18

smudge cells
-which leukemia?

CLL

19

Small lymphocytic lymphoma
-which leukemia?

CLL
-small = chronic, b/c more mitoses have gone by (compared to blast stage) so cell has gotten smaller.

20

Most pts w/CLL die how?

-infection.
-these neoplastic naive B cells do NOT become plasma cells = hypogammaglobinemia = will die of infection.
*the ones that do make Ig are messed up and will target your own RBCs and cause autoimmune hemolytic anemia.

21

Why would you see spherocytes in CLL?

b/c you can get autoimmune hemolytic anemia in CLL.

22

Richter syndrome

CLL transforming into diffuse large B cell lymphoma = Richter syndrome.

23

Hairy cell leukemia
-neoplasm of which cells?
-marker?

-B-Cells (its a variant of CLL)
-TRAP (+)

24

Hairy cell leukemia
-whats it do to bone marrow?

-marrow fibrosis => dry tap.

25

Hairy cell leukemia
-seen in which pt pop?
-Tx:

-elderly
-cladribine an adenosine analog inhibits adenosine deaminase (like in SCID).

26

AML
-risk factors

-prior exposure to alkylating chemotherapy
-radiation
-myeloproliferative disorders
-down syndrome.

27

M3 AML
-translocation?
-Tx?
-how does it cause DIC?

-t(15;17)
-reitnoic acid
-DIC is a common presentation in M3 AML and can be induced by chemotherapy due to release of Auer rods.
*since auer rods seen mostly in M3.

28

Which leukemia classically affects gums?

-acute monocytic leukemia.
-obviously a sect of AML

29

CML
-whats the main cell?
-Tx:

-myeloprolif. disorder, main cell = neutrophil.
-imatinib (gleevec): tyrosine kinase inhibitor

30

t(9;22), bcr-abl
-which leukemia?

CML

31

CML
-whats a "blast crisis"?

CML may accelerate and transform to AML or ALL (“blast crisis”).

32

Basophils increased in which leukemia?

CML

33

"-Nib" =

kinase inhibitor

34

Langerhans cell histiocytosis

-Child w/lytic bone lesions and skin rash
or
-Recurrent otitis media with a mass involving the mastoid bone.

35

Langerhans cell histiocytosis
-markers?

S-100, CD1a, birbeck granules

36

chronic myeloproliferative disorders
-risk of transforming into which leukemia?

AML

37

polycythemia vera & peptic ulcers
-connection?

Extra mast cells - lots of histamine.

38

Weightlifters abusing steroids can have high hct, why?

Androgens stimulate RBC production.
-which is also why men generally have higher hct than women.

39

Only myeloproliferative disorder w/inc in plasma volume?
-what can that lead to?

-polycythemia vera
-HTN

40

Essential thrombocytosis
-bleeding or thrombosis?
-Tx:

-either, depends on if the platelets are functional or not.
-hydroxyurea

41

Is there a big risk for hyperuricemia/gout in essential thrombocytosis?

No bc platelets dont have nuclei!

42

Myelofibrosis
-whats causing the fibrosis? what cells and what cytokine?

-Megakaryocytes produce excess PDGF (platelet derived growth factor) which results in marrow fibrosis.

43

leukoerythroblastic smear
-seen when?

Extra-medullary hematopoiesis
-marrow usually prevets blasts from leaving b/c they're too large. But spleen and liver do not do that, so you get blasts in peripheral smear.
-can be seen in myelofibrosis.

44

CML
-JAK2 mutation?

NO
-other myeloprolif disorders do have JAK2 mutation.

45

antithrombin 3
-dec levels of which 2 coag factors the most?

-thrombin & 10a

46

Protamine sulfate
-More useful against unfractionated or LMWH?

unfractionated

47

LMWH
-difference vs unfractionated?

-act more on factor Xa
-have better bioavailability
-2–4 times longer half-life
*not easily reversible

48

Heparin-induced thrombocytopenia
-heparin is an anti-coagulant, so why would it cause a dec. in platelets?

Type 2 HSR
-development of IgG antibodies against heparin bound to platelet factor 4 (PF4).
-Antibody-heparin-PF4 complex activates platelets Ž thrombosis and thrombocytopenia.

*IgG tagged stuff destroyed by splenic macrophages.

49

Heparin-induced thrombocytopenia
-so what do you give them instead of heparin?

argatroban, bivalirudin.

50

Warfarin
-metabolized by which enzymes?

cytochrome P450

51

INR
-PT or PTT vs normal?
-heparin or warfarin?

-PT
-warfarin

52

Warfarin
-how is it administered?
-what do you need to watch out for?

-its lipid soluble, administered orally.
-absorbed like a fat so anything causing malabsorption might affect it.
-watch out when using w/cholestyramine, etc.

