Drug Examples Mechanism Uses Side EffectsWarfarin Blocks γ carboxylation

(Vitamin K clotting factors)Follow PT/INR

Chronic anticoagulation(Atrial fibrillation)

Teratogenic (do not use w/ pregnancy)BleedingSkin necrosisP450 interactionsSlow reversal: Vitamin KRapid reversal: fresh frozen plasma

Heparin Unfractionated Inhibits IIa, Xa(binds antithrombin III)Short half lifeImmediate anticoagulationDoes not cross placentaMonitor w/ PTT

Pulmonary embolismAcute coronary syndromeMI, DVT

BleedingHeparin-induced thrombocytopenia(anti-heparin-PF4)OsteoporosisTreat w/ protamine sulfate(only for unfractionated)

DalteparinEnoxaparin

Inhibits Xa(binds antithrombin III)Better bioavailabilityLonger half lifeNot easily reversible

Fondaparinux

Direct thrombinInhibitors

ArgatrobanBivalirudinDabigatran

Inhibits IIa(free and clot-associated)Does not require monitoring

Atrial fibrillationVenous thromboembolismHIT

BleedingNo specific reversal agent(PCC, fibrinolytics AKA tranexamic acid)

Direct Xa inhibitors ApixabanRivaroxaban

Inhibits Xa DVT/PE prophylaxisStroke prophylaxis w/ A. fib

BleedingNo reversal agent

Thrombolytics AlteplaseReteplaseStreptokinaseTenecteplase

Activates plasminInc. PT/PTTNo change in platelets

Early MI/strokeDirect thrombolysis of PE

BleedingContraindications:-Active/intracranial bleeding-Recent surgery, severe HTN-Bleeding diathesesTreat w/ aminocaproic acid, fresh frozen plasma, cryoprecipitate

ADP receptorInhibitors

ClopidogrelPrasugrelTiclopidineTicagrelor

Irreversibly block ADP receptorPrevent Gp IIb/IIIa expressionInhibit platelet aggregationTicagrelor is reversible

Acute coronary syndromeCoronary stentingDec. thrombotic stroke

Neutropenia (ticlopidine)TTP

Gp IIb/IIIa inhibitors AbciximabEptifibatideTirofiban

Bind Gp IIb/IIIaInhibit platelet aggregationAbciximab-MAb fragments

Unstable anginaCoronary angioplasty

BleedingThrombocytopenia

PDE III inhibitors CilostazolDipyridamole

Inhibit PDE III, incr. cAMPInhibit platelet aggregationVasodilation

Intermittent claudicationCoronary vasodilationPrevents stroke/TIAAngina prophylaxis

Nausea, headache, hypotensionFacial flushing, GI pain

Antineoplastic agents

Drug Examples Mechanism Uses Side EffectsAntibiotics Bleomycin Free radical formation

DNA strand breaksTesticular cancerHodgkin lymphoma

Pulmonary fibrosisHyperpigmentationMinimal myelosuppression

Dactinomycin DNA intercalator Wilms tumorEwing sarcomaRhabdomyosarcoma

Myelosuppression

DoxorubicinDaunorubicin

Free radical formationDNA intercalatorDNA strand breaks

Solid tumorsLeukemias, lymphomas

Dilated cardiomyopathyMyelosuppressionAlopeciaTreat w/ dexrazoxane

Alkylating agents Busulfan DNA cross linkages CMLAblate marrow before BMT

Severe myelosuppressionPulmonary fibrosisHyperpigmentation

CyclophosphamideIfosfamide

DNA cross linkage(guanine N-7)Requires liver bioactivation

Solid tumorsLeukemias, lymphomas

MyelosuppressionHemorrhagic cystitis(treat w/ mesna)

CarmustineLomustineSemustineStreptozocin

DNA cross linkagesCross blood/brain barrierRequires liver bioactivation

Brain tumors(glioblastoma multiforme)

CNS toxicity-convulsions-dizziness-ataxia

Microtubuleinhibitors

Paclitaxel Hyperstabilize microtubulesSpindle cannot break down(block anaphase)

