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STEP 1 Pharm > Hematology and Oncology > Flashcards

Hematology and Oncology Flashcards

1
Q

Heparin mechanism of action

A

Activates antithrombin 3 to inactivate thrombin and factor Xa. Negatively charged molecule. Follow using PTT. Safe during pregnancy because it doesn’t cross placenta.

Used for immediate anticoagulation following PE, MI, DVT, ACS.

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2
Q

Heparin Toxicity

A

Causes bleeding, can also cause HIT where IgG form to heparin and PF4 complex and cause thrombosis/thrombocytopenia.

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3
Q

Heparin Antidote?

A

Protamine Sulfate (binds negatively charged molecule)

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4
Q

Argatroban and bivalrudin mechanism

A

Derivatives of Hirudin, directly block thrombin. Safe to use in patients with HIT.

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5
Q

Warfarin

A

Small lipid-soluble molecule that blocks epoxide reductase. No vitamin k dependent gamma carboxylation of factors II VII IX X C and S. Long half life and long time to start working because factors aren’t destroyed. Used for DVT prophylaxis, prevention of ACS and MI. Not used in pregnant women (can cross placenta). Does not cause anticoagulation in vitro. Follow PT/INR

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6
Q

Warfarin toxicity

A

Bleeding, warfarin skin necrosis (due to loss of C and S first and prothrombotic state), terratogenicity. Metabolized by CYP450 system.

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7
Q

Warfarin antidote?

A

Vitamin K IV or fresh frozen plasma (to replenish factors)

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8
Q

Apixaban, rivaroxaban

A

Direct factor X inhibitors taken orally for prevention of stroke from afib, and DVT/PE. Don’t require monitoring.

Adverse effects include bleeding with no reversal agent available.

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9
Q

Alteplase, reteplase, tenecteplase

A

TPA used to bust clots. Activates tissue plasminogen to plasmin to lyse clots. Used in early stroke, MI, DVT. Increases PTT and PT both.

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10
Q

Alteplase, reteplase, tenecteplase toxicity and antidote?

A

Bleeding. Give aminocaproic acid with overdose to block fibrinolysis. Can also give fresh frozen plasma and cryoprecipitate.

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11
Q

Aspirin

A

Irreversibly acetylate platelet COX 1 and 2. No TXA2 so platelets cannot be activated to aggregate. Lasts until new platelets are produced, so increases bleeding time.

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12
Q

Aspirin adverse effects?

A

Gastric ulceration, tinnitus, acute renal failure, upper GI bleeding. Reye syndrome of fever and encephalitis with children with viral illness.

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13
Q

Clopidogrel, ticagrelor, prasugrel, ticopidine

A

ADP receptor inhibitors. Block activation of platelets so can’t elaborate GP2B3A and bind fibrinogen. Increases bleeding time. Used for ACS, stenting, decrease stroke

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14
Q

Toxicity of ticlopidine and other ADP receptor blockers?

A

Neutropenia for ticlop. TTP/HUS for others

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15
Q

Cilostazol, dipyridamole

A

PDE3 inhibitors so increase platelet cAMP and prevent aggregation. Used for claudication, coronary vasodilation, prevention of stroke.

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16
Q

Cilostazol, dipyridamole adverse effects

A

Flushing, abdominal pain, nausea, headache.

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17
Q

Abciximab, eptifibatide, tirofiban

A

GP2B3A inhibitors. Fibrinogen can’t cross link platelets, no aggregation. Used for unstable angina. Can cause bleeding and thrombocytopenia.

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18
Q

Methotrexate

A

Inhibitor of dihydrofolate reductase, blocks creation of dTMP from dUMP. Thus preventing DNA and protein synthesis. Used in leukemia, lymphoma, choriocarcinoma, sarcoma, abortion, ectopic pregnancy, RA, psoriasis, IBD

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19
Q

MTX toxicity

A

Myelosuppression that is reversible with leukovorin (folinic acid). Macrovesicular fatty change in liver, mucositis, teratogenic.

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20
Q

5FU

A

Pyrimidine analog that inhibits thymidylate synthase. Less dTMP, less DNA and protein synthesis. Used for colon cancer, pancreatic cancer, and basal cell carcinoma.

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21
Q

5FU toxicity

A

Myelosuppression that isn’t reversible with leukovorin. Rescue with uridine. Causes photosensitivity

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22
Q

Cytarabine

A

Pyrimidine analog that blocks DNA polymerase. Used for leukemia and lymphoma.

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23
Q

Cytarabine toxicity

A

Cytarabine causes pancytopenia and a megaloblastic anemia.

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24
Q

6MP, azathioprine, 6TG

A

Purine analog activated by HGPRT that blocks de novo purine synthesis. Used in organ rejection, SLE, RA, leukemia, IBD

25
Q

6MP toxicity

A

Bone, GI, liver. Metabolized by xanthine oxidase so can’t take allopurinol.

