Hematology and Oncology Flashcards
Heparin mechanism of action
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.
Heparin Toxicity
Causes bleeding, can also cause HIT where IgG form to heparin and PF4 complex and cause thrombosis/thrombocytopenia.
Heparin Antidote?
Protamine Sulfate (binds negatively charged molecule)
Argatroban and bivalrudin mechanism
Derivatives of Hirudin, directly block thrombin. Safe to use in patients with HIT.
Warfarin
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
Warfarin toxicity
Bleeding, warfarin skin necrosis (due to loss of C and S first and prothrombotic state), terratogenicity. Metabolized by CYP450 system.
Warfarin antidote?
Vitamin K IV or fresh frozen plasma (to replenish factors)
Apixaban, rivaroxaban
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.
Alteplase, reteplase, tenecteplase
TPA used to bust clots. Activates tissue plasminogen to plasmin to lyse clots. Used in early stroke, MI, DVT. Increases PTT and PT both.
Alteplase, reteplase, tenecteplase toxicity and antidote?
Bleeding. Give aminocaproic acid with overdose to block fibrinolysis. Can also give fresh frozen plasma and cryoprecipitate.
Aspirin
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.
Aspirin adverse effects?
Gastric ulceration, tinnitus, acute renal failure, upper GI bleeding. Reye syndrome of fever and encephalitis with children with viral illness.
Clopidogrel, ticagrelor, prasugrel, ticopidine
ADP receptor inhibitors. Block activation of platelets so can’t elaborate GP2B3A and bind fibrinogen. Increases bleeding time. Used for ACS, stenting, decrease stroke
Toxicity of ticlopidine and other ADP receptor blockers?
Neutropenia for ticlop. TTP/HUS for others
Cilostazol, dipyridamole
PDE3 inhibitors so increase platelet cAMP and prevent aggregation. Used for claudication, coronary vasodilation, prevention of stroke.
Cilostazol, dipyridamole adverse effects
Flushing, abdominal pain, nausea, headache.
Abciximab, eptifibatide, tirofiban
GP2B3A inhibitors. Fibrinogen can’t cross link platelets, no aggregation. Used for unstable angina. Can cause bleeding and thrombocytopenia.
Methotrexate
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
MTX toxicity
Myelosuppression that is reversible with leukovorin (folinic acid). Macrovesicular fatty change in liver, mucositis, teratogenic.
5FU
Pyrimidine analog that inhibits thymidylate synthase. Less dTMP, less DNA and protein synthesis. Used for colon cancer, pancreatic cancer, and basal cell carcinoma.
5FU toxicity
Myelosuppression that isn’t reversible with leukovorin. Rescue with uridine. Causes photosensitivity
Cytarabine
Pyrimidine analog that blocks DNA polymerase. Used for leukemia and lymphoma.
Cytarabine toxicity
Cytarabine causes pancytopenia and a megaloblastic anemia.
6MP, azathioprine, 6TG
Purine analog activated by HGPRT that blocks de novo purine synthesis. Used in organ rejection, SLE, RA, leukemia, IBD
6MP toxicity
Bone, GI, liver. Metabolized by xanthine oxidase so can’t take allopurinol.
S-Phase antineoplastics
MTX, 5FU, Cytarabine, 6MP, Azathioprine, 6-TG
Dactinomycin
Intercalates in DNA. Used for childhood tumors like Ewing’s sarcoma, wilms tumor, rhabdomyosarcomas. Adverse effect is myelosuppression
Daunorubicin, Doxorubicin (adriamycin)
Intercalate DNA causing strand breaks. Generate free radicals. Decrease replication. Used for solid tumors, leukemias and lymphomas.
Bleomycin
Induce free radicals, intercalate DNA, decrease replication. used for Hodgkin Lymphoma and testicular cancer.
Daunorubicin/Doxorubicin Toxicity
Dilated cardiomyopathy (cardiotoxic) *****
Myelosuppression
Mucositis
Alopecia
How to prevent Doxo/dauno cardiomyopathy
Use an iron chelator called dexrazoxane
Dezrazoxane
Iron chelator used to prevent cardiotoxicity in dauno/doxo use.
Cyclophosphamide
Cross links DNA and guanine N7. Requires bioactivation by liver. Used for solid tumors, lymphomas, leukemias, and some brain cancers.
Cyclophosphamide toxicity
Hemorrhagic cystitis, myelosuppression.
Hemorrhagic cystitis can be prevented with mesna.
How to prevent hemorrhagic cystitis with cyclophosphamide?
Mesna (binds toxic metabolites)
Nitrosureas (carmustine, lomustine, semustine, stretozosin)
Alkylating agent that cross links DNA after crossing the blood brain barrier. Requires bioactivation. Used in brain tumors.
Nitrosureas (carmustine, semustine, lomustine, streptozosin) toxicity
CNS symptoms like dizziness, ataxia, convulsions.
Bisulfan
Cross links DNA. Used for CML, also used to ablate bone marrow before transplant.
Bisulfan toxicity
Severe myelosuppression, pulmonary fibrosis, hyperpigmentation.
Vincristine, vinblastine
Bind beta tubulin so MTs cannot assemble. Mitotic spindle cannot form and therefore M phase is arrested. Used in solid tumors, leukemias, and lymphomas.
Vincristine, vinblastine toxicity
Vinchristine causes neuropathy.
Vinblastine blasts bone marrow.
Cisplatin, Carboplatin
Cross link DNA, used for testicular, bladder, ovary, and lung carcinomas.
Cisplatin carboplatin toxicity
Oto and nephrotoxic. Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis.
Etoposide, teniposide
DNA topoisomerase II inhibitors, cause DNA degradation. Used in solid tumors like testicular and small cell lung cancer, leukemias and lymphomas.
Etoposide, teniposide toxicity
GI upset, myelosuppression, alopecia
Topotecan, irinotecan
DNA topoisomerase I inhibitors and prevent unwinding and replication. used for colon cancer, ovarian and small cell lung cancers.
Topotecan, irinotecan toxicity
Severe diarrhea, myelosuppression
Hydroxyurea
Inhibits ribonucleotide reductase so decreases DNA synthesis in S phase. used in melanoma, CML and sickle cell to increase HbF.
Hydroxyurea toxicity
Bone marrow suppression, gi upset.
Prednisone
Can trigger apoptosis of non-dividing cells and especially lymphocytes. Causes neutrophilia. Used in many cancers and autoimmune diseases. Causes cushingoid syndrome.
Tamoxifen, raloxifene
Is a selective estrogen receptor modulator, antagonist in breast and agonists in bone. Used for breast cancer. Can cause endometrial cancer. NOT RALOXIFENE though.
Advantage of raloxifene over tamoxifen?
raloxifene has no increased risk of endometrial carcinoma because it is an antagonist there too.
Trastuzumab
Monoclonal antibody against HER2/neu (RTK). Can kill breast cancer cells if Her2 positive. Also can be used in gastric cancer.
Trastuzumab toxicity
Trastuzumab is cardiotoxic. (HEARTceptin)
Imatinib
RTK inhibitor of BCR-ABL and C-KIT. Causes fluid retention
Rituximab
Anti CD-20 MAB used in NHL and RA. Can cause progressive multifocal leukoencephalopathy.
Vemurafenib
Small molecule inhibitor of B-RAF kinase with V600E mutation used in melanoma.
Bevacizumab
MAB against VEGF, prevents angiogenesis. Used in solid tumors. Can cause hemorrhage and impaired wound healing.
