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Heparin
- Mechanism:
- -cofactor for activation of antithrombin
- -decreases thrombin and factor Xa
- -short half life
- Clinical Use:
- -PE
- -acute coronary syndrome
- -MI
- -DVT
- Toxicity:
- -bleeding
- -Heparin induced thrombocytopenia
- -osteoporosis
- -drug-drug interactions
- *antidote = protamine sulfate
- Notes:
- -LMWH: act more on factor Xa and have longer half life, not easily reversible
- -follow PTT
-
Heparin Induced Thrombocytopenia
-development of IgG antibodies against heparin bound to platelet factor 4 (PF4)
-antibody-heparin-PF4 complex activates platelets → thrombosis and thrombocytopenia
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Lepirudin
Bivalirudin
- Mechanism:
- -derivatives of leech anticoagulant
- -inhibit thrombin
- Clinical Uses:
- -alternative to heparin for patients with HIT
-
Warfarin (Coumadin)
- Mechanism:
- -interferes with synthesis and carboxylation of vitamin K dependent clotting factors (II, VII, IX, X, protein C and S)
- Clinical Use:
- -chronic anticoagulation
- -STEMI
- -venous thromboembolism prophylaxis
- -prevent of stroke in AFib
- Toxicity:
- -bleeding
- -teratogenic (CI in pregnancy)
- -skin/tissue necrosis
- -drug-drug interactions
- Notes:
- -reverse with vitamin K or fresh frozen plasma
- -follow PT
"The EX-PresidenT went to war(farin)"
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Thrombolytics
- Ateplase (tPA)
- Reteplase (rPA)
- Tenecteplase (TNK-tPA)
- Mechanism:
- -aid conversion of plasminogen to plasmin (cleaves thrombin and fibrin clots)
- -increase PT and PTT, no change in platelet count
- Clinical Use:
- -early MI
- -early ischemic stroke
- -direct thrombolysis of severe PE
- Toxicity:
- -bleeding
- -CI: active bleeding, hx of intracranial bleeding, recent surgery, severe HTN
- -tx toxicity with aminocaproic acid
-
Aspirin
- Mechanism:
- -irreversibly binds COX (1 and 2)
- -platelets cannot synthesize new enzymes (effects last until new platelets are produced)
- -decrease TXA2 and PG formation
- -increase bleeding time, no effect on PT/PTT
- Clinical Uses:
- -antipyretic (intermediate dose)
- -analgesic (intermediate dose)
- -anti-inflammatory (high dose)
- -antiplatelet (low dose)
- Toxicity:
- -gastric ulceration
- -tinnitus
- -chronic use: renal failure, interstitial nephritis, GI bleeding
- -Reye's syndrome in children with viral infection
- -OD: metabolic acidosis and respiratory alkalosis
-
ADP Receptor Inhibitors
- Clopidogrel
- Ticlopidine
- Prasugrel
- Ticagrelor
- Mechanism:
- -inhibit platelet aggregation by irreversibly blocking ADP receptors
- -inhibit fibrinogen binding (block GpIIb/IIIa)
- Clinical Use:
- -acute coronary syndrome
- -coronary stenting
- -decrease incidence or recurrence of thrombotic stroke
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Cilostazol
Dipyridamole
- Mechanism:
- -Phosphodiesterase III inhibitor
- -increase cAMP in platelets (inhibiting aggregation)
- -vasodilators
- Clinical Uses:
- -intermittent claudication
- -coronary vasodilation
- -prevention of stroke or TIA (combined with ASA)
- -angina prophylaxis
- Toxicity:
- -Nausea
- -HA
- -facial flushing
- -hypotension
- -abdominal pain
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Gp IIb/IIIa Inhibitors
- Abciximab
- Eptifibatide
- Tirofiban
- Mechanism:
- -bind GpIIb/IIIa and prevent platelet aggregation
- Clinical Use:
- -acute coronary syndrome
- -percutaneous transluminal coronary angioplasty
- Toxicity:
- -bleeding
- -thrombocytopenia
-
Cancer Cell Drug Types
-location of action in cell cycle
-
Methotrexate
- Mechanism:
- -folic acid analog that inhibits DHFR
- -decrease DNA and protein synthesis
- Clinical Use:
- -leukemias
- -lymphomas
- -choriocarcinoma
- -sarcomas
- -abortion
- -ectopic pregnancy
- -RA-psoriasis
- Toxicity:
- -myelosuppression (leucovorin rescue)
- -macrovesicular fatty change in liver
- -mucositis
- -teratogenic
-
5-FU
- Mechanism:
- -pyrimidine analog
- -inhibits DNA and protein synthesis
- Clinical Use:
- -colon cancer
- -basal cell carcinoma
- Toxicity:
- -myelosuppression (not reversible)
- -OD: rescue with thymidine
- -photosensitivity
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Cytarabine
- Mechanism:
- -pyrimidine analog
- -inhibition of DNA polymerase
- Clinical Use:
- -leukemias
- -lymphomas
- Toxicity:
- -Leukopenia
- -thrombocytopenia
- -megaloblastic anemia
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Azathioprine
6-MP
6-TG
- Mechanism:
- -purine analogs
- -decrease de novo purine synthesis
- -activated by HGPRT
- Toxicity:
- -BM
- -GI
- -Liver
- -increase toxicity with allopurinol
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Dactinomycin
- Mechanism:
- -antitumor antibiotics
- -intercalates in DNA
- Clinical Use:
- -Wilm's tumor
- -Ewing's sarcoma
- -Rhabdomyosarcoma
- -childhood tumors
- "Children act out"
- Toxicity:
