Anticoagulation Agents Flashcards
Where is prostacyclin made?
Increased prostacyclin leads to an increase of what second messenger?
Vascular Endothelial Cells
cAMP
cAMP does what to platelets?
Inhibits platelet activation & release of platelet aggregating factors
What drugs inhibit platelet aggregation & platelet-fibrinogen interaction by blocking ADP receptors?
- CLOPIDOGREL
- TICLOPIDINE
- Prasugrel
- Ticagrelor
What are the major adverse effects of Ticlopidine?
How should pts on Ticlopidine therapy be monitored?
NEUTROPENIA, agranulocytosis, TTP
CBC w differential every 2 weeks for 1st 3 months of therapy & PRN thereafter
(Reason why CLOPIDOGREL is usually preferred)
How do DIPYRIDAMOLE & CILOSTAZOL work as platelet aggregation inhibitors?
Inhibits phosphodiesterase3 (PDE3) thereby increasing cAMP levels
constant high cAMP potentiates prostacyclin & inhibits TXA2, thus inhibiting plt aggregation
Dipyridamole is usually given in combination with what drug?
ASA
Activation of which clotting factor makrs the beginning of the common pathway?
Activation of factor X to Xa
What is another name for factor II?
What is another name for factor IIa
Factor II= Prothrombin
Factor IIa= Thrombin
What factor is also known as “Christmas factor”?
Factor IX
How does haparin work as an anticoagulant?
Which system of the clotting cascade is mainly affected by heparin?
Complexes w antithrombin-III to increase inactivation of clotting factors IIa, Va, IXa, Xa, XIa, XIIa
Intrinsic System- PTT
How is heparin administered? What is the onset of action?
IV= immediate onset of action
SQ= 20-30 minutes
Why is IM administration of Heparin contraindicated?
Hematoma formation
What are the therapeutic indications of heparin?
IMMEDIATE anticoagulation for PE, acute coronary syndrome, MI, & DVT
SAFE for preggos- DOES NOT CROSS PLACENTA
What are the adverse effects of heparin?
Bleeding
OSTEOPOROSIS
HIT (Heparin Induced Thrombocytopenia)
What drug is used to reverse heparin overdose?
What is the onset of action?
PROTAMINE SULFATE (positively charged molecule that binds negatively charged heparin)
Onset of action ~5 minutes
~1mg of Protamine Sulfate neutralize ~100 units of Heparin
What paradoxical adverse effect can protamine cause at high doses?
Anticoagulation leading to hemorrhage
What is the MOA of Enoxaparin & Dalteparin?
Low-Molecular-Weight-Heparin (LMWH) act more on factor Xa
Have better bioavailability & 2-4 times longer half-life versis unfractionated heparin (UFH)
Does PTT need to be monitored in pts on LMWH?
No
What synthetic pentasaccharide causes an antithrombin-III mediated selective inhibition of factor Xa?
Fondaparinux
What laboratory tests are used to monitor warfarin therapy?
Which system of the clotting cascade is mainly affected by warfarin?
PT; International Normalized Ration (INR)
Therapeutic INR levels are between 2-3
Extrinsic System
What is the MOA of warfarin?
Inhibits vitamin K Epoxide Reductase which inhibits synthesis & y-carboxylation of vitamin-K dependent clotting factors 2, 7, 9, 10 & proteins C & S.
What is the onset of action of warfarin?
How long after initiation of warfarin therapy is the full therapeutic effect seen?
36-72 hours (anticoagulant action)
5-7 days (antithrombotic action)
What happens to the INR of warfarin pts who begin thyroid replacement medication?
INR increases
Thyroid hormone increases the metabolism of clotting factors, thereby potentiating the effects of warfarin
Does warfarin cross the placenta?
YES- it is contraindicated in preggos due to its teratogenicity
What are the adverse effects of warfarin?
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)
What can be used to counteract the effects of warfarin?
Vitamin K (slow onset)
Fresh Frozen Plasma (rapid onset)
The synthesis of what two factors is inhibited first when warfarin therapy is initiated?
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
What is the MOA of Abciximab, Eptifibatide, & Tirofiban?
Blockade of the glycoprotein IIb/IIIa receptor on activated plts & prevention of aggregation
What is the physiologic ligand for the glycoprotein IIb/IIIa receptor?
Fibrinogen
What is the MOA of thrombolytic agents? “-TEPLASE”
Conversion of plasminogen to plasmin;
plasmin cleaves fibrin & thrombin thereby leading to lysis of thrombi
Increase in PT & PTT
no change in plt count
