LECTURE 12 ANTICOAGULANTS-4.pdf

Drugs for Circulatory Disorders REAGAN KABUKA (B.PHARM, MPH) Circulatory Disorders Anticoagulants & antiplatelets (antithrombotics), thrombolytics Anticoagulants - prevent formation of clots that inhibit circulation Antiplatelets - prevent platelet aggreg...

Drugs for Circulatory Disorders REAGAN KABUKA (B.PHARM, MPH) Circulatory Disorders Anticoagulants & antiplatelets (antithrombotics), thrombolytics Anticoagulants - prevent formation of clots that inhibit circulation Antiplatelets - prevent platelet aggregation Thrombolytics- dissolve formed clots  Thrombus Formation Clot is a Thrombus formed in an arterial or venous vessel thrombophlebitis - Both inflammation and clots are present Some thrombus can be superficial but it’s the DVT that’s a concern  embolism to lungs Thrombus Formation Arterial formation- begins with platelet adhesion to arterial vessel wall  Adenosine diphosphate (ADP) released from platelets  more platelet aggregation  Blood flow inhibited  fibrin, platelets & RBC’s surround clot  build up of size structure  occludes blood vessels  tissue ischemia The result of Arterial Thrombus is localized tissue injury from lack of perfusion Thrombus Formation Venous Formation - Usually from slow blood flow - Stagnation of the blood flow initiate the coagulation cascade production of fibrin  enmeshes RBC’s & platelets to form the thrombus. Venous thrombus has a long tail that can break off to produce an embolus. These travel to faraway sites then lodge  in lung (capillary level)  inadequate O2 & CO2 exchange occur (ie. pulmonary embolism & cerebral embolism)  Thrombus Formation Hemostasis is the normal homeostatic process of blood clotting. Clotting proteins normally circulate in an inactive state & must be activated to form a fibrin clot. When there is a trigger, the clotting cascade is activated Blood vessel injured  platelets adhering to site of injury  release of ADP a platelet plug - is example of Intrinsic clotting path Tissue injury (outside blood vessels) = extrinsic pathway activated Thrombus Formation Risk Factors for Deep Vein Thrombophlebitis and Thromboembolism Three factors increasing risk 1) Stasis of venous flow, 2) Damage of the endothelium(inner lining of vein) 3) Hypercoagulability of the blood RISK FACTORS History of thrombophlebitis Abdominal & pelvic surgery Obesity, neoplasms (lung), CHF, Advanced age Vasospasm Prolonged immobility (bed-rest, long trip spinal cord injury, FX. hip) CVA MI PG, post partum, Estrogen TX (oral contraceptives), trauma, Sepsis, Hypercoagulable states (Polycythemia, severe anemias, Dehydration or malnutrition), Antithrombin III deficiency Anticoagulants Inhibit clot formation - Do NOT dissolve clots already formed, but prophylactically prevent new clots Used in clients with venous and arterial disorders that put them at increased risk of clot formation Venous = DVT & Pulmonary embolism Arterial = Coronary thrombosis (MI), artificial heart valves, CVA Heparin A natural substance in the liver that prevents clot formation Primary use is to prevent venous thrombosis that can lead to pulmonary embolism (PE) or stroke Combines with antithrombin III  inactivates thrombin and other clotting factors then the conversion of fibrinogen to fibrin doesn’t occur so the clot is prevented Poorly absorbed through GI mucosa - given SQ & IV Prolongs clotting time - partial thromboplastin time (PTT) & activated partial thromboplastin time (aPTT) - both blood tests are monitored during therapy Heparin Use - DVT, PE, & CVA, Clients with heart valve prosthesis, during CV surgery, post operative, during hemodialysis * Low doses = prophylactically to prevent DVT * Full doses = treats a thromboembolism & promotes neutralization of activated clotting factors = prevents extension of thrombi & formation of emboli * If started shortly after formation of a thrombus - heparin will also prevent it from developing into an insoluble stable thrombus = reduced tissue damage Heparin Side effects - Decreased platelet count (thrombocytopenia), hemorrhage - give protamine sulfate IV (an anticoagulant antagonist) Drug Interactions - Increased effects with ASA, NSAIDs, thrombolytics, decreased effect with NTG LMWH Low Molecular Weight Heparins (LMWHs) - recently introduced to prevent venous thromboembolism Binds to Antithrombin III which inhibits the synthesis of factor Xa & formation of thrombin - Enoxaparin & dalteparin - more stable dose, lower risk of bleeding, frequent laboratory monitoring not required LMWHs Can be administered at home Administered less frequently Available in prefilled syringes with attached needles Bleeding less likely to occur DI - caution client not to take antiplatelet drugs (ASA) during therapy Warfarin Action - Inhibits activity of vitamin K required for the activation of clotting factors II, VII, IX, & X. Blocking these factors prevents clot formation Use - prophylactically to prevent venous thrombosis, A. fibrillation, PE, coronary occlusion, thrombophlebitis Prolongs clotting time & is monitored by the laboratory blood tests Prothrombin time (PT) & International normalized ratio (INR) - usually before administering the next dose until therapeutic levels are reached INR is 1.3 - 2.0 therapeutic levels on Warfarin = 2.0 - 3.0  Warfarin INR is replacing the PT  INR more accurate. Need higher levels for prosthetic heart valves, cardiac valvular disease and recurrent emboli. PT not consistent lab to lab or reagents used. PT is 1.5 – 2 times the reference value to be therapeutic Regular monitoring is required for the duration of drug therapy Warfarin is well absorbed through the G.I. tract. Food decreases absorption TSOACs Target-specific oral anticoagulants (TSOACs). dabigatran, rivaroxaban, and apixaban Dabigatran- direct thrombin inhibitor Rivaroxaban, apixaban- direct factor Xa inhibitor TSOACs have several advantages: fixed-dose oral dosing, fewer drug–drug and dietary interactions, no need for routine coagulation monitoring Challenges- no proven antidotes yet, half-life shorter than warfarin, cleared by the kidney Antiplatelet Drugs Aspirin, Clopidogrel, Dipyridamole Action: To prevent thrombosis in the arteries by suppressing platelet aggregation Use: Prevention of MI/stroke Thrombolytics Thromboembolism - Occlusion of an artery or vein caused by a thrombus or embolus - results in ischemia that causes necrosis of the tissue - it takes about 1 to 2 weeks for the blood clot to disintegrate by natural fibrinolytic mechanisms - if new thrombus dissolved quicker damage minimized & blood flow restored faster  purpose of therapy Thrombolytics promote fibrinolytic mechanism (convert plasminogen to plasmin & destroys the fibrin in the clot) - administering a thrombolytic drug = clot disintegrates Thrombolytics Streptokinase, Urokinase, Tissue plasminogen activator (t- PA) Streptokinase & Urokinase are enzymes that act to convert plasminogen to plasmin t-PA and APSAC activate plasminogen by acting specifically on clot Thrombolytics All 3 drugs induce fibrinolysis (fibrin breakdown) Side effects: hemorrhage, allergic reactions (anaphylaxis) & vascular collapse causing hypotension THANK YOU!!!