A patient with acute STEMI receives tenecteplase (TNK-tPA) instead of alteplase. What property of tenecteplase makes it suitable for bolus administration, unlike alteplase?
- A Tenecteplase has a longer plasma half-life (~20 min vs ~5 min for alteplase) due to its T103N mutation reducing hepatic clearance, T117N mutation increasing fibrin specificity, and KHRR296-299AAAA mutation increasing resistance to PAI-1 inhibition, allowing single-bolus administration ✓
- B Tenecteplase is an irreversible plasminogen activator requiring only a single binding event
- C Tenecteplase directly activates plasmin without a fibrin-binding step, enabling rapid systemic lytic action
- D Tenecteplase has absolute fibrin selectivity, making systemic plasminogen activation impossible
Explanation
Tenecteplase is an engineered variant of tPA with three mutations: Thr103Asn (T103N) reducing hepatic clearance, a glycosylation change at Asn117 increasing fibrin specificity, and tetra-alanine substitution at Lys296-His297-Arg298-Arg299 (KHRR→AAAA) conferring 80-fold resistance to PAI-1. These combined changes extend the plasma half-life from ~5 minutes (alteplase) to ~20 minutes and increase fibrin selectivity ~14-fold, enabling weight-adjusted IV bolus administration without infusion—operationally advantageous in the catheterization laboratory or prehospital setting.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.