26
Q

S-Phase antineoplastics

A

MTX, 5FU, Cytarabine, 6MP, Azathioprine, 6-TG

27
Q

Dactinomycin

A

Intercalates in DNA. Used for childhood tumors like Ewing’s sarcoma, wilms tumor, rhabdomyosarcomas. Adverse effect is myelosuppression

28
Q

Daunorubicin, Doxorubicin (adriamycin)

A

Intercalate DNA causing strand breaks. Generate free radicals. Decrease replication. Used for solid tumors, leukemias and lymphomas.

29
Q

Bleomycin

A

Induce free radicals, intercalate DNA, decrease replication. used for Hodgkin Lymphoma and testicular cancer.

30
Q

Daunorubicin/Doxorubicin Toxicity

A

Dilated cardiomyopathy (cardiotoxic) *****
Myelosuppression
Mucositis
Alopecia

31
Q

How to prevent Doxo/dauno cardiomyopathy

A

Use an iron chelator called dexrazoxane

32
Q

Dezrazoxane

A

Iron chelator used to prevent cardiotoxicity in dauno/doxo use.

33
Q

Cyclophosphamide

A

Cross links DNA and guanine N7. Requires bioactivation by liver. Used for solid tumors, lymphomas, leukemias, and some brain cancers.

34
Q

Cyclophosphamide toxicity

A

Hemorrhagic cystitis, myelosuppression.

Hemorrhagic cystitis can be prevented with mesna.

35
Q

How to prevent hemorrhagic cystitis with cyclophosphamide?

A

Mesna (binds toxic metabolites)

36
Q

Nitrosureas (carmustine, lomustine, semustine, stretozosin)

A

Alkylating agent that cross links DNA after crossing the blood brain barrier. Requires bioactivation. Used in brain tumors.

37
Q

Nitrosureas (carmustine, semustine, lomustine, streptozosin) toxicity

A

CNS symptoms like dizziness, ataxia, convulsions.

38
Q

Bisulfan

A

Cross links DNA. Used for CML, also used to ablate bone marrow before transplant.

39
Q

Bisulfan toxicity

A

Severe myelosuppression, pulmonary fibrosis, hyperpigmentation.

40
Q

Vincristine, vinblastine

A

Bind beta tubulin so MTs cannot assemble. Mitotic spindle cannot form and therefore M phase is arrested. Used in solid tumors, leukemias, and lymphomas.

41
Q

Vincristine, vinblastine toxicity

A

Vinchristine causes neuropathy.

Vinblastine blasts bone marrow.

42
Q

Cisplatin, Carboplatin

A

Cross link DNA, used for testicular, bladder, ovary, and lung carcinomas.

43
Q

Cisplatin carboplatin toxicity

A

Oto and nephrotoxic. Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis.

44
Q

Etoposide, teniposide

A

DNA topoisomerase II inhibitors, cause DNA degradation. Used in solid tumors like testicular and small cell lung cancer, leukemias and lymphomas.

45
Q

Etoposide, teniposide toxicity

A

GI upset, myelosuppression, alopecia

46
Q

Topotecan, irinotecan

A

DNA topoisomerase I inhibitors and prevent unwinding and replication. used for colon cancer, ovarian and small cell lung cancers.

47
Q

Topotecan, irinotecan toxicity

A

Severe diarrhea, myelosuppression

48
Q

Hydroxyurea

A

Inhibits ribonucleotide reductase so decreases DNA synthesis in S phase. used in melanoma, CML and sickle cell to increase HbF.

49
Q

Hydroxyurea toxicity

A

Bone marrow suppression, gi upset.

50
Q

Prednisone

A

Can trigger apoptosis of non-dividing cells and especially lymphocytes. Causes neutrophilia. Used in many cancers and autoimmune diseases. Causes cushingoid syndrome.

51
Q

Tamoxifen, raloxifene

A

Is a selective estrogen receptor modulator, antagonist in breast and agonists in bone. Used for breast cancer. Can cause endometrial cancer. NOT RALOXIFENE though.

52
Q

Advantage of raloxifene over tamoxifen?

A

raloxifene has no increased risk of endometrial carcinoma because it is an antagonist there too.

53
Q

Trastuzumab

A

Monoclonal antibody against HER2/neu (RTK). Can kill breast cancer cells if Her2 positive. Also can be used in gastric cancer.

54
Q

Trastuzumab toxicity

A

Trastuzumab is cardiotoxic. (HEARTceptin)

55
Q

Imatinib

A

RTK inhibitor of BCR-ABL and C-KIT. Causes fluid retention

56
Q

Rituximab

A

Anti CD-20 MAB used in NHL and RA. Can cause progressive multifocal leukoencephalopathy.

57
Q

Vemurafenib

A

Small molecule inhibitor of B-RAF kinase with V600E mutation used in melanoma.

58
Q

Bevacizumab

A

MAB against VEGF, prevents angiogenesis. Used in solid tumors. Can cause hemorrhage and impaired wound healing.

STEP 1 Pharm (17 decks)

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