Usage
Streptokinase is a thrombolytic agent prescribed for the management of acute myocardial infarction (AMI), deep vein thrombosis (DVT), pulmonary embolism (PE), and arterial thromboembolism. It’s also used to clear thrombosed arteriovenous cannulae. It belongs to the pharmacological classification of fibrinolytic agents, specifically thrombolytics, also known as “clot busters.” Streptokinase works by activating plasminogen, a precursor of the enzyme plasmin. Plasmin then degrades fibrin, the primary component of blood clots, thereby dissolving existing clots and preventing new clot formation.
Alternate Names
The generic name is streptokinase. A former brand name was Streptase, which is no longer available in the U.S. However, generic versions may be available.
How It Works
Pharmacodynamics: Streptokinase binds to plasminogen, forming a complex that converts other plasminogen molecules into plasmin. Plasmin, a serine protease, breaks down fibrin, leading to thrombolysis.
Pharmacokinetics: Streptokinase is administered intravenously. Due to its bacterial protein origin, it can trigger antibody formation, requiring a loading dose. It is primarily cleared by the liver with no identified metabolites. The half-life is variable, about 23 minutes, affected by the presence of anti-streptococcal antibodies. Elimination pathways involve hepatic clearance.
Mode of Action: Streptokinase forms a 1:1 stoichiometric complex with plasminogen. This complex catalytically converts other plasminogen molecules to plasmin. Plasmin then acts on fibrin, dissolving the clot. This process occurs systemically, affecting both fibrin and fibrinogen, resulting in a generalized lytic state.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Streptokinase primarily functions through enzymatic activation of plasminogen, not through receptor binding or neurotransmitter modulation. It effectively indirectly promotes enzyme activity (plasmin).
Dosage
Standard Dosage
Adults:
- AMI: 1.5 million IU IV infusion over 60 minutes.
- DVT/PE: 250,000 IU IV bolus over 30 minutes, followed by 100,000 IU/hour for 72 hours (DVT) or as indicated (PE).
- Arterial Thromboembolism: Regimen varies depending on location and severity; consult specific guidelines.
- Arteriovenous Cannula Occlusion: 250,000 IU in each cannula limb over 25-35 minutes.
Children:
Limited data exists for pediatric use; dosing is based on weight and the specific clinical scenario. Safety and efficacy have not been established for children under 18. Consider consulting with a pediatric specialist.
Special Cases:
- Elderly Patients: While effective, monitor for bleeding complications.
- Patients with Renal Impairment: Dosage adjustments based on creatinine clearance are not explicitly defined; monitor renal function and clotting parameters.
- Patients with Hepatic Dysfunction: No specific dosage adjustments; careful monitoring for bleeding complications.
- Patients with Comorbid Conditions: Individualized dosing based on risk-benefit assessment, especially in patients with recent surgery/trauma, bleeding disorders, or cerebrovascular disease.
Clinical Use Cases
Dosage guidelines are similar to the standard adult dosing. Clinical use cases include:
- Intubation (for cannula occlusion): As above
- Surgical Procedures (post-op DVT prevention): As above
- Mechanical Ventilation (for cannula occlusion): As above
- Intensive Care Unit (ICU) Use (for various thrombotic complications): As above
- Emergency Situations (AMI, PE): As above
Dosage Adjustments:
Individualized dosing is necessary, considering renal and hepatic function, comorbid conditions, and concomitant medications. Closely monitor coagulation parameters (e.g., aPTT, PT, INR, fibrinogen).
Side Effects
Common Side Effects:
Bleeding (at injection site, gums, wounds), bruising, nausea, vomiting, hypotension, fever, allergic reactions (rash, itching).
Rare but Serious Side Effects:
Intracranial hemorrhage, stroke, major bleeding (GI, GU), anaphylaxis.
Long-Term Effects:
No specific long-term side effects directly attributed to streptokinase itself have been established. However, sequelae from bleeding events or the underlying condition treated with streptokinase may contribute to long-term health implications.
Adverse Drug Reactions (ADR):
Major bleeding, allergic reactions requiring immediate intervention, including anaphylaxis, and stroke.
Contraindications
- Absolute: Active internal bleeding, recent intracranial/intraspinal surgery, history of intracranial hemorrhage, aortic dissection, severe hypertension, known intracranial neoplasm.
- Relative: Pregnancy, recent surgery/trauma, history of stroke, active peptic ulcer, severe liver disease.
Drug Interactions
Anticoagulants (heparin, warfarin), antiplatelet agents (aspirin, clopidogrel) increase bleeding risk. Aminocaproic acid reverses streptokinase’s effects.
Pregnancy and Breastfeeding
Pregnancy Category C. Use only if the potential benefits outweigh the risks to the fetus. It’s unknown if streptokinase is excreted in breast milk; consider discontinuing breastfeeding during treatment and for 24 hours after the last dose.
Drug Profile Summary
- Mechanism of Action: Activates plasminogen to form plasmin, which degrades fibrin.
- Side Effects: Bleeding, bruising, hypotension, fever, allergic reactions.
- Contraindications: Active bleeding, recent intracranial events, history of intracranial hemorrhage.
- Drug Interactions: Anticoagulants, antiplatelet agents.
- Pregnancy & Breastfeeding: Category C; use with caution.
- Dosage: See detailed section above.
- Monitoring Parameters: aPTT, PT, INR, fibrinogen, Hgb, Hct, platelet count, signs of bleeding.
Popular Combinations
Often used in conjunction with heparin after the initial streptokinase treatment, though this increases bleeding risk.
Precautions
Screen for contraindications, including recent bleeding or trauma, intracranial abnormalities, and hypersensitivity to streptokinase. Monitor vital signs and signs of bleeding during and after administration. Avoid invasive procedures during and shortly after treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Streptokinase?
A: See the detailed dosage section above.
Q2: What are the major side effects of streptokinase?
A: Bleeding is the most significant side effect. Ranging from minor bleeding at the injection site to life-threatening intracranial hemorrhage. Other side effects include allergic reactions, hypotension, and fever.
Q3: When is streptokinase contraindicated?
A: Streptokinase is contraindicated in patients with active internal bleeding, recent intracranial events, or a history of intracranial hemorrhage. It should be used with caution in those with a history of stroke, recent surgery or trauma, uncontrolled hypertension, or active bleeding disorders.
Q4: How does streptokinase interact with other drugs?
A: Combining streptokinase with anticoagulants or antiplatelet medications significantly increases the risk of bleeding.
Q5: Can streptokinase be used during pregnancy or breastfeeding?
A: Streptokinase is a Pregnancy Category C drug. Its use during pregnancy requires a careful risk-benefit assessment. Its presence in breast milk isn’t fully established, and caution is advised.
Q6: How soon should streptokinase be administered after an AMI?
A: Ideally within 12 hours of symptom onset, aiming for earlier administration when possible for maximum benefit.
Q7: What should be monitored during streptokinase therapy?
A: Vital signs, signs of bleeding, and coagulation parameters (aPTT, PT, INR, fibrinogen) should be closely monitored.
Q8: Can streptokinase be administered a second time?
A: A second use is generally not recommended due to the risk of allergic reactions and antibody formation reducing efficacy.
Q9: How is streptokinase administered?
A: Streptokinase is administered as an intravenous infusion.
Q10: What is the mechanism of action of streptokinase?
A: Streptokinase forms a complex with plasminogen, converting it to plasmin, which degrades fibrin, leading to clot dissolution.
