Anticoagulation Agents

Question 1

Where is prostacyclin made?

Increased prostacyclin leads to an increase of what second messenger?

Answer 1

Vascular Endothelial Cells

cAMP

Question 2

cAMP does what to platelets?

Answer 2

Inhibits platelet activation & release of platelet aggregating factors

Question 3

What drugs inhibit platelet aggregation & platelet-fibrinogen interaction by blocking ADP receptors?

Answer 3

1. CLOPIDOGREL
2. TICLOPIDINE
3. Prasugrel
4. Ticagrelor

Question 4

What are the major adverse effects of Ticlopidine?

How should pts on Ticlopidine therapy be monitored?

Answer 4

NEUTROPENIA, agranulocytosis, TTP

CBC w differential every 2 weeks for 1st 3 months of therapy & PRN thereafter

(Reason why CLOPIDOGREL is usually preferred)

Question 5

How do DIPYRIDAMOLE & CILOSTAZOL work as platelet aggregation inhibitors?

Answer 5

Inhibits phosphodiesterase3 (PDE3) thereby increasing cAMP levels

constant high cAMP potentiates prostacyclin & inhibits TXA2, thus inhibiting plt aggregation

Question 6

Dipyridamole is usually given in combination with what drug?

Answer 6

ASA

Question 7

Activation of which clotting factor makrs the beginning of the common pathway?

Answer 7

Activation of factor X to Xa

Question 8

What is another name for factor II?

What is another name for factor IIa

Answer 8

Factor II= Prothrombin

Factor IIa= Thrombin

Question 9

What factor is also known as “Christmas factor”?

Answer 9

Factor IX

Question 10

How does haparin work as an anticoagulant?

Which system of the clotting cascade is mainly affected by heparin?

Answer 10

Complexes w antithrombin-III to increase inactivation of clotting factors IIa, Va, IXa, Xa, XIa, XIIa

Intrinsic System- PTT

Question 11

How is heparin administered? What is the onset of action?

Answer 11

IV= immediate onset of action

SQ= 20-30 minutes

Question 12

Why is IM administration of Heparin contraindicated?

Answer 12

Hematoma formation

Question 13

What are the therapeutic indications of heparin?

Answer 13

IMMEDIATE anticoagulation for PE, acute coronary syndrome, MI, & DVT

SAFE for preggos- DOES NOT CROSS PLACENTA

Question 14

What are the adverse effects of heparin?

Answer 14

Bleeding

OSTEOPOROSIS

HIT (Heparin Induced Thrombocytopenia)

Question 15

What drug is used to reverse heparin overdose?

What is the onset of action?

Answer 15

PROTAMINE SULFATE (positively charged molecule that binds negatively charged heparin)

Onset of action ~5 minutes

~1mg of Protamine Sulfate neutralize ~100 units of Heparin

Question 16

What paradoxical adverse effect can protamine cause at high doses?

Answer 16

Anticoagulation leading to hemorrhage

Question 17

What is the MOA of Enoxaparin & Dalteparin?

Answer 17

Low-Molecular-Weight-Heparin (LMWH) act more on factor Xa

Have better bioavailability & 2-4 times longer half-life versis unfractionated heparin (UFH)

Question 18

Does PTT need to be monitored in pts on LMWH?

Answer 18

No

Question 19

What synthetic pentasaccharide causes an antithrombin-III mediated selective inhibition of factor Xa?

Answer 19

Fondaparinux

Question 20

What laboratory tests are used to monitor warfarin therapy?

Which system of the clotting cascade is mainly affected by warfarin?

Answer 20

PT; International Normalized Ration (INR)

Therapeutic INR levels are between 2-3

Extrinsic System

Question 21

What is the MOA of warfarin?

Answer 21

Inhibits vitamin K Epoxide Reductase which inhibits synthesis & y-carboxylation of vitamin-K dependent clotting factors 2, 7, 9, 10 & proteins C & S.

Question 22

What is the onset of action of warfarin?

How long after initiation of warfarin therapy is the full therapeutic effect seen?

Answer 22

36-72 hours (anticoagulant action)

5-7 days (antithrombotic action)

Question 23

What happens to the INR of warfarin pts who begin thyroid replacement medication?

Answer 23

INR increases

Thyroid hormone increases the metabolism of clotting factors, thereby potentiating the effects of warfarin

Question 24

Does warfarin cross the placenta?

Answer 24

YES- it is contraindicated in preggos due to its teratogenicity

Question 25

What are the adverse effects of warfarin?

Answer 25

Bleeding

Skin/Tissue necrosis within the first few days of warfarin therapy (esp in pts with protein C deficiency)

Drug-Drug interactions (cyt P450 metabolism)

Question 26

What can be used to counteract the effects of warfarin?

Answer 26

Vitamin K (slow onset)

Fresh Frozen Plasma (rapid onset)

Question 27

The synthesis of what two factors is inhibited first when warfarin therapy is initiated?

Answer 27

Factor VII

Protein C (therefore pts may initially be hypercoagulable when warfarin is first initiated)

These proteins have the shortest half-lives when compared to the half-lives of factors 2, 9, 10 & protein S

Question 28

What is the MOA of Abciximab, Eptifibatide, & Tirofiban?

Answer 28

Blockade of the glycoprotein IIb/IIIa receptor on activated plts & prevention of aggregation

Question 29

What is the physiologic ligand for the glycoprotein IIb/IIIa receptor?

Answer 29

Fibrinogen

Question 30

What is the MOA of thrombolytic agents? “-TEPLASE”

Answer 30

Conversion of plasminogen to plasmin;

plasmin cleaves fibrin & thrombin thereby leading to lysis of thrombi

Increase in PT & PTT

no change in plt count