Thrombolytic Therapy Summary, MCQs, and SAQ PDF

‫‪Thrombolytic‬‬ ‫‪therapy‬‬ ‫)‪ Summary. (Slides 2,3 and 4‬‬ ‫)‪ MCQs. (slide 5‬‬ ‫ال تطرق باب الماضي وتنتظر كثيرا فيضيع المستقبل‪،‬‬ ‫بل قف على ناصية الحلم و قاتل‪.‬‬ ‫)‪ SAQ. (slide 6‬‬ ...

‫‪Thrombolytic‬‬ ‫‪therapy‬‬ ‫)‪ Summary. (Slides 2,3 and 4‬‬ ‫)‪ MCQs. (slide 5‬‬ ‫ال تطرق باب الماضي وتنتظر كثيرا فيضيع المستقبل‪،‬‬ ‫بل قف على ناصية الحلم و قاتل‪.‬‬ ‫)‪ SAQ. (slide 6‬‬  Types of Thrombolytic agents: thrombolytic Drugs used to lyse already formed blood clot in clinical sittings where ischemia may be fatal. agents Mechanism of action of thrombolytic agents: They have common mechanism of action by stimulating activation of plasminogen via converting plasminogen to “pro-enzyme” to Fibrin specific Non-fibrin specific plasmin ”active enzyme” which leads to lysis of the insoluble fibrin into soluble derivatives. Activate mainly plasminogen Activate plasminogen in general located on the surface of the with no specificity to either free Types of thrombolytic agents: clot. plasminogen or the Thrombolytic agents produces there action by activation of This group includes: plasminogen located on the plasminogen. How ever, the activation of free plasminogen could - Alteplase. surface of a clot. lead to a serious side effects like bleeding and to prevent that we had - Reteplase. This group includes: to make a new drugs that is fibrin specific which activate - Tenecteplase. - Streptokinase. plasminogen located in an already formed colt with a little affinity to - Anistreplase. the free plasminogen. - Urokinase. 2  Non-fibrin specific agents Streptokinase Anistreplase Urokinase Acts indirectly by forming streptokinase-plasminogen It is an anisoylated plasminogen- An human enzyme that is secreted form the kidney which Mechanism of action complex which then convert plasminogen to active streptokinase complex and it’s a prodrug. is a direct plasminogen activator. plasmin. T ½ less than 20 min. Longer duration of action. Elimination t ½ 12 to 20 min. Pharmacokinetics Given as IV infusion. Greater clot selectivity. Given IV infeusion. and uses Used in arterial and venous thrombosis. Given as IV bolus. Used in acute massive pulmonary embolism. Antigenicity. Allergic reaction. Side effects and Bleeding Minimal fibrin selectivity. contraindications Should not be given to Expensive and to used nowadays. Patient with resent streptococcus infection. Previous administration of the drug. Fibrin specific agents Alteplase. Reteplase tenecteplase Another modified human t-PA. Is a recombinant form of human t-PA. A variant of recombinant t-PA. Prepared by recombinant DNA technology. Has a very short duration of action ”5 min”. It has longer duration of action (15 min). Has t ½ of more than 30 min. It’s usually administered as an intravenous Has enhanced fibrin specificity. Can be administered as a single IV bolus. bolus followed by an infusion. (60 mg IV bolus More fibrin-specific with longer duration of Given as 2 IV bolus injections of 10 U each. (NO INFUSION) then 40 mg infusion over 2 hours). action. Used in: Used in: Elevation of ST segment. ❖ Approved only to be used in acute myocardial Elevation of ST segment. infarction. Pulmonary embolism. 3 Pulmonary embolism  Fibrinolytic Inhibitors (Antiplasmins) inhibit plasminogen activation and thus inhibit fibrinolysis and promote clot stabilization. Drug Aminocaproic Acid & tranexamic acid Aprotinin Mechanism Competitive Inhibition of Plasminogen Activation. inhibits fibrinolysis by blocking the action of plasmin (Plasmin antagonist). Administration Orally. Orally or IV. ▪ Adjuvant therapy in hemophilia. Uses ▪ Postsurgical bleeding. ▪ Antidote for Fibrinolytic therapy-induced bleeding. These drugs work like antidotes for fibrinolytic drugs. Similar to Protamine (Antidote of the anticoagulant, heparin) or Vitamin K (Antidote of the oral anticoagulant warfarin). 4  MCQs 1. Which id considered ”fibrin selective” because it rapidly activate plasminogen that is 4. Which one of the following has the longest duration of action? bound to fibrin. A. Urokinase. A. Alteplase. B. Anistreplase. B. Fondaparinux. C. Streptokinase. C. Streptokinase. D. Tenecteplase. D. Urokinase. 5. Which of the following is a prodrug? 2. which of the following drugs is approved to be used in ST segment elevation with A. Urokinase. longer half-life? B. Streptokinase. A. Urokinase. C. Tenecteplase. B. Alteplase. D. Anistreplase. C. Reteplase. D. Anistreplase. 6. Which of the following is a relative contraindication for using thrombolytic agents? A. Major surgery within 2 weeks. 3. Streptokinase is a bacterial protein that is produced by: B. Pulmonary fat embolism after multiple fraction. A. Alpha-hemolytic streptococci. C. Severe uncontrolled hypertension. B. Beta-hemolytic streptococci. D. Active internal bleeding. C. Staphylococcus aureus. D. Escherichia coli. 7. Which one of the following can be used as antidote for warfarin? A. Aminocarpoic acid. 4. Which is can’t be used in patient with previous streptococcal infection? B. Aprotinin. A. Streptokinase. C. Protamine. 8. D B. Anistreplase. D. Vitamin K. 7. C 6. D C. Urokinase. 5. B D. A and B. 4. D 3. B 2. C 1. A Answers: 5 A 66-year-old man presents to the emergency room with 10/10 substernal chest pain, and pressure radiating into his jaw that has been occurring for the last six hours. He has a history of coronary artery disease, hypertension, diabetes, and dyslipidemia. After examination the ECG shows ST segment elevation. They diagnosed him with ST segment elevation Myocardial infarction. Q1: What is the drug of choice in this situation? All tissue plasminogen activator can be used specially tenecteplase because it’s approved to be used in such an acute situation. Q2: What is the mechanism of action of this drug? It’s a tissue plasminogen activator which is fibrin specific that works by activating plasminogen bound to the clot surface. Q3: What is the time frame should this drugs be administered in and why? 4 hours. Because the clot get resistant to the thrombolytic agents with aging and there will be a massive tissue damage which that can’t be reversible with the reperfusion. Q4: List 3 absolute contraindication of thrombolytic agents. Intracranial hemorrhage. Major surgery with 2 weeks. Active internal bleeding. Q5: Write ONE major advantage of fibrin specific thrombolytic over non-fibrin specific agents. Less affinity to systemic circulating plasminogen which makes the risk of bleeding much less. 6  Done by: Revised by: Abdulrahman Thekry Ghadah Almuhana Contact us : @Pharma436 [email protected]