FIBRINOLYTIC DRUGSSTREPTOKINASE:-produced by B-hemolytic streptococci-forms a stable, non-covalent 1:1 complex with plasminogen that induces a conformational change and leads to formation of free plasmin-rarely used clinically
FIBRINOLYTIC DRUGSTISSUE PLASMINOGEN ACTIVATOR (t-PA):-a serine protease that is a POOR plasminogen activator IN THE ABSENCE OF FIBRIN-ACTIVATES BOUND plasminogen several hundredfold MORE THAN it activates FREE plasminogen-clearance occurs by HEPATIC metabolism-t1/2: 5-10 minutes-indications: acute MI-dosage: for coronary thrombolysis – 15mg IV bolus followed by 0.75 mg/kg of body wt over 30 minutes. Not to exceed 50mg-0.5 mg/kg up to 35mg over the following hour-t-PA variants differ from native t-PA by having increased half- lives, and resistant to t-PA inhibitor-1.
FIBRINOLYTIC DRUGSTOXICITIES:-MAJOR TOXICITY IS HEMORRHAGE, which results from 2 factors: 1. lysis of fibrin in “physiological thrombi” at sites of vascular injury 2. systemic lytic state that results from systemic formation of plasmin, which produces fibrinogenolysis and destruction of other coagulation factors
FIBRINOLYTIC DRUGSCONTRAINDICATIONS:-invasive procedures should be avoided-concurrent use of heparin-surgery within 10 days-serious GI bleeding within 3 months-history of hypertension (diastolic pressure >110 mmHG)-active bleeding or hemorrhagic disorder-previous cerebrovascular accident or active intracranial process-aortic dissection-acute pericarditis
FIBRINOLYTIC DRUGSINHIBITION OF FIBRINOLYSIS:-Aminocaproic Acid -Lys analog that competes for Lys binding sites on plasminogen and plasmin, thus blocking the interaction of plasmin with fibrin -main problem: thrombi formed during treatment are not lysed -absorbed rapidly after oral administration -50% is excreted in the urine within 12 hours -loading dose: IV 4-5 g over 1 hour -succeeding dose: infusion 1g/h until bleeding is controlled *no more than 30g should be given in 24 hours -adverse effects: myopathy, muscle necrosis