Flashcards in Pharmacology of Anticoagulation Therapy Deck (45)
Name the anticoagulant drugs that interfere with the coagulation cascade and prevent formation of thrombin, which converts fibrinogen to fibrin.
Heparin and oral anticoagulants
What agent promotes lysis of clots by increasing formation of plasmin, a serine protease that degrades fibrin?
What drug inhibits the formation of platelet products or blocks platelet adhesion thus preventing platelet aggregation and clot formation?
What are the three forms of Heparin?
1. Unfractionated Heparin
2. Low molecular weight heparins
Describe unfractionated heparin.
-Proteoglycans containing covalently linked sulfated polysaccharide chains
-Highest negative charge density
Describe low molecular weight heparins like
-produced by chemical or enzymatic depolymerization of heparin
Describe Fondaparinux (Arixtra)
Minimal sequence in heparin for binding antithrombin
What is the mechanism of action of heparin?
Heparins bind antithrombin III
Antithromin III is a natural protease inhibitor that inactivates coagulation factors
Heparin accelerates the rate of decay of IXa, Xa, and XIIa by antithrombin III
Which type of heparin is able to bind to the antithrombin/thrombin complex?
LMWH and Fondaparinux can only bind AT-III
Which drug does not absorb well from the GI tract and can't be given orally. This drug also has poor bioavailability and relatively short half-life?
Hint: Requires careful monitoring in hospital but can be given to pregnant women.
What drug is given SQ, has a long half life, requires less monitoring, and has a better bioabailability than unfractionated heparin?
Low molecular weight heparins and fondaparinux
What conditions would you use heparins to treat?
-Venous thrombosis and pumonary embolism
-management of unstable angina or acute myocardial infarction
-During and after coronary angioplasty or stent placement
During surgery requiring cardiopulmonary bypass
What drug can you use to reverse the toxic affects of heparin?
Protamine sulfate, a positively charged compound that neutralizes heparin
Name three toxic effects of heparin.
2. Heparin-induced thrombocytopenia syndrome (HIT)
3. Allergic Events
Describe the onset of heparin-induced thrombocytopenia syndrome.
Platelet cound decreases 5-10 after heparin
Caused by development of antibodies that bind to and activate platelets resulting in a prothrombotic state
What is the treatment for patients who have heparin-induced thrombocytopenia syndrome?
TX with direct thrombin inhibitors:
-Argatroban (Novastan): a small molecule inhibitor
-Lepirudin (Refludan): recombinant form of hirudin, the antivoagulant from leeches
Allergic reactions are sometimes seen in patients on Heparin. What is the root cause of thos allergic reaction?
Contaminant over sulfated chondroitin sulfate
What drug is a derivative of dicumarol and is a vitamin K analogue?
What is the mechanism of action of warfarin?
Warfarin inhibits reductases that reduce vitamin K.
Reduced vitamin K is used as a cofactor for certain enzymes
These enzymes undergo vitamin K-dependent gamma carboxylation of N-terminal glutamate
What are the pharmacokinetic characteristics of warfarin?
It is readily absorbed
Does not achieve affect until 2-3 days
What are the clinical uses of warfarin?
Used to prevent:
-Systemic embolism in patients with prosthetic heart valves or atrial fibrillation
-Stroke, recurrent infarction, or death in patients with acute myocardial infarction
What are some of the adverse effects of warfarin?
TX: Drug stopped, Vitamin K administered, Plasma can be transfused to replace coag. factors
What drugs can increase the action of warfarin?
1. Drugs that inhibit platelet function (aspirin)
2. Drugs that decrease vit. K synthesis by intestinal microbes (antibiotics)
3. Drugs that replace warfarin from plasma proteins (clofibrate, phenytoin)
-Drugs that reduce the metabolism and elimination of warfarin in the liver
What drug decrease the effect of warfarin?
-Drugs that increase the metabolism by inducing metabolic enzymes in the liver (barbiturates, rifampin)
-Drugs that decrease warfarin absorption from the GI tract (cholestyramine)
There are new oral anticoagulants that are direct thrombin or Factor Xa inhibitors. Name some advantages of these drugs.
-Rapid onset of action
-Absence of food interactions
-Do not require monitoring
There are new oral anticoagulants that are direct thrombin or Factor Xa inhibitors. Name some disadvantages of these drugs.
-Contraindicated with kidney disease
-Greater GI bleeding than with warfarin
-No antidote available to reverse effects
There are new oral anticoagulants that are direct thrombin or Factor Xa inhibitors. Name three of these new drugs.
-Dabigatran etexilate: Prodrug, lowers rate of stroke and systemic embolism, less intracranial hemorrhage. More myocardial infarctions
-Rivaroxaban- Synthetic, lower rates of strokes and emboli for the TX or atrial fibrillation
All three have been approved for the treatment of atrial fibrillation
What is the mechanism of action for fibrinolytic agents?
Convert plasminogen to plasmin, a protease that degrades fibrin clots.
What is tissue plasminogen activator and what is its mechanism of action?
-Fibrinolytic drug that binds to fibrin, which increases cleavage of plasminogen to plasmin.