Dipyridamole
1063753
224802899
2008-07-10T14:08:19Z
Fvasconcellos
1051513
consistency
{{drugbox
| IUPAC_name = 2-{[9-(bis(2-hydroxyethyl)amino)-2,7-bis(1-piperidyl)-<br>3,5,8,10-tetrazabicyclo[4.4.0]deca-2,4,7,9,11-pentaen-<br>4-yl]-(2-hydroxyethyl)amino}ethanol
| image = Dipyridamole.svg
| CAS_number = 58-32-2
| ATC_prefix = B01
| ATC_suffix = AC07
| PubChem = 3108
| DrugBank = APRD00360
| C = 24 |H = 40 |N = 8 |O = 4
| molecular_weight = 504.626 [[Gram|g]]/[[Mole (unit)|mol]]
| bioavailability =
| protein_bound = 99%
| metabolism = Hepatic
| elimination_half-life = Alpha (40 mins), Beta (10 Hours)
| pregnancy_category = B
| legal_status =
| routes_of_administration = PO, IV
}}
'''Dipyridamole''' is a [[medication|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 cell]]s and [[endothelial cell]]s 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 [[arteriole|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 names ''Aggrenox'' in the [[USA]] or ''Asasantin Retard'' in the [[UK]]) in the secondary prevention of [[stroke]] and [[transient ischaemic attack]]. Dipyridamole absorption is [[pH]]-dependent and concomitant treatment with gastric acid suppressors (such as a [[proton pump inhibitor]]) will inhibit uptake significantly.<ref name="Diener-1996">{{cite journal | author=Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. | title=European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke | journal=J Neurol Sci | year=1996 | volume=143 | issue=1-2 | pages=1–13 | pmid=8981292 | doi=10.1016/S0022-510X(96)00308-5}}</ref> This practice was now confirmed by the ESPRIT trial.<ref name="ESPRIT">{{cite journal |author=Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A |title=Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial |journal=Lancet |volume=367 |issue=9523 |pages=1665–73 |year=2006 |month=May |pmid=16714187 |doi=10.1016/S0140-6736(06)68734-5 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(06)68734-5}}</ref>
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.<ref name="Dipyridamole for preventing stroke and other vascular events in patients with vascular disease">{{cite journal |author=De Schryver ELLM, Algra A, van Gijn J. |title=Dipyridamole for preventing stroke and other vascular events in patients with vascular disease. |journal=Cochrane Database of Systematic Reviews 2007 |issue=2 |year=2007 |pages=CD001820 |doi=10.1002/14651858.CD001820.pub3 |url=http://www.cochrane.org/reviews/en/ab001820.html}}</ref>
==Use in nuclear stress testing==
Dipyridamole ('''Persantine''') is also used in pharmacological [[nuclear medicine|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 [[stenosis|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 camera]]s and [[SPECT]] using nuclear imaging agents such as [[Thallium]]-201 and [[Technetium-99m|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]]<ref>Aggrenox. RxList.com. URL: [http://www.rxlist.com/cgi/generic/aggrenox_od.htm http://www.rxlist.com/cgi/generic/aggrenox_od.htm]. Accