Coagulation Drugs Flashcards
Hemostasis
Occurs in two stages: Formation of a platelet plug followed by coagulation (production of fibrin, a protein that reinforces the platelet plug)
Platelet aggregation depends on activation of GP IIb/IIIa receptors, which bind fibrinogen to form cross-links between platelets.
Fibrin is produced by two pathways: 1) the contact activation pathway (intrinsic pathway) and 2) the tissue factor pathway (extrinsic pathway). These patways converge at clotting factor Xa, which catalyzes the formation of fibrin.
Thrombosis
Four factors in the coagulation pathways require an activated form of vitamin K for their synthesis.
Plasmin, the active form of plasminogen, degrades the fibrin meshwork of clots.
A thrombus is a blood clot that forms within a blood vessel or within the heart.
Arterial thrombi begin with the formation of a platelet plug, which then is reinforced with fibrin.
Venous thrombi begin with the formation of fibrin, which then enmeshes RBCs and platelets.
Whereas arterial thrombi are best prevented with ________ (asa, clopidogrel) venous thrombi are prevented with _______ (warfarin, heparin, dabigatran).
antiplatelet drugs
anticoagulatants
Heparin
Suppresses coagulation by helping antithrombin inactivate thrombin and factor Xa.
IV or subcu.
Anticoagulation effects develop within minutes of IV administration.
AE of heparin is bleeding
Heparin induced thrombocytopenia
Potentially fatal condition caused by the development of antibodies against heparin-platelet protein complexes.
Heparin Contraindications
In patients with thrombocytopenia or uncontrollable bleeding. Must be used with extreme caution in all patients with a high likelihood of bleeding.
Heparin Monitoring
measuring the activated partial thromboplastin time (aPTT). The target aPTT is 60 to 80 seconds (1.5 to 2 times the normal value of 40 seconds).
Low Molecular Weight Heparin
inactivate factor Xa, whereas unfractionated heparin inactivates factor Xa and thrombin equally
do not bind nonsepcifically to plasma proteins and tissues. bioavailability is high, making plasma levels predictable.
Because plasma levels of LMW heparins are predictable, these drugs can be administered ona fixed schedule with no need for routine laboratory monitoring. Therefore, LMW heparins can be used at home.
Warfarin
Prevents the activation of vitamin K, thereby blocking the biosynthesis of vitamin K-dependent clotting factors.
Anticoagulant repsonses to warfarin develop slowly and presist for several days after the drug is discontinued.
Used dto prevent VTE and to prevent stroke and systemic embolism in patients with a-fib.
Monitored by measuring PT. INR. 2-3 for most patients. 2.5-3.5 mechanical valves.
Reversal agent Vit. K.
Cannot give during pregnancy can cause fetal abnormalities, CNS defects, optic atrophy.
Dabigatran
Oral anticoagulant that works by direct inhibition of thrombin.
Alternative to warfarin for chronic anticoagulation in patients with a-fib.
Advantages: rapid onset, fixed dosage, no need for coagulation testing, few drug-food interactions.
Disadvantages: no antidote, limited clinical experience, and more GI disturbances
Administered PO
Direct Factor Xa Inhibitors
Rivaroxaban
Apixaban
Edoxaban
Antiplatelet Drugs
Suppress thrombus formation in the arteries.
ASA- inhibits platelet aggregation by causing irreversible inhibition of cyclooxygenase. Bc platelets are unable to synthesize new COX, inhibition persists for the life of the platelet (7-10 days).
ASA given for
primary prophylaxis of MI, prevention of MI recurrence, and prevention of stroke in patients with a history of TIAs.
When used to suppress platelet aggregation, asa is administred in low doses 8–325mg/day.
Plavix
Clopedogril suppresses platelet aggregation by causing irreversible blockade of P2Y12ADP receptors on the platelet surface.
Prodrug that undergoes conversion to its active form by hepatic CYP2C19.
Adverse effect: bleeding
Watch herbal products
Brilynta, Efnia
Cardiac stent: CVA