53

Apixaban, rivaroxaban

-anti-coagulant.
-Bind and directly inhibit the activity of factor Xa.

54

Does warfarin work in vitro?

-NO
-acts in vivo in the liver to prevent formation of new coag. factors.

55

How soon after original insult do you want to administer thrombolytics.

within 3 hours

56

Whats % of strokes are ischemic?

85% ischemic
15% hemorrhagic

57

Aspirin poisoning
-Sxs:
-Tx:

-resp. alkalosis initially, followed by metabolic acidosis.
-sodium bicarb

58

Two drugs that can cause tinnitus

-aspirin & quinidine

59

ticlopidine
-tox?

Neutropenia

60

Cilostazol, dipyridamole

-Phosphodiesterase III inhibitor; inc. cAMP in platelets, thus inhibiting platelet aggregation; vasodilators.

61

eptifibatide, tirofiban
-mech?

Same as abciximab

62

Methotrexate
-tox:

-Myelosuppression (leucovorin)
-Macrovesicular fatty change in liver.
-Mucositis
-Teratogenic

63

5-fluorouracil (5-FU)
-mech:

-Pyrimidine analog bioactivated to 5F-dUMP, which
covalently complexes folic acid.
-This complex then inhibits thymidilate synthase.

64

5-fluorouracil (5-FU)
-Tx for OD?

uridine (kinases will convert to UMP).
-this is the substrate that thymidilate synthase works on.

65

Cytarabine (arabinofuranosyl cytidine)
-mech
-tox:

-Pyrimidine analog => inhibition of DNA polymerase.
-panCYTopenia

66

Azathioprine
-converted into what?
-metabolized by what?

-6-MP
-xanthine oxidase

67

6-MP, 6-TG
-activated by what enzyme?
-mech:

-Activated by HGPRT.
-inhibit PRPP amidotransferase (formation of IMP)

68

HGPRT
-which anti-neoplastics does this drug activate?

6-MP, 6-TG

69

Dactinomycin (actinomycin D)
-mech:
-use:
-mnemonic:

-Intercalates DNA.
-Used for childhood tumors (“children ACT out”)

70

Doxorubicin (Adriamycin), daunorubicin
-mech:
-use:

-free radicals & intercalates DNA.
-Solid tumors, leukemias, lymphomas.

71

Doxorubicin (Adriamycin), daunorubicin
-tox:
-antidote:

-Cardiotoxicity (dilated cardiomyopathy)
-alopecia.

-Dexrazoxane (iron chelating agent), used to prevent
cardiotoxicity.

72

Dexrazoxane
-use?

-iron chelating agent, used to prevent cardiotoxicity w/doxorubicin use.

73

Bleomycin
-mech:

free radicals

74

Bleomycin
-tox:

Pulmonary fibrosis, skin changes, mucositis.

75

Drugs that can cause pulmonary fibrosis.

Bleomycin, busulfan, methotrexate & amiodarone

76

Alkylating agents
-how do they work?
-are they cell cycle specific?

-attach alkyl group to DNA = DNA damage.
-NOT cell cycle specific.

77

Cyclophosphamide, ifosfamide
-mech:

-alkylating agent, Covalently X-link (interstrand) DNA at guanine N-7.
*Require bioactivation by liver.

78

Nitrosoureas
-suffix?
-use?
-tox?

-"-ustine"
-carmustine, lomustine, semustine, streptozocin.

-brain tumors (crosses BBB).
-tox: CNS toxicity

79

Which alkylating agents cross the BBB?

Nitrosoureas

80

Busulfan
-mech:
-use:

-alkylating agent
-CML. Also used to ablate patient’s bone marrow before
bone marrow transplantation.

81

Nitrosoureas
-mech:

-alkylating agent

82

Busulfan
-tox:

-severe myelosuppression
-pulmonary fibrosis
-hyperpigmentation

83

Alkylating agents
-mnemonic

Beat Cancer Now!
-busulfan, nitrosoureas, cyclophosphamide, ! = I = ifosfamide

84

Vinca Alkaloids
-name some
-what do they bind?

-Vincristine, vinblastine
-β-tubulin

85

Vincristine: tox?
Vinblastine: tox?

-Vincristine—neurotoxicity (areflexia, peripheral neuritis),
paralytic ileus.

-Vinblastine blasts bone marrow (suppression).

86

Taxanes
-name some
-tox:

-paclitaxel
-Myelosuppression, alopecia, hypersensitivity.

87

Cisplatin, carboplatin
-mech:
-tox:
-antidote:

-Cross-link DNA
-Nephrotoxicity and acoustic nerve damage.
-Prevent nephrotoxicity with amifostine (free radical
scavenger) and chloride diuresis.

88

Chloride diuresis
-prevents toxicity from which drug?
-how?

