Chap 26 Coagulation Modifier Drugs Flashcards
(37 cards)
Hemostasis
General term for any process that stops bleeding
Coagulation is hemostasis that occurs because of the physiologic clotting of blood.
Complex relationship between substances that promote clot formation and either inhibit coagulation or dissolve a formed clot
Thrombus*: technical term for a *blood clot *
Embolus: thrombus that moves through blood vessels
Embolus
Thromboembolic events
Myocardial infarction (MI): embolus lodges in a coronary artery
Stroke:* embolus obstructs a brain vessel
Pulmonary emboli:* embolus in the pulmonary circulation
Deep vein thrombosis (DVT): embolus goes to a vein in the leg
Coagulation System
Cascade”
Each activated factor serves as a catalyst that amplifies the next reaction.
Result is fibrin, a clot-forming substance.
Intrinsic pathway and extrinsic pathway
Fibrinolytic System
Initiates the breakdown of clots and serves to balance the clotting process
Fibrinolysis*: mechanism by which formed thrombi are lysed to prevent excessive clot formation and blood vessel blockage
Hemophilia
Rare genetic disorder
Natural coagulation and hemostasis factors are limited or absent.
Patients with hemophilia can bleed to death if coagulation factors are not given.
Two types inhibit platelet aggregation
Factor VII deficiency
Factor VIII and/or factor IX deficiency
Coagulation Modifier Drugs
Anticoagulants
Inhibit the action or formation of clotting factors
Prevent clot formation
Antiplatelet drugs
Inhibit platelet aggregation
Prevent platelet plugs
Hemorheologic drugs
Alter platelet function without preventing the platelets from working
Thrombolytic drugs
Lyse (break down) existing clots
Antifibrinolytic or hemostatic
Promote blood coagulation
Anticoagulants
Also known as antithrombotic drugs
Have no direct effect on a blood clot that is already formed
Prevent intravascular thrombosis by decreasing blood coagulability
Used prophylactically to prevent
Clot formation (thrombus)*
An embolus (dislodged clot)*
Heparins
Action: inhibit clotting factors IIa (thrombin) and Xa
Unfractionated heparin: “heparin”
Lo–molecular-weight heparins (LMWHs)
Enoxaparin (Lovenox)
Dalteparin (Fragmin)
Anticoagulant Heparin
Natural anticoagulant obtained from the lungs or intestinal mucosa of pigs
10 to 40,000 units/mL
DVT prophylaxis: 5000 units subcutaneously two or three times a day; does not need to be monitored when used for prophylaxis
When heparin is used therapeutically (for treatment), continuous IV infusion.
Measurement of aPTT (usually every 6 hours until therapeutic effects are seen) is necessary.
Heparin for catheter flush (10 to 100 units/mL): no monitoring is needed**
Low Molecular Weight Heparin
Pre-filled syringes
Do not expel air bubble**
Anticoagulant Enoxaparin (Lovenox)
Prototypical LMWH
Greater affinity for factor Xa than for factor Iia
Higher degree of bioavailability and longer elimination half-life
Lab monitoring is not necessary.
Injectable form
Used for prophylaxis and treatment
Pre-filled syringes**
Do not expel air bubble**
Treatment: Toxic Effects of Heparin
Symptoms: hematuria* melena (blood in the stool), petechiae, ecchymoses, and gum or mucous membrane bleeding
Stop* drug immediately.*
Intravenous (IV) protamine sulfate: 1 mg of protamine can reverse the effects of 100 units of heparin.
Anticoagulant Coumarins
Action: inhibit vitamin K–dependent clotting factors II, VII, IX, and X
Warfarin (Coumadin)
Warfarin (Coumadin)**
Most commonly prescribed oral anticoagulant
Inhibits vitamin K synthesis by bacteria in the gastrointestinal tract
Inhibits production of vitamin K–dependent clotting factors II, VII, IX, and X, which are normally synthesized in the liver
Final effect prevention of clot formation
Careful monitoring of the prothrombin time/international normalized ratio (PT/INR)
A normal INR (without warfarin) is 1.0, but a therapeutic INR (with warfarin) ranges from 2 to 3.5, depending on the indication for use of the drug (e.g., atrial fibrillation, thromboprevention, prosthetic heart valve).
