Hem-Onc Flashcards
Heparin
Large anionic acidic polymer that activates antithrombin (decreases action of thrombin and factor Xa)
Parenteral administration, rapid onset of action, acute duration of action, does NOT cross the placenta
Monitor with PTT
Antidote: protamine sulfate
Enoxparin, dalteparin
Low molecular weight heparins.
Act more on factor Xa, have better bioavailability, and longter half-life than regular heparin.
Monitoring not required. Not easily reversible
Heparin-induced thrombocytopenia (HIT)
Development of IgG antibodies against heparin bound to platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets, leading to thrombosis and thrombocytopenia.
Argatroban, Bivalirudin - derived from anticoagulant used by leeches, inhibit thrombin directly, used to anticoagulate patients with HIT
Warfarin
Small lipid-soluble molecule that impairs synthesis of Vit K-dependent clotting factors (II, VII, IX, and X; as well as proteins C and S)
Oral administration, slow onset, chronic duration of action, crosses the placenta (teratogen)
Monitor with PT/INR
Antidote: IV Vit K and FFP
Decreased efficacy with concurrent use of P-450 enhancers (rifampicin, phenobarbital, phenytoin)
Increased efficacy with cimetidine, amiodarone, and TMP-SMX, which inhibit warfarin metabolism.
Apixaban, rivaroxaban
Direct factor Xa inhibitors
Used for Tx and PPx of DVT and PE (rivaroxaban), and stroke PPx in patients with A-fib
Oral agents do not require coag monitoring
Alteplase (tPA), retplase (rPA), tenecteplase (TNK-tPA)
Thrombolytics that convert plasminogen to plasmin, which cleaves thrombin and fibrin clots
Increase PT and PTT. No change in PC
Used in early MI, early ischemic stroke, and direct thrombolysis of severe PE
Antidote: aminocaproic acid (inhibitor of fibrinolysis)
Aspirin
Irreversible inhibition of COX-1 and COX-2 by covalent acetylation
Increased BT, decreased TXA2 and prostaglandins. No effect on PT or PTT
Antipyretic, analgesic, anti-inflammatory, antiplatelet aggregation
Toxicity: gastric ulcers, tinnitus, interstitial nephritis with chronic use. Reye syndrome in children with viral infection.
Clopidogrel, ticlopidine, prasugrel, ticagrelor
Irreversible ADP inhibitors. Inhibit platelet aggregation by preventing glycoprotein IIb/IIIa from binding fibrinogen
Used in ACS, coronary stenting, and to reduce recurrence of thrombotic stroke.
Toxicity: neutropenia with **ticlodipine **(presents as fever and mouth ulcers. TTP/HUS may occur
Cilostazole, dipyridamole
Phosphodiesterase III inhibitors that increase cAMP in platelets, thus inhibiting platelet aggregation. Increased cAMP in vessels cause vasodilation.
Used in intermittent claudication, coronary vasodilation, stroke PPx, angina PPx
Abciximab, eptifibatide, tirofiban
GP IIb/IIIa inhibitors that prevent platelet aggregation.
Used in unstable angina and percutaneous transluminal coronary angioplasty.
Methotrexate
Antimetabolite. Folate analog that inhibits dihydrofolate reductase, leading to decreased production of dTMP, dAMP, dGMP
Treats leukemias, lymphoma, choriocarcinomas, sarcomas
Also used for abortion, ectopic pregnancy, RA, psoriasis, and IBD
Toxicity: myelosuppression (reversible with leucovorin aka N-formyl-THF), macrovesicular change in liver, mucositis, teratogen
5-fluorouracil (5-FU)
Antimetabolite. Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folate and inhibits thymidylate synthase (decreases dTMP)
Treats colon cancer, pancreatic cancer, and basal cell carcinoma
Toxicity: myelosuppression (not reversible with leucovorin, aka N-formyl-THF), photosensitivity
Treat overdose with uridine
Cytarabine
Antimetabolite. Pyrimidine analog that inhibits DNA polymerase
Treats leukemias and lymphomas
Toxicity: leukemia, thrombocytopenia, megaloblastic anemia
Azathioprine, 6-mercaptopurine, 6-thioguanine
Antimetabolites. Purine (thiol) analogs that are activated by HGPRT and decrease de novo purine synthesis.
Prevent organ rejection.
