Hematology/Oncology Pharmacology Flashcards
(34 cards)
Hematology/Oncology Pharmacology
Heparin
MOA: Lowers the activity of thrombin and factor Xa. Short half-life.
Use: Immediate anticoagulation for PE, acute coronary syndrome, MI, DVT. Used during pregnancy (does not cross placenta). Follow PTT. LMWH (enoxaparin, dalteparin) and fondaparinux act more on factor Xa, have better availability, and 2-4x longer half-life; can be administered subcutaneously and without lab monitoring.
Adverse Effects: Bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions.
Rapid reversal: Protamine sulfate (⊕ molecule that binds ⊖ heparin)
Hematology/Oncology Pharmacology
Bivalirudin
MOA: Direct thrombin inhibitor. Directly inhibits activity of free and clot-associated thrombin.
Use: Venous thromboembolism, atrial fibrillation. Can be used in HIT. Does not require lab monitoring.
Adverse Effects: Bleeding; no specific reversal agent. Can attempt to use activated prothrombin complex concentrates and/or fibrinolytics.
Hematology/Oncology Pharmacology
Warfarin
MOA: Interferes with γ-carboxylation of vitamin K-dependent clotting factors II, VII, IX, and X, and proteins C and S. Metabolism affected by polymorphism in the gene for vitamin K epoxide reductase complex. In laboratory assay, has effect on extrinsic pathway and ↑ PT. Long half-life.
Use: Chronic anticoagulation. Not used in pregnant women. Follow PT/INR.
Adverse Effects: Bleeding, teratogenic, skin/tissue necrosis, drug-drug interactions. Proteins C and S have shorter half-lives than clotting factors II, VII, IX, and X, resulting in early transient hypercoagulability with warfarin use. Skin/tissue necrosis within first few days of large doses believed to be due to small vessel microthromboses.
Hematology/Oncology Pharmacology
Apixaban, rivaroxaban
MOA: Direct factor Xa inhibitors. Bind to and directly inhibit factor Xa.
Use: Treatment and prophylaxis for DVT and PE (rivaroxaban); stroke prophylaxis in patients with atrial fibrillation.
Adverse Effects: Bleeding (no reversal agent available)
Hematology/Oncology Pharmacology
Alteplase (tPA), reteplase (rPA), streptokinase, tenecteplase (TNK-tPA)
MOA: Thrombolytics. Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. ↑ PT, ↑ PTT, no change in platelet count.
Use: Early MI, early ischemic stroke, direct thrombolysis of severe PE.
Adverse Effects: Bleeding. Contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension.
Toxicity treatment: Aminocaproic acid. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.
Hematology/Oncology Pharmacology
Clopidogrel, prasugrel, ticagrelor (reversible), ticlopidine
MOA: ADP receptor inhibitors. Inhibit platelet aggregation by irreversibly blocking ADP receptors. Prevent expression of glycoproteins IIb/IIIa on platelet surface.
Use: Acute coronary syndrome; coronary stenting. ↓ incidence or recurrence of thrombotic stroke.
Adverse Effects: Neutropenia (ticlopidine). TPP may be seen.
Hematology/Oncology Pharmacology
Cilostazol, dipyridamole
MOA: Phosphodiesterase III inhibitor; ↑ cAMP in platelets → inhibition of platelet aggregation; vasodilators.
Use: Intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with aspirin), angina prophylaxis.
Adverse Effects: Nausea, headache, facial flushing, hypotension, abdominal pain.
Hematology/Oncology Pharmacology
Abciximab, eptifibatide, tirofiban
MOA: Bind to glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation. Abciximab is made from monoclonal antibody Fab fragments.
Use: Unstable angina, percutaneous transluminal coronary angioplasty.
Adverse Effects: Bleeding, thrombocytopenia
Hematology/Oncology Pharmacology
Azathioprine, 6-mercaptopurine
MOA: Purine (thiol) analogs → ↓ de novo purine synthesis. Activated by HGPRT. Azathioprine is metabolized into 6-MP. S-phase specific.
Use: Preventing organ rejection, rheumatoid arthritis, IBD, SLE; used to wean patients off steroids in chronic disease and to treat steroid-refractory chronic disease.
Adverse Effects: Myelosuppression, GI, liver. Azathioprine and 6-MP are metabolized by xanthine oxidase; thus both have ↑ toxicity with allopurinol or febuxostat.
Hematology/Oncology Pharmacology
Cladribine
MOA: Purine analog → multiple mechanisms (eg. inhibition of DNA polymerase, DNA strand breaks) S-phase specific.
Use: Hairy cell leukemia
Adverse Effects: Myelosuppression, nephrotoxicity, neurotoxicity.
Hematology/Oncology Pharmacology
Cytarabine (arabinofuranosyl cytidine)
MOA: Pyrimidine analog → inhibition of DNA polymerase. S-phase specific.
Use: Leukemias (AML), lymphomas.
Adverse Effects: Myelosuppression with megaloblastic anemia. Cytrabine causes pancytopenia.
Hematology/Oncology Pharmacology
5-fluorouracil
MOA: Pyrimidine analog bioactivated to 5-FdUMP, which covalently complexes folic acid → inhibits thymidylate synthase → ↓ dTMP → ↓ DNA synthesis. S-phase specific.
Use: Colon cancer, pancreatic cancer, basal cell carcinoma (topical). Effects enhanced with the addition of leucovorin.
Adverse Effects: Myelosuppression - worsened with the addition of leucovorin (folinic aicid)
Hematology/Oncology Pharmacology
Methotrexate
MOA: Folic acid analog that competitively inhibits dihydrofolate reductase → ↓ dTMP → ↓ DNA synthesis. S-phase specific.
Use: Cancers (ALL, lymphomas, choriocarcinoma, sarcomas). Non-neoplastic: ectopic pregnancy, medical abortion (with misoprostol), rheumatoid arthritis, psoriasis, IBD, vasculitis.
Adverse Effects: Myelosuppression, which is reversible with leucovorin “rescue”. Hepatotoxicity, mucositis, pulmonary fibrosis.
Hematology/Oncology Pharmacology
Bleomycin
MOA: Induces free radical formation → breaks in DNA strands
Use: Testicular cancer, Hodgkin lymphoma.
Adverse Effects: Pulmonary fibrosis, skin hyperpigmentation. Minimal myelosuppression.
Hematology/Oncology Pharmacology
Dactinomycin (actinomycin D)
MOA: Intercalates in DNA
Use: Wilms tumor, Ewing sarcoma, rhabdomyosarcoma. Used for childhood tumors.
Adverse Effects: Myelosuppression.
Hematology/Oncology Pharmacology
Doxorubicin, daunorubicin
MOA: Generate free radicals. Intercalate in DNA → breaks in DNA → ↓ replication.
Use: Solid tumors, leukemias, lymphomas.
Adverse Effects: Cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia. Dexrazoxane (iron chleating angent) used to prevent cardiotoxicity.
Hematology/Oncology Pharmacology
Busulfan
MOA: Cross-links DNA
Use: CML, also used to ablate patient’s bone marrow before bone marrow transplantation.
Adverse Effects: Severe myelosuppression (in almost all cases), pulmonary fibrosis, hyperpigmentation.
Hematology/Oncology Pharmacology
Cyclophosphamide, ifosfoamide
MOA: Cross-link DNA at guanine N-7. Require bioactivation by liver.
Use: Solid tumors, leukemia, lymphomas.
Adverse Effects: Myelosuppression; hemorrhagic cystitis, prevented with mesna (thiol group of mesna binds toxic metabolites) or N-acetylcysteine
Hematology/Oncology Pharmacology
Nitrosureas (carmustine, lomustine, semustine, streptozocin)
MOA: Require bioactivation. Cross blood-brain-barrier → CNS. Cross-link DNA.
Use: Brain tumors (including glioblastoma multiforme)
Adverse Effects: CNS toxicity (convulsions, dizziness, ataxia).
Hematology/Oncology Pharmacology
Paclitaxel, other taxols
MOA: Hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur).
Use: Ovarian and breast carcinomas
Adverse Effects: Myelosuppression, neuropathy, hypersensitivity.
Hematology/Oncology Pharmacology
Vincristine, vinblastine
MOA: Vinca alkaloids that bind β-tubulin and inhibit its polymerization into microtubles → prevent mitotic spindle formation (M-phase arrest)
Use: Solid tumors, leukemias, Hodgkin (vinblastine) and non-Hodgkin (vincristine) lymphomas.
Adverse Effects:
Vincristine: neurotoxicity (areflexia, peripheral neuritis), constipation (including paralytic ileus)
Hematology/Oncology Pharmacology
Cisplatin, carboplatin
MOA: Cross-link DNA
Use: Testicular, bladder, ovary, and lung carcinomas
Adverse Effects: Nephrotoxicity, peripheral neuropathy, ototoxicity. Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride (saline) diuresis)
Hematology/Oncology Pharmacology
Etoposide, teniposide
MOA: Inhibits topoisomerase II → ↑ DNA degradation
Use: Solid tumors (particularly testicular and small cell lung cancer), leukemias, lymphomas
Adverse Effects: Myelosuppression, alopecia
Hematology/Oncology Pharmacology
Irinotecan, topotecan
MOA: Inhibits topoisomerase I and prevent DNA unwinding and replication
Use: Colon cancer (irinotecan); ovarian and small cell lung cancers (topotecan)
Adverse Effects: Severe myelosuppression, diarrhea
