HEME

Question 1

Rivaroxaban and dabigatran

Answer 1

are both oral anticoagulants; rivaroxaban inhibits factor Xa and dabigatran inhibits factor IIa. Both cause elevations in the international normalized ratio, although in the case of dabigatran, the elevation is not sensitive enough to detect clinically relevant changes in drug concentration. aPTT is sensitive to dabigatran and a normal level indicates a minimal drug effect. If necessary, factor Xa levels can be used to monitor rivaroxaban and the thrombin clotting time to monitor dabigatran. However, 1 of the advantages of these drugs over warfarin is that both are intended to be used without monitoring.
Both agents are effective in both prophylaxis and treatment of venous thromboembolic disease as well as the prevention of stroke in patients with nonvalvular atrial fibrillation.
Neither drug has a risk of heparin-induced thrombocytopenia. The major disadvantage of both drugs is the lack of a direct reversal agent or direct antidote. Dabigatran can be removed with dialysis, rivaroxaban cannot. After dialysis for 2–3 hours, approximately 60% of dabigatran is removed. Prothrombin complex concentrates and activated factor VIIa are suggested for treatment in patients who suffer bleeding complications related to these drugs, traumatic injury, or require emergent operation, but there are no data on the effectiveness of these or other procoagulant therapies.

Question 2

antiplatelet effect of aspirin is caused by

Answer 2

blocking the production of
thromboxane A2

via deactivating cyclooxygenase-1 (COX-1).

Because the platelets do not synthesize new proteins, this inhibition on COX-1 is permanent for the life of the platelet.

Question 3

Clopidogrel’s antiplatelet effect is through

Answer 3

permanently inhibiting

purine receptor P2Y-12,

blocks the ADP-activated activation and aggregation.

Question 4

Fondaparinux inhibits

Answer 4

Factor Xa

initial line of treatment for venous thromboembolic disease except in the presence of

CONTRAINDICATION:
renal insufficiency (like lepirudin = leaches ar good for the liver sucking out toxins in the liver)

Question 5

argatroban

Answer 5

snake vipor venim

hepatic cleared

direct thrombin inhibitor

Question 6

lepirudin

Answer 6

leaches are good for the liver

direct thrombin inhibitor;

Question 7

bivalirudin

Answer 7

a direct thrombin inhibitor;

Question 8

danaparoid

Answer 8

enhances antithrombin

and

heparin cofactor II.

Question 9

dabigatran

Answer 9

fixed oral dosing and no requirement for laboratory monitoring.

direct action against, Factor IIa (thrombin)

new anticoagulants are much shorter than that of warfarin, making anticoagulation bridging unnecessary before surgery.

oral direct thrombin inhibitor administered twice a day in fixed doses of 110 mg or 150 mg.

half-life is 12–17 hours.

In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with similar rates of stroke and systemic embolism but lower rates of major hemorrhage compared with warfarin.

Dabigatran administered at a dose of 150 mg was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage compared with warfarin.

By selectively inhibiting only thrombin, dabigatran has antithrombotic efficacy while preserving other hemostatic mechanisms in the coagulation system, thereby reducing the risk of bleeding.

Question 10

rivaroxaban

Answer 10

Factor Xa inhibitor (like funda)

the first oral, specific Factor Xa inhibitor to be approved for clinical use in the prevention of venous thromboembolism.

It inhibits prothrombinase and clot-bound Factor Xa activity.

Peak plasma concentrations are achieved after 2–4 hours.

half-life of 7–11 hours is between that of low molecular weight heparin and fondaparinux and much shorter than that of warfarin.

Extended prophylaxis with rivaroxaban 10 mg once daily is superior to short-term prophylaxis with enoxaparin 40 mg once daily for the prevention of venous thromboembolism, including symptomatic events.

new anticoagulants are much shorter than that of warfarin, making anticoagulation bridging unnecessary before surgery.

Question 11

UFH mech

Answer 11

binds to antithrombin III (ATIII) (def requires paradoxical FFP admin)

inactivation of factor Xa and other clotting factors.

Question 12

UFH is inactivated by

Answer 12

a number of plasma proteins,
endothelial cells,
macrophages.

Question 13

LMWH

Answer 13

greater inhibitory activity against factor Xa (also mech of Unfrac heparin)

and

thrombin (instead of antithrombin III)

longer half-life than UFH,

lower risk of nonhemorrhagic side effects.

excreted by the kidney and must be used with caution in patients with impaired renal function.