Fibrinolytic agent

Local intra-arterial thrombolysis (lAT) has several theoretical advantages over IV thrombolysis. For instance, by using coaxial microcatheter techniques, the occluded intracranial vessel is directly accessible and the fibrinolytic agent can be infused directly into the thrombus. This permits a smaller dose of fibrinolytic agent to reach a higher local concentration than that reached by systemic infusion, and ideally it allows for more complete recanalization with lower total doses of thrombolytic. With the smaller dose, complications from systemic fibrinolytic effects, including ICH, can theoretically be reduced. 

Fibrinolytic agents have prothrombotic properties as well. The plasmin generated by thrombolysis leads to the production of thrombin, which is a potent platelet activator and converts fibrinogen to fibrin. Indeed, studies have shown early reocclusion in as many as 17% of the patients treated with lAT and 34% of the patients treated with IV rt-PA. Therefore, a strong rationale exists for the adjuvant use of antithrombotic agents. 

Early reperfusion therapy with either primary percutaneous coronary intervention or administration of a fibrinolytic agent within 3 hours of symptom onset is the recommended therapy for patients presenting with ST-segment elevation acute coronary syndrome. 

An exogenous plasminogen activator that has been used in clinical trials as a fibrinolytic agent is the 53-kDa single-chain polypeptide called streptokinase (SK). It forms a complex with plasminogen on an equimolar basis. The resulting 156-kDa streptokinase-plasminogen complex (plg-SK) converts Glu-plasmino-gen to Glu-plasmin (41). 

A fibrinolytic agent is indicated in patients with STE ACS presenting within 12 hours ofthe onset of chest discomfort who have at least 1 mm of STE in two or more contiguous ECG leads or a new left bundle-branch... 

If a fibrinolytic agent is administered, UFH is given concomitantly with alteplase, reteplase, and tenecteplase, but UFH is not administered with streptokinase because no benefit of combined therapy has been demonstrated. Rates of reinfarction are higher if UFH is not given with the fibrin-selective agents. 

Although most of the enzyme-based drugs are inhibitors of enzymes, a number of enzyme preparations have also been developed as drugs for the treatment of a number of diseases. The development of enzymes as therapeutics has been made easier due to the advances in biotechnology. Most successful example of enzyme therapy includes various preparations of plasminogen activators (thrombolytic or fibrinolytic agents) such as a bacterial protein streptokinase and two plasminogen activators... 

Fibrinolytic agents. Intravenous fibrinolysis has been assessed in at least six major international studies. Streptokinase has been abandoned (haemorrhage) while rt-PA is given in the 3-6 hour therapeutic window (secondary analysis disclosed significant results on the RANKIN scale at 3 months (NINDS) and at 3 months (ECASS II)). 

Ellis K, Brener S. New fibrinolytic agents for MI as effective as current agents, but easier to administer. Cleve Clin J Med. 2004 71 20, 23-25, 29-30. 

The cost of fibrinolytic agents is considerable streptokinase costs about US 100, and rt-PA and its mutants about US 2000, However, these agents have different early (90 minutes) recanalization rates over 50% for front-loaded tissue rt-PA versus only 30% to 35% for streptokinase. Since early patency is correlated with early survival (12), the initial cost of the thrombolytic drug alone is not important. Patients who present early with a large myocardial infarction benefit more from a drug with a high early patency rate than patients presenting late with a small myocardial infarction. 

Denda et al. previously demonstrated40 that tran.s-4-aminomethyl cyclohexane carboxylic acid (/-AMCIIA), an anti-fibrinolytic agent that activates plasminogen, improved the barrier homeostasis and whole skin condition. After barrier disruption, proteolytic activity in the epidermis increased within 1 to 2 h. This increase was inhibited by t-AMCHA. Topical application of r-AMCHA or... 

Denda, M., Kitamura, K., Elias, P.M., and Feingold, K.R. (1997) 7>ares -4-(aminomethyl) cyclohexane carboxylic acid (T-AMCHA), an anti-fibrinolytic agent, accelerates barrier recovery and prevents the epidermal hyperplasia induced by epidermal injury in hairless mice and humans. J. Invest. Dermatol. 109 84-90. 

Fibrinolytic agents such as reteplase enhance the breakdown of occlusive thromboses by the activation of plasminogen to form plasmin. 

Only one fibrinolytic agent has been recommended in the United Kingdom for treatment of acute stroke alteplase, a plasminogen activator. This is used only under specialist supervision as there is a significant risk of intracranial haemorrhage. 

Hospital patients at risk of inappropriate clotting may be given intravenous heparin and prescribed oral warfarin on discharge. Fibrinolytic agents such as streptokinase are used therapeutically to lyse clots formed in the coronary or pulmonary circulation. 

Ultrasound-assisted soft digestion has been used for other practical purposes from which analytical chemists can derive new applications. One case in point is in medicine, where ultrasound has been used as an adjunctive therapeutic treatment for clot dissolution of pharmacological thrombolysis. The combination of externally applied low-frequency high-intensity US with fibrinolytic therapy resulted in more rapid and complete reperfusion than the application of US or administration of fibrinolytic agents alone [42]. 

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