Tenecteplase.pptx

Tenecteplase, the most fibrin specific agent, the prefer drug for AIS and ASTEMI especially if PPCI is not possible within 120min of STEMI diagnosis.

1. Tenecteplase : A Thrombolytic Agent with Life-Saving Potential Dr.Md.Jashim Uddin MD(cardiology) Phase-B Resident Dhaka Medical College.

2. Introduction Tenecteplase , a recombinant tissue plasminogen activator (rt-PA), has emerged as a powerful tool in the fight against cardiovascular emergencies. Its journey, from lab development to clinical application, holds significant milestones and advancements in treating stroke and heart attack.

3. Background History The development of Tenecteplase began in the 1980s when researchers were exploring ways to enhance the effectiveness and specificity of naturally occurring tPA. The aim was to overcome the limitations of first-generation fibrinolytics like streptokinase, which were associated with potential bleeding risks and a shorter half-life . Scientists in Frankfurt, Germany created Tenecteplase , a fibrin-specific binding drug with a longer lifespan in the body.

4. Clinical Trials and Approval: During the 1990s, Tenecteplase underwent extensive clinical trials to assess its effectiveness and safety in treating acute ischemic stroke (AIS) and ASTEMI . The GUSTO-III trial demonstrated the potential of treating ASTEMI within 3 hours.

5. Clinical Trials and Approval: Similarly, The ASSENT-2 trial established Tenecteplase as an effective treatment for AIS within 3 hours of symptom onset. After successful trials, Tenecteplase received FDA approval in 1996 for treating both AIS and ASTEMI patients. Cont.

6. Classification of Fibrinolytic According to the mechanism of action Plasminogen Activators (tPA & Alteplase) Plasminogen Cleavers (streptokinase and anistreplase) According to the origin Recombinant (tPA and reteplase) Non-recombinant (streptokinase and urokinase)

7. Classification of Fibrinolytics According to the generation First Generation (1950s-1960s): Streptokinase, Urokinase Second Generation (1980s-1990s): Alteplase (tPA), Anistreplase Third Generation (1990s-present): Reteplase, Tenecteplase

8. Decoding the Hero: What is Tenecteplase? Recombinant tissue plasminogen activator ( rtPA ) is a modified form of natural tPA that has a longer half-life and is more specific to fibrin. It dissolves blood clots by converting plasminogen to plasmin.

9. Mechanism of Tenecteplase Activates plasminogen, converting it to plasmin, an enzyme that breaks down fibrin Dissolves the clot, restoring blood flow

10. Pharmacokinetics Half-Life: 90-130 min Onset: 30 min Metabolism: Liver

11. Indications of Tenecteplase A Lifeline for Myocardial Infarction : Acute ST-segment elevation myocardial infarction (STEMI) within 3 hours of symptom onset Racing Against Time in Stroke : Acute ischemic stroke within 4.5 hours of symptom onset Beyond the Heart and Brain: Pulmonary embolism with hemodynamic instability

12. Time is Brain, Time is Heart: Understanding Tenecteplase, a Thrombolytic Hero Before Tenecteplase After Tenecteplase

13. Time is Brain, Time is Heart: Understanding Tenecteplase, a Thrombolytic Hero Before Tenecteplase After Tenecteplase

14. After Tenecteplase: Coronary angiography RAO cranial view showing normal coronary artery patency ( TIMI flow 2/3)

15. Myocardial Infarction The CAPTIM study demonstrated that Tenecteplase might be as effective as PCI in treating acute STEMI when administered in the prehospital setting. This strategy is ideal for STEMI patients who cannot receive PCI within 90 minutes after first medical contact.

16. Acute Ischemic Stroke There have been several randomized controlled trials conducted to compare Tenecteplase and alteplase for the treatment of acute ischemic stroke. The EXTEND-1A TNK trial showed that Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset .

17. Acute Ischemic Stroke The ATTEST trial compared 0.25 mg/kg of Tenecteplase and the standard dose of IV alteplase and found no differences in the outcomes. Tenecteplase noninferior to Alteplase for Ischemic Stroke: TRACE-2 The Canadian AcT trial found that Tenecteplase at 0.25mg/kg is non-inferior to alteplase in a large randomized open-label study. The 2019 AHA/ASA Guidelines provide the most current recommendations for Tenecteplase use in AIS.

18. Pulmonary Embolism Tenecteplase may be used for high-risk or massive pulmonary embolism (PE), although it is not FDA-approved for this use. The PEITHO study showed that Tenecteplase may improve hemodynamics in patients with acute PE with right heart strain, but it also increases the risk of intracranial haemorrhage compared to placebo (6.3% vs 1.2%).

19. Administration Tenecteplase is supplied as a powder in a 50 mg vial and must be mixed with sterile water to obtain a final concentration of 5 mg/ mL. Tenecteplase is administered as a single 5-second intravenous bolus at weight-based tiered doses of 0.25 mg/kg or 0.50 mg/kg with a maximum dose of 50 mg. The STREAM trial demonstrated a lower incidence of intracranial hemorrhage (ICH) in patients over 75 who received half doses of Tenecteplase (0.25 mg/kg) compared to the standard dose of 0.5 mg/kg.

20. Pre-hospital fibrinolysis Consider initiating fibrinolytic therapy in pre-hospital setting if trained medical or allied health staff are available to interpret ECG. A fibrin-specific agent (i.e. Tenecteplase , Alteplase, or Reteplase) is the preferred agent. The goal is to start fibrinolytic therapy within 10 min of the STEMI diagnosis . Fibrinolytic therapy should not be delayed for cardiac biomarker testing results.

21. Benefit and indication of fibrinolysis Fibrinolytic therapy is an important reperfusion strategy for STEMI patients presenting within 12 h of symptom onset when PPCI cannot be performed promptly; it prevents 30 early deaths per 1000 patients treated within 6 h of symptom onset . Successful reperfusion is generally associated with significant improvement in ischaemic symptoms, ≥50% ST-segment resolution, Reperfusion arrhythmias and haemodynamic stability.

22. Adverse Effects Bleeding*** Allergic reaction Cholesterol embolization Fever Nausea Vomiting

23. Risk factors of Intracerebral hemorrhage Age≥75 years Female sex African American race Prior stroke SBP≥160mmHg INR>4 PT>24sec

24. Contraindications

25. Contraindications

26. Monitoring Tenecteplase patients need regular neurologic and cardiovascular monitoring. Avoid nonessential handling and puncture. Check vital signs frequently for fever, hypotension, and tachycardia. Perform serial neurological exams to check for bleeding events. Assess clinical signs of anaphylaxis.

27. Toxicity Overdose of Tenecteplase results in serious bleeding. There is no antidote or reversal agent for Tenecteplase. In the event of bleeding, Tenecteplase must be immediately discontinued and supportive care provided

28. Brain Storming A 80-year-old man presents to a rural hospital with STEMI. He receives Tenecteplase and is getting transferred to a PCI facility for catheterization. What drug should he receive before transfer? A. Clopidogrel 75 mg B. Clopidogrel 300 mg C. Clopidogrel 600 mg D. Prasugrel 10 mg

29. Take Home Messages Tenecteplase is a valuable thrombolytic agent for various conditions It’s faster clot dissolution & single-dose administration offer advantage Careful patient selection and monitoring are essential for safe and effective use.

30. References Braunwald's Heart Disease-12 th Hurst`s the heart-15 th Practical Cardiovascular Medicine-2 nd The Washington Manual of Cardiology Subspecialty Consult-4 th ESC STEMI guidelines-2017 & ESC ACS guidelines-2023 Medscape Bach KT, Lui F. Tenecteplase. [Updated 2023 Jun 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK592420/

31. Thank You All