Ch 52: Anticoagulant, Antiplatelet, and Thrombolytic Drugs Flashcards
What are the 2 stages of hemostasis?
formation of a platelet plug, and reinforcement of the platelet plug with fibrin
(p. 594)
The intrinsic clotting pathway is also known as…
…the contact activation pathway.
p. 594
The extrinsic clotting pathway is also known as…
…the tissue factor pathway.
p. 594
At what factor do the two pathways converge?
Factor Xa
p. 594
What is tissue factor?
a complex of several compounds, also known as tissue thromboplastin.
(p. 594)
Each platelet has ______ to ______ GP IIa/IIIb receptors.
50,000 - 80,000
p. 594
What does the letter “a” after a factor’s name indicate?
active form
p. 596
Which clotting factors are vitamin K-dependent for their synthesis?
II, VII, IX, and X
(2, 7, 9, 10)
(p. 597)
What does antithrombin do?
it forms a complex with clotting factors, inhibiting their activity.
(p. 597)
What is plasmin?
An enzyme that degrades the fibrin meshwork of a clot.
p. 597
The fibrinolytic drugs act by…
…promoting the conversion of plasminogen into plasmin
p. 597
The antiplatelet drugs are most effective at…
…preventing arterial thrombosis.
p. 597
Anticoagulants are most effective against…
They work by reducing…
…venous thrombosis.
…the formation of fibrin.
(p. 597)
What is the MOA of heparin?
Enhancement of the activity of antithrombin, a protein that inactivates thrombin (factor IIa) and factor Xa; the ultimate effect is suppression of fibrin formation.
(p. 597, 598)
What are the pharmacokinetics of heparin?
Hepatic metabolism followed by renal excretion.
The half life is about 1.5 hrs.
(p. 599)
What does aPTT stand for?
activated partial thromboplastin time
p. 599
What is the underlying cause of HIT?
development of antibodies against heparin-platelet protein complexes.
(p. 601)
HIT should be suspected whenever platelet counts…
…fall significantly or when thrombosis develops despite adequate anticoagulation.
(p. 601)
In heparin-treated patients, platelet aggregation is the major…
…remaining defense against hemorrhage.
p. 601
What are the 3 advantages of LMW heparins?
As effective as unfractionated heparin.
Easier to use because of fixed dosage.
No aPTT monitoring.
(p. 602)
What are the pharmokinetic advantages of LMW heparins over unfractionated heparin?
LMW heparins have a higher bioavailability (d/t a lack of nonspecific binding) and a longer half-life.
(p. 603)
What 2 LMW heparins are available in the U. S.?
enoxaparin and daltaparin
p. 603
In contrast to overdose with heparin or LMW heparins, fondaparinux…
…cannot be treated with protamine sulfate.
p. 604
True or false? Fondaparinux can promote immune-mediated HIT.
FALSE, it cannot, although it still can lower platelet counts.
(p. 604)
What can spinal or epidural hematoma result in?
permanent paralysis
p. 604
How does heparin differ from LMW heparins and fondaparinux?
The LMW heparins and fondaparinux preferentially inactivate factor Xa, not thrombin (factor IIa).
(p. 600)
Warfarin works by inhibiting vitamin K epoxide reductase complex 1 (VKORC1), the enzyme needed to…
…convert vitamin K to its active form.
p. 604
Warfarin is inactivated in the liver, mainly by…
…CYP2C9.
p. 604
What are the 3 new oral anticoagulants?
dabigatran (Pradaxa), apixaban (Eliquis), and rivaroxaban (Xarelto)
(p. 604)
The new oral anticoagulants pose a significantly lower…
…risk of serious bleeding.
p. 605
Warfarin is inactivated in the liver, mainly by…
…CYP2C9.
p. 604
What are the 3 new oral anticoagulants?
dabigatran (Pradaxa), apixaban (Eliquis), and rivaroxaban (Xarelto)
(p. 604)
The new oral anticoagulants pose a significantly lower…
…risk of serious bleeding.
p. 605
Warfarin is in what pregnancy risk category?
