Views: 32 Author: Unibest Digital Publish Time: 2024-12-17 Origin: Unibest Digital
Thrombolytic drugs play a crucial role in treating various venous and arterial thromboembolic conditions, particularly acute myocardial infarction. These agents, primarily plasmin activators, convert plasminogen to plasmin, which dissolves insoluble fibrin clots through its fibrinolytic action.
- Non-fibrin-specific agents: streptokinase and urokinase
- Fibrin-specific agents: tissue plasminogen activator (tPA)
- Next-generation agents: reteplase, tenecteplase, monteplase, lanoteplase, pamiteplase, desmoteplase (Bat-PA), and chimeric thrombolytics
- Molecular weight: 39 kDa
- Composition: 355 amino acids (starting with serine, ending with proline)
- Structure: Single-chain deletion mutant of tPA with nine disulfide bonds
- Retained domains: Kringle-2 and serine protease (activity-related)
- Deleted domains: Kringle-1, finger, and epidermal growth factor (EGF)
Tissue plasminogen activator and reteplase schematic figure. src: Mohammadi, E., Seyedhosseini-Ghaheh, H., Mahnam, K., Jahanian-Najafabadi, A. & Mir Mohammad Sadeghi, H. Reteplase: Structure, Function, and Production. Adv Biomed Res 8, 19 (2019).
- Binding to fibrin-rich clots via the Kringle-2 domain
- Cleaving the Arg/Val bond in plasminogen to form plasmin (via the protease domain)
- Degrading the fibrin matrix of the thrombus through plasmin action
Thrombolytic action of plasminogen activators. src: Mohammadi, E., Seyedhosseini-Ghaheh, H., Mahnam, K., Jahanian-Najafabadi, A. & Mir Mohammad Sadeghi, H. Reteplase: Structure, Function, and Production. Adv Biomed Res 8, 19 (2019).
Key advantages over tPA include:
- Extended plasma half-life
- Reduced fibrin specificity
- Enhanced ability to penetrate blood clots
- Acute myocardial infarction
- Cerebral infarction
- Pulmonary embolism
- Deep vein thrombosis
- Significant reduction in post-infarction transient ischemia burden
- Lower early and late mortality rates
- Improved patient recovery