CV - Dipyridamole

Question 1

Clinical pharmacology?

Common indications

Answer 1

• Cerebrovascular disease for secondary prevention of stroke.
• Dipyridamole is currently first-line therapy following a transient ischaemic attack,and second-line therapy following an ischaemic stroke where clopidogrel is contraindicated or not tolerated.
• It should usually be given in combination with aspirin but can be used as monotherapy if aspirin is contraindicated or not tolerated.
• To induce tachycardia during a myocardial perfusion scan in the diagnosis of ischaemic heart disease.

Question 2

Mechanisms of action?

Answer 2

• Dipyridamole has both antiplatelet and vasodilatory effects.
• Although the exact mechanism of its antiplatelet action is controversial, the end effect is an increase in intra-platelet cyclic adenosine monophosphate (cAMP) that inhibits platelet aggregation, reducing the risk of arterial occlusion.
• Dipyridamole also blocks cellular uptake of adenosine, prolonging its effect on blood vessels to produce vasodilation.

Question 3

Important adverse effects?

Answer 3

• The side effects of dipyridamole relate to its vasodilatory effects and include headache, flushing, dizziness and gastrointestinal symptoms that normally improve with time.
• As with other antiplatelet agents there is an increased risk of bleeding.
• Rarely dipyridamole can affect platelet numbers as well as function, causing thrombocytopaenia.

Question 4

Warnings?

Answer 4

• Dipyridamole should be used with caution in patients with ischaemic heart disease, aortic stenosis and heart failure as it causes vasodilatation and tachycardia that can exacerbate these conditions.
• This effect is exploited diagnostically in myocardial perfusion scans, where radionucleotide distribution is compared in heart muscle at baseline and during tachycardia induced by intravenous dipyridamole.
• Reduced perfusion after dipyridamole indicates cardiac ischaemia.

Question 5

Important interactions?

Answer 5

• Dipyridamole inhibits cellular uptake of adenosine. This prolongs its effects on the heart, increasing the risk of cardiac arrest.
• The dose of adenosine should therefore be reduced in patients treated with dipyridamole.
• There is an increased risk of bleeding where dipyridamole is combined with other antiplatelet agents (aspirin, clopidogrel) and anticoagulants (heparin, warfarin).

Question 6

Practical prescribing

Prescription

Answer 6

• For therapeutic purposes, dipyridamole is given orally. Current evidence is strongest for the use of modified-release (MR) preparations in secondary prevention of stroke.
• For this indication you should prescribe dipyridamole MR, 200 mg twice daily. Dipyridamole is a long-term treatment that should only usually be stopped if adverse effects are intolerable or new contraindications develop.