Cisplatin stays in a nonreactive state when in a higher chloride concentration.

89

Etoposide, teniposide
-same mechanism as what other drugs?
-tox:

Fluoroquinolones
-inhibits topoisomerase 2
-tox: Myelosuppression, GI irritation, alopecia.

90

Irinotecan, topotecan
-mech:
-tox:

-Inhibit topoisomerase I.
-Severe myelosuppression, diarrhea.

91

Hydroxyurea
-mech:

-Inhibits ribonucleotide reductase
-

92

Most commonly used glucocorticoids in cancer chemotherapy.

Prednisone (prednisolone)

93

Tamoxifen, raloxifene

Both = antagonists at breast
Both = agonist at bone

Tamoxifen = partial agonist at endometrium (hot flashes)
Raloxifene = antagonist at endometrium

94

HER-2 (c-erbB2)
-codes for what?
-involved in what types of cancers?
-which drug helps w/this type of cancer?

-tyrosine kinase receptor
-breast & gastric
-Trastuzumab (Herceptin)

95

Trastuzumab (Herceptin)
-toxicity?
-mnemonic:

-Cardiotoxicity.
“HEARTceptin” damages the HEART.

96

Imatinib (Gleevec)
-tox?

fluid retention

97

Rituximab
-mech:
-tox:

-Mab against CD20 (found on most B-cell neoplasms).
-risk of progressive multifocal leukoencephalopathy.

*PML also associated w/JC virus = polyomavirus

98

Vemurafenib
-mech:
-use:

-inhibitor B-Raf kinase with the V600E mutation.
-Metastatic melanoma.

99

Bevacizumab
-mech:
-tox:

-Mab against VEGF. Inhibits angiogenesis.
-tox: Hemorrhage and impaired wound healing.

100

Drugs that cause alopecia
-mnemonic?

Propecia Every Day = PED
P = paclitaxel
E = Etoposide (& teniposide)
D = Doxorubicin (& daunorubicin)

101

Michaelis menton constant

Km

102

Lineweaver-Burk plot
-is this the inverse one? or is that michaelis menton?
-slope =?
-y-intercept =
-x-intercept =

-this = inverse/reciprocal one.
-slope = Km/Vmax

-y-int = 1/Vmax
-x-int = 1/-Km

103

Effects of comp/noncomp inhibitors on Lineweaver-Burk plot.

-competetive inhib: inc. Km (closer to 0)
-noncomp inhib: dec. Vmax = higher y-int.

104

Irreversible competetive inhibitors
-what do they do to lineweaver burke plot?
-do they resemble a comp or noncomp inhibitor?

-just like a non-comp inhibitor
-Km same, Vmax dec. (higher y-int).

105

The effects of the body on the drug.
-pharmacokinetics or dynamics?

Pharmacokinetics

ADME:
ƒ Absorption
ƒ Distribution
ƒ Metabolism
ƒ Excretion

106

The effects of the drug on the body.
-pharmacokinetics or dynamics?

Pharmacodynamics
-Includes concepts of receptor binding, drug efficacy, drug potency, toxicity.

107

Link btwn wide-spectrum antibiotics and bleeding disorders?

May kill off bugs that are making vitamin K.

108

Diamond-Blackfan anemia

Pure RBC aplasia
-anemia, not pancytopenia.
-radial abnormalities
-cleft lip
-shield chest
-web neck
-short stature

109

Pancytopenia w/thumb anomalies

Fanconis anemia
-auto recessive aplastic anemia

110

Which leukemia was most associated w/radiation exposure?

AML

111

greater than 10% band neutros, tachy.
-think what?

sepsis
-bands are present during a systemic inflammatory response.

112

ribavirin
-use:
-tox:

-RSV, chronic hepatitis C
-hemolytic anemia, teratogen

113

Volume of distribution (Vd)
-equation?
-will they give you the Vd of the particular drug?

-Vd = total dose/plasma conc.
-yes, for instance they'll say 1L/kg. So if you weigh 70kg, the Vd will be 1*70 = 70L

114

How many half-lives to reach 90% of the steady-state level.

3.3 half lives.

115

Half life
-equation:

t1/2 = (.693*Vd)/Cl

116

How to Dx B12 deficiency definitively?

blood methylmalonic acid levels.
-cant do serum B12 b/c there can be B12 bound to protein in blood but its not free B12 so they can still have B12 deficiency.

117

Why do you see target cells in hemoglobinopathies?
(ie. beta-thal)

Not enough Hb = RBC less full = membrane blebs in the middle.

118

Sideroblastic anemia
-iron status?

Iron overloaded state.
-high ferritin

119

hydrops fetalis
-which thalassemia?

alpha-thal
-4 allele deletion.

120

anaphylaxis: complement components that cause degranulation?

C3a, C4a, C5a