-
Activates antithrombin III
- Hepairn
- Decreased thrombin and Xa
- Immediate anticoagulation, anticoagulation in pregnancy
- Parenteral
- Follow PTT
- Tox: bleeding, HIT, osteoporosis, drug-drug interactions
- Reverse with protamine sulfate
-
Enoxaparin
- Low-molecular weight heparin
- Acts on Xa
- Greater bioavailability, longer 1/2 life, subQ, no lab monitoring
-
Heparin-induced thrombocytopenia
- Heparin binds to platelets -> autoAb production ->
- destruction/activation of platelets -> thrombocytopenic,
- hypercoagulable state
-
Lepirudin, bivalirudin
- Direct thrombin inhibitors
- Used in pts with HIT
-
Warfarin
- Interferes with gamma carboxylation of vitamin K dependent clotting factors (II, VII, IX, X, protein C and S)
- Oral
- Metabolized by P450
- Monitor PT/INR (extrinsic pathway)
- Chronic anticoagulation, not in pregnancy
- Can cause skin necrosis in protein C or S deficiency
-
Converts plasminogen to plasmin
- tPA (alteplase), also streptokinase and urokinase
- Results in cleavage of thrombin and fibrin clots
- Increased PT and PTT
- Used in early MI and early ischemic stroke
- Treat toxicity with aminocaproic acid
-
Irreversibly inhibits COX1 and 2
- Aspirin
- Prevents conversion of arachidonic acid to TxA2, increased bleeding time
- Antipyretic, analgesic, antiinflammatory, antiplatelet
- Can cause CN VIII tinnitus
-
Inhibit platelet aggregation by irreversibly blocking ADP receptors
- Clopidogrel, ticlopidine
- Inhibit fibrinogen binding by preventing GpIIb/IIIa expression
- Used in acute coronary syndrome, coronary stenting, decreased thrombotic stroke
-
Binds to GbIIb/IIIa, preventing aggregation of activated platelets
- Abciximab (monoclonal Ab)
- Acute coronary syndromes, coronary angioplasty
-
Folic acid analog that binds dihydrofolate reductase
- Methotrexate (antimetabolite)
- Decreases dTMP and thus DNA and protein synthesis
- Tox: myselosuppression reversible with leucovorin (folinic acid)
- Macrovesicular fatty change in liver, mucositis, teratogen
-
Pyrimidine analog inhibiting thymidylate synthase
- 5-FU
- Bioactivated to 5F-dUMP
- Leucovorin stabilizes TS-FdUMP complex -> decreased dTMP, decreased DNA and protein synthesis
- Tox: myelosuppression not reversible with leucovorin, photosensitivity
- Thymidine rescue
-
Purine analog, decreases de novo purine synthesis
- 6-MP
- Activated by HGPRTase
- Tox: BM, GI, liver
- Metabolized by xanthine oxidase -> increased tox with allopurinol
-
6-TG
- Purine analog (same as 6-MP)
- Can be given with allopurinol
-
Pyrimidine antagonist
- Cytarabine (ara-C)
- Inhibits DNA polymerase
- Leukopenia, thrombocytopenia, megaloblastic anemia
-
Dactinomycin
- Antitumor antibiotic, intercalates in DNA
- Childhood tumors
- Myelosuppression
-
Doxorubicin/adriamycin, daunorubicin
- Antitumor antibiotic
- Generate free radicals, intercalate in DNA and cause breaks, inhibit Topo II
- Cardiotoxicity
-
Bleomycin
- Antitumor antibiotic
- G2-phase specific
- Free radical formation -> breaks in DNA
- Pulmonary fibrosis
-
Etoposide
- Late S to G2 phase-specific
- Inhibit topo II
- Myelosuppression, GI irritation, alopecia
-
Cyclophosphamide, ifosfamide
- Alkylating agent
- Covalently crosslinks DNA at guanine N-7; requires activation by liver
- Hemorrhagic cystitis from acrolein (prevented with mesna), myelosuppression
-
Nitrosureas
- Alkylating agent
- -mustine, streptozocin
- Requires bioactivation, crosses BBB
- CNS toxicity
-
Busulfan
- Alkylating agents
- Alkylates DNA
- Pulmonaryfibrosis, hyperpigmentation
-
Vincristine, vinblastine
- Alkaloid, binds tubulin in M phase -> block polymerization of microtubules
- Vincristine - neurotoxicity
- VinBLASTine - BLASTS BM
-
Paclitaxel
- Hyperstabilizes polymerized microtubules in M phase
- Myelosuppression and hypersensitivity
-
Cisplatin
- Cross-link DNA
- Nephrotoxicity and acoustic nerve damage
- Amifostene prevents nephrotoxicity
-
Hydroxyurea
- Inhibits ribonucleotide reductes -> decreased DNA synthesis (S phase)
- Used in sickle cell disease (increases HbF)
- BM suppression, GI upset
-
Prednisone
- May trigger apoptosis
- Cushing-like symptoms, immunosuppression
-
Tamoxifen, raloxifene
- SERMs - estrogen receptor antagonists in breast, agonists in bone
- Tamoxifen for estrogen + breast cancer
- Raloxifene for osteoporosis
- Tamoxifen may increase risk of endometrial cancer
-
Trastuzumab
- = Herceptin
- Monoclonal Ab against HER-2 (erb-B2)
- Metastatic breast cancer
- Cardiotoxicity
-
Imatinib
- = Gleevec
- TK inhibitor
- CML
- Fluid retention
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