Pharm: Anti-platelets and Anti-Coagulants Flashcards
Warfarin
anticoagulant (Coumadin)
- inhibits vitamin K -dependent posttranslation modification of clotting factors: thrombin, VII, IX, X protein C and S
- onset is 36-72 hours (t1/2 is 25-60 hours)
- highly fat soluble, delayed termination
- taken orally
Unfractionated Heparin
- anticoagulant
- binds Antithrombin III which inactivates: thrombin, IX, X, XI, XII
- Given IV or SQ (for surgeries)
- NOT given orally
- onset is immediate w/ bolus injection
- t1/2 = 1-2 hours
Low MW Heparin
anticoagulant
ex. Enoxaparin (Lovenox)
Fondaparinux
synthetic analog of heparin; injected SQ
indicated: tx of UA/NSTEMI, acute MI, prevention of DVT, tx of PE
Dabigatran
= new oral antigoaculant
- direct thrombin inhibitor
- used for prevention of stroke
- monitoring via INR is not required and bleeding is less than warfarin
- more expensive than warfarin
Aspirin
= Anti-platelet
- irreversibly inhibits thromboxane formation (activator of platelet aggregation), via inhibition of COX-1
- higher doses inhibit formation of prostacyclin (vasodilator)
- used to tx MI, stroke and PAD
Clopidogrel
= Anti-platelet
-blocks platelet aggregation by inhibiting ADP receptor, thus blocking ADP mediated activation of GPIIB/IIIa complex –> inhibits fibrinogen binding and platelet aggregation
- indications: prophylaxis of stroke, MI, PAD, ACS
Dipyridamole
= Anti-platelet- blocks platelet aggregation through inhibiting cAMP, weak vasodilator
- used to prevent MI and stroke, and thromboembolism
** often used in combo with aspirin **
headaches are a problem
Abciximab
= Anti-platelet, GPIIb/IIIa inhibitor
- prevents fibrinogen from binding to GP IIb-IIIa, thus inhibiting platelet aggregation
- greater antithrombotic activity than aspirin or heparin
tx: used for acute coronary syndromes, PCI, angiopalsty
Alteplase
rt-PA
= thrombolytic
Reteplase
= thrombolytic
Tenecteplase
= thrombolytic
Streptokinase
= thrombolytic
how to prevent pathologic thrombus?
- used to just use heparin/warfarin
- now try to inhibit platelet aggregation with aspirin, clopidogrel or abciximab
white clot vs. red clot?
white clot = due to arterial wall damage, atherosclerotic plaque - plugs break away asn arterial thrombus
red clot = due to stasis, see long fibrin tail with central core of RBCs that are clotted. Fibrin tail or red clot breaks away as venous trhombus –> distant embolism
to check UFH?
aPTT time: 1.5-2.5
thrombin time
(at high dose it will also increase PT)
to check LMWH?
no testing necessary
to check Warfarin
PT test converted to INR
INR should be 2.5-3.5
S/E of Heparin?
- hemorrhage
- thrombocytopenia: HIT syndrome (due to formation of Abs directed against the heparin-platelet factor 4 complexes)
If overdose: stop administration, administer protamine Sulfate (binds to and inactivates heparin, but is not an antidote for warfarin), give fresh-frozen plasma
indications of UFH?
- prophylaxis of postop thrombosis (SQ)
- MI or unstable angina
- DVT or PE
- DIC
- TIA - effective but risky, not used if stroke is in progress
small doses: prevent thromboembolism
medium doses: prevent propogation of thrombus
large doses: inhibit established PE
If prolonged anticoagulation is necessary, the initial heparin therapy is overlapped with and then replaced with oral anticoagulant, i.e., warfarin
HIT type 1
Heparin induced thrombocytopenia
transient, reversible clumping of platelets
platelet count >100,000
Usually occurs within first few days of therapy
Usually asymptomatic and recover OK even if heparin continued.
HIT Type II
delayed onset (5-14 days)
severe thrombocytopenia (platelet counts< 100,000).
This is an immune-mediated reaction, a heparin-antibody complex caused significant platelet aggregation.
Recovery can be delayed and consequences of peripheral thrombosis can be severe, including stroke, acute MI, skin necrosis. Amputation is necessary in up to 25% of patients with Type II HIT and mortality approaches 25%.
Incidence of Type II HIT is about 3% of all treated
Heparin CI’s?
Any site of active or potential bleeding
Severe hypertension or known vascular aneurysm
Recent head, eye, or spinal cord surgery
Head trauma
Lumbar puncture or regional anesthetic block
Tuberculosis, visceral carcinoma, GI ulcers
aPTT
tests intrinsic pathway: Ca2+ ion is added and charged surface are contacted
used to monitor unfractionated heparin therapy: 1.5 to 2.0 times control