Variations in certain genes, CYP2CP and VKORC1
Many drug interactions
Dietary considerations
Treatment: Toxic Effects of Warfarin
Discontinue the warfarin.**
May take 36 to 42 hours before the liver can resynthesize enough clotting factors to reverse the warfarin effects
Vitamin K1 (phytonadione) can hasten the return to normal coagulation.
High doses of *vitamin K (10 mg) given IV will reverse the anticoagulation within 6 hours.**
Caution: when vitamin K is given, warfarin resistance will occur for up to 7 days.
Severe bleeding: transfusions of human plasma or clotting factor concentrates.
Life-threatening bleeding from warfarin: Kcentra and Profiline
IV vitamin K: risk of anaphylaxis. Risk is diminished by diluting it and giving it over 30 minutes.
Anticoagulants: Factor Xa Drugs**
Fondaparinux (Arixtra)
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Edoxaban (Savaysa)
Betrixaban (Bevyxxa)
Inhibits thrombosis by its specific action against factor Xa
Anticoagulant Fondaparinux (Arixtra)
Selective inhibitor of factor Xa
Prophylaxis or treatment of DVT or PE**
Bleeding* is most common* and serious* adverse reaction.*
Anemia, wound drainage, hematoma, confusion, UTI, hypotension, dizziness, hypokalemia
Thrombocytopenia can occur
Should not be given for at least 6 to 8 hours after surgery
Use withcaution with warfarin
Subcutaneous injections
Anticoagulant Rivaroxaban (Xarelto)*
First oral factor Xa inhibitor
Used for prevention of strokes in patients with a-fib; post-op thromboprophylaxis with ortho surgeries; treatment of DVT and PE
Adverse reactions: Peripheral edema, dizziness, headache, bruising, diarrhea, hematuria, and bleeding
Anticoagulants Direct Thrombin Inhibitors
Action: inhibit thrombin (factor IIa)
Human antithrombin III (Thrombate)
Lepirudin (Refludan)
Argatroban (Argatroban)
Bivalirudin (Angiomax)
Dabigatran (Pradaxa)
Argatroban
Synthetic direct thrombin inhibitor
Used for active HIT and percutaneous coronary intervention procedures in patients at risk for HIT
Only given IV
Dabigatran (Pradaxa)
First oral direct thrombin inhibitor that is approved for prevention of strokes and thrombosis in patients with nonvalvular atrial fibrillation
Prodrug that becomes activated in the liver
Specifically, and reversibly binds to both free and clot-bound thrombin
Dose dependent on renal function
Adverse effects: bleeding, GI bleeding
No coagulation monitoring is required.
Idarucizumab (Praxbind)*
Specific dabigatran antidote**
Reverses the anticoagulant effects for dabigatran for emergency surgery or in life-threatening or uncontrolled bleeding
Anticoagulants: Contraindications
Drug allergy
Any acute bleeding process or high risk for such an occurrence.
Warfarin* is strongly *contraindicated in pregnancy.**
Other anticoagulants are rated in lower pregnancy categories (B or C).
LMWHs are contraindicated in patients with an indwelling epidural catheter risk of epidural hematoma.
Anticoagulants: Adverse Effects
Bleeding**
Risk increases with increased dosages.
May be localized or systemic
May also cause:
Heparin-induced thrombocytopenia**
Nausea, vomiting, abdominal cramps, thrombocytopenia, others
Drug Interactions: Anticoagulants**
Enzyme inhibition of metabolism
Displacement of the drug from inactive protein-binding sites
Decrease in vitamin K absorption or synthesis by the bacterial flora of the large intestines
Alteration in the platelet count or activity
Antiplatelet Drugs
Work to prevent platelet adhesion at the site of blood vessel injury
Platelets normally flow through blood vessels without adhering to their surfaces
Collagen from damaged vessels stimulate platelet adhesion
Prevent platelet adhesion
Aspirin*
Cilostazol (Pletal)
Clopidogrel (Plavix)*
Prasugrel (Effient)*
Treprostinil (Remodulin)
Abciximab (ReoPro)*
Eptifibatide (Integrilin)*
Tirofiban (Aggrastat)*
Anagrelide (Agrylin)
Dipyridamole (Persantine)*
Aspirin
Available in many combinations with other prescription and nonprescription drugs
Contraindicated for flulike symptoms in children and teenagers
Reye’s syndrome**
Aspirin and dipyridamole (Aggrenox)
Used for antiplatelet purposes
