Anticoagulants

Question 1

What do protein C and S do?

Answer 1

Cleave factor 5a and 8a to stop coagulation cascade

Question 2

What is the structural features of heparin? route of administration, half life, cross placenta?

Answer 2

Large and water soluble
IV/short half life 2hrs
Do not cross placenta (too big)

Question 3

What is the structural features of warfarin? route of administration, half life, cross placenta?

Answer 3

Small and lipid soluble
oral/long half life 30+hrs
Cross placenta

Question 4

Which is teratogenic, heparin or warfarin?

Answer 4

Warfarin

Question 5

What is the MOA of warfarin?

Answer 5

Inhibit Vitamin K epoxide reductase—>prevent recycling of Vitamin K—>no effect on active Vitamin K—>thus slow onset

Question 6

What is the MOA of heparin?

Answer 6

Bind to antithrombin III and activate it—>ATIII inactivate thrombin (factor 2)/9/10/11/12
Rapid onset

Question 7

What do we use to monitor heparin and warfarin?

Answer 7

Heparin—>PPT

Warfarin—>PT and INR

Question 8

How to do rapidly counter warfarin?

Answer 8

Give fresh frozen plasma

Question 9

How does protamine antagonize heparin?

Answer 9

Protamine bind to heparin and inactivate it—>chemical antagonism

Question 10

What are the toxicities for heparin and warfarin?

Answer 10

Heparin—>heparin induced thrombocytopenia (HIT)/hypersensitivity
Warfarin—->skin necrosis/drug interaction/teratogen

Question 11

Why do we use low molecular weight heparin and what are they?

Answer 11

Smaller—>longer half life/no need to monitor PTT

Dalteparin/enoxaparin

Question 12

What drug would displace warfarin from protein binding and increase PT and INR?

Answer 12

NSAIDs/sulfonamide/phenytoin

Question 13

What clotting factors do warfarin inhibit and why do we use heparin with warfarin in the beginning?

Answer 13

2/7/9/10/C/S

Factor 7 and C have short half life—>go away first—>transient hyper-coagulate state (skin necrosis)

Question 14

How to treat HIT?

Answer 14

Stop heparin—>switch to direct thrombin inhibitors (argatroban/dabigatran/bivalirudin)

Question 15

What else can bivalirudin used for?

Answer 15

PCI

Question 16

What are direct factor 10 inhibitors and what are they used for?

Answer 16

“xaban”

Alternative to warfarin/prevent DVTs after surgery/prevent stroke and embolism from a fib

Question 17

What are thrombolytics and what do they do?

Answer 17

tPA (tissue plasminogen activator)—>alteplae/reteplase/tenecteplase (teplase)
Convert plasminogen into plasmin to cleave fibrin and break the clot—>use acutely for MI/DVT/PE/stroke

Question 18

What’s the difference between tPA and streptokinase?

Answer 18

Streptokinase—>act on both bound and free plasminogen (not clot specific)/cause allergy
tPA—>act on only fibrin bound plasminogen/cause NO allergy

Question 19

What are the antidotes for excessive bleeding from tPA or streptokinase? and how do they worK?

Answer 19

Antifibrinolysin—>aminocaproic and tranexamic acids

Stop the conversion from plasminogen to plasmin

Question 20

What are the 3 classes of antiplatelet drugs?

Answer 20

Inhibit TXA2 (aspirin)
Inhibit ADP receptor (clopidogrel/ticagrelor/ticlopidine)
Inhibit GP2a3b receptor (abciximab/eptifibatide/tirofiban)

Question 21

Which ADP receptor blocker has the side effect of thrombocytopenic purpura?

Answer 21

Ticlopidine—>thus not really used

Question 22

How are ADP receptor block used?

Answer 22

Alternative to aspirin (post MI and unstable angina)

Question 23

What are GP2b3a receptor blockers used?

Answer 23

Acute coronary syndrome and post PCI