Stroke

Question 1

Antiplatelet therapy

Clopidogrel (1st line) Other indications

Answer 1

• ACS- where rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce subsequent mortality
• Prevent occlusion of coronary artery stents
• CV, cerebrovascular and peripheral arterial disease
• Reduce the risk of embolic stroke in atrial fibrillation where WARFARIN and NOACs are contraindicated

Question 2

Clopidogrel MOA

Answer 2

• Thrombotic events occur when platelet-rich thrombus forms in atheromatous arteries and occludes circulation
• Clopidogrel prevents platelet aggregation and reduces the risk of arterial occlusion by binding irreversibly to adenosine diphosphate (ADP) receptors (P2Y12) on the surface of the platelet
• As this process is independent of the cyclo-oxygenase pathway, its actions are synergistic with those of aspirin.

Question 3

Clopidogrel

Important adverse effects

Answer 3

• The most common adverse effect of clopidogrel is Bleeding, which can be serious, particularly, GI, intracranial or after surgery
• GI upset, including dyspepsia, ab pain, diarrhoea is also common
• RARE but can cause Thrombocytopenia

Question 4

Clopidogrel

Warnings

Answer 4

• Active bleeding- may need to be stopped for 7 days
• Elective surgery-
  
  • Clopidogrel binds irreversibly, therefore takes lifespan of platelet for the antiplatelet effect to wear off (7-10 days)
• Renal and Hepatic impairment- when they have a bleeding risk

Question 5

Antiplatelet

Aspirin MOA

Answer 5

• Aspirin irreversibly inhibits Cyclo-oxygenase enzyme to reduce the production of the pro-aggregate factor thromboxane from arachidonic acid
• Reducing platelet aggregation and the risk of arterial occlusion
• The Antiplatelet effect occurs at a low dose and lasts a lifetime of platelet

Question 6

Aspirin

Important adverse effect

Answer 6

• GI irritation
• GI ulceration and haemorrhage
• Tinnitus
• Aspirin overdose- hyperventilation, hearing changes, metabolic acidosis and convulsion

Question 7

Aspirin

Warnings

Answer 7

• Children aged under 16 years- Reyes syndrome
• Aspirin hypersensitivity
• Third trimester of pregnancy
• Peptic ulceration
• Gout
• GIVE with PPI

Question 8

Dipyridamole

MOA

Answer 8

• Dipyridamole has both antiplatelet and vasodilatory effects
• Although the exact mechanism of its antiplatelet action is controversial
• It increases cAMP that inhibits platelet aggregation, reducing the risk of arterial occulsion
• Dipyridamole also blocks cellular uptake of adenosine, prolonging its effect on blood vessels to produce vasodilation

Question 9

Dipyridamole

Side effects

Answer 9

• Headache- common but wears off with time
• Flushing
• Dizziness
• GI symptoms
• Increased risk of bleeding
• Thrombocytopaenia

Question 10

Dipyridamole

Answer 10

• Ischaemic heart disease, aortic stenosis, HF
  
  • Vasodilation, tachycardia that can exacerbate these conditions
• Adenosine uptake is blocked, increasing its effects on the heart leading to cardiac arrests

Question 11

Lipid modification

Answer 11

See hyperlipidaemia

Question 12

Fibrinolytic drugs (alteplase)

Common indications

Answer 12

1. Acute ischaemic stroke- alteplase increases the chance of living independently if it is given within 4.5 hours of the onset of the stroke
2. 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
3. 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 13

Fibrinolytic drugs (alteplase)

MOA

Answer 13

• Fibrinolytic drugs, also known as thrombolytic drugs, catalyse the conversion of plasminogen to plasmin, which 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 14

Fibrinolytic drugs (alteplase)

Adverse effects

Answer 14

• Common: N&V, bruising around the injection site and hypotension
• 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 15

Fibrinolytic drugs (alteplase)

Warnings

Answer 15

• There are many contraindications to thrombolysis, which are mostly factos that predispose to bleeding- recent haemorrhage, surgery
• In acute stroke, intracranial haemorrhage must be excluded with CT scan before treatment
• Previous streptokinase treatment is a contraindication to repeat dosing (although other fibrinolytics can be used), as development of anti-streptokinase Abs can block its effect

Question 16

Fibrinolytic drugs (alteplase)

Interactions

Answer 16

• The risk fo haemorrhage is increased in patients taking anticoagulants, and antiplatelet agents
• ACEI appear to increase the risk of anaphylactoid reactions

Question 17

Fibrinolytic drugs (alteplase)

Communication

Answer 17

• The decision to ‘thrombolyse’ (prescribe fibrinolytic therapy) should be made by a senior clinician and the risks and benefits discussed with the patient and next of kin.
• For example, in acute stroke, explain that part of the brain is being starved of blood and oxygen due to a blocked artery, which will cause long-term damage.
• Giving a ‘clot-busting’ drug can prevent damage to the brain by dissolving the blood clot and restoring blood flow. However, it only works when given soon after the onset of the stroke.
• With or without treatment people may show some improvement, but symptoms may also get worse and one in three strokes are fatal. Although the chance of death is increased initially after receiving a clot-busting drug (due to bleeding), after the first week the chances of living independently are increased.
• For licensed indications, written consent is not essential but verbal consent should be obtained. If neurological impairment prevents consent, treatment can still be given if judged to be in the patient’s best interests.

Question 18

Fibrinolytics (Alteplase)

Monitoring

Answer 18

• Patients should be monitored in a high dependency area, with vital signs checked every 15 minutes for the first 2 hours
• This should include observation for signs of bleeding, anaphylaxis and in the case of acute stroke, neurological deterioration