Heme Onc

Question 1

Heparin

Answer 1

Cofactor for activation of Antithrombin
decreases thrombin and Xa
PE, MI, DVT, okay in pregnancy, follow PTT
can cause acute bleeding and osteoporosis
for OD- protamine sulfate
HIT- IgG against heparin/PF4 complex
Ab/hep/PF4 activates platelets

Question 2

argatroban, bivalirudin, dabigatran

Answer 2

derivatives of hirudin (leeches)
inhibit thrombin directly
Use on patients with HIT

Question 3

Warfarin

Answer 3

Block synthesis and y-carboxylation of II,VII, IX, X, C and S
metabolized by p450, PT, extrins, no preg, oral
use after STEMI and Afib
can cause tissue necrosis (first week, C/S short half life), many drug interactions,
reverse w/ vit K or FFP for faster

Question 4

Direct Xa inhibitors

Answer 4

Apixaban, rivaroxiban, enoxaparin
Bind/inhibit Xa
treatment and prophylaxis of DVT/PE/stroke w Afib (especially rivaroxiban)
don’t need monitoring but no antidote

Question 5

Thrombolytics

Answer 5

Alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA)
Aids in conversion of plasminogen to plasmin
cleaves thrombin and fibrin clots
increase PTT and PT, no change in platelet ct
Early MI/stroke, severe PE
contraindicated in active bleeding or history of intracranial hemorrage
treat toxicity w/ aminocaproic acid (or FFP, cryoprecipitate to restore factor levels)

Question 6

Asprin

Answer 6

covalent acetylation of COX
increase bleeding time, no PT/PTT change
can cause tinnitis, reye’s, gastric etc

Question 7

ADP receptor inhibitors

Answer 7

Clopidogrel, ticlodipine, prasugrel, ticagrelor
Irreversibly blocks ADP receptors, fibrinogen can’t bind GpIIb/IIIa
use for acute coronary syndrome and stenting
can cause TTP/HUS
ticlodipine can cause neutropenia

Question 8

Cilostazol, dipyridamole

Answer 8

PDEIII inhibitors
increase cAMP in platelets (no agg), vasodilate
use for intermittent claudication, coronary vasodilation, angina prophylaxis
can cause nausea, H/A, flushing

Question 9

GpIIb/IIIa inhibitors

Answer 9

Abciximab, eptifibatide, tirofiban
abciximab is monoclonal Ab
Use for unstable angina, percutaneous transluminal coronary angioplasty
can cause thrombocytopenia

Question 10

Methotrexate

Answer 10

folic acid analog, inhibits DHFR, no dTMP
Some cancers, abortion, PAIR
myelosuppression reversible w/ leukovorin, macrovesicular fatty liver changes, mucositis, teratogenic

Question 11

5-FU

Answer 11

pyrimidine analog activated to 5F-dUMP, complexes with folic acid, inhibits thymidylate synthase
Myelosuppression not reversible with leucovorin, treat overdose with uridine

Question 12

Cytarabine

Answer 12

Pyrimidine analog, inhibits DNA polymerase

megaloblastic anemia and pancytopenia

Question 13

Azathioprine, 6-MP, 6-TG

Answer 13

Purine analogues activated by HGPRT
Transplant, SLE, RA, Leukemia, IBD
azathioprine and 6-MP toxicity with allopurinol (metabolized by xanthine oxidase)

Question 14

Dactinomycin

Answer 14

Intercolates into DNA
Childhood tumors
Wilms, ewing, rhabdomyosarcoma
myelosuppression

Question 15

Doxy/daunorubicin

Answer 15

Generates free radicals, intercalates into DNA, DNA breaks
Cardiomyopathy, myelosuppression, alopecia, toxic to tissues following extravasation

Dexrazoxane (iron chelator) to prevent cardiotoxicity

Question 16

Bleomycin

Answer 16

Induce free radical formation (DNA breaks)
Testicular cancer, hodgkin lymphoma
Pulmonary fibrosis, skin changes, mucositis
MINIMAL MYELOSUPPRESSION

Question 17

cyclophosphamide/ifosfamide

Answer 17

covalently X-link DNA guanine at N-7. Bioactivation by liver
Hemorrhagic cystitis prevented with MESNA

Question 18

Nitrosoureas

Answer 18

Carmustine, lomustine, semustine, streptozocin
Crosslinks DNA, requires bioactivation
crosses BBB
Use for brain tumors but has CNS toxicity

Question 19

Busulfan

Answer 19

Crosslinks DNA
use for CML or to ablate bone marrow pre-transplant
Severe myelosuppression, Pulmonary fibrosis, hyperpigmentation

Question 20

Vincristine/Vinblastine

Answer 20

vinca alkaloids that bind B-tubulin, inhibits polymerization into microtubules, prevents mitotic spindle formation (m-phase arrest)
vincristine- neurotoxic, paralytic ileus
vinblastine- bone marrow suppression

Question 21

Taxols

Answer 21

hyperstabilize polymerized microtubules in M phase so mitotic spindle can’t break down- no anaphase
ovarian and breast cancers
myelosuppression, alopecia

Question 22

Cisplatin/carboplatin

Answer 22

cross-links DNA
nephrotoxic and acoustic nerve damage
prevent nephrotoxicity with amifostine and Cl diuresis

Question 23

Etoposide, teniposide

Answer 23

inhibits topisomerase II- DNA degredation

testicular and SCLC

Question 24

irinotecan, topotecan

Answer 24

inhibit topisomerase I, revent DNA unwinding
Irinotecan- colon cancer
Topotecan- ovarian and SCLC
severe myelosuppression

Question 25

hydroxyurea

Answer 25

inhibits ribonucleotide reductase- decrease DNA synthesis (s-phase specific)
melanoma, CML, Sickle cell disease

Question 26

tamoxifen, raloxifene

Answer 26

selective estrogen receptor modulators, block estrogen binding in ER+ cells
tamoxifen-BC treatment and prevention, partial agonist in endometrium (cancer risk), hot flash
Raloxifene- BC prevention, prevent osteoporosis, endometrial antagonist

Question 27

Trastuzumab

Answer 27

mAb against Her-2/neu (c-erbB2), an RTK
Her-2+ breast and gastric cancer
Cardiotoxic

Question 28

Imatinib

Answer 28

Tyrosine kinase inhibitor of bcr-abl and c-Kit (gastric stromal tumors)
Can get fluid retention

Question 29

Rituximab

Answer 29

mAb against CD20, most B cell cancers
also used w/ MTX in RA
Increased risk of PML

Question 30

Vemurafenib

Answer 30

small molecule inhibitor of B-Raf kinase with V600E mutation

used for metastatic melanoma

Question 31

Bevacizumab

Answer 31

Monoclonal Ab against VEGF, inhibits angiogen
solid tumors
can cause impaired wound healing