Download Free Medical Antithrombotic Anticoagulants and Thrombolytic agents PowerPoint Presentation

Antithrombotic Anticoagulants and Thrombolytic agents PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Antithrombotic Anticoagulants and Thrombolytic agents.

Tags : Antithrombotic Anticoagulants, Thrombolytic agents, Anti-coagulants, Anti-thrombotics, Anti-platelets, Thrombolytic, Fibrinolytics, Coagulation Drugs

Published on : Nov 06, 2020 | Views : 3915 | Downloads : 28

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Antithrombotic Anticoagulants and Thrombolytic agents Dr. Mohammed Samir Hussein BCs of Pharmaceutical Science MDs of Clinical Pharmacology
Slide 2-

TERMINOLOGIES Anti-coagulants : Drugs used to reduce the coagulability of blood. Anti-thrombotics (Anti-platelets) : Drugs which interfere with platelet functions (Thrombocytes – Platelets). Thrombolytic (Fibrinolytics) : Drugs used to lyse thrombin clot (reduces blood clots)
Slide 3-

HEMOSTASIS Hemo=Blood Stasis=Stop or Still Hemostasis is a complex process involving a number of clotting factors that are activated in a series of sequential steps, or cascade, to prevent or stop bleeding. 1. Vascular phase 2. Platelet phase 3. Coagulation phase 4. Fibrinolytic phase PHASES OF HEMOSTASIS
Slide 4-

HEMOSTASIS
Slide 5-

HEMOSTASIS Response to vessel injury 1. Vasoconstriction to reduce blood flow 2. Platelet plug formation (von willebrand factor binds damaged vessel and platelets) 3. Activation of clotting cascade with generation of fibrin clot formation 4. Fibrinolysis (clot breakdown)
Slide 6-

VASCULAR PHASE - When a blood vessel is damaged, vasoconstriction results - Cutting or damaging blood vessels leads to vascular spasm of the smooth muscle in the vessel wall. - This produces a vasoconstriction which will slow or even stop blood flow. - This response will last up to 30 minutes and is localized to the damaged area.
Slide 7-

PLATELET PHASE - Platelets adhere to damaged surface and form a temporary plug - Damaged endothelial cells lining the blood vessel release von Willebrand's Factor. This substance makes the surfaces of the endothelial cells "sticky” & to close called as Platelet Adhesion. - The platelets that adhere to the vessel walls now begin to secrete Adenosine diphosphate (ADP) which is released from "stuck" platelets to aggregate nearby free platelets. This aggregation of platelets leads to the formation of a platelet plug.
Slide 8-

COAGULATION PHASE - involves the formation of the insoluble protein Fibrin from the plasma protein Fibrinogen through the action of enzyme Thrombin. - Fibrin forms a network of fibers which traps blood cells and platelets forming a thrombus or clot. - This process depends on the presence in the blood of 11 different clotting factors (proteins) and calcium (Factor IV). Ultimately, these factors will generate production of Prothrombin Activator (Factor X). - There are two pathways leading to the formation of the thrombus; the Extrinsic Pathway and the Intrinsic Pathway.
Slide 9-

COAGULATION PHASE
Slide 10-

FIBRINOLYTIC PHASE - The overall process involves the formation of the insoluble protein Fibrin from the plasma protein Fibrinogen through the action of enzyme Thrombin. - Fibrin forms a network of fibers which traps blood cells and platelets forming a thrombus or clot. - This process depends on the presence in the blood of 11 different clotting factors (proteins) and calcium (Factor IV). Ultimately, these factors will generate the production of Prothrombin Activator (Factor X). - There are two pathways leading to the formation of the thrombus; the Extrinsic Pathway and the Intrinsic Pathway.
Slide 11-

NATURAL ANTICOAGULANT MECHANISMS Antithrombin (AT) : Inactivates factors like IIa, IXa, Xa, XIa & XIIa Endothelial Prostacyclin (PGI2): inhibits thrombus formation Endogenous anticoagulants: protein C and S inactivates factors like Va & VIIIa THROMBUS FORMATION White thrombus: forms in arteries by adherence of platelets. Red thrombus: forms around a white thrombus or in low-pressure veins. Consists of a fibrin network in which red cells are trapped. The platelets dominate the arterial thrombus and the fibrin tail dominates the venous thrombus
Slide 12-

DISSEMINATED INTRAVASCULAR COAGULATION (DIC) There are inhibitors that inactivate the coagulation proteins as they escape from the site of vessel injury. They include: α1-antiprotease, α2-macroglobulin, α2-antiplasmin, and antithrombin. If this system is working, Disseminated Intravascular Coagulation (DIC) occurs DIC is seen in: massive tissue injury, abruptio placentae, or bacterial sepsis
Slide 13-

CLASSIFICATION OF ANTICOAGULANTS ANTICOAGULANT DRUGS Parenteral: - Indirect thrombin inhibitors Heparin- Low molecular weight heparin- Fondaparinux- Danaparoid- Lepirudin - Direct thrombin inhibitors Hirudin – Bivalirudin - Argatroban Oral: Warfarin Rivaroxaban Apixaban Dabigatran Melagatran
Slide 14-