- -myelosuppression
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Doxorubicin (Adriamycin)
Daunorubicin
- Mechanism:
- -antitumor antibiotics
- -generate free radicals
- -intercalate in DNA and generate breaks
- -reduces replication
- Clinical Use:
- -solid tumors
- -leukemias
- -lymphomas
- Toxicity:
- -cardiotoxicity (dilated cardiomyopathy)
- -myelosuppressive
- -alopecia
- -toxic to tissues following extravasation
- -dexrazoxane used to prevent cardiotoxicity
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Bleomycin
- Mechanism:
- -antitumor antibiotic
- -induces free radical formation causing breaks in DNA strands
- Clinical Use:
- -testicular cancer
- -Hodgkin's lymphoma
- Toxicity:
- -pulmonary fibrosis
- -skin changes
- -minimal myelosuppression
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Cyclophosphamide
- Mechanism:
- -alkylating agent
- -cross linked into DNA
- -requires bioactivation by liver
- Clinical Use:
- -solid tumors
- -leukemias
- -lympomas
- -some brain cancers
- Toxicity:
- -myelosuppression
- -hemorrhagic cystitis
- -partially prevented with mensa
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Nitrosoureas
- Carmustine
- Lomustine
- Semustine
- Streptozocin
- Mechanism:
- -alkylating agents
- -require bioactivation
- -cross BBB
- Clinical Use:
- -brain tumors (glioblastoma multiforme)
- Toxicity:
- -CNS toxicity (dizziness, ataxia)
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Busulfan
- Clinical Use:
- -CML
- -ablate marrow before HSCT
- Toxicity:
- -pulmonary fibrosis
- -hyperpigmentation
-
Vincristine
Vinblastine
- Mechanism:
- -microtubule inhibitors
- -prevent mitotic spindle formation in M phase
"microtubules are the vines of your cells"
- Clinical Use:
- -solid tumors
- -leukemias
- -lymphomas
- Toxicity:
- -Vincristine: neurotoxic, paralytic ileus
- -Vinblastine: blasts BM
- "Vinblastine blasts bone marrow"
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Paclitaxel
- Mechanism:
- -microtubule inhibitor
- -prevent mitotic spindle breakdown in M phase
" it's taxing to stay polymerized"
- Clinical Use:
- -ovarian carcinoma
- -breast carcinoma
- Toxicity:
- -myelosuppression
- -hypersensitivity
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Cisplatin
Carboplatin
- Clinical Use:
- -testicular carcinoma
- -bladder carcinoma
- -ovary carcinoma
- -lung carcinoma
- Toxicity:
- -nephrotoxicity (prevent with amifostine and chloride diuresis)
- -acoustic nerve damage
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Etoposide
Teniposide
- Mechanism:
- -inhibit topoisomerase II
- -increased DNA degradation
- Clinical Use:
- -solid tumors
- -leukemias
- -lymphomas
- Toxicity:
- -myelosuppression
- -GI irritation
- -alopecia
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Hydroxyurea
- Mechanism:
- -inhibits ribonucleotide reductase
- -decreases DNA Synthesis (S phase specific)
- Clinical Use:
- -Melanoma
- -CML
- -Sickle cell disease (increase HbF)
- Toxicity:
- -BM suppression
- -GI upset
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Prednisone
Prednisolone
- Mechanism:
- -may trigger apoptosis
- -may even work on non-dividing cells
- Clinical Use:
- -most commonly used GC in cancer chemotherapy
- -CLL
- -non-Hodgkin's lymphoma
- -immunosuppressant (autoimmune diseases)
- Toxicity:
- -Cushing like sx
- -immunosuppression
- -cataracts
- -acne
- -osteoporosis
- -HTN
- -Peptic ulcers
- -hyperglycemia
- -psychosis
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Tamoxifen
Raloxifene
- Mechanism:
- -SERMs
- -Estrogen R antagonists in breast
- -Estrogen R agonists in bone
- Clinical Use:
- -breast cancer treatment and prevention
- -prevent osteoporosis
- Toxicity:
- -T: partial agonist in endometrium (increased risk of endometrial cancer), hot flashes
- -R: no increased risk of endometrial cancer
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Trastuzumab (Herceptin)
- Mechanism:
- -anti-HER2
- -may cause antibody-dependent cytotoxicity of Her2+ cells
- Clinical Use:
- -HER2+ breast cancer
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Imatinib (Gleevac)
- Mechanism:
- -philadelphia chromosome bcr-abl inhibitor
- Clinical Use:
- -CML
- -GI stromal tumors
- Toxicity:
- -fluid retention
-
Rituximab
- Clinical Use:
- -Non-Hodgkin's lymphoma
- -RA (with methotrexate)
-
Vemurafenib
- Mechanism:
- -small molecule inhibitor of B-Raf with V600E mutation
- Clinical Use:
- -metastatic melanoma
-
Bevacizumab
- Mechanism:
- -anti-VEGF
- -inhibits angiogenesis
- Clinical Use:
- -solid tumors
-
Chemo-tox Man!
- Cisplatin/Carboplatin
- -acoustic nerve damage
- -nephrotoxicity
- Vincristine
- -peripheral neuropathy
- Bleomycin, Busulfan
- -pulmonary fibrosis
- Doxorubicin
- -cardiotoxicity
- Trastuzumab
- -cardiotoxicity
- CYclophosphamide
- -hemorrhagic cystitis
- Methotrexate
- -myelosuppression
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