Streptokinase and tissue plasminogen activator (t-PA) are fibrinolytic drugs that activate plasminogen to induce fibrinolysis. Streptokinase forms a complex with plasminogen to activate it, while t-PA activates plasminogen bound to fibrin hundreds of times more than free plasminogen. The major toxicity of these drugs is hemorrhage from lysis of physiological thrombi and a systemic lytic state. Contraindications include recent surgery, bleeding disorders, and hypertension. Aminocaproic acid inhibits fibrinolysis by competing for lysine binding sites on plasminogen and plasmin.

1. PHARMACOLOGY:
Fibrinolytic Drugs
nianderthalNOTES

2. FIBRINOLYTIC DRUGS
STREPTOKINASE:
-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

3. FIBRINOLYTIC DRUGS
TISSUE 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.

4. FIBRINOLYTIC DRUGS
TOXICITIES:
-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

5. FIBRINOLYTIC DRUGS
CONTRAINDICATIONS:
-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

6. FIBRINOLYTIC DRUGS
INHIBITION 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