Dipyridamole inhibits the phosphodiesterase enzymes that normally break down cAMP (increasing cellular cAMP levels and blocking the platelet response to ADP) and/or cGMP (resulting in added benefit when given together with nitric oxide [NO] or statins).
Dipyridamole blocks the thromboxane synthase as well as the thromboxane receptor.
Modified release dipyridamole is used in conjunction with aspirin (under the trade names Aggrenox in the USA or Asasantin Retard in the UK) in the secondary prevention of stroke and transient ischaemic attack. This practice has been confirmed by the ESPRIT trial. Dipyridamole absorption is pH-dependent and concomitant treatment with gastric acid suppressors (such as a proton pump inhibitor) will inhibit the absorption of liquid & plain tablets. Modified release preparations are buffered and absorption is not affected.
It is not, however, licensed as monotherapy for stroke prophylaxis, although a Cochrane Review has suggested that dipyridamole may reduce the risk of further vascular events in patients presenting after cerebral ischaemia.
A triple therapy of aspirin, clopidogrel, and dipyridamole has been investigated, but this combination led to an increase in adverse bleeding events.
Via the mechanisms mentioned above, when given as 3 to 5 min infusion it rapidly increases the local concentration of adenosine in the coronary circulation which causes vasodilation.
Vasodilation occurs in healthy arteries, whereas stenosed arteries remain narrowed. This creates a "steal" phenomenon where the coronary blood supply will increase to the dilated healthy vessels compared to the stenosed arteries which can then be detected by clinical symptoms of chest pain, electrocardiogram and echocardiography when it causes ischemia.
Flow heterogeneity (a necessary precursor to ischemia) can be detected with gamma cameras and SPECT using nuclear imaging agents such as Thallium-201, Tc99m-Tetrofosmin and Tc99m-Sestamibi. However relative differences in perfusion do not necessarily imply any absolute decrease in blood supply in the tissue supplied by a stenosed artery.
Dipyridamole overdose can be treated with aminophylline which reverses its hemodynamic effects (vasodilation). Symptomatic treatment is recommended, possibly including a vasopressor drug. Gastric lavage should be considered. Administration of xanthine derivatives (e.g., aminophylline) may reverse the hemodynamic effects of dipyridamole overdose. Since dipyridamole is highly protein bound, dialysis is not likely to be of benefit.