Treat RA, SLE (azathioprine), leukemia, IBD (6-MP, 6-TG)
Toxicity: bone marrow, GI, liver
Azathioprine and 6-MP are metabolized by xanathine oxidase so their toxicities increase with allopurinol administration
Dactinomycin (actinomycin D)
Antitumor antibody that intercalates in DNA
Used for Wilms tumor, Ewing sarcoma, rhabdomyosarcoma (childhood tumors)
Toxicity: myelosuppression
Doxorubicin (Adriamycin), daunorubicin
Antitumor antibiotics that generate free radicals and intercalate in DNA
Used for solid tumors, leukemias, and lymphomas
Toxicity: dilated cardiomyopathy (prevented with dexrazoxane, an iron chelating agent), myelosuppresion, alopecia
Bleomycin
Antitumor antibiotic that induces free radical formation, causing breaks in DNA strands
Treats testicular cancer and Hodgkin lymphoma
Toxicity: pulmonary fibrosis, skin changes, mucositis
Cyclophosphamide, ifosfamide
Alkylating agents that covalently cross-link DNA at guanine N-7 following bioactivation by the liver
Treat solid tumors, leukemia, lymphomas, and some brain cancers
Toxicity: myelosuppresion, hemorrhagic cysitis (mesna partially binds toxic metabolites)
Nitrosoureas (carmustine, lomustine, semustine, streptozocin)
Alkylating agents that cross the BBB and cross-link DNA following bioactivation.
Treat brain tumors (glioblastoma multiforme)
CNS toxicity (convulsions, dizziness, ataxia)
Busulfan
Alkylating agent that cross-links DNA
Treats CML. Also ablates patient’s bone marrow before bone marrow transplantation
Toxicity: severe myelosuppresion, pulmonary fibrosis, hyperpigmentation
Vincristine, vinblastine
Vinca alkaloids that bind beta-tubulin and inhibit its polymerization into microtubules (prevents mitotic spindle formation)
Treats solid tumors, leukemia, and lymphomas
Vincristine toxicity: neurotoxicity (areflexia, peripheral neuritis), paralytic ileus
Vinblastine toxicity (myelosuppression; “blasts bone marrow”)
Paclitaxel, other taxols
Hyperstabilize polymerized microtubules in M phase so that mitotis spindle cannot break down and anaphase cannot occur
Treats ovarian and breast carcinomas
Toxicity: myelosuppresion, alopecia, hypersensitivity
Cisplatin, carboplatin
Cross-link DNA
Treat testicular, bladder, ovary, and lung carcinomas
Toxicity: acoustic nerve damage and nephrotoxicity (prevent with amifostine, a free radical scavenger, and chloride diuresis)
Etoposide, teniposide
Inhibits topoisomerase II, increases DNA degredation
Treats solid tumors (especially testicular and small cell lung cancer), leukemias, lymphomas
Toxicity: myelosuppresion, GI irritation, alopecia
Irinotecan, topotecan
Inhibit topoisomerase I and prevent DNA unwinding and replication
Irinotecan treats colon cancer
Topotecan treats ovarian and small cell lung cancer
Toxicity: severe myelosuppresion, diarrhea
Hydroxyurea
Inhibits ribonucleotide reductase, decreasing DNA synthesis
Treats melanoma, CML, sickle cell disease (increases HbF)
Toxicity: myelosuppresion, GI upset
Prednisone, prednisolone
Most commonly used glucocorticoids in cancer chemotherapy. May trigger apoptosis.
Used in CLL, non-Hodgkin lymphomas
Toxicity: Cushing-like symptoms
Trastuzumab (Herceptin)
Monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase receptor
Treats HER-2 positive breast cancer and gastric cancer (“tras2zumab”)
Toxicity: cardiotoxicity (“heartceptin”)
Tamoxifen, raloxifene
SERMs - receptor antagonists in breast and agonists in bone
Tamoxifen treats breast cancer. Raloxifene prevents osteoporosis.
Toxicity: tamoxifen is a partial agonist in the endometrium (increases risk of endometrial cancer); raloxifene has no effect in the endometrium
Imatinib (Gleevec)
Tyrosine kinase inhibitor of bcr-abl (Philadelpha chromosome fusion gene in CML) and c-Kit (GI stromal tumors)
Treats CML and GI stromal tumors
Toxicity: fluid retention
Rituximab
Monoclonal antibody against CD20 (found on most B-cell neoplasms)
Treats non-Hodgkin lymphoma, RA (with MTX), ITP
Toxicity: increases risk of progressive multifocal leukoencephalopathy
Vemurafenib
Small molecule inhibitor of the B-Raf kinase with the V600E mutation
Treats metastatic melanoma
Bevacizumab
Monoclonal antibody against VEGF. Inhibits angiogenesis
Treats solid tumors (colorectal cancer, RCC)
Toxicity: hemorrhage, impaired wound healing
