Activates antithrombin so it can inactivate clotting factors. Works primarily on decreasing thrombin (IIa) and factor Xa.
Used for immediate anticoagulation (e.g. MI, DVT, stroke) and in pregnant women who need anticoagulation because it doesn't cross the placenta. Needs to be given parenterally (IV)
Side effects include bleeding (need to monitor PTT) and heparine induced thrombocytopenia (heparin activates antibodies that bind platelets thus causing both thrombosis (new or enlargement of existing clot) AND increased platelet clearance resulting in thrombocytopenia. Give protamine sulfate to reverse heparin OD.
Low Molecular Weight Heparin
Work to reduce Xa primarily and thus there is a decreased bleed risk - no need to monitor PTT - plus it has a longer half life and can be given subcutaneously. However, it is not easily reversible.
Lepirudin and Bivalirudin
Directly inhibit thrombin directly. Can be used as alternatives to heparin in someone who developes heparin induced thrombocytopenia.
Interferes with activation of vitamin K, thus causing decreased activation of factors II, VII, IX, X, and proteins C and S.
Use for chronic anticoagulation. Can be taken orally
Side effects include bleeding (monitor PT/INR) and teratogenicity (don't use in pregnant women). Also can cause skin ulcering, especially in people who are vitamin K deficient.
Streptokinase, urokinase, alteplase (tPA), and anistrplase
These drugs help increase activation of plasmin (from plasminogen) and thus increase plasmin cleavage of fibrin clots. Will cause prolonged PT and PTT.
Used to treat ischemic stroke and early MI.
Side effects include bleeding risk (i.e. contraindicated in people who have bleeds, recent surgery, bleeding disorders, etc.)
Treat OD with aminocaproic acid which is an inhibitor of fibrinolysis
Irreversible inhibitor of cycloxygenase (COX1 and COX2) thus inhibiting CO2 conversion of arachidonic acid to thromboxane A2 (which promotes platelet aggregation and reduced blood flow).
Use as antipyretic, anti-inflammatory, anti-platelet, and analgesic.
Can cause increased bleeding time (but no effects on PT or PTT). Can also cause gastric ulceration and bleeding (due to decreased mucosal protection via inhibition of COX1), Reye's syndrome in children, and tinnitus.
Clopidogrel and ticlopidine
Binds to the ADP receptor on platelets and inhibits the signal to increase GIIb/IIIa expression (thus decreasing binding to fibrinogen and platelet aggregation).
Use in acute coronary syndrome. Also decreases the risk of thrombotic stroke recurrence.
Can cause neutropenia
Cilostazol and dipyridamole
Phosphodiesterase 3 inhibitor that increases cAMP levels and thus decreases platelet aggregation. Also vasodilates.
Use in intermittent claudication, for angina and for coronary vasoconstriction. Also good for prevention of stroke or TIAs
Can cause side effects related to vasodilation (e.g. flushing, nausea, headache, hypotension).
Monoclonal AB against the GIIb/IIIa receptor and thus decreases platelet aggregation.
Use for acute coronary syndromes.
Can cause bleeding and thrombocytopenia (AB binding causes platelet clearance).
Folic acid analog that inhibits dihydrofolate reductase and thus inhibits synthesis of dTMP from dUMP --> decreased DNA synthesis and protein synthesis.
Used for blood cancers (leukemias and lymphomas) as well as for immune suppression (RA, psoriasis) and ectopic pregnancies.
- Bone marrow suppression that is reversible by leucovorin rescue.
- Fatty change in the liver
- Teratogenicity (neural tube defects)
Pyrimidine analog that binds thymidylate synthase and thus inhibits production of dTMP from dUMP --> decreased DNA and protein synthesis.
Use for colon cancer and solid tumors.
- Bone marrow suppression that can't be rescued with leucovorin. Can rescue with thymidine (which competes with 5FU for binding to TS)
6-mercaptopurine (or azathioprine)
Purine analog that inhibits de-novo purine synthesis.
Use for leukemias and lymphomas (but not CLL or hodgkin's)
Side effects include bone marrow suppression, liver toxicity, and GI problems.
