Drugs in Clotting Abnormalities

Question 1

What is the activation of platelets controlled by?

Answer 1

variety of surface receptors that regulate various

functions in the activation process.

Question 2

What does stimulation of platelet receptors result in?

Answer 2

(1) activation of internal
signaling pathways that lead to further platelet activation and granule release and

(2) the capacity of the platelet to bind to other adhesive proteins/platelets

Question 3

What facilitates binding of GpIIb/IIIa to fibrinogen?

Answer 3

A calcium-sensitive conformational change in the

extracellular domain of GPIIb/IIIa

Question 4

What are P2Y1 and P2Y12?

Answer 4

GPCR purinergic receptors for ADP on platelets

Question 5

What does an ADP-activated platelet P2Y1 receptor do?

Answer 5

induces a shape change and aggregation of platelets

Question 6

How does an activated P2Y12 receptor work to promote aggregation?

Answer 6

The P2Y12 receptor couples to Gi and, when activated by ADP, inhibits adenylyl
cyclase, resulting in lower levels of cyclic AMP and thereby less cyclic AMP–
dependent inhibition of platelet activation.

Question 7

T or F. P2Y1 AND P2Y12 must be activated to result in platelet activation.

Answer 7

T. Thus, inhibition of either receptor is sufficient to block platelet activation.

Question 8

So what do Clopidogrel, Ticlopidine, and Prasugrel do?

Answer 8

They bind to the ADP binding site on the receptor, thereby preventing ADP from activating the receptor

Question 9

Why is Ticlopidine a second line therapy choice?

Answer 9

due to related hematological toxicity

Question 10

What enzyme is the most sensitive to inhibition by heparin/ATIII?

Answer 10

thrombin

Question 11

T or F. The inactivation of factor Xa does not require the heparin/ATIII complex formation and occurs via binding of ATIII to factor Xa.

Answer 11

T. Heparin only catalyzes the ATIII inactivation of thrombin by acting as a template to which both thrombin and ATIII bind to form a ternary complex.

Question 12

How large must Heparin molecules be to bind to thrombin and ATIII simultaneously?

Answer 12

greater than 18 monosaccharides

Question 13

What is Low molecular weight heparin?

Answer 13

aka enoxaparin or dalteparin, -differs from heparin as being unable to accelerate the inactivation of thrombin by ATIII, but it retains the ability to catalyze the inhibition of factor Xa by ATIII.

Question 14

What are the names of some low weight heparin prepations?

Answer 14

• dalteparin
• tinzaparin
• nadroparin (lower odds of major bleeding)
• reviparin
• enoxaparin (higher risk of major bleeding than unfractionated heparin)

Overall, no low-molecular-weight heparin was found to be significantly better or worse than another

Question 15

How is therapeutic monitoring of heparin done?

Answer 15

using the aPTT test

Question 16

IF aPTT gets too high following heparin administration, what should be done?

Answer 16

slow heparin infusion rate or briefly discontinue

Question 17

What drugs can be given to down regulate the effects of heparin?

Answer 17

protamine sulfate or whole blood/plasma

Question 18

T or F. LMWH inhibits only factor Xa

Answer 18

T.

Question 19

What affect does LMWH have on aTTP?

Answer 19

it has a lower impact upon the aPTT test than does heparin, which acts at several points in the intrinsic pathway.

Question 20

How is LMWH better monitored?

Answer 20

LMWH dosing may be monitored using the factor Xa assay, a chromogenic test.

Question 21

Which plasminogen activator has the longest half life?

Answer 21

Reteplase- 170hrs
Tenecteplaste -110 hrs
Atleplase -30 hrs
Streptokinase -20 hrs

Question 22

Describe the metabolism of the plasminogen activators

Answer 22

Reteplase- hepatic and renal
Tenecteplaste - hepatic
Atleplase - hepatic

Question 23

What are the side effects of plasminogen activators?

Answer 23

bleeding and rarely a small risk of allergic reaction