Drugs - Hematology and Oncology Flashcards
Unfractionated heparin
MOA: activates antithrombin, decreasing thrombin and factor Xa; short half life
Use: immediate anticoagulation for PE, MI, DVT; used during pregnancy because does not cross placenta
Adverse effects: bleeding, heparin-induced thrombocytopenia (higher risk that LMWH or fondapurinix), osteoporosis; level increased with simultaneous isoniazid treatment
Antidote: protamine sulfate
Protamine sulfate
MOA: positively charged molecule that binds to negatively charged heparin
Use: heparin toxicity
Low molecular weight heparin
MOA: activates antithrombin, decreaseing factor Xa; better bioavailability than unfractionated and longer half life; admistered SC and requires less monitoring but not easily reversible
Use: immediate anticoagulation for PE, MI, DVT
Adverse effects: bleeding, heparin-induced thrombocytopenia, osteoporosis; level increased with simultaneous isoniazid treatment
Fondaparinux
MOA: synthetic factor that activates antithrombin, decreaseing factor Xa; better bioavailability than unfractionated and longer half life; admistered SC and requires less monitoring but not easily reversible
Use: immediate anticoagulation for PE, MI, DVT
Adverse effects: bleeding, heparin-induced thrombocytopenia, osteoporosis; level increased with simultaneous isoniazid treatment
Warfarin
MOA: interferes with gamma carboxylation of vitamin K dependent clotting factors (II, VII, IX, X, C, S) by affecting vitamin K epoxide reductase complex; increases PT through effect on extrinsic pathway; long half life and takes a few days to take effect, a few weeks to find proper therapeutic dose
Use: chronic anticoagulation to prevent thromboembolism; prevent stroke in setting of atrial fibrillation or mechanical valve; avoided in pregnancy; monitored with MT/INR
Adverse effects: bleeding, teratogenic, skin/tissue necrosis, early transient hypercoagulability due to faster effect on proteins C and S (often do heparin bridging to prevent); interactions with certain foods
Antidote: vitamin K
Apixaban and rivaroxaban
MOA: direct factor Xa inhibitors
Use: treat and prevent DVT and PE, superior for stroke prophylaxis in atrial fibrillation patients compared with warfarin; does not require coagulation monitoring
Adverse effects: bleeding with no available reversal agent
Thrombolytics
Drugs: tPA, rPA, streptokinase
MOA: aid conversion of plasminogen to plasmin, increasing both PT and PTT
Use: used in early MI, early ischemic stroke, and severe PE (within 3 hours)
Toxicity: bleeding
Antidote: toxicity treated with aminocaproic acid which prevents conversion of plasminogen to plasmin; can also use fresh frozen plasma and cryoprecipitate to correct associated factor deficiencies
Aspirin
MOA: irreversibly inhibits COX 1 and COX 2 preventing TXA2 formation; platelets can’t synthesize a new enzyme; increases bleeding time, decreases TXA2 and prostaglandins
Use: antipyretic, analgesic, anti-inflammatory, decreases platelet aggregation; used post MI and post thrombotic stroke for secondary prevention
Adverse effects: gastric ulceration, tinnitus, acute renal failure, interstitial nephritis, upper GI bleeding, Reye syndrome in kids with viral infection
Overdose: hyperventilation and respiratory alkalosis that transitions to mixed metabolic acidosis-respiratory alkalosis
Antidote: alkalinize urine with sodium bicarbonate to promote renal excretion
ADP receptor inhibitors
Drugs: Clopidogrel, prasugrel, ticagrelor, ticlopidine
MOA: inhibit platelet aggregation by blocking ADP receptors; prevents GIIb/IIIa expression and prevents alpha granule secretion
Use: acute coronary syndrome, coronary stenting, decrease thrombotic stroke; used alongside aspirin
Adverse effects: neutropenia, TTP
cilostazol and dipyridamole
MOA: phosphodiesterase III inhibitors that inhibit platelet aggregation and vasodilate
Use: intermittent claudication, coronary vasodilation, prevent stroke or TIA when used in combo with aspirin, angina prophylaxis
Adverse effects: headache, facial flushing, hypotension, abdominal pain
GP IIb/IIIa inhibitors
Drugs: abciximab, eptifibatide, tirofiban
MOA: bind to GIIb/IIIa on activated platelets and prevent aggregation; prevents fibrin cross linking
Use: unstable angina, percutaneous transluminal coronary angioplasty
Adverse effects: bleeding, thrombocytopenia
Azathioprine, 6-mercaptopurine (6-MP), and 6-thioguanine (6-TG)
MOA: antimetabolite that inhibits DNA synthesis; purine analogs that decrease de novo purine synthesis
Use: prevent organ rejection, RA, IBD, SLE, steroid-refractory chronic disease
Adverse effects: myelosuppression, GI, liver; metabolized by xanthine oxidase and so have increased toxicity with allopurinol or febuxostat
Cladribine (2-CDA)
MOA: antimetabolite; purine analog
Use: hairy cell leukemia
Adverse effects: myelosuppression, nephrotoxicity, neurotoxicity
Cytarabine
MOA: antimetabolite; pyrimiding analog that inhibits DNA polymerase
Use: AML, lymphomas
Adverse effects: leukopenia, thrombocytopenia, megaloblastic anemia
5-fluorouracil
