Pharmacology Chapter 52: Drugs Affecting Coagulation

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how is enoxaparin administered?

SQ

how is selective factor Xa inhibitors (fondaparinux) administered?

SQ

what is the mechanism of action of warfarin?

acts in the liver to prevent synthesis of vitamin K-dependent clotting factors VII, IX, X and prothrombin by 30%-50%

what are thrombolytics mainly used for?

acute MI, acute massive pulmonary embolus and acute ischemic stroke

what causes an arterial thoromboembolic disorder?

adhesion of platelets to the arterial wall (adhesion is stimulated by damage to the wall or by rupture of an atherosclerotic plaque)

what do heparin, warfarin, and dabigatran activate?

antithrombin

what are the types of thromboembolic disorders?

arterial and venous

what are antiplatelets used to prevent?

arterial thrombosis

what are the four types of antiplatelets?

aspirin, ADP receptor blockers, glycoprotein IIb/IIIa receptor antagonists, and agents for intermittent claudication

what do antiplatelets do?

diminishes the clotting action of platelets

drugs that increase effects of warfarin?

displacement of warfarin from albumin, hepatic enzyme inhibition, decreased synthesis of clotting factors

what is the mechanism of action for selective factor Xa inhibitors (fondaparinux)?

enhances the activity of anithrombin to cause selective inhibition of factor Xa

what is the prototype used for low molecular weight heparin?

enoxaparin

thrombolytics promote what?

fibrinolysis

what is the prototype used for selective factor Xa inhibitors?

fondaparinux

why would an anticoagulant be given?

given to prevent formation of new clots and prevents extension of existing clots

what does unfractionated heparin binding with antithrombin cause?

greatly enhances its ability to inactivate both thrombin and factor Xa (the inactivation of these 2 factors differs)

what does warfarin have no effect on?

has no effect on circulating clotting factors or on platelet function

what drugs are included in the anticoagulant category?

heparin, warfarin, dabigatran

when would heparin be contraindicated?

in pts with thrombocyotpenia or uncontrollable bleeding

enoxaparin mechanism of action

inhibition is more specific to active factor Xa

what is involved in the promotion of clot formation?

inhibition of fibrin destruction and administration of missing clotting factors

drugs that promote bleeding?

inhibition of platelet aggregation/clotting factors (anticoagulants)

what must be inhibited to prevent clot formation?

inhibition of specific clotting factors and inhibition of platelet actions

drugs that decrease effects of warfarin?

inhibition of warfarin absorption, hepatic enzyme induction, and increased synthesis of clotting factors

mechanism of action of aspirin?

inhibits synthesis of prostaglandins and can also inhibit the synthesis of prostacyclin by blood vessel wall

what does warfarin inhibit?

inhibits the enzyme needed to convert vitamin K to its active form to make this factors

what is aspirin primarily used for?

prevention of MI

what does aspirin prevent?

prevents TXA2- mediated platelet aggregation and vasoconstriction

what is the mechanism of action of direct thrombin inhibitors?

prevents conversion of fibrinogen to fibrin and prevents activation of factor XII inhibiting conversion of soluble fibrin into insoluble fibrin

what is the antidote to severe heparin overdose?

protamine sulfate (1mg inactivates 100 units of heparin)

how do anticoagulants work?

reduce the formation of fibrin

how is the heparin dose regulated?

regulated by the activated partial thromboplastin time (aPTT)

what is the prototype used for direct factor Xa inhibitors?

rivaroxaban

what are the 2 stages of hemostasis?

1. formation of a platelet plug, followed by 2. reinforcement of the platelet plug with fibrin. both processes are set in motion by blood vessel injury

what are the five stages of hemostasis?

1. vessel spasm 2. formation of platelet plug 3. blood coagulation or development of an insoluble fibrin clot 4. clot retraction 5. clot dissolution (fibrinolysis)

what are the most target INR values?

2-3

how can unfractionated heparin be administered?

IV or SQ

Regulation of coumadin dose

International normalized ratio (INR)

when is the blood coagulation: intrinsic pathway (contact activation) activated?

activated in response to injury

when is the blood coagulation: extrinsic pathway (tissue factor) activated?

activated when blood leaks out of a vessel and enters tissue spaces

what does aspirin bind to?

binds irreversibly to cyclooxygenase, the enzyme in platelets that synthesize TXA2

what does unfractionated heparin bind to?

binds with antithrombin

what is the major adverse effect of coumadin?

bleeding

what is the most common adverse effect of heparin?

bleeding

what is the most common adverse effect of alteplase?

bleeding with intracranial hemorrhage being the most serious

what do direct thrombin inhibitors act on?

both clot bound and circulating thrombin

what can heparin interfere with if taken more than 6 months?

calcium absorption

how can the antidote for coumadin be given?

can be given PO or IV in small doses

glycoprotein IIB/IIIA receptor antagonists mechanism of action?

cause reversible blockade of platelet GPIIb/IIIa receptors which then inhibits the final step in aggregation

what is the prototype used for ADP receptor blockers (adenosine diphosphate receptor blockers)?

clopidogrel

alteplase would be contraindicated for what pts?

contraindicated in pts with active internal bleeding, prior intracranial hemorrhage, iscehmic stroke within last 3 months, intracranial neoplasm, severe, uncontrolled HTN (>180/110)

what is the coagulation cascade?

conversion of fibrinogen into fibrin

what is the prototype for direct thrombin inhibitors?

dabigatran

how is enoxaparin dose determined?

determined by weight

ADP receptor blocker (clopidogrel) mechanism of action?

irreversibly inhibits platelet aggregation by preventing ADP-induced binfing between platelets and fibrinogen

what is alteplase identical to?

naturally occurring human tPA

what do direct factor Xa inhibitors do?

oral anticoagulant which causes selective inhibition of factor Xa and binds directly with the active center factor Xa and inhibits production of thrombin

what prevention are ADP receptor blockers used in?

secondary prevention of thrombotic events in those with acute coronary syndrome (ACS)

what is hemostasis?

stoppage of blood flow

glycoprotein IIB/IIIA receptor antagonist are AKA what?

super aspirins

disorders of hemostasis fall into what 2 main categories?

the inappropriate formation of clots within the vascular system and the failure of blood to clot in response to an appropriate stimuli

what type of drug is alteplase?

thrombolytic

what is the goal of heparin?

to reduce blood coagulability to a level low enough to prevent thrombosis but not to promote spontaneous bleeding

what are glycoprotein IIb/IIIA receptor antagonists used after?

used after PCI to reduce reocclusion of treated arteries (angioplasty, stent or atherectomy)

what is warfarin used for?

used for long-term maintenance and as a prophylaxis in high-risk pts

what does a venous thromboembolic disorder effect?

usually effects the deep veins of the legs (DVT) or the pulmonary circulation (PE)

what dietary vitamin can reduce warfarin's anticoagulant effect?

vitamin K

what is the antidote for coumadin?

vitamin K1 (phytonadione) reduces warfarin induced inhibition of clotting factor synthesis

when must alteplase be given to obtain optimal effectiveness?

within 6 hours of onset of symptoms of MI and within 3 hours of thrombotic CVA


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