Mechanism of Action
Structurally and origin-wise, streptokinase is a foreign protein synthesized by $\beta$-hemolytic streptococci.
A key pharmacological feature of the drug is its indirect activation of fibrinolysis. Streptokinase itself is not an enzyme and lacks intrinsic proteolytic activity. Upon entering the systemic circulation, it binds to plasminogen molecules to form an equimolar streptokinase-plasminogen complex.
It is this newly formed complex that acquires catalytic properties. It acts on remaining (free) plasminogen molecules, converting them into the active proteolytic enzyme — plasmin.
Pharmacological Effects
The primary goal of thrombolytic therapy is the dissolution (lysis) of pre-existing thrombi and reperfusion of ischemic tissues.
Streptokinase action lacks high thrombus-selectivity. The drug exerts a systemic effect, activating both plasminogen localized on fibrin strands inside the thrombus and plasminogen circulating freely in blood plasma.
Excessive generation of plasmin in the circulation leads to systemic fibrinogenolysis — the destruction of circulating fibrinogen. The resulting fibrinogen degradation products exert an additional anticoagulant effect by inhibiting platelet aggregation.
Indications
The drug is indicated exclusively for acute thromboses. Clinical efficacy is highest when administered within the first few hours following a vascular occlusion.
- ST-elevation myocardial infarction (STEMI) / Acute coronary syndrome (ACS) (coronary thrombosis, myocardial infarction). The optimal "therapeutic window" is 3–6 hours.
- Pulmonary embolism (PE).
- Deep vein thrombosis (DVT).
- Acute peripheral arterial occlusion.
- Retinal vascular thrombosis.
Adverse Effects and Limitations
- Hemorrhage: The primary and most dangerous complication of therapy, resulting directly from systemic fibrinogenolysis and depletion of clotting factors.
- Immunogenicity (Antigenic properties): Being a bacterial protein, the drug stimulates antibody production. There is a high risk of allergic reactions, up to anaphylactic shock. The probability of severe immune complications increases critically upon repeat administration.
- Resistance: Circulating antibodies (resulting from prior streptococcal infections or previous thrombolytic administration) can bind and inactivate the drug, neutralizing therapeutic efficacy.
- General reactions: Arterial hypotension (hemodynamic disturbances) and gastrointestinal symptoms (nausea, vomiting) may occur.
Formulations and Administration
The drug is dosed in International Units (IU) and administered via intravenous infusion. Available in vials of 250,000 IU and 500,000 IU. The infusion solution is prepared immediately before use (ex tempore).
Prescription Example: Rp.: Streptokinasi 250,000 IU D.t.d. No. 1 S. Dissolve the contents of the vial in 50 mL of sterile 0.9% sodium chloride solution (prepare ex tempore). Administer as an IV infusion at 25–30 drops per minute.