X
p. 606
When the __________ effects of warfarin are coupled with the antiplatelet and ___________ effects of aspirin, the potential for hemorrhage is significant.
antifibrin; ulcerogenic
p. 606
Even though it has not been proven acetaminophen is believed to _______ warfarin ___________.
inhibit; degradation
p. 607
Name at least 5 of the many circumstances in which warfarin is contraindicated.
(1) severe thrombocytopenia
(2) uncontrolled bleeding
patients undergoing (3) lumbar puncture, (4) regional anesthesia, or surgery of the (5) eye, (6) brain, or (7) spinal cord
(8) vitamin K deficiency
(9) liver disease
(10) alcoholism
(p. 607)
Where heparin inhibits only free thrombin, dabigatran (Pradaxa) binds with and inhibits thrombin that is…
…free in the blood as well as thrombin that is bound to clots.
(p. 608)
In the event of life-threatening hemorrhage in a patient taking dabigatran, treatment should include…
…recombinant factor VIIa or factor IX complex.
p. 608
What kind of drug is bivalirudin (Angiomax)?
an IV direct thrombin inhibitor
p. 610
What is the half-life of bivalirudin (Angiomax) in patients with normal renal function?
25 minutes
p. 610
Bivalirudin is intended to be given in combination with…
…aspirin, clopidogrel, or prasugrel to prevent clots during coronary angioplasty.
(p. 610)
Desirudin (Iprivask) is what kind of drug?
How is it given?
a direct thrombin inhibitor; it is given subQ
p. 610
What kind of drug is rivaroxaban (Xarelto)?
an oral anticoagulant that causes selective inhibition of factor Xa.
(p. 610)
Fondaparinux is closely related in structure and function to…
…heparin and the LMW heparins.
p. 603
Fondaparinux is a ____ anticoagulant that ________ the activity of ____________, causing selective __________ of factor __.
subQ; enhances; antithrombin; inhibition; factor Xa.
p. 603
The term nonvalvular atrial fibrillation pertains to patients who do not have a __________ heart valve or _______________ significant valve disease.
prosthetic; hemodynamically
p. 611
What are the implications of treatment for overdose with a drug that is highly protein bound?
Dialysis is unlikely to remove it from the blood.
p. 611
What type of drug is apixaban (Eliquis)?
an oral anticoagulant that causes selective inhibition of factor Xa.
(p. 612)
What is antithrombin?
An endogenous compound that suppresses coagulation by inhibiting thrombin and factor Xa.
(p. 612)
Recombinant antithrombin (rhAT) sold as ATryn, is produced in…
…the milk of goats that have been given the DNA sequence for human AT.
(p. 612)
What are the 3 major groups of antiplatelet drugs?
aspirin, P2Y 12 ADP receptor antagonists, and GP IIb/IIIa receptor antagonists
(p. 613)
Aspirin and the P2Y 12 ADP receptor antagonists affect only one pathway in platelet aggregation, hence…
…their antiplatelet effects are limited.
p. 613
Aspirin suppresses platelet aggregation by…
…causing irreversible inhibition of cyclooxygenase, an enzyme required by platelets to synthesize TXA2 (thomboxane A2).
(p. 613)
Since inhibition of cyclooxygenase by aspirin is irreversible, and since platelets lack the machinery to synthesize new cyclooxygenase, the effects of a single dose of aspirin persist for…
…the life of the platelet (7-10 days).
p. 613
Which 3 of the 4 P2Y12 ADP receptor antagonists cause irreversible receptor blockade?
clopidogrel (Plavix), prasugrel (Effient), and ticlopidine
p. 614
Which of the 4 P2Y12 ADP receptor antagonists cause reversible receptor blockade?
ticagrelor (Brilinta)
p. 614
It patients with ACS, clopidogrel should…
…always be combined with aspirin.
p. 614
What is one important aspect of treatment in patients who develop TTP from taking clopidogrel?
plasmapheresis
p. 614
PPIs may reduce the antiplatelet effects of ___________ because they inhibit CYP___.
clopidogrel; 2C19
p. 614
The GP IIb/IIIa receptor blockers include what 3 drugs?
abciximab (ReoPro)
tirofiban (Aggrastat)
eptifibatide (Integrilin)
(p. 616)
