HemOnc--Pharmacology

Question 1

heparin moa?

Answer 1

cofactor for atIII, decreases thrombin and factor Xa

Question 2

direct thrombin inhibitors

Answer 2

argatroban, bivalirudin–derivatives of hirudin

Question 3

in HIT, what to use for anticoagulation?

Answer 3

argatroban or bivalirudin

Question 4

warfarin moa?

Answer 4

interferes with synthesis and gamma-carboxlyation of vitamin K dependent clotting factors (2, 7, 9, 10 and proteins C and S)

Question 5

how to follow warfarin effect?

Answer 5

extrinsic pathway–use PT/INR to monitor

Question 6

warfarin tox?

Answer 6

bleeding, teratogenic (do not use in preg); skin/tissue necrosis esp if patient has genetic protein C/S deficiency; drug-drug interactions

Question 7

Direct factor Xa inhibitors?

Answer 7

apixaban, rivaroxaban;

Question 8

aspirin overdose? A/B derrangement

Answer 8

initially a respiratory alkalosis then superimposed by metabolic acidosis

Question 9

ADP receptor inhibitors? moa?

Answer 9

clopidogrel, ticlopidine, prasugrel, ticagrelor; inhibits platelet aggregation by irreversibly blocking ADP receptors and prevents GPIIb/IIIa receptor expression, preventing fibrinogen binding

Question 10

ADP receptor inhibitor that can cause neutropenia?

Answer 10

ticlopidine

Question 11

ADP receptor inhibitors can cause..?

Answer 11

TTP or HUS

Question 12

cilostazol, dipyradamole?

Answer 12

PDEIII inhibitors, increase cAMP in platelets–>inhibiting platelet aggregation; also vasodilates

Question 13

GP IIb/IIIa inhibitors?

Answer 13

abciximab,eptifibatide, tirofiban; can cause thrombocytopenia

Question 14

Cell cycle effect: vinca alkaloids and taxols

Answer 14

inhibit M phase

Question 15

Cell cycle effect: antimetabolites

Answer 15

S phase; eg MTX, 5-FU, cytarabine, 6MP, 6TG, hdroxyurea

Question 16

Cell cycle effect: etoposide

Answer 16

S and G2 phase

Question 17

Cell cycle effect: bleomycin

Answer 17

G2 phase

Question 18

methotrexate moa?

Answer 18

folic acid analog that inhibits DHF reductase–>decreases dTMP–>decreases DNA and protein synthesis

Question 19

methotrexate tox?

Answer 19

myelosuppression (reverse with folinic acid); macrovesicular fatty change in liver, mucositis, teratogen

Question 20

5-FU moa?

Answer 20

pyrimide analog bioactivated to 5F-dUMP which covalently complexes folic acid to inhibit thymidylate synthase–>decrease dTMP–>decrease DNA and protein synthesis

Question 21

5FU tox?

Answer 21

myelosupression which cannot be reversed with folinic acid; overdose rescue with uridine; photosensitivty

Question 22

cytarabine moa?

Answer 22

pyrimidine analog–>inhibits DNA polymerase;

Question 23

cytarabine tox?

Answer 23

pancytopenia

Question 24

azathioprine, 6MP, 6TG moa? tox?

Answer 24

purine (thiol) analogs–>decrease de novo purine synthesis; activated by HGPRT; tox to bone marrow/GI/liver

Question 25

do not mix azathioprine or 6MP with...?

Answer 25

allopurinol (XO inhibitor)

Question 26

dactinomycin moa? tox? use?

Answer 26

intercalates DNA; myelosuppresion; used in wilms tumor, ewing sarcoma, rhabomyosarcoma; childhood tumors

Question 27

doxorubicin, daunorubicin moa? tox?

Answer 27

generate free radicals-->intercalate in DNA-->breaks DNA->decr replication; used in solid tumors, leukemias, lymphomas; cardiotoxic (dilated CM), myelosuppresion, alopecia

Question 28

treat doxorubicin tox?

Answer 28

dexrazoxane (iron chelating agent) used to prevent cardiotoxicity

Question 29

Bleomycin moa? tox?

Answer 29

induces free radical formation-->DNA strand breaks; pulmonary fibrosis, skin changes, mucositis; hyperpigmentation; use in testicular cancer/hodgkins

Question 30

which antitumor antibiotic has minimal myelosuppresion?

Answer 30

bleomycin

Question 31

what are some alkylating agents?

Answer 31

cyclophosphamide, ifosfamide, nitrosoureas, busulfan; all cross link DNA

Question 32

cyclophosphamide, ifosfamide moa?

Answer 32

covalently x-link (interstrand) DNA at guanine N-7; requires bioactivation by liver

Question 33

cyclophosphamide tox?

Answer 33

myelosuppresion; hemorrhagic cystitis that can be prevented with mesna (thiol group bind toxic metabolites)

Question 34

nitrosuoureas moa? tox?

Answer 34

requires bioactivation and cross links DNA; CNS tox (convulsions/dizziness/ataxia)

Question 35

what type of tumors is nitrosoureas specially used for?

Answer 35

CNS tumors including glioblastoma multiforme because it can penetrate BBB

Question 36

busulfan is used for?

Answer 36

CML; and to ablate bone marrow before transplant

Question 37

busulfan tox?

Answer 37

severe myelosuppression, pulmonary fibrosis, hyperpigmentation

Question 38

what are some microtubule inhibitors?

Answer 38

vincristine, vinblastine, paclitaxols and other -taxols

Question 39

vincristine, vinblastine moa? use?

Answer 39

vinca alkaloids that bind B-tubulin, inhibit polymerization and prevent mitotic spindle formation (M phase arrest); use in solid tumors/leukemia/lymphomas

Question 40

vincristine tox?

Answer 40

neurotoxicity (areflexia, peripheral neuritis, paralytic ileus)

Question 41

vinblastine tox?

Answer 41

bone marrow supression

Question 42

paclitaxol moa?

Answer 42

hyperstabilize polymerized mtubules in M phase so that mitotic spindle cannot break down; use in ovarian and breast carcinomas

Question 43

paclitaxel tox?

Answer 43

myelosuppression, alopecia, hypersensitivity

Question 44

cisplatin, carboplatin moa? use?

Answer 44

cross links DNA; testicular/bladder/ovary/lung carcinoma

Question 45

cisplatin/carboplatin tox?

Answer 45

nephrotoxic, acoustic nerve damage

Question 46

prevent nephrotox of cisplatin?

Answer 46

amifostine (free radical scavenger) and chloride diuresis

Question 47

etoposide, teniposide moa? tox?

Answer 47

inhibits topoisomerase II-->increase DNA degradation; myelosuppresion, GI irritation, alopecia

Question 48

irinotecan, topotecan moa? tox?

Answer 48

topoisomerase I inhibition and prevents DNA unwinding and replication; severe myelosuppresion and diarrhea

Question 49

hydroxyurea moa? tox?

Answer 49

inhibits ribonucleotide reductase-->decreases dna synthesis (S phase specific); bone marrow suppression, GI upset

Question 50

hydroxyurea use?

Answer 50

melanoma, CML, sickle cell disease (increased HbF)

Question 51

traztuzumab tox?

Answer 51

cardiotoxic

Question 52

imatinib moa? tox?

Answer 52

tyrosine kinase inhibitor of bcr-abl (CML) and c-kit (GI and stromal tumors); fluid retention

Question 53

test before giving rituximab?

Answer 53

increased risk of PML, test for JC virus