Heme Onc Flashcards
Heparin
Cofactor for activation of Antithrombin
decreases thrombin and Xa
PE, MI, DVT, okay in pregnancy, follow PTT
can cause acute bleeding and osteoporosis
for OD- protamine sulfate
HIT- IgG against heparin/PF4 complex
Ab/hep/PF4 activates platelets
argatroban, bivalirudin, dabigatran
derivatives of hirudin (leeches)
inhibit thrombin directly
Use on patients with HIT
Warfarin
Block synthesis and y-carboxylation of II,VII, IX, X, C and S
metabolized by p450, PT, extrins, no preg, oral
use after STEMI and Afib
can cause tissue necrosis (first week, C/S short half life), many drug interactions,
reverse w/ vit K or FFP for faster
Direct Xa inhibitors
Apixaban, rivaroxiban, enoxaparin
Bind/inhibit Xa
treatment and prophylaxis of DVT/PE/stroke w Afib (especially rivaroxiban)
don’t need monitoring but no antidote
Thrombolytics
Alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA)
Aids in conversion of plasminogen to plasmin
cleaves thrombin and fibrin clots
increase PTT and PT, no change in platelet ct
Early MI/stroke, severe PE
contraindicated in active bleeding or history of intracranial hemorrage
treat toxicity w/ aminocaproic acid (or FFP, cryoprecipitate to restore factor levels)
Asprin
covalent acetylation of COX
increase bleeding time, no PT/PTT change
can cause tinnitis, reye’s, gastric etc
ADP receptor inhibitors
Clopidogrel, ticlodipine, prasugrel, ticagrelor
Irreversibly blocks ADP receptors, fibrinogen can’t bind GpIIb/IIIa
use for acute coronary syndrome and stenting
can cause TTP/HUS
ticlodipine can cause neutropenia
Cilostazol, dipyridamole
PDEIII inhibitors
increase cAMP in platelets (no agg), vasodilate
use for intermittent claudication, coronary vasodilation, angina prophylaxis
can cause nausea, H/A, flushing
GpIIb/IIIa inhibitors
Abciximab, eptifibatide, tirofiban
abciximab is monoclonal Ab
Use for unstable angina, percutaneous transluminal coronary angioplasty
can cause thrombocytopenia
Methotrexate
folic acid analog, inhibits DHFR, no dTMP
Some cancers, abortion, PAIR
myelosuppression reversible w/ leukovorin, macrovesicular fatty liver changes, mucositis, teratogenic
5-FU
pyrimidine analog activated to 5F-dUMP, complexes with folic acid, inhibits thymidylate synthase
Myelosuppression not reversible with leucovorin, treat overdose with uridine
Cytarabine
Pyrimidine analog, inhibits DNA polymerase
megaloblastic anemia and pancytopenia
Azathioprine, 6-MP, 6-TG
Purine analogues activated by HGPRT
Transplant, SLE, RA, Leukemia, IBD
azathioprine and 6-MP toxicity with allopurinol (metabolized by xanthine oxidase)
Dactinomycin
Intercolates into DNA
Childhood tumors
Wilms, ewing, rhabdomyosarcoma
myelosuppression
Doxy/daunorubicin
Generates free radicals, intercalates into DNA, DNA breaks
Cardiomyopathy, myelosuppression, alopecia, toxic to tissues following extravasation
Dexrazoxane (iron chelator) to prevent cardiotoxicity
Bleomycin
Induce free radical formation (DNA breaks)
Testicular cancer, hodgkin lymphoma
Pulmonary fibrosis, skin changes, mucositis
MINIMAL MYELOSUPPRESSION
cyclophosphamide/ifosfamide
covalently X-link DNA guanine at N-7. Bioactivation by liver
Hemorrhagic cystitis prevented with MESNA
Nitrosoureas
Carmustine, lomustine, semustine, streptozocin
Crosslinks DNA, requires bioactivation
crosses BBB
Use for brain tumors but has CNS toxicity
Busulfan
Crosslinks DNA
use for CML or to ablate bone marrow pre-transplant
Severe myelosuppression, Pulmonary fibrosis, hyperpigmentation
Vincristine/Vinblastine
vinca alkaloids that bind B-tubulin, inhibits polymerization into microtubules, prevents mitotic spindle formation (m-phase arrest)
vincristine- neurotoxic, paralytic ileus
vinblastine- bone marrow suppression
Taxols
hyperstabilize polymerized microtubules in M phase so mitotic spindle can’t break down- no anaphase
ovarian and breast cancers
myelosuppression, alopecia
Cisplatin/carboplatin
cross-links DNA
nephrotoxic and acoustic nerve damage
prevent nephrotoxicity with amifostine and Cl diuresis
Etoposide, teniposide
inhibits topisomerase II- DNA degredation
testicular and SCLC
irinotecan, topotecan
inhibit topisomerase I, revent DNA unwinding
Irinotecan- colon cancer
Topotecan- ovarian and SCLC
severe myelosuppression
