Dipyridamole (trademarked as Persantine and Curantyl) is a medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a short time.
Mechanism and effects
Dipyridamole inhibits the phosphodiesterase enzymes that normally break down cAMP (increasing cellular cAMP levels and blocking the platelet aggregation response to ADP) and/or cGMP.
It inhibits the cellular reuptake of adenosine into platelets, red blood cells, and endothelial cells leading to increased extracellular concentrations of adenosine.
Dipyridamole is used to dilate blood vessels in people with peripheral arterial disease and coronary artery disease
Dipyridamole has been shown to lower pulmonary hypertension without significant drop of systemic blood pressure
It inhibits formation of pro-inflammatory cytokines (MCP-1, MMP-9) in vitro and results in reduction of hsCRP in patients.
It inhibits proliferation of smooth muscle cells in vivo and modestly increases unassisted patency of synthetic arteriovenous hemodialysis grafts.
It increases the release of t-PA from brain microvascular endothelial cells
It results in an increase of 13-HODE and decrease of 12-HETE in the subendothelial matrix (SEM) and reduced thrombogenicity of the SEM.
Pretreatment it reduced reperfusion injury in volunteers.
It has been shown to increase myocardial perfusion and left ventricular function in patients with ischemic cardiomyopathy.
It results in a reduction of the number of thrombin and PECAM-1 receptors on platelets in stroke patients.
cAMP impairs platelet aggregation and also causes arteriolar smooth muscle relaxation. Chronic therapy did not show significant drop of systemic blood pressure.
It inhibits the replication of mengovirus RNA.
It can be used for myocardial stress testing as an alternative to exercise-induced stress methods such as treadmills.
A combination of dipyridamole and aspirin (acetylsalicylic acid/dipyridamole) is FDA-approved for the secondary prevention of stroke and has a bleeding risk equal to that of aspirin use alone. Dipyridamole absorption is pH-dependent and concomitant treatment with gastric acid suppressors (such as a proton pump inhibitor) will inhibit the absorption of liquid and plain tablets. Modified release preparations are buffered and absorption is not affected.
However, it is not licensed as monotherapy for stroke prophylaxis, although a Cochrane Review suggested that dipyridamole may reduce the risk of further vascular events in patients presenting after cerebral ischemia.
A triple therapy of aspirin, clopidogrel, and dipyridamole has been investigated, but this combination led to an increase in adverse bleeding events.
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 also has non-medicinal uses in a laboratory context, such as the inhibition of cardiovirus growth in cell culture.
Dipyridamole overdose can be treated with aminophylline which reverses its dilating effect on the blood vessels. 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.