MOA: antimetabolite; pyrimidine analog; complexes with folic acid and inhibits thymidylate synthesis
Use: colon cancer, pancreatic cancer, BCC
Adverse effects: myelosuppression
Methotrexate
MOA: folic acid analog; inhibits dihydrofolate reductase which is nevessary for making tymadine and thus DNA
Use: ALL, lymphomas, choriocarcinoma, sarcoma, ectopic pregnancy, medical abortion, RA, psoriasis, IBD, vasculitis
Adverse effects: myelosuppression, hepatotoxicity, mucositis, pulmonary fibrosis
Antidote: leucovorin can reverse the myelosuppression
Bleomycin
MOA: induces free radical formation resulting in DNA strand breaks
Use; testicular cancer, Hodgkin lymphoma
Adverse effects: pulmonary fibrosis, skin hyperpigmentation, minimal myelosuppression
Dactinomycin
MOA: intercalates in DNA
Use: childhood tumors: Wilms tumor, Ewing sarcoma, rhabdomyosarcoma
Adverse effects: myelosuppression
Doxorubicin and daunorubicin
MOA: generates free radicals and intercalates in DNA
Use: sold tumors, leukemias, and lymphomas
Adverse effects: dilated cardiomyopathy (can prevent to some degree with chelators- dexrazoxane), myelosuppression, alopecia
Leucovorin
used to reverse the myelosuppression seen with methotrexate therapy
dexrazoxane
chelator used to prevent the cardiotoxicity seen with doxorubicin therapy
Busulfan
MOA: alkylating agent- cross links DNA
Use: CML
Adverse effects: severe myelosuppression, pulmonary fibrosis
Cyclophosphamide and ifsosfamide
MOA: alkylating agent that cross links DNA; requires activation by liver
Use: solid tumors, leukemia, lymphoma
Adverse effects: myelosuppression, hemorrhagic cystitis, partically prevented with mesna
Mesna
used to prevent the myelosuppression and hemorrhagic cystitis of cyclophosphamide therapy by binding to toxic metabolites
Nitrosoureas
Drugs: carmustine, lomustine, semustine, streptozocin
MOA: alkylating agent- cross link DNA; cross the BBB
Use: brain tumors
Adverse effects: CNS toxicity
G-CSF (filgrastim)
used in conjunction with myelosuppressive chemotherapeutics to stimulate neutrophil production and maturation
Allopurinol
MOA: xanthine oxidase inhibitor
Use: used to prevent acute tumor lysis syndrome where a bunch of cells all die at once and release toxic substances
Oprelvekin (IL-11)
MOA: thrombopoeitic growth factor
Use: combat thrombocytopenia seen with chemotherapy
Paclitaxel
MOA: microtubule inhibitor; stabilizes MTs in M phase so that the mitotic spindle can’t break down
Use: ovarian and breast carcinoma
Adverse effects: myelosuppression, alopecia, hypersensitivity
Vincristine and vinblastine
MOA: microtubule inhibitors; inhibit beta tubulin polymerization preventing mitotic spindle formation
Use: solid tumors, leukemias, hodgkin and non-hodgkin lymphoma
Adverse effects: neurotoxicity for vincristine, myelosuppression for vinblastine
Cisplatin and carboplatin
MOA: cross links DNA
Use: testicular, bladder, ovary, lung carcinomas
Adverse effects: nephrotoxicity, ototoxicity; prevented with amifostine and chloride diuresis
Etoposide and teniposide
MOA: inhibits topoisomerase II increasing DNA degradation
Use: solid tumors, leukemias, lymphomas
Adverse effects: myelosuppression, GI upset, alopecia
Irinotecan and topotecan
MOA: inhibits topoisomerase I; prevents DNA unwinding and replication
Use: colon cancer, ovarian and small cell lung cancer
Adverse effects: severe myelosuppression, diarrhea
Hydroxyurea
MOA: inhibits ribonucleotide reductase, decreasing DNA synthesis; also increases fetal hemoglobin
Use: melanoma, CML, sickle cell disease
Adverse effects: severe myelosuppression, GI upset
Prednisone and prednisolone
MOA: alters gene transcription
Use: in cancer used to treat CLL, non-Hodgkin lymphoma; also used as immunosuppressants for autoimmune disease
Adverse effects: Cushing-like symptoms, weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis
Bevacizumab
MOA: monoclonal against VEGF; inhibits angiogenesis
Use: colorectal cancer, renal cell carcinoma
Adverse effects: hemorrhage, blood clots, impaired wound healing
Erlotinib
MOA: inhibitor of EGFR tyrosine kinase
Use: non-small cell lung cancer
Adverse effects: rash
Imatinib
MOA: tyrosine kinase inhibitor of BCR-ABL
Use: CML, GI stromal tumors
Adverse effects: fluid retention
Rituximab
MOA: monoclonal antibody against CD20 which is on most B cell neoplasms
Uses: non-hodgkin lymphoma, CLL, IBD, RA
Adverse effects: increased risk of progressive multifocal leukoencephalopathy
Tamoxifen and raloxifene
MOA: selective estrogen receptor modulators; block estrogen binding to ER+ cells
Uses: breast cancer treatment and prevention, prevention of osteoporosis
Adverse effects: increased risk of endometrial cancer for tamoxifen only due to partial agonist activity in endometrium
Trastuzumab (Herceptin)
MOA: monoclonal against HER-2 tyrosine kinase receptor; kills cancer cells that overexpress HER-2
Uses: HER-2 positive breast cancer and gastric cancer
Adverse effects: cardiotoxicity
Vermurafenib
MOA: small molecule inhibitor of BRAF oncogene positive melanoma
Use: metastatic melanoma
