Thrombolytic promoters

Discuss ways to promote an optimal response to therapy, how to manage common adverse reactions, and important points to keep in mind when educating patients about the use of an anticoagulant or thrombolytic drug. 

Plasminogen, an inactive precursor, is activated to plasmin which as a protease is able to break down fibrin clots. The thrombolytic agents in use promote the conversion of plasminogen to plasmin at the site of a thrombus. Indications include post-myocardial infarction treatment. The thrombolytic must be administered within 6 hours for an optimal effect. Other indications are treatment of acute pulmonary thromboembolism, deep-vein thrombosis, acute arterial thrombosis and thromboembolism, as well as in the clearance of arteriovenous catheters and can-nulae. Agents are streptokinase, anistreplase, urokinase, alteplase, reteplase and tenecteplase. 

Platelet aggregation inhibitors decrease the formation or the action of chemical signals that promote platelet aggregation. These agents have proven beneficial in the prevention and treatment of occlusive cardiovascular diseases, the maintenance of vascular grafts and arterial patency, and as adjuncts to thrombolytic therapy in myocardial infarction. 

Q9 Several pharmacological agents could theoretically be used to promote cerebral blood flow and potentially improve the outcome from a stroke. Are thrombolytic agents or anticoagulants likely to be suitable treatments for all cases of stroke ... 

In suitable patients a thrombolytic agent such as streptokinase may be given soon after a coronary occlusion to dissolve the thrombus and promote restoration of blood flow. 

Thrombolytic agents interfere with the measurement of plasma fibrinogen and other coagulation tests by promoting continuing fibrinolysis after the specimen is taken thus, fibrinogen cannot be measured in a sample that is taken less than an hour after the administration of a thrombolytic agent. 

Certain physiologic and dietary materials affect the platelet reactions. Catechol amines enhance platelet aggregation and promote thrombus formation. Fatty acids appear to enhance platelet aggregation, with saturated fatty acids being more effective than unsaturated fatty acids. Thrombosis is produced in the dog by single rapid infusion of long-chain saturated fatty acids but chronic slow infusions are nonthrombogenlc. Apparently the dog has sufficient thrombolytic power to handle the latter situation. 

B. Mechanism of Action Plasmin is the normal endogenous fibrinolytic enzyme. By splitting fibrin into fragments, plasmin promotes the breakdown and dissolution of clots (Figure 34-3). The thrombolytic enzymes catalyze the activation of the inactive precursor, plasminogen, to plasmin. 

Thrombolytics are dmgs that promote the fibronolytic mechanism if administered within 4 hours following an acute myocardial infarction (AMI). An acute myocardial infarction (heart attack) can be caused by a thromboembolism blocking a coronary artery. This results in decreased circulation to that part of the heart. The ischemic (without oxygen) tissue becomes necrotic (dies) if left without an oxygen supply. Thrombolytics prevent or minimize necrosis that results from the blocked artery and therefore decreases hospitalization time. After thrombolytic treatment, the patient is evaluated for cardiac bypass or coronary angioplasty procedures. 

When blood is lost or clotting is initiated in some other way, a complex cascade of biochemical reactions is set in motion, which ends in the formation of a network or clot of insoluble protein threads enmeshing the blood cells. These threads are produced by the polymerisation of the molecules of fibrinogen (a soluble protein present in the plasma) into threads of insoluble fibrin. The penultimate step in the chain of reactions requires the presence of an enzyme, thrombin, which is produced from its precursor prothrombin, already present in the plasma. This is initiated by factor lit (tissue thromboplastin), and subsequently involves various factors including activated factor Vn, DC, X, XI and XII, and is inhibited by antithrombin in. Platelets are also involved in the coagulation process. Fibrinolysis is the mechanism of dissolution of fibrin clots, which can be promoted with thrombolytics. For further information on platelet aggregation and clot dissolution, see Antiplatelet drugs and thrombolytics , (p.697). 

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