Warfarin / Blocks γ carboxylation
(Vitamin K clotting factors)
Follow PT/INR / Chronic anticoagulation
(Atrial fibrillation) / Teratogenic (do not use w/ pregnancy)
Bleeding
Skin necrosis
P450 interactions
Slow reversal: Vitamin K
Rapid reversal: fresh frozen plasma
Heparin / Unfractionated / Inhibits IIa, Xa
(bindsantithrombin III)
Short half life
Immediate anticoagulation
Does not cross placenta
Monitor w/ PTT / Pulmonary embolism
Acute coronary syndrome
MI, DVT / Bleeding
Heparin-induced thrombocytopenia
(anti-heparin-PF4)
Osteoporosis
Treat w/ protamine sulfate
(only for unfractionated)
Dalteparin
Enoxaparin / Inhibits Xa
(bindsantithrombin III)
Better bioavailability
Longer half life
Not easily reversible
Fondaparinux
Direct thrombin
Inhibitors / Argatroban
Bivalirudin
Dabigatran / Inhibits IIa
(free and clot-associated)
Does not require monitoring / Atrial fibrillation
Venous thromboembolism
HIT / Bleeding
No specific reversal agent
(PCC, fibrinolytics AKA tranexamic acid)
Direct Xa inhibitors / Apixaban
Rivaroxaban / Inhibits Xa / DVT/PE prophylaxis
Stroke prophylaxis w/ A. fib / Bleeding
No reversal agent
Thrombolytics / Alteplase
Reteplase
Streptokinase
Tenecteplase / Activates plasmin
Inc. PT/PTT
No change in platelets / Early MI/stroke
Direct thrombolysis of PE / Bleeding
Contraindications:
-Active/intracranial bleeding
-Recent surgery, severe HTN
-Bleeding diatheses
Treat w/ aminocaproic acid,
fresh frozen plasma, cryoprecipitate
ADP receptor
Inhibitors / Clopidogrel
Prasugrel
Ticlopidine
Ticagrelor / Irreversibly block ADP receptor
Prevent GpIIb/IIIa expression
Inhibit platelet aggregation
Ticagrelor is reversible / Acute coronary syndrome
Coronary stenting
Dec. thrombotic stroke / Neutropenia (ticlopidine)
TTP
GpIIb/IIIa inhibitors / Abciximab
Eptifibatide
Tirofiban / Bind GpIIb/IIIa
Inhibit platelet aggregation
Abciximab-MAb fragments / Unstable angina
Coronary angioplasty / Bleeding
Thrombocytopenia
PDE III inhibitors / Cilostazol
Dipyridamole / Inhibit PDE III, incr. cAMP
Inhibit platelet aggregation
Vasodilation / Intermittent claudication
Coronary vasodilation
Prevents stroke/TIA
Angina prophylaxis / Nausea, headache, hypotension
Facial flushing, GI pain
Antineoplastic agents
Drug / Examples / Mechanism / Uses / Side EffectsAntibiotics / Bleomycin / Free radical formation
DNA strand breaks / Testicular cancer
Hodgkin lymphoma / Pulmonary fibrosis
Hyperpigmentation
Minimal myelosuppression
Dactinomycin / DNA intercalator / Wilms tumor
Ewing sarcoma
Rhabdomyosarcoma / Myelosuppression
Doxorubicin
Daunorubicin / Free radical formation
DNA intercalator
DNA strand breaks / Solid tumors
Leukemias, lymphomas / Dilated cardiomyopathy
Myelosuppression
Alopecia
Treat w/ dexrazoxane
Alkylating agents / Busulfan / DNA cross linkages / CML
Ablate marrow before BMT / Severe myelosuppression
Pulmonary fibrosis
Hyperpigmentation
Cyclophosphamide
Ifosfamide / DNA cross linkage
(guanine N-7)
Requires liver bioactivation / Solid tumors
Leukemias, lymphomas / Myelosuppression
Hemorrhagic cystitis
(treat w/ mesna)
Carmustine
Lomustine
Semustine
Streptozocin / DNA cross linkages
Cross blood/brain barrier
Requires liver bioactivation / Brain tumors
(glioblastomamultiforme) / CNS toxicity
-convulsions
-dizziness
-ataxia
Microtubule
inhibitors / Paclitaxel / Hyperstabilize microtubules
Spindle cannot break down
