Heme Drugs II Flashcards
aspirin class
cyclooxygenase inhibitor
abciximab, eptifibatide, tirofiban class
glycoprotein Iib/IIIa inhibitors
clopidogrel, prasurgel ticlopine class
ADP receptor inhibitor
agratroban, bivalirudin, dabigatran class
direct thrombin inhibitors
fondaparinux, rivaroxaban, apixaban class
Factor 10 inhibitors
streptokinase class
fibrinolytic
TPA class
serine protease
romiplostin, eltrombopag, erythropoetin, filgrastim class
factors (stimulate differation of committed progenitor cells by receptor dimerization, kinase activity; some stimulate stem cells to commit upon a particular line)
folic acid mechanism
Functions to transfer one-carbon fragments between molecules
B12 (cobalamin) mechanism
Required for demethlyation of methyl-THF, converstion of methylmalonyl CoA to succinyl CoA, and methylation of myelin in folate metabolism
aspirin mechanism
Irreversibly acetylates and blocks action of cyclooxygenase (COX1), which is an enzyme in arachidonic acid TXA2 pathway, on platelets
abciximab, eptifibatide, tirofiban mechanism
Reversibly inhibits binding of activated platelet GP IIb/IIIa receptors to fibrinogen and VWF, inhibiting platelet from sticking together
clopidogrel, prasurgel ticlopine mechanism
After conversion to active metabolites in the liver, inhibits ADP-mediated activation of platelets by irreversibly binding to P2Y12
dipyramole mechanism
May act by increasing cAMP levels, either by inhibiting phosphodiesterase or blocking cellular uptake and destruction of endogenous adenosine
agratroban, bivalirudin, dabigatran mechanism
Inhibit circulating and clot-bound thrombin activity independently of antithrombin
fondaparinux mechanism
Complexes with antithrombin to inactivate factor Xa
streptokinase mechanism
Produces extra plasmin to break down fibrin in clots
TPA mechanism
Catalyzes conversion of plasminogen to plasmin
thrombopoietin, romiplostin, eltrombopag mechansim
platelet production!
Stimulates differentiation and maturation of megakaryocytes to platelets; Stimulates pluripotent stem cells to divide and commit to megakaryocytic development
erythropoietin mechanism
Cytokine produced in kidney and necessary for erythroid proliferation and differentiation; bind to erythropoietin receptor leading to dimerization of that receptor leading to activation of tyrosine kinase activity
absence of erythropoietin
apoptosis of committed erythroid cells and anemia of renal failure
filgrastim mechanism
Stimulates differentiation/maturation of neutrophils; Puts pluripotent stem cells into cycle and commits to neutrophil development
Supplementation required in poor diet (alcoholism and extreme poverty); increased folate requirement (pregnancy, severe hemolytic anemia, severe psoriasis); drug therapy (certain abx, chemotherapy); malabsorption (tropical sprue, celiac disease)
folic acid
required in gastric failure (pernicious anemia, total gastrectomy); ilial failure (Chrohn’s disease, ileal resection, tropical sprue, Celiac disease); competing organisms (bacterial overgrowth/ blind loop, diphyllobothrium latum)
B12
Used to treat iron deficiency
ferrous sulfate
Indications for aspirin, abciximab, eptifibatide, tirofiban, clopidogrel, prasurgel, ticlopidine
Principally used for preventing/treating arterial thromboembolitic disease
No cardiac benefits alone, but can be used with warfarin for an augmented antithrombotic effect for patients with recurrent thromboembolism
dipyridamole
Anticoagulation for prophylaxis, tx of thrombosis, or PCI in pts with Heparin-induced thrombocytopenia
argatroban
unstable angine/angioplasty (cath lab only)
bivalirudin
superior to warfarin in preventing embolism in Afib
dabigatran
superior to LMWH in DVT pre- and post-op, PE in stable patients, VTE prophylaxis
fondaparinux
treat VTE, prophylaxis for VTE in ortho, stroke prevention in nonvalvular a fib
rivaroxiban
better than warfarin for nonvalve afib, VTE prohylaxis in knee/hip replacements
apixaban
dissolves thrombi in MI and PE
streptokinase
dissolves thrombi in stroke
TPA
used to be post-chemo, but caused thrombocytopenia. Now treat ITP
thrombopoietin, romiplostin, eltrombopag
treats anemia associated with kidney failure
erythropoietin
treats neutropenia
filgrastim
don’t give in liver disease (hepatic metabolized)
bivalirudin
don’t give in renal failure
dagibitran, fondaparinux, rivaroxaban, apixiban
may cause TTP, clear before surgery
clopidogrel, prasurgel, ticlopidine
caution to pregnant, elderly, obese; may cause wound hematomas
fondaparinux, rivaroxaban, apixiban
not for pregnant, can cause nerve damage, nausea, dizziness, hypotension, mild fever
streptokinase
contraindicated in hemorrhagic stroke and head trauma
TPA
dangerous if injected (athletes)
erythropoietin
can cause hyperleukocytosis, capillary leak syndrome (fluid in the lungs)
filgrastim
folic acid is absorbed where, stored how long?
duodenum/jejunum, 4-5 months
B12 comes from, absorbed where, stored how long?
animals, ileum, 2-12 years
Oral aborption and good bioavailability
clopidogrel, prasurgel, ticlopidine
Delayed onset due to CYP450-mediated biotransformation
clopidogrel, prasurgel, ticlopidine
Inhibited by omeprazole, esomeprazole, ketoconazole
clopidogrel, prasurgel, ticlopidine
No cross-reactivity with heparin-induced antibodies, no antidote, short half life
agratroban
Levels tightly regulated by levels of O2 delivery to the kidneys; Low Hgb increased levels
erythropoietin
