Dipyridamole detailed information

Overview
Dipyridamole is a drug that inhibits thrombus formation when given chronically and causes vasodilation when given at high doses over short time.


 * It inhibits the cellular reuptake of adenosine into platelets, red blood cells and endothelial cells leading to increased extracellular concentrations of adenosine.
 * It also inhibits the enzyme adenosine deaminase which normally breaks down adenosine into inosine. This inhibition leads to further increased levels of extracellular adenosine.
 * Dipyridamole also inhibits the enzyme phosphodiesterase- 5 (PDE 5) which normally breaks down cGMP. This results in added benefit when given together with NO or statins.
 * Dipyridamole has shown to lower pulmonary hypertension without significant drop of systemic blood pressure
 * Dipyridamole inhibits formation of pro-inflammatory cytokines (MCP-1, MMP-9) in vitro and results in reduction of hsCRP in patients.
 * Dipyridamole inhibits proliferation of smooth muscle cells in vivo and has shown to prevent AV-shunt failure in dialysis patients.
 * Dipyridamole increases release of t-PA from brain microvascular endothelial cells
 * Dipyridamole treatment in vivo results in increase of 13 - HODE and decrease of 12 - HETE in the subendothelial matrix (SEM) and reduced thrombogenicity of the SEM.
 * Dipyridamole pretreatment reduced reperfusion injury in volunteers.
 * Dipyridamole treatment has shown to increase myocardial perfusion and left ventricular function in patients with ischemic cardiomyopathy.
 * Dipyridamole treatment resulted in reduction of the number of thrombin and PECAM-1 receptors on platelets in stroke patients.
 * Adenosine interacts with the adenosine receptors to cause increased cAMP via adenylate cyclase.
 * cAMP impairs platelet aggregation and also causes arteriolar smooth muscle relaxation. Chronic therapy did not show significant drop of systemic blood pressure.

Use in individuals with a history of stroke
Modified release dipyridamole is used in conjunction with aspirin (under the trade name Aggrenox®) in the secondary prevention of stroke and transient ischemic attack. Dipyridamole absorption is pH dependent and concomitant treatment with gastric acid suppressors will inhibit uptake significantly. The sustained formulation in Aggrenox® also corrects for this impairment. This practice is now confirmed by the ESPRIT trial.

It is not, however, licensed as monotherapy for stroke prophylaxis.

Use in nuclear stress testing
Dipyridamole (Persantine) is also used in pharmacological nuclear cardiac stress testing mediating coronary vasodilation.


 * 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 and Tc99m-Sestamibi. However relative differences in perfusion not necessarily imply absolute decrease in blood supply in the tissue supplied by a stenosed artery.

Other uses of dipyridamole
Dipyridamole also has non-medicinal uses in a laboratory context, such as the inhibition of cardiovirus growth in cell culture.

Overdose
Dipyridamole overdose can be treated with aminophylline and reverses its hemodynamic effects (vasodilation).

External Link

 * Dipyridamole in the laboratory:.

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