HemeOnc Drugs

hezikry's version from 2015-09-08 17:42

Bleeding/Clotting drugs

Question Answer
Heparin mechCofactor for the activation of antithrombin, ↓ thrombin, and ↓ factor Xa
Short half-life
Warfarin mechInterferes with normal synthesis/γ-carboxylation of vitamin K-dependent clotting factors 2, 7, 9, 10 and proteins C and S. Long half life
Heparin follow the PT or PTTPTT monitoring
Warfarin follow the PT or PTTPT works on extrinsic pathway
warfarin skin necrosismore likely in protein C or S deficiency
Heparin's bridgingHeparin's effect on antithrombin enables anticoagulation during intital, transient hypercoagulable state caused by warfarin.
HITdevelopment of IgG antibodies against heparin bound platelet four (PF4). Antibody-heparin-PF4 activates platelets and leads to thrombosis and thrombocytopenia.
If a person develops HIT what anticoagulant should be givenbivalirduin, hirudin, lipriudin, argatroban. direct inhibitor of thrombin. Do not give LMW heparin or normal heparin
Treatment for heparin overdoseprotamine sulfate
Other a/e of heparinosteoporosis
LMWHeparinsEnoxaparin, dalteparin andfondaparinux
Act more on factor Xa, better bio-availability, 2-4x longer half life
SubQ without lab monitoring. Less HIT
What is the reversibility like of LMW heparinsnot easily reversible
Lepirudin, bivalirudin, agrotrobanDerivates of hirudin: the anticoagulant used by leeches
Inhibits thrombin
Alternative to heparin for anticoagulating pts with HIT
Direct factor Xa inhibitorsapixaban, rivaroxaban increase PT and PTT not thrombin time (unlike Heparin)
Warfarin toxBleeding, teratogenic, skin/tissue necrosis, drug-drug interactions
Reversal: give vitamin K; rapid reversal - give fresh frozen plasma
Heparin useImmediate anticoag for PE, ACS, MI, DVT
Used during pregnancy
Follow the PTT
Warfarin useChronic anticoag
Not used in pregnant women
Follow the PT/INR
what happens when you first administer warfarin?initially, there is pro-coagulant phase bc of C and S action --> therefore give heparin with it at first
Hep/warfarin route of administrationHep: IV, SubQ
Warfarin: Oral
Which inhibits coagulation in vitro?Heparin
ThrombolyticsAlteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA)
Thrombolytics mechAlteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA)
Aids conversion of plasminogen to plasmin → cleaves thrombin and fibrin clots
↑ PT, ↑ PTT, no change in platelet count
Thrombolytics toxAlteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA)
Bleeding. Contraindicated in anyone who's bleeding or recent history of bleeding or who is at risk of bleeding.
How should you treat thrombolytics toxicityaminocaproic acid
Fondaparinuxactivates antithrombin. Inhibits Xa.
Aspirin mechIrreversibly inhibits COX1&2 enzyme by covalent acetylation.
↑ bleeding time, ↓ TXA2 and prostaglandins
No effect on PT or PTT
Aspirin toxGastric ulcers, tinnitus (CN 8)
Chronic use: acute renal failure, interstitial nephritis, upper GI bleeding
Reye's syndrome in children with viral infection
Acid base disturbance in aspirin toxicityrespiratory alkalosis then metabolic acidosis
ADP receptor inhibitors mechClopidogrel, ticlopidine, prasugrel, ticagrelor
Inhibits platelet aggregation by irreversibly blocking ADP receptors.

Prevents expression of glycoproteins IIb/IIIa on platelet surface. Inhibit platlet aggregation
ADP receptor inhibitors toxNeutropenia (ticlopidine)
Cilostazol, dipryridamole mechPhosphodiesterase III inhibitor
↑ cAMP in platelets thus inhibiting platelet aggregation
Cilostazol, dipyridamole toxNausea, HA, facial flushing, hypotension, abdominal pain
Treatment of PADcliostazol
Gp IIb/IIIa inhibitors mechAbciximab, eptifibatide, tirofiban
by binding to Gp IIb/IIIa receptors prevents aggregation of platelets
Abciximab is made from MAB Fab fragments
Gp IIb/IIIa deficiencyGlanzmann thrombasthenia
Relationship between ADP and GPIIb/IIIaATP binding to receptor induces GpIIb/IIIa expression at platelet surface.
Protein C/S inhibitorsinactivate V and VII
Two drugs can used to lower risk for MI after stentaspirin and clopidogrel
ClopidogrelADP receptor inhibitor
TiclopidineADP receptor inhibitor
PrasugrelADP receptor inhibitor
TicagrelorADP receptor inhibitor
CilostazolPDE III Inhibitor
DipyridamolePDE III inhibitor
AbciximabGP IIb/IIIa inhibitor
EptifibatideGp IIb/IIIa inhibitor
TirofibanGp IIb/IIIa inhibitor


