CV Fibrinolytic drugs-

Question 1

Fibrinolytic drugs: alteplase, streptokinase

Clinical pharmacology

Common indications

Answer 1

• In acute ischaemic stroke, alteplase increases the chance of living independently if it is given within 4.5 hours of the onset of the stroke.
• In acute ST elevation myocardial infarction,alteplase and streptokinase can reduce mortality when they are given within 12 hours of the onset of symptoms in combination with antiplatelet agents and anticoagulants.
• However, primary percutaneous coronary intervention (where available) has largely superseded fibrinolytics in this context.
• For massive pulmonary embolism with haemodynamic instability fibrinolytic drugs reduce clot size and pulmonary artery pressures, but there is no clear evidence that they improve mortality.

Question 2

Mechanisms of action

Answer 2

• Fibrinolytic drugs, also known as thrombolytic drugs, catalyse the conversion of plasminogen to plasmin,
• acts to dissolve fibrinous clots and re-canalise occluded vessels.
• This allows reperfusion of affected tissue, preventing or limiting tissue infarction and cell death and improving patient outcomes.

Question 3

Fibrinolytic Drugs

Important adverse affects

Answer 3

• Nausea and vomiting, bruising around the injection site and hypotension.
• Adverse effects that require treatment to be stopped include serious bleeding, allergic reaction, cardiogenic shock and cardiac arrest.
• Serious bleeding may require treatment with coagulation factors and antifibrinolytic drugs, e.g. tranexamic acid, but this is usually avoidable as fibrinolytic agents have a very short half-life.
• Reperfusion of infarcted brain or heart tissue can lead to cerebral oedema and arrhythmias,respectively.

Question 4

Fibrinolytic Drugs

Contraindications?

Answer 4

Bleeding including:

• recent haemorrhage;
• recent trauma or surgery;
• bleeding disorders;
• severe hypertension;
• and peptic ulcers.

In acute stroke:

• Intracranial haemorrhage must be excluded with a CT scan before treatment.
• Previous streptokinase treatment is a contraindication to repeat dosing (although other fibrinolytics can be used), as development of anti-streptokinase antibodies can block its effect

Question 5

Fibrinolytic Drugs

Important Reactions?

Answer 5

• The risk of haemorrhage is increased in patients taking anticoagulants, and antiplatelet agents.
• ACE inhibitorsappear to increase the risk of anaphylactoid reactions.

Question 6

Fibrinolytic Drugs

Px and Administration?

Answer 6

• They are only available as injectable preparations. A bolus dose is usually given first, followed by an IV infusion.
• Fibrinolytic drugs should be administered in a high dependency area such as the emergency department, hyperacute stroke unit or coronary care unit, by staff experienced in their use.
• Alteplase comes as a powder, which is reconstituted with water for injection then either given directly as an IV bolus injection or diluted further in 0.9% sodium chloride and given as an IV infusion.