Anti-coags Flashcards
What are the 4 oral anti-platelet drugs?
Aspirin, clopidogrel, Ticgrelor, dipyridamole + ASA
ASA MOA?
Irreversibly acetylates COX, preventing platelet syn of TXA2 and thus platelet aggregation
3 non-cardio uses of ASA?
anti-pyretic, analgesic, anti-inflamm
PK of ASA?
half = 2-3 hours; Tx effect = 7-10 days (life of platelet)
MOA of clopidogrel and ticagrelor? Difference?
Antagonist of ADP receptor P2Y12 on platelets - prevents ADP induced cAMP decrease and subsequent aggregation
C is irreversible, T is reversible
Half life and metabolism of clopidogrel?
- t1/2 = 7-10 days (irreversible)
- CYP2C19 pro-drug metal (some are ‘slow’ metabolizers, inhibited by omeprazole)
Half life and metab of ticagrelor?
- active drug
- 7 hours (9 for active metabolite)
- CYP3A metabolism (watch for inducers, inhibitors)
MOA of dipyridamole? Why combine with ASA?
- blocks adenine uptake, inhibits phoshodiesterase (increased cAMP, decreased aggregation, vasodilation)
- not very effective alone
What anti-platelet drug is parenteral?
Abciximab
Dual f(x)/MOA of Abciximab?
- antagonist of GP IIb/IIIa – prevents fibrinogen and vWF from binding platelets
- prevents PT binding to platelets, decreasing thrombin formed = ANTI-COAG
Half life of abciximab?
free drug = 30 min bound drug = 18-24 hours platelet f(x) returns in 48 hours
What are the parenteral anti-coagulants?
Heparin, enoxaparin, fondaparinux, bivalirudin
How does UFH work?
Complexes with AT, increasing its activity – inactivation of IIa, IXa, Xa
How is UFH administered?
IV or SC - large molecules
Half life of heparin? Monitoring?
DOSE DEPENDENT - 30-150 min
Must monitor using aPTT
Three AE’s of heparin?
- HI thrombocytopenia
- heparin hypersensitivity
- osteoporosis
Heparin antidote?
protamine sulfate
What kind of drug is enoxaparin?
- LMWH
- complexes AT increasing its activity – inactivates Xa ONLY
How do LMWH’s compare to UFH pharmacokinetically?
- longer t1/2 = 3-6 hours
- equally efficacious
- greater SC bioavailability (fewer doses)
- more predictable levels/PK - Xa monitoring not required
What is fondaparniux? Administration? Metabolism?
- synthetic heparin-like pentasaccharide
- SC
- t1/2 = 17 HOURS 1x day injection
aPTT therapeutic goal in heparin Tx?
2-3x patient’s normal aPTT
Bivalirudin MOA and metabolism?
direct irreversible inhibition of circulating and clot-bound thrombin
IV infusion t1/2 = 25 MINUTES
When is bivalirudin indicated?
Pt’s who require hep but have had HIT; microvascular surgery to re-attach digits
Which coag factors depend on Vitamin K?
2, 7, 9, 10, C, S
Warfarin MOA and onset?
- inhibits Vit K epoxide reductase
- onset observed in 8-12 hours; full effect in 3 days
Warfarin administration and metabolism?
- PO
- long plasma half-life, highly plasma protein bound, hepatic metab via VARIOUS CYPS (many interactions)
Four AE’s of warfarin?
- bleeding
- skin necrosis due to early imbalance of pro/anti coag factors
- purple toe syndrome (cholesterol microemboli)
- teratogen cat X
Warfarin antidotes?
- Vit K, FFP, PT complex or recombinant VIIa
Advantages of Dabigatran over Warfarin?
direct action on II, no CYP450 interactions, more effective with fewer interactions
Dabigatran MOA?
competitive inhibitor of thrombin activity on both fibrinogen and platelets decreasing both coag and platelet activity; PO
Dabigatrain metabolism? Half life? Special dosing considerations?
- prodrug cleaved by esterases and glucuroniated without CYP450 activity
- 14 HOURS = LONG
- dose adjustment needed in RENAL DISEASE
How does Rivaroxaban work? Administration?
DIRECTLY inhibits Xa; oral 1x day t1/2 = 9 hours LONG
Metabolism and administration of Alteplase tPA?
IV ONLY; t 1/2 = 5-10 minutes
How does tPA work?
binds fibrin and converts plasminogen to plasmin permitting clot degradation
Fibrinolytic antidote?
Epsilon aminocaproic acid, PO, IV tranxenamic acid – inhibits plasminogen activation
