Which of the following can be given as a single weight- based intravenous bolus over 10 seconds?
Correct Answer: Tenecteplase (TNK)
Description: Ans. B. Tenecteplase (TNK). (Ref. H-17th/pg. 1537)Harrison's 17th/pg. 1537..........."Tenecteplase (TNK) is given as a single weight-based intravenous bolus of 0.53 mgfkg over 10 s."Role of Fibrinolysis in Myocardial Infarction# If no contraindications are present, fibrinolytic therapy should ideally be initiated within 30 min of presentation (i.e., door-to-needle time ?30 min). The principal goal of fibrinolysis is prompt restoration of full coronary arterial patency. The fibrinolytic agents tissue plasminogen activator (tPA), streptokinase, tenecteplase (TNK), and reteplase (rPA) have been approved by the U.S. FDA for IV use in patients with STEMI. These drugs all act by promoting the conversion of plasminogen to plasmin, which subsequently lyses fibrin thrombi.# When assessed angiographically, flow in the culprit coronary artery is described by a simple qualitative scale called the thrombolysis in myocardial infarction (TIMI) grading system:- Grade 0 indicates complete occlusion of the infarct-related artery;- Grade 1 indicates some penetration of the contrast material beyond the point of obstruction but without perfusion of the distal coronary bed;- Grade 2 indicates perfusion of the entire infarct vessel into the distal bed but with flow that is delayed compared with that of a normal artery; and- Grade 3 indicates full perfusion of the infarct vessel with normal flow.# While the upper time limit depends on specific factors in individual patients, it is clear that "every minute counts" and that patients treated within 1-3 h of the onset of symptoms generally benefit most. Although reduction of the mortality rate is more modest, the therapy remains of benefit for many patients seen 3-6 h after the onset of infarction, and some benefit appears to be possible up to 12 h, especially if chest discomfort is still present and ST segments remain elevated.# Compared with PCI for STEMI (primary PCI), fibrinolysis is generally the preferred reperfusion strategy for patients presenting in the first hour of symptoms, if there are logistical concerns about transportation of the patient to a suitable PCI center (experienced operator and team with a track record for a "door-to-balloon" time of <2 h), or there is an anticipated delay of at least 1 h between the time that fibrinolysis could be started versus implementation of PCI.# tPA and the other relatively fibrin-specific plasminogen activators, rPA and TNK, are more effective than streptokinase at restoring full perfusion--i.e., TIMI grade 3 coronary flow--and have a small edge in improving survival as well.# The current recommended regimen of tPA consists of a 15 mg bolus followed by 50 mg intravenously over the first 30 min, followed by 35 mg over the next 60 min.# Streptokinase is administered as 1.5 million units (MU) intravenously over 1 h.# rPA is administered in a double-bolus regimen consisting of a 10-MU bolus given over 2-3 min, followed by a second 10-MU bolus 30 min later.# TNK is given as a single weight-based intravenous bolus of 0.53 mg/kg over 10 s.# Pharmacologic reperfusion also typically involves adjunctive antiplatelet and antithrombotic drugs.# Alternative pharmacologic regimens for reperfusion combine an intravenous glycoprotein Ilb/IIIa inhibitor with a reduced dose of a fibrinolytic agent.# Contraindications and Complications- Clear contraindications to the use of fibrinolytic agents include:* a history of cerebrovascular hemorrhage at any time, a nonhemorrhagic stroke or other cerebrovascular event within the past year, marked hypertension (a reliably determined systolic arterial pressure >180 mmHg and/or a diastolic pressure >110 mmHg) at any time during the acute presentation, suspicion of aortic dissection, and active internal bleeding (excluding menses). While advanced age is associated with an increase in hemorrhagic complications, the benefit of fibrinolytic therapy in the elderly appears to justify its use if no other contraindications are present and the amount of myocardium in jeopardy appears to be substantial.- Relative contraindications to fibrinolytic therapy, which require assessment of the risk. benefit ratio, include:* current use of anticoagulants (international normalized ratio ?2), a recent (<2 weeks) invasive or surgical procedure or prolonged (> 10 min) cardiopulmonary resuscitation, known bleeding diathesis, pregnancy, a hemorrhagic ophthalmic condition (e.g., hemorrhagic diabetic retinopathy), active peptic ulcer disease, and a history of severe hypertension that is currently adequately controlled. Because of the risk of an allergic reaction, patients should not receive streptokinase if that agent had been received within the preceding 5 days to 2 years.- Allergic reactions to streptokinase occur in ~2% of patients who receive it. While a minor degree of hypotension occurs in 4-10% of patients given this agent, marked hypotension occurs, although rarely, in association with severe allergic reactions.- Hemorrhage is the most frequent and potentially the most serious complication. Hemorrhagic stroke is the most serious complication and occurs in ~0.5-0.9% of patients being treated with these agentsLarge-scale trials have suggested that the rate of intracranial hemorrhage with tPA or rPA is slightly higher than with streptokinase.- Cardiac catheterization and coronary angiography should be carried out after fibrinolytic therapy if there is evidence of either:* (1) failure of reperfusion (persistent chest pain and ST-segment elevation >90 min), in which case a rescue PCI should be considered; or* (2) coronary artery re-occlusion (re-elevation of ST segments and/or recur- rent chest pain) or the development of recurrent ischemia (such as recurrent angina in the early hospital course or a positive exercise stress test before discharge), in which case an urgent PCI should be considered.
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