Ovarian carcinomaBreast carcinoma

MyelosuppressionNeuropathyHypersensitivity

VincristineVinblastine

Bind B-tubulinPrevent microtubule polymers(M-phase arrest)

Solid tumorsLeukemiasHodgkin (vinblastine)Non-Hodgkin (vincristine)

Neurotoxicity(peripheral neuropathy)Constipation(paralytic ileus)

Platins CisplatinCarboplatin

DNA cross linkage Testicular carcinomaBladder carcinomaOvarian carcinomaLung carcinoma

Nephrotoxicity(treat w/ amifostine)Peripheral neuropathyOtotoxicity

Toposiomeraseinhibitors

IrinotecanTopotecan

Inhibit topoisomerase IPrevent unwinding/replication

Colon carcinoma(irinotecan)Ovarian/small cell carcinoma(topotecan)

Severe myelosuppressionDiarrhea

EtoposideTeniposide

Inhibit topoisomerase IIIncrease DNA degradation

Solid tumors(testicular/small cell lung)Leukemias, lymphomas

MyelosuppressionAlopecia

Hydroxyurea Inhibit ribonucleotide reductaseInhibit DNA synthesis

MelanomaCMLSickle cell disease

Severe myelosuppression

Steroids PrednisonePrednisolone

Bind intracytoplasmic receptorAlter gene transcription

CLLNon-Hodgkin lymphomaImmunosuppression

Cushing-like symptoms-obesity, muscle breakdown-cataracts, acne, ulcers-osteoporosis, psychosis

SERMs TamoxifenRaloxifene

Estrogen antagonist in breastEstrogen agonist in bone

Breast carcinoma(treatment/prevention)Osteoporosis prevention

Endometrial carcinoma(tamoxifen is agonist)DVT, PE

Specific inhibitors

Drug Examples Mechanism Uses Side EffectsMonoclonalantibodies

Bevacizumab Anti-VEGFInhibit angiogenesis

Solid tumors(colon, renal)

HemorrhageBlood clotsImpaired wound healing

Cetuximab Anti-EGFR Stage IV colon carcinomaHead & neck carcinoma

RashElevated LFTsDiarrhea

Rituximab Anti-CD20(found on B-cells)

Non-Hodgkin lymphomaCLL, ITP, RA

Incr. risk of PML

Trastuzumab Anti-HER-2Inhibits HER-2 cell signalingAntibody dependent cytotoxicity

HER-2 + breast carcinomaGastric carcinoma

Cardiotoxicity

Tyrosine kinaseinhibitors

Erlotinib EGFR inhibitor Non-small cell lung carcinoma RashImatinib BCR-ABL inhibitor

c-kit inhibitorCMLGI stromal tumors

Fluid retention

Vemurafinib BRAF inhibitor(V600E mutations)

Metastatic melanoma

Antimetabolites

Examples Mechanism Uses Side EffectsAzathioprine6-mercaptopurine

Purine analogInhibit de novo purine synth.Activated by HGPRT

Prevent organ rejectionRA, IBD, SLEWean off steroids

MyelosuppressionGI/liver toxicityInc. toxicity w/ allopurinol

Cladribine(2-CDA)

Purine analogInhibit DNA polymeraseCause DNA strand breaks

Hairy cell leukemia MyelosuppressionNephrotoxicityNeurotoxicity

Cytarabine Pyrimidine analogInhibit DNA polymerase

LeukemiasLymphomas

MyelosuppressionMegaloblastic anemia

5-fluorouracil Pyrimidine analogInhibit thymidylate synthaseInhibit DNA synthesisEnhanced w/ leucovorin

Colon, pancreatic cancerBasal cell carcinoma

Myelosuppression(worsened w/ leucovorin)

Methotrexate Folic acid analogInhibit dihydrofolate reductaseInhibit DNA synthesis

Leukemias, lymphomasChoriocarcinomaSarcomasEctopic pregnancyMedical abortion (misoprostol)RA, IBD, psoriasis, vasculitis

Myelosuppression(reversible w/ leucovorin)HepatotoxicityMouth ulcersPulmonary fibrosis