Question Answer
MethotrexateFolic acid analog → Inhibits dihydrofolate reductase → ↓ dTMP → ↓ DNA and ↓ protein synthesis
5-FUPyrimidine analog as 5F-dUMP inhibits thymidylate synthase → ↓ dTMP → ↓ DNA and ↓ protein synthesis
Cytarabine (arabinofuranosul cytidine)Pyrimidine analog → inhibition of DNA polymerase
Azathioprine, 6-MP, 6-thioguaninePurine (thiol) analogs → ↓ de novo purine synthesis
Activated by HGPRT
Clinical use of azathiopurinepreventing organ rejection, RA< IBD, used ot wean patients off steroids
A/E of azathiopurineincreased toxicity with allopurinol. because metabolized by XO.
Clinical use of cladribinehairy cell leukemia
A/E of cytarabinepancytopenia
Clinical use of 5-FUbasal cell carcinoma, colon cancer, pancreatic cancer
A/E of methotrexatemyelosupresion which is reversible with leucovorin Pulmonary fibrosis. Contraindicated in pregnancy bc leads to NTD
What is the effect of leucovorin on methotrexate and 5-FUleucovorin can be used to rescue normal cells from toxicity of methotrexate. On the other hand leucovorin can potentiate flurouracil


Question Answer
DactinomycinIntercalates DNA
Doxorubicin (Adriamycin)
Generates free radicals
Noncovalently intercalates in DNA → breaks in DNA → ↓ replication
BleomycinInduces free radical formation, which causes breaks in DNA strands
Bleomycin toxicitypulmonary fibrosis
Doxorubicin/daunorubicin toxicitycardiotox
What agent can be used to prevent cardiotox from doxorubicindexrazoxane
used for childhood tumorsdactinomycin think "children act out"

Alkylating Agents/Microtubule inhibitors

Question Answer
Cyclophosphamde, ifosfamideCovalently X-link (interstrand) DNA at guanine N-7
Requires bioactivation by liver
(carmustine, lomustine, semustine, streptozocin)
DNA Alkylating agent that crosses the blood-brain barrier
Requires bioactivation
Busulfancrosslinks DNA
A/E busulfanpulmonary fibrosis
A/E cyclophosphamidehemorrhagic cystitis can give MESNA to prevent. Increases transitional cell bladder cancer
Vincristine, vinblastineAlkaloids, bind to tubulin in M phase and block polymerization of microtubules so that mitotic spindle cannont form
"Microtubules are the vines of your cells"
Paclitaxel, other taxolsHyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur)
"It is taxing to stay polymerized"


Question Answer
Cisplatin "platins"Cross-link DNA
Etoposide, teniposideInhibit topoisomerase II → ↑ DNA degradation
ironotecan, topotecaninhibit DNA topo I and prevent DNA unwinding and replication
use topotecan forsmall cell lung cancers
use irinotecan forcolon cancer
HydroxyureaInhibits ribonucleotide reductase → ↓ DNA Synthesis (S-phase specific)
Prednisone, prednisoloneMay trigger apoptosis
May even work on nondividing cells
Tamoxifen, raloxifeneSERMs - receptor antagonists in breast and agonists in bone
Blocks binding of estrogen to estrogen receptor-positive cells
tamoxifenpartial agonist in endometrium
raloxifeneestrogen receptor antagonist in endometrial tissue
Trastuzumab (Herceptin)Monoclonal antibody against HER-2 (c-erbB2) a typrosine kinase.
A/E trastuzumab (herceptin)Cardiotoxicity. Think HEARTceptin damages the heart.
Imatinib (Gleevec)Philadelphia chromosome bcr-abl tyrosine kinase inhibitor
RituximabMAB against CD20, which is found on most B-cell neoplasms
VemurafenibSmall molecule inhibitor of forms of the B-Raf kinase with the V600E mutation
Treats late-stage melanoma
BevacizumabMAB against VEGF. Inhibits angiogenesis
ErlotinibEGFR tyrosine kinase inhibitor. Can be used in non-small cell lung cancer

Important Associations Cancer Drugs

Question Answer
Hemorrhagic cystitiscyclophosamide (partially prevented with MESNA)
pulmonary fibrosisbleomycin, busulfan
NitrosureasCNS toxicity
GIve leucovorinfor methotrexate myelosuppression toxicity
Pregnancy and methotrexatecontraindicated. leads to NTD bc decreases folic acid
6-mercaptopurine metabolized byXO
Allopurinol and 6-Mercaptopurineincreases toxicity of 6-MP because no longer being metabolized by XO. So, more 6-MP around.
Dilated cardiomyopathydoxorubicin, daunorubicin
Partial agonist in endometriumtamoxifen
Toxicity of vinblastineblasts blone
Nephrotoxicity and ototoxicitycisplatin
Toxicity of trastuzumab (herceptin)cardiotoxicity
VIncristine toxicityperipheral neuropathy