Anticoagulants Flashcards
(41 cards)
Anticoagulants
Heparin, Enoxaparin, Lepirudin, Dabigatran, Rivaroxaban, Warfarin
Fibrinolytics
Streptokinase, Alteplase
Antithrombotics
Aspirin, Clopidogrel, Vorapaxar, Abciximab
Thrombogenesis
Immediate hemostatic response of a damaged vessel, Vasospasm
Within seconds, Platelets stick to the exposed collagen of the damaged endothelium, Platelet adhesion
& then to each other, Platelet aggregation
Platelet plug quickly arrests bleeding
Must be reinforced by fibrin for long-term effectiveness
White thrombus
Forms in high-pressure arteries & decreases arterial flow, Stasis triggers fibrin formation → Stroke, MI
Red thrombus
Can form around a white thrombus or in low-pressure veins, Platelets form a long tail consisting of a fibrin network in which RBC are enmeshed → DVT → PE
Blood Coagulation
Blood coagulates by the transformation of soluble fibrinogen → insoluble fibrin
At each step of this cascade, a clotting factor, i.e., zymogen undergoes limited proteolysis & becomes an active protease, VII is activated to VIIa
Protease activates the next clotting factor, Until a solid fibrin clot is formed
Regulation of Coagulation & Fibrinolysis
Blood coagulation must be confined to the smallest possible area to achieve local hemostasis in response to bleeding, Without causing disseminated coagulation or impaired blood flow
Blood contains ________ that rapidly inactivate the coagulation proteins as they leave the site of injury, e.g.,
protease inhibitors; antithrombin
Critical step in fibrinolysis
Conversion of inactive plasminogen into the proteolytic enzyme plasmin
Heparin
about 50 monosaccharides in a chain
Greatly increases the rate of activity of antithrombin, Heparin (-) binds with antithrombin (+) which inhibits serine protease clotting enzymes
Heparin inhibits
Inhibits clotting factors IIa (thrombin) & Xa, (IXa, XIa, & XIIa)
Heparin uses
Thrombosis/Embolism: Prophylaxis (e.g., after major surgery) & active Treatment (e.g., PE, DVT)
Disseminated Intravascular Coagulation (DIC)
Heparin side effects
Hemorrhage (<10%) anywhere in the body (e.g., GI)
Allergy (chills, fever, urticaria)
Thrombocytopenia (HIT) (Heparin induces antibodies which destroy platelets, also attack the lining of blood vessels which can trigger a coagulation cascade
HIT can cause stroke & other thrombotic complications which can be life threatening)
Heparin antidote/Hep’s activity measured by
protamine; aPTT
Heparin drug interactions
Cephalosporins, penicillins, NSAIDs (ex aspirin)
Enoxaparin mech of action
(smaller version of heparin) more sensitive for Xa than IIa
Enoxaparin therapuetic uses
DVT prophylaxis
DVT Tx (+/- PE)
Unstable angina/Non-Q-wave MI
Enoxaparin side effects/drug interactions
similar effects to heparin, also hematomas; interacts w/ same drugs as heparin
Rivaroxaban mech of action; thera uses
Direct Xa inhibitor; Atrial fibrillation: Prevent → Stroke, Systemic embolism
Prophylaxis of DVT: Knee, Hip replacement
Rivaroxaban side effects and pharmacodynamics
Hemorrhage: Spinal or Epidural anesthesia or puncture; CYP3A4, P-gp
Severe renal & hepatic impairment (↑AUC)
Lepirudin; thera use
Polypeptide analog of hirudin → Hirudo medicinalis (leech); Heparin-induced thrombocytopenia
Lepirudin, Argatroban, Dabigatran mech of act
Inhibits thrombin (IIa) by binding to it (1:1 stoichiometry)
Lepirudin side efect; pharmocokinectics
Allergy- Antibody inhibition b/c of yeast expression; Adjust dose with hepatic function