Since it is metabolized by xanthine oxidase, concurrent use of allopurinol, a gout medication that inhibits XO, can increase toxicity of 5FU
Purine analog that inhibits de-novo purine synthesis.
Use for ALL
Side effects include bone marrow suppression and liver toxicity but is not worsened by allopurinol use (unlike 6MP)
Pyrimidine analog that inhibits DNA polymerase and thus reduces DNA synthesis.
Use for acute leukemias (AML and ALL) as well as high-grade, non-hodgkin lymphomas. Can cause leukopenia, thrombocytopenia, and megaloblastic anemia
Dactinomycin (actinomycin D)
Works by intercalating DNA, this breaking it and causing decreased replication.
Use for childhood tumors - Wilms, Ewings sarcoma, Rhadomyosarcomas.
Side effect = myelosuppression
Doxorubicin (adriamycin) and Daunorubicin
Works by causing free radicals and by intercalating DNA, this breaking it and causing decreased replication.
Use for hodgkin's lymphoma, solid tumors of the breast, ovary, and lung, sarcomas and myelomas.
Side effects include cardiotoxicity (DCM) which can be prevented with dexrazoxane (an iron chelator). Also myelosuppression and alopecia.
Works by causing free radical formation and thus causing ds DNA breaks and decreased replication.
Use for testicular cancer and hodgkin's lymphoma.
Side effects include pulmonary fibrosis and skin changes.
Etoposide or Teniposide
Works by inhibiting DNA topoisomerase II and thus reducing DNA replication.
Use for small cell lung and prostate cancers and testicular carcinomas.
Can cause myelosuppression and alopecia. Also causes GI irritation.
Cyclophosphamide or ifosfamide
Need to be activated in the liver. Then works by covalently cross linking DNA at guanine N-7.
Use for non-hodgkin's lymphoma, breast and ovarian carcinomas, and for immune suppression.
Can cause myelosuppression. Can also cause hemorrhagic cystitis that can be prevented by using mesna (which binds the toxic metabolite).
Carmustine, lomustine, semustine, stretozocin.
After being activated, they can cross the blood brain barrier and act as an alkylating agent for brain tumors.
Side effects include CNS toxicity (e.g. ataxia and dizziness)
DNA alkylating agent.
Used in CML and to ablate bone marrow before bone marrow transplant.
Can cause pulmonary fibrosis and skin color changes (similar to bleomycin).
Vincristine or vinblastine
Alkaloids that bind tubulin and prevent their polyermization to form microtubules. Thus, mitotic spindles cannot form and M phase cannot proceed.
Use for hodgkin's lymphoma, Wilm's tumor, and ALL.
Side effects include neurotoxicity (areflexia nad peripheral neuritis), paralytic ileus, and myelosuppression.
Binds to and hyperstabilizes the microtubules, thus preventing breakdown of the mitotic spindle (i.e. prevents anaphase from occuring).
Use for ovarian and breast carcinomas.
Side effects include myelosuppression and hypersensitivity.
Cisplatin and carboplatin
Used for testicular, bladder, ovary, and lung cancers
Side effects include nephro- and oto-toxicity. Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis.
Ribonucleotide reductase inhibitor and thus decreases DNA synthesis.
Use for melanoma, CML.
Also use for sickle cell disease because it increases HbF.
Side effects include bone marrow suppression and GI symptoms.
Steroid triggers apoptosis, even in nondividing cells.
Use for CLL and hodgkin's lymphoma.
Also used for immune suppression in autoimmune diseases.
Can cause cushings syndrome-like side effects.
Tamoxifen and raloxifen
SERMs - estrogen R agonists in the bone, antagonists in the breast.
Used for breast cancer and to prevent osteoporosis.
Tamoxifen can cause hot flashes and increase the risk of endometrial cancer. Raloxifene does not.
Monoclonal AB against the erb2/HER2 tyrosine kinase which can be overexpressed in breast cancers.
Used to treat breast cancers tat overexpress HER2.
Can cause cardiotoxicity
Inhibits the bcr-abl tyrosine kinase.
Good for treating CML
Can cause fluid retention
Monoclonal AB against CD20 (B cells). Thus good for treating Hodgkin's Lymphoma.
Also used for RA.