3/14 heme/onc Flashcards
1
Q
Myelodysplastic syndromes
-can progress to what cancer?
A
AML
2
Q
Myelodysplastic syndromes
-cause?
A
-Caused by de novo mutations or environmental exposure (e.g., radiation, benzene, chemotherapy)
3
Q
Myelodysplastic syndromes
-whats marrow look like?
A
Hypercellular bone marrow, but the cells are not
formed properly and dont get released into blood,
so pts have cytopenias.
4
Q
Pseudo–Pelger-Huet anomaly
- seen in what disease?
- what is it?
A
Bilobed neutrophils seen in myelodysplastic syndromes following chemotherapy.
5
Q
TDT
- what is it?
- which cells/disease is it found it?
A
- 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
Q
Whats the marker for myeloblasts (AML)?
A
- myeloperoxidase => Auer rods
- AML only.
7
Q
Age: <15
-which leukemia(s)?
A
ALL
8
Q
Age: >60
-which leukemia(s)?
A
CLL
9
Q
Age: 15-60
-which leukemia(s)?
A
AML
10
Q
Age: 40-59
-which leukemia(s)?
A
CML
11
Q
Mediastinal mass
- which leukemia?
- whats the mass?
- mnemonic?
A
- T-cell ALL
- leukemic infiltration of the thymus
- T cell, T-hymus
12
Q
CD10+
-T or B cell marker?
A
pre-B cell marker.
13
Q
Down Syndrome
-associated w/which leukemias?
A
ALL
AML
14
Q
ALL
- most often spreads to where?
- is it responsive to chemo?
A
- CNS and testes.
- Yes it is.
15
Q
Does normal chemo help CNS & testes?
A
-Normal chemo doesn’t pass BBB or B-testicle-barrier. So give those two their own chemo.
16
Q
Which ALL translocation has a better prognosis?
A
-t(12;21) = better prognosis
17
Q
CLL
- neoplasm of which cell? T or B cells?
- markers?
A
- B cells
- CD20+, CD5+
*CD5 surprisingly.
18
Q
smudge cells
-which leukemia?
A
CLL
19
Q
Small lymphocytic lymphoma
-which leukemia?
A
CLL
-small = chronic, b/c more mitoses have gone by (compared to blast stage) so cell has gotten smaller.
20
Q
Most pts w/CLL die how?
A
- 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
Q
Why would you see spherocytes in CLL?
A
b/c you can get autoimmune hemolytic anemia in CLL.
22
Q
Richter syndrome
A
CLL transforming into diffuse large B cell lymphoma = Richter syndrome.
23
Q
Hairy cell leukemia
- neoplasm of which cells?
- marker?
A
- B-Cells (its a variant of CLL)
- TRAP (+)
24
Q
Hairy cell leukemia
-whats it do to bone marrow?
A
-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 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:
Absorption
Distribution
Metabolism
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
