Fibrinolytic

Question 1

explain the role of plasminogen/plasmin in the process of blood clotting

Answer 1

• plasminogen= inactive form
• t-PA (tissue plasminogen activator), a serine protease, activates plasminogen to plasmin
• plasmin digests fibrin & fibrinogen

Question 2

explain the mechanism for the conversion of plasminogen to active plasmin

Answer 2

• tPA or uPA activates plasminogen -> plasmin by cleaving arg-val bond
• PAI-1 and PAI-2 inhibit tPA
• plasmin then digests fibrin and fibrinogen
• α2AP (alpha-antiplasmin) inhibits plasmin

Question 3

give the names and specific MOA of the drugs used to dissolve blood clots

Answer 3

• Tenecteplase, Alteplase, Reteplase
• indication: acute MI, PE, acute ischemic thrombotic stroke
• Tenecteplase and alteplase bind fibrin, reteplase does not
• Tenecteplase longest half-life

Question 4

explain the differences between alteplase, reteplase, and tenecteplase in terms of structure and selectivity

Answer 4

• Tenecteplase and alteplase bind fibrin, reteplase does not
• All have Kringle 1/2 and protease domain
• Tenecteplase mutation at Kringle 1/2 and protease domain which incr half-life and reduces PAI inhibition
• Alteplase: recombinant human t-PA, same structure as tenecteplase except no mutation

Question 5

explain the structural similarities of tranexamic acid, amino-caproic acid, and lysine in terms of their MOA in stabilizing blood clots

Answer 5

• amine (base) and carboxylic acid (acid) functional group
• bind to site where plasminogen & plasmin binds to fibrin, thus blocking plasmin binding to fibrin