hem/onc Flashcards
heparin MOA?
activates antithrombin –> decreased thrombin and Xa
LMWH vs heparin?
LMWH (enoxaparin, dalteparin) and fondaparinux = FXa inhib
- more Xa action
- better bioavail
- longer T1/2
- don’t need monitoring
- less easily reversible
how to reverse heparin?
protamine sulfate ( + charge –> binds heparin)
HIT?
IgG against heparin-bound platelet factor 4 (PF4)
Ab-heparin-PF4 complex –> platelet activation –> thrombosis and TCP
direct thrombin inhibitors?
argatroban
bivalirudin
dabigatran
** alternatives to heparin in pts with HIT
warfarin MOA?
blocks gamma-carboxylation of vit K dependent factors
metabolism affected by polymorphisms in VKORC1 gene (vit K epoxide reductase complex)
** affects extrinsic pathway, PT/INR
mechanism of warfarin-induced tissue necrosis?
small vessel microthromboses
direct F Xa inhibitors?
apixaban, rivaroxaban
uses: tx and ppx for DVT/PE, stroke ppx in afib
how to tx thrombolytic tox?
aminocaproic acid (inhibits fibrinolysis)
aspirin MOA?
irreversible COX1/2 inhib via acetylation
increases bleeding time, decreases TXA2 and PGs
** no effect on PT or PTT
ADP receptor inhibitors/
clopidogrel, prasugrel, ticagrelor, ticlopidine
irreversible block of ADP receptor –> prevent expression of GPIIb/IIIa –> inhibit platelet agg
- ticagrelor = reversible
- ticlopidine –> neutropenia
cilostazol, dipyramidole?
PDEIII inhib –> increased cAMP in platelets –> inhib of aggregation; vasodilation
- used in intermittent claudication, coronary syndromes
- tox: nausea, HA, flushing, hypoT, abd pain
GP IIb/IIIa inhibs?
abciximab, eptifibatide, tirofiban
used for unstable angina, PTCA
** tox: bleeding, TCP
antimetabolites that are purine analogs?
6MP
azathioprine
cladribine
azathioprine/6MP MOA?
purine analogs, activated by HGPRT
inhibit de novo purine synth
azathioprine/6MP uses?
rejection ppx, RA, IBD, SLE
weaning pts off steroids in chronic dz
azathioprine/6MP toxicity?
myelosuppression
GI
liver
** increased toxicity with allopurinol and febuxostat (metab by XO)
cladribine MOA?
purine analog
multiple mechanisms: DNA pol inhib, DNA breaks
cladribine uses?
hairy cell leukemia
cladribine toxicity?
myelosuppresssion
nephrotoxicity
neurotoxicity
antimetabolites that inhibit pyrimidine synthesis?
cytarabine
5FU
methotrexate
cytarabine MOA?
pyrimidine analog
inhibit DNA pol
cytarabine uses?
leukemia - AML
lymphomas
cytarabine toxicity?
pancytopenia, megaloblastic anemia
5FU MOA?
pyrimidine analog, activated to 5F-dUMP –> covalently complexes folate
complex inhibits thymidylate synthase –> decreased dTMP –> decreased DNA synthesis
5FU uses?
colon cancer
pancreatic cancer
topical –> basal cell carcinoma