Parenteral Anticoagulant Drugs
Slide 15-

Parenteral Indirect thrombin inhibitors HEPARIN Heparin activity depends on endogenous anticoagulant – Antithrombin (ATIII), which inhibits thrombin (II), VIIa, IXa, Xa, XIa and XIIa Heparin accelerates the reaction 1000 fold. Heparins are NOT direct thrombin inhibitors MOA: Heparins (Unfractionated Heparin (UFH), low molecular weight heparin (LMWH) & fondaparinux) prevent thrombin formation by binding to clotting factors in the circulation. Drug of choice for pregnant women
Slide 16-

Heparin Mechanism of Action
Slide 17-

LMW HEPARIN Examples: Enoxaparin, Dalteparin & Tinzaparin Uses: To prevent and treat all types of thromboses and emboli Prophylactically to prevent blood clotting in surgery of heart, blood vessel, blood transfusion In patients with disseminated intravascular coagulation (DIC) and in hemodialysis Drug of choice for sudden arterial occlusion Superior over coumarin drugs in preventing pulmonary complications in cases of thrombophlebitis (even during pregnancy) When rapid anticoagulation is needed before oral anticoagulants
Slide 18-

Fondaparinux Synthetic pentasaccharide, analog of antithrombin III binding subunits of heparin It is the lowest molecular weight heparin Inactivates only factor Xa Only parenteral use, s.c.- 100% bioavailabilty, t1/2 = 15-17hrs Used in preventation and treatment of venous thromboembolism Could be used for Heparin-induced thrombocytopenia (HIT) patients Longer acting analogue: Idraparinux – one s.c inj/week
Slide 19-

Heparin Toxicity The major adverse effect is bleeding. Elderly women and patients with renal failure are more prone to hemorrhage. It causes transient thrombocytopenia in 25% of patients. The heparin-induced antibody, causes platelet aggregation and thromboembolism.
Slide 20-

Heparin Contraindications Hypersensitivity to the drug. Active bleeding & hemophilia. Thrombocytopenia & purpura. Severe hypertension, intracranial hemorrhage. Infective endocarditis & active tuberculosis. Ulcerative lesions of the GI tract. Threatened abortion. Visceral carcinoma & advanced hepatic or renal disease. Recent surgery of the brain, spinal cord or eye. Patients undergoing lumbar puncture or regional anesthesia.
Slide 21-

Reversal Of Heparin action Antidote: protamine sulphate Complete neutralization 100 units of heparin + 1mg of protamine SO4 Incomplete neutralization with LMW heparin Does not reverse fondaparinux Partially neutralizes enoxaparin
Slide 22-

Parenteral Direct thrombin inhibitors HIRUDIN MOA: Specific irreversible thrombin inhibitor from medicinal leeches (Hirudo medicinalis) saliva. Recombinant form is Lepirudin. Little effects on platelets / bleeding time. Uses: Heparin induced thrombocytopenia (HIT). Great caution in renal insufficiency (NO antidote available) Adverse effects: Increased anticoagulant effect due to Ab against thrombin-lepirudin complex's form long term use. Life threatening anaphylactic reactions on re-exposure.
Slide 23-

Parenteral Direct thrombin inhibitors Bivalirudin Synthetic hirudin-like compound More rapid onset, short duration of action than hirudin Only i.v. use – percutaneous coronary angioplasty Elimination – independent of kidney Argatroban Synthetic thrombin inhibitor Short half-life, influenced by liver diseases, Elimination – independent of kidney Used in i.v. for HIT Dabigatran The only orally active direct thrombin inhibitor. Dabigatran is only approved for the prevention of stroke in nonvalvular atrial fibrillation; it is not approved for the treatment of acute DVT Antidot: Idarucizumab
Slide 24-

Parenteral Direct thrombin inhibitors Bivalirudin Synthetic hirudin-like compound More rapid onset, short duration of action than hirudin Only i.v. use – percutaneous coronary angioplasty Elimination – independent of kidney Argatroban Synthetic thrombin inhibitor Short half-life, influenced by liver diseases, Elimination – independent of kidney Used in i.v. for HIT Dabigatran The only orally active direct thrombin inhibitor. Dabigatran is only approved for the prevention of stroke in nonvalvular atrial fibrillation; it is not approved for the treatment of acute DVT Antidot: Idarucizumab
Slide 25-

ORAL ANTICOAGULANT DRUGS
Slide 26-

WARFARIN MOA: It prevents activation of vitamin K leading to blocking synthesis of prothrombin (II), VII, IX, and X as well as the anticoagulant proteins C and S There is an 8 to 12 hour delay in its action. Inhibition of coagulation is dependent on the half-lives of inhibited factors. Warfarin does not require dosage adjustment in renal dysfunction. The INR is monitored and dosage adjustments are made on the basis of this information.
Slide 27-

WARFARIN Found in spoiled sweet clover silage causing bleeding in cattle. Warfarin Uses: For prophylaxis and treatment of Deep Vein Thrombosis and pulmonary thromboembolism. Prophylaxis of thromboembolism associated with chronic atrial fibrillation or Myocardial Infarction (MI).
Slide 28-

Warfarin Drug Interaction The most serious are those that increase the risk of bleeding and include: Phenylbutazone, also inhibits platelet function and may induce peptic ulcer. Trimethoprim-sulfamethoxazole (increase warfarin activity). Aspirin, hepatic disease, and hyperthyroidism. The third-generation cephalosporins. Heparin. Warfarin Toxicity Warfarin crosses the placenta readily and can cause a hemorrhagic disorder in the fetus. The drug can also cause abnormal bone formation. Warfarin should NEVER be administered during pregnancy.
Slide 29-

FIBRINOLYTIC DRUGS
Slide 30-

FIBRINOLYTIC DRUGS Fibrinolysis is achieved by conversion of plasminogen to plasmin (which is then able to degrade the fibrin present in clots). Injured cells release activators of plasminogen. Plasmin limits thrombosis by digestion of fibrin. Fibrinolysis is therapeutic for thrombotic disease. Heparin and the oral anticoagulant drugs do not affect the fibrinolytic mechanism. Their primary uses is: to break apart pulmonary emboli and coronary artery thromboses during acute MI.
Slide 31-

FIBRINOLYTIC DRUGS The drugs include: Streptokinase & Urokinase (IV) Tissue plasminogen activator (t-PA) Alteplase (IV) Reteplase (IV) Tenecteplase (IV) Indications of Fibrinolytic Drugs: Multiple pulmonary emboli Central deep venous thrombosis Acute myocardial infarction Contraindications: Active bleeding or high risk for bleeding is contraindication for use.
Slide 32-

ANTIPLATELET AGENTS The 3 subclasses of antiplatelet agents are: A. Nonselective COX inhibitors B. Adenosine diphosphate (ADP) receptor blockers C. Glycoprotein IIb/IIIa Inhibitors
Slide 33-

A. Nonselective COX inhibitors MOA: Aspirin irreversibly blocks a step in this pathway, preventing the synthesis of thromboxane A2 by blocking cyclooxygenase enzyme. Therefore, thromboxane will not be active until new platelets are formed. Example: Aspirin
Slide 34-

B. ADP receptor blockers MOA: Adenosine diphosphate (ADP) normally binds to these membrane receptors in platelets, resulting in the coagulation of the platelets. The drugs in this class block the receptor so that ADP cannot bind. Examples: Clopidogrel Anagrelide Clinical uses: Indicated for the prophylaxis of MI, thromboembolic stroke, and vascular death. More effective than aspirin. Anagrelide indicated for the treatment of essential thrombocythemia
Slide 35-

C. Glycoprotein IIb/IIIa Inhibitors MOA: Glycoprotein IIb/IIIa receptors are targets for fibrinogen and von Willebrand factors that allows platelets to adhere to each other & to foreign surfaces. Drugs occupying these receptors glycoprotein IIb/IIIa inhibitors prevents platelet aggregation. Examples: Abciximab; Eptifibatide; Tirofiban Clinical uses: Abciximab for Adjunct therapy (to aspirin and heparin for prevention of acute cardiac vessel ischemic complications). Management of unstable angina.
Slide 36-

DRUGS USED IN BLEEDING DISORDERS AND FIBRINOLYTIC INHIBITORS
Slide 37-

FIBRINOLYTIC INHIBITORS MOA: Inhibit plasminogen activation. Examples: Aminocaproic acid Tranexamic acid Clinical uses: Adjunctive therapy in hemophilia. Therapy for bleeding from fibrinolytic drugs. Antidote for overdose of fibrinolytic drugs. Adverse effect: Intravascular thrombosis. Should not be used in DIC or bleeding of the kidney and urethras.
Slide 38-

FIBRINOLYTIC INHIBITORS Serine Protease Inhibitor – Aprotinin MOA: Aprotinin inhibits fibrinolysis by free plasmin. Also inhibits the plasmin-streptokinase complex in patients who have received it Uses: In cardiopulmonary bypass surgery to reduce blood loss. Approved for use in patients undergoing coronary artery bypass grafting
Slide 39-

FIBRINOLYTIC INHIBITORS PLASMA FRACTIONS Spontaneous bleeding occurs when factor activity is less than 5–10% of normal Factor VIII deficiency (classic hemophilia) & factor IX deficiency (Christmas disease) are the most common heritable coagulation defects Cryoprecipitate is used to treat fibrinogen defects in DIC & liver disease Desmopressin acetate increases the factor VIII activity and is used for minor surgery (tooth extraction)
Slide 40-

FIBRINOLYTIC INHIBITORS VITAMIN K Vitamin K has biologic activity upon prothrombin and factors VII, IX, and X by participating in their postribosomal modification. Vitamin K is a fat-soluble substance found primarily in leafy green vegetables Vitamin K is currently administered to all newborns to prevent the hemorrhagic disease of vitamin K deficiency, which is especially common in premature infants Vitamin K takes about 24 hours to see a reduction in the INR. This is due to the time required for the body to synthesize new coagulation factors.
Slide 41-

THANK YOU FOR YOUR ATTENTION