Pharmacology
Summary
Thrombolytics, often referred to as fibrinolytic agents, are designed to break down blood clots. When blood clots form, platelets come together to produce a platelet plug, further reinforced by a fibrin mesh. The primary objective of fibrinolytic therapy is to dissolve these thrombi by targeting the fibrin mesh. The drugs utilized for this are the tissue plasminogen activator (tPA) and streptokinase, which facilitate the conversion of plasminogen into plasmin. Plasmin targets and digest fibrin, which helps to dissolve clots.
Thrombolytics act on the common pathway, resulting in disruption of both the intrinsic and extrinsic coagulation pathways. This leads to extended PT and PTT times. As fibrinolysis progresses, markers such as D-dimer are released into the circulation, serving as indicators of ongoing thrombosis. In emergencies like ischemic strokes, acute DVTs and PEs, or acute myocardial infarctions, fibrinolytics are crucial as they dissolve clots and restore blood supply. However, they must be used within 3-4.5 hrs of clot formation, and can increase the risk of bleeding, especially critical events like intracranial hemorrhages. Furthermore, fibrinolytic therapy is contraindicated for patients with recent head traumas, prior intracranial surgeries, severe hypertension, visible hemorrhage on CT scans, or any form of active internal bleeding.
Lesson Outline
Don't stop here!
Get access to 133 more Pharmacology lessons & 13 more medical school learning courses with one subscription!
FAQs
Thrombolytics, often termed fibrinolytic agents, are drugs designed to dissolve harmful blood clots within vessels, thereby restoring blood flow and averting tissue damage. Their primary mechanism involves catalyzing fibrinolysis, a process that breaks down the protein fibrin, a major component in blood clots.
Tissue plasminogen activator (tPA) is an serine protease present in endothelial cells. It promotes fibrinolysis by transforming plasminogen into plasmin. Plasmin then targets and digests fibrin, dismantling the clot. Some thrombolytic drugs such as alteplase, reteplase, and tenecteplase, are synthetic versions of tPA.
Various thrombolytic agents find use in the clinical realm. alteplase, reteplase, and tenecteplase, all recombinant tPA variants, are favored due to their clot-targeted action. On the other hand, streptokinase, derived from bacteria, is less clot-specific, potentially causing wider systemic fibrinolysis. The agent chosen hinges on the clinical context and individual patient considerations.
Intracranial hemorrhage is a serious potential complication of thrombolytic therapy. By breaking down clots, thrombolytics also increase the risk of bleeding, including the risk of intracranial hemorrhage. Therefore, it is essential to balance the benefits of clot breakdown with the risk of severe bleeding when considering thrombolytics in certain patient populations..
Aminocaproic acid is a potent inhibitor of fibrinolysis. It binds to plasminogen and blocks its conversion to plasmin, the enzyme responsible for degrading fibrin clots. In situations where excessive fibrinolysis is a problem, such as certain bleeding disorders, aminocaproic acid can be used to mitigate bleeding.
