Hema/Onco Flashcards
Heparin
MOA
Antithrombin activator.
Dec. thrombin, Dec. FXa.
Short half life.
Heparin
Clinical use
Immediate anticoagulation (PE, ACS, MI, DVT).
Can be used in pregnancy.
Monitor w/ PTT.
Heparin
[Toxicity, antidote]
Bleeding, thromboctyopenia
Osteoporosis
Drug-drug interactions
Antidote: Protamine sulfate
Heparin-induced Thrombocytopenia
Develop IgG-Abs against heparin-bound platelet factor 4 (PF4).
Complex activates platelets – thrombosis, thrombocytopenia.
Warfarin
MOA
Blocks epoxide reductase – prevents gamma-carboxylation of vit k-dependent clotting factors.
(Effects extrinsic pathway)
Warfarin
Clinical use
Chronic anticoagulation – venous thromboemobolism prophylaxis, prevent stroke in A-fib.
Not for pregnancy.
Follow w/ PT/INR.
Warfarin
Toxicity
Bleeding, teratogenic, skin/tissue necrosis.
Early transient hypercoagulability – proteins C and S have short half-lives.
Heparin Bridging
Heparin used when starting warfarin.
Heparin allows anticoagulation when in initial, transient hypercoagulable state caused by warfarin.
Reduces risk of venous thromboembolism and skin/tissue necrosis.
Thrombolytics
Drug names
Alteplase (tPA)
Reteplase (rPA)
Streptokinase
Tenecteplase (TNK-tPA)
Thrombolytics
MOA
Convert Plasminogen –> Plasmin.
Plasmin cleaves thrombin –> fibrin clots.
Inc. PT/PTT
Thrombolytics
Clinical use
Early MI
Early ischemic stroke
Severe PE
Thrombolytics
[Toxicity, CI, antidote]
Bleeding.
CI in pts. w/ active bleeding, hx of intracranial bleed, recent surgery, bleeding diatheses, severe HTN.
Antidote: aminocaproic acid (fibrinolysis inhibitor).
ADP receptor inhibitors
Drug names
Clopidogrel
Prasugrel
Ticagrelor (reversible)
Ticlodipine
ADP receptor inhibitors
MOA
Irreversibly blocks ADP receptors – Prevents GpIIb/IIIa expression on platelet surface – inhibits platelet aggregation
ADP receptor inhibitors
Clinical use
Acute coronary syndrome.
Dec. incidence/recurrence of thrombotic stroke.
Factor Xa inhibitors (Apixaban, Rivaroxaban)
[MOA, clinical use]
Bind and directly inhibit FXa.
For DVT, PE (rivaroxaban).
Stroke prophylaxis in pts w/ AFib.
Aspirin
[MOA, Labs, clinical use, Toxicity]
> Irreversibly inhibits COX-1 and COX-2.
Inc. BT, dec. TXA2, dec. PGs.
No effect on PT, PTT.
Antipyretic, analgesic, anti-inflammatory, Antiplatelet.
Toxicity: ARF, gastric ulcer, tinnitus; Reye syndrome in kids w/ viral infection.
Gp IIb/IIIa inhibitors (Abciximab, Eptifibatide, Tirofiban)
[MOA, clinical use]
> Binds receptor for Gp IIb/IIIa on activated platelets – prevents aggregation.
For unstable angina, PTCA (percutaneous transluminal coronary angioplasty).
Azathioprine, 6-MP, 6-TG
[MOA, clinical use, toxicity]
> Purine analogs; dec. de novo purine synthesis.
Activated by HGPRT.
Prevent organ rejection, RA, IBD, SLE.
Tox: myelosuppression; Azathioprine and 6-MP metabolized by xanthine oxidase – toxicity w/ Allopurinol or febuxostat.
Cladribine (2-CDA)
[MOA, clinical use, toxicity]
> Purine analog; inhibits DNAp; DNA strand breaks.
For Hairy cell leukemia.
Tox: nephrotoxicity, neurotoxicity, myelosuppression.
Cytarabine (arabinofuranosyl cytidine)
[MOA, clinical use, toxicity]
Pyrimidine analog – inhibits DNAp.
For AML, lymphomas.
Tox: pancytopenia
5-FU
[MOA, clinical use, toxicity]
> Active metabolite is 5F-dUMP, w/c complexes w/ Folic acid – inhibits Thymidylate synthase – dec. dTMP – dec. DNA synthesis.
For colon cancer, pancreatic cancer, basal cell CA.
Tox: not reversible w/ Leucovorin (folinic acid, vs. Methotrexate)
Methotrexate
[MOA, clinical use, toxicity]
> Folic acid analog; competitively inhibits dihydrofolate reductase – dec. dTMP – dec. DNA synthesis.
For cancers, ectopic pregnancy, medical abortion, RA, psoriasis, IBD, vasculitis.
Tox: hepatotoxic, pulmo fibrosis; reversible w/ Leucovorin (vs. 5-FU)
Bleomycin
[MOA, clinical use, toxicity]
> Induces free radical formation – breaks in DNA strands.
For testicular cancer, Hodgkin Lymphoma.
Tox: pulmo fibrosis, skin hyperpigmentation
Dactinomycin
[MOA, clinical use]
> Intercalates in DNA –> causes breaks in DNA.
For Wilms tumor, Ewing sarcoma, rhabdomyosarcoma.
Used for kids tumors.
Doxorubicin, Daunorubicin
[MOA, clinical use, toxicity]
> Generates free radicals.
Intercalates in DNA –> causes breaks in DNA –> dec. replication.
For solid tumors, leukemias, lymphomas.
Tox: cardiotoxicity (prevent w/ Dexrazoxane, an iron chelator), myelosuppression, alopecia.
Busulfan
[MOA, clinical use, toxicity]
Crosslinks DNA
For CML
Tox: severe myelosuppression (almost all cases)
Cyclophosphamide, Ifosfamide
[MOA, clinical use, toxicity]
> Crosslink DNA at guanine N7. Needs bioactivation by liver.
For solid tumors, leukemia, lymphoma.
Tox: hemorrhagic cystitis – partially prevented w/ mesna, w/c binds to toxic metabs.
Nitrosureas (Carmustine, Lomustine, Semustine, Streptozocin)
[MOA, clinical use, toxicity]
> Needs bioactivation. Cross BBB into CNS, where it crosslinks DNA.
For brain tumors (glioblastoma multiforme)
Tox: CNS toxicity
Paclitaxel (other taxols)
[MOA, clinical use, toxicity]
> Hyperstabilizes polymerized microtubules in M phase so mitotic spindle can’t break down (prevents anaphase).
For ovarian and breast CA.
Tox: alopecia
Vincristine, Vinblastine
[MOA, clinical use, toxicity]
> Bind B-tubulin, inhibit its polymerization into microtubules – prevent mitotic spindle formation (M phase arrest).
For Hodgkin (vinblastine), NHL (vincristine), solid tumors, leukemias.
Tox: neurotoxicity (vincristine), bone marrow suppression (vinblastine).
Cisplatin, Carboplatin
[MOA, clinical use, toxicity]
> Crosslink DNA.
For bladder, lung, ovary, testicular CA (BLOT).
Tox: nephrotoxic, ototoxic.
*Prevent nephrotoxicity w/ amifostine (free radical scavenger) and chloride (saline) diuresis.
Etoposide
[MOA, clinical use]
> Inhibits topoisomerase II – inc. DNA degradation.
>For solid tumors (testicular, small cell lung cancer), leukemias, lymphomas.
Irinotecan, topotecan
[MOA, clinical use]
> Inhibits topoisomerase I and prevents DNA unwinding and replication.
For colon cancer (irinotecan); ovarian and small cell lung cancers (topotecan).
Hydroxyurea
[MOA, clinical use]
Inhibits ribonucleotide reductase – dec. DNA synthesis (S phase).
For melanoma, CML, sickle cell dse (inc. HbF).
Prednisone, Prednisolone
[MOA, clinical use, toxicity]
> Binds intracytoplasmic receptors; alters gene transcription.
Mostly for Chemotherapy. Use in CLL, NHL. Can be an immunosuppressant (autoimmune diseases).
Tox: Cushing-like ssx, weight gain, muscle breakdown, osteoporosis, peptic ulcers, psychosis.
Imatinib
[MOA, clinical use]
Tyrosine kinase inhibitor of BCR-ABL and c-kit (GI stromal tumors).
For CML, GI stromal tumors.
Rituximab
[MOA, clinical use, toxicity]
> Monoclonal antibody vs. CD20 on most B cell neoplasms.
For NHL, CLL, IBD, rheumatoid arthritis.
Tox: inc. risk of progressive multifocal leukoencephalopathy.
Tamoxifen, Raloxifene
[MOA, clinical use]
> SERMs: receptor antags in breast, agonists in bone – block estrogen binding to ER-positive cells.
For breast cancer treatment (tamoxifen only) and prevention; can also prevent osteoporosis (raloxifene).
Tamoxifen vs. Raloxifene
Toxicity
> Tamoxifen: partial agonist in endometrium – inc. risk of endometrial cancer.
Raloxifene: estrogen receptor antag in endometrial tissue – doesn’t inc. risk of cancer.
Trastuzumab (Herceptin)
[MOA, clinical use, toxicity]
> Monoclonal antibody vs. HER2 (c-erbB2). >Kills cancer cells that overexpress HER2 by inhibiting HER2-initiated cell signaling and Ab-dependent cytotoxicity.
For HER2-positive breast cancer, gastric cancer.
Tox: cardiotoxicity
Vemurafenib
[MOA, clinical use]
Inhibitor of BRAF oncogene-positive melanoma.
For metastatic melanoma.
