Heme Onc Part III Flashcards
1
Q
Auer rods seen mostly in
A
APL (formerly M3 AML)
2
Q
Other impt finding in AML
A
Increased myeloblasts on peripheral smear
3
Q
APL subtype translocation
A
t(15;17)
4
Q
effect of all-trans retinoid acid?
A
Induces differentiation of promyelocytes.
5
Q
RF’s for AML
A
1) alkylating therapy
2) radiation
3) myeloproliferative disorders
4) Down syndrome
6
Q
median age at diagnosis in CML
A
64
7
Q
Blast crisis
A
CML acceleration and transformation to AML or ALL.
8
Q
How do you distinguish CML from leukemoid reaction?
A
Very low LAP in CML (low activity in malignant neutrophils) vs benign neutrophilic with leukemia in which LAP is increased.
9
Q
Burkitt’s translocation
A
8,14
10
Q
What happens with chromosome 14 translocations?
A
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
Q
ALL translocation can rarely be…
A
9;22, BCR-ABL/philadelphia chromosome
12
Q
Mantle cell activation
A
Cyclin D1
13
Q
mantle cell translocation
A
11,14
14
Q
Folicular lymphoma translocation
A
14,18
15
Q
APL translocation
A
15,17
16
Q
Langerhans presentation
A
lytic bone lesions in a child + skin rash or recurrent otitis media with a mass involving the mastoid bone.
17
Q
Cell markers in langerhans
A
S-100 or CD1a
18
Q
Chronic myeloproliferative disorder gene association
A
V617F JAK2 mutation
19
Q
myeloproliferative disorders…
A
1) polycythemia vera
2) ET
3) myelofibrosis
4) CML
20
Q
Causes of relative polycythemia
A
1) dehydration
2) burns
21
Q
Relative polycythemia
1) plasma volume
2) RBC mass
3) O2 sat
4) EPO levels
A
1) decreased
2) no difference
3) no difference
4) no difference
22
Q
Appropriate absolute
1) plasma volume
2) RBC mass
3) O2 sat
4) EPO levels
A
1) no difference
2) increased
3) decreased
4) increased
23
Q
Causes of appropriate absolute polycythemia
A
1) lung disease
2) congenital heart disease
3) high altitude
24
Q
INAppropriate absolute
1) plasma volume
2) RBC mass
3) O2 sat
4) EPO levels
A
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.