(block anaphase) / Ovarian carcinoma
Breast carcinoma / Myelosuppression
Neuropathy
Hypersensitivity
Vincristine
Vinblastine / Bind B-tubulin
Prevent microtubule polymers
(M-phase arrest) / Solid tumors
Leukemias
Hodgkin (vinblastine)
Non-Hodgkin (vincristine) / Neurotoxicity
(peripheral neuropathy)
Constipation
(paralytic ileus)
Platins / Cisplatin
Carboplatin / DNA cross linkage / Testicular carcinoma
Bladder carcinoma
Ovarian carcinoma
Lung carcinoma / Nephrotoxicity
(treat w/ amifostine)
Peripheral neuropathy
Ototoxicity
Toposiomerase
inhibitors / Irinotecan
Topotecan / Inhibit topoisomerase I
Prevent unwinding/replication / Colon carcinoma
(irinotecan)
Ovarian/small cell carcinoma
(topotecan) / Severe myelosuppression
Diarrhea
Etoposide
Teniposide / Inhibit topoisomerase II
Increase DNA degradation / Solid tumors
(testicular/small cell lung)
Leukemias, lymphomas / Myelosuppression
Alopecia
Hydroxyurea / Inhibit ribonucleotidereductase
Inhibit DNA synthesis / Melanoma
CML
Sickle cell disease / Severe myelosuppression
Steroids / Prednisone
Prednisolone / Bind intracytoplasmic receptor
Alter gene transcription / CLL
Non-Hodgkin lymphoma
Immunosuppression / Cushing-like symptoms
-obesity, muscle breakdown
-cataracts, acne, ulcers
-osteoporosis, psychosis
SERMs / Tamoxifen
Raloxifene / Estrogen antagonist in breast
Estrogen agonist in bone / Breast carcinoma
(treatment/prevention)
Osteoporosis prevention / Endometrial carcinoma
(tamoxifen is agonist)
DVT, PE
Specific inhibitors
Drug / Examples / Mechanism / Uses / Side EffectsMonoclonal
antibodies / Bevacizumab / Anti-VEGF
Inhibit angiogenesis / Solid tumors
(colon, renal) / Hemorrhage
Blood clots
Impaired wound healing
Cetuximab / Anti-EGFR / Stage IV colon carcinoma
Head & neck carcinoma / Rash
Elevated LFTs
Diarrhea
Rituximab / Anti-CD20
(found on B-cells) / Non-Hodgkin lymphoma
CLL, ITP, RA / Incr. risk of PML
Trastuzumab / Anti-HER-2
Inhibits HER-2 cell signaling
Antibody dependent cytotoxicity / HER-2 + breast carcinoma
Gastric carcinoma / Cardiotoxicity
Tyrosine kinase
inhibitors / Erlotinib / EGFR inhibitor / Non-small cell lung carcinoma / Rash
Imatinib / BCR-ABL inhibitor
c-kit inhibitor / CML
GI stromal tumors / Fluid retention
Vemurafinib / BRAF inhibitor
(V600E mutations) / Metastatic melanoma
Antimetabolites
Examples / Mechanism / Uses / Side EffectsAzathioprine
6-mercaptopurine / Purine analog
Inhibit de novo purine synth.
Activated by HGPRT / Prevent organ rejection
RA, IBD, SLE
Wean off steroids / Myelosuppression
GI/liver toxicity
Inc. toxicity w/ allopurinol
Cladribine
(2-CDA) / Purine analog
Inhibit DNA polymerase
Cause DNA strand breaks / Hairy cell leukemia / Myelosuppression
Nephrotoxicity
Neurotoxicity
Cytarabine / Pyrimidine analog
Inhibit DNA polymerase / Leukemias
Lymphomas / Myelosuppression
Megaloblastic anemia
5-fluorouracil / Pyrimidine analog
Inhibit thymidylate synthase
Inhibit DNA synthesis
Enhanced w/ leucovorin / Colon, pancreatic cancer
Basal cell carcinoma / Myelosuppression
(worsened w/ leucovorin)
Methotrexate / Folic acid analog
Inhibit dihydrofolatereductase
Inhibit DNA synthesis / Leukemias, lymphomas
Choriocarcinoma
Sarcomas
Ectopic pregnancy
Medical abortion (misoprostol)
RA, IBD, psoriasis, vasculitis / Myelosuppression
(reversible w/ leucovorin)
Hepatotoxicity
Mouth ulcers
Pulmonary fibrosis