Heme Oncology Pharmacology

Front 1

mechanism of heparin?

Back 1

catalyzes the activation of antithrombin III, decreases thrombin and Xa

Front 2

which can be used during pregnancy - heparin or warfarin?

Back 2

heparin

Front 3

what drug can be used for rapid reversal of heparin?
How does it work?

Back 3

protamine sulfate - positively charged molecule that acts by binding negatively charged heparin

Front 4

what lab values do you monitor with heparin use?

Back 4

PTT

Front 5

mechanism of warfarin?

Back 5

interferes with normal synthesis and gamma-carboxylation of vitamin K-dependent clotting factors II, VII, IX, and X and proteins C and S

Front 6

what pathway does warfarin affect?

Back 6

extrinsic - increases PT

Front 7

how do you reverse warfarin?

Back 7

vitamin K of FFP

Front 8

what labs do you follow with warfarin use?

Back 8

PT or INR

Front 9

onset of action of heparin? warfarin?

Back 9

heparin - fast
warfarin - slow (limited by half-lives of vitamin K-dependent clotting factors)

Front 10

how do thrombolytics work?

Back 10

directly or indirectly aid conversion of plasminogen to plasmin, the major fibrinolytic enzyme, which cleaves thrombin and fibrin clots

Front 11

What is the toxicity of thrombolytic therapy?
how do you treat tPA toxicity?

Back 11

aminocaproic acid, an inhibitor of fibrinolysis

Front 12

mechanism of aspirin?

Back 12

acetylates and irreversibly inhibits cyclooxygenase to prevent conversion of arachidonic acid to prostaglandins

Front 13

how does aspirin affect bleeding time, PT, PTT

Back 13

increases bleeding time, no effect on PT or PTT

Front 14

these inhibit platelet aggregation by irreversibly blocking ADP receptors; inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa expression

Back 14

clopidogrel, ticlopidine

Front 15

toxicity of ticlopidine?

Back 15

neutropenia

Front 16

What is the mechanism of action of Abciximab?

Back 16

monoclonal antibody that binds to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation

Front 17

methotrexate mechanism?

Back 17

folic acid analog that inhibits dihydrofolate reductase, resulting in decreased dTMP and therefore decreased DNA and protein synthesis
S-phase specific

Front 18

toxicity of methotrexate? what can reverse it?

Back 18

myelosuppression - leucovorin (folinic acid) rescue

Front 19

this is an S-phase specific antimetabolite

Back 19

5-FU + methotrexate

Front 20

5-fluorouracil

Back 20

pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid - this complex inhibits thymidylate synthase, resulting in decreaed dTMP and inhibition of DNA synthesis

Front 21

toxicity of 5-FU?

Back 21

myelosupression - not reversible with leucovorin

Front 22

blocks de novo purine synthesis; activated by HGPRTase

Back 22

6-mercaptopurine

Front 23

cancer drug that is metabolized by xanthine oxidase

Back 23

6-mercaptopurine - thus increased toxicity with allopurinol

Front 24

inhibits DNA polymerase; used in AML

Back 24

cytarabine

Front 25

alkylating agents that covalently x-link (interstrand) DNA at guanine N-7

Back 25

cyclophosphamide, ifosfamide

Front 26

What is the major toxicity of cyclophosphamide and ifosfamide?
How is it prevented?

Back 26

hemorrhagic cystitis; mesna offers partial prevention

Front 27

carmustine, lomustine, semustine, and streptozocin are what kind of drug?

Back 27

nitrosureas

Front 28

clinical use of nitrosureas?

Back 28

brain tumors

Front 29

mechanism of nitrosureas?

Back 29

alkylate DNA; require bioactivation

Front 30

these drugs act like alkylating agents and are used for testicular, bladder, ovary, and lung carcinomas

Back 30

cisplatin, carboplatin

Front 31

drug that alkylates DNA and is used for CML

Back 31

busulfan

Front 32

toxicity of busulfan?

Back 32

pulmonary fibrosis, hyperpigmentation

Front 33

drugs that generate free radicals and noncovalently intercalate in DNA (creating breaks in DNA strand to reduce replication)

Back 33

doxorubicin, daunorubicin

Front 34

toxicity of doxorubicin, daunorubicin

Back 34

cardiotoxicity; myelosuppression and marked alopecia

Front 35

drug used for Wilms' tumor, Ewing's sarcoma, rhabdomyosarcoma?

Back 35

dactinomycin (actinomycin D) - used for childhood tumors - children ACT out

Front 36

toxicity of bleomycin?

Back 36

pulmonary fibrosis, skin changes, but minimal myelosuppression

Front 37

toxicity of vincristine?

Back 37

neurotoxicity (areflexia, peripheral neuritis), paralytic ileus

Front 38

toxicity of vinblastine?

Back 38

vinBLASTine BLASTs bone marrow (suppression)

Front 39

what is the most commonly used glucocorticoid used in cancer chemo?

Back 39

prednisone

Front 40

monoclonal antibody against HER-2 (erb-B2)

Back 40

trastuzumab (Herceptin)

Front 41

M-phase-specific alkaloids that bind to tubulin and block polymerization of microtubules so that mitotic spindle cannot form

Back 41

vincristine, vinblastine - arrest cell at metaphase

Front 42

estrogen receptor mixed agonist/antagonists that block the binding of estrogen to estrogen receptor-positive cells

Back 42

tamoxifen, raloxifene

Front 43

G2-phase-specific agent that inhibits topoisomerase II and increases DNA degradation

Back 43

etoposide

Front 44

monoclonal antibody agains the Philadelphia chromosome bcr-abl tyrosine kinase

Back 44

imatinib (Gleevec)

Front 45

What is the toxicity of warfarin?

Back 45

bleeding, teratogenic, drug/drug interactions

Front 46

What is used for short term anti-coagulation? Long term?

Back 46

Heparin - short
Warfarin - Long

Front 47

What lab changes are expected with thrombolytic use?

Back 47

increased PT and PTT

Front 48

What are the major toxicities of aspirin

Back 48

gastric ulceration, bleeding, tinnitus (CNVIII), Reye's syndrome

Front 49

What happens with acute aspirin toxicity?

Back 49

initial respiratory alkalosis that depletes bicarb buffering capacity. Then ASA crosses BBB and induces metabolic acidosis and directly inhibits breathing to cause respiratory acidosis.

Front 50

Abciximab toxicity?

Back 50

bleeding, thrombocytopenia

Front 51

Cisplatin, carboplatin toxicity?

Back 51

nephrotoxicity and acoustic nerve damage

Front 52

mechanism of dactinomycin?

Back 52

intercalates in DNA

Front 53

toxicity of dactinomycin?

Back 53

myelosuppression

Front 54

mechanism of bleomycin?

Back 54

induces formation of free radicals, which cause breaks in DNA strands

Front 55

mechanism of hydroxyurea?

Back 55

inhibits Ribonucleotide reductase --> decreases DNA synthesis (S-phase specific)

Front 56

toxicity of hydroxyuria?

Back 56

bone marrow suppression, GI upset

Front 57

Toxicity of Etoposide (VP-16)?

Back 57

myelosuppression, GI irritation, alopecia

Front 58

toxicity of prednisone?

Back 58

cushing-like symptoms

Front 59

toxicity of Tamoxifen and raloxifene?

Back 59

tamoxifen: increased risk of endometrial carcinoma
Raloxifene: endometrial antagonist so no increase in endometrial carcinoma

Front 60

toxicity of Trastuzumab (Herceptin)?

Back 60

cardiotoxicity

Front 61

toxicity of Imatinib (Gleevec)

Back 61

fluid retention

Front 62

mechanism of Paclitaxel?

Back 62

M-phase-specific. binds to tubulin and hyperstabilize polymerized microtubules so that mitotic spindle cannot break down. --> arrests in metaphase

Front 63

toxicity of paclitaxel

Back 63

myelosuppression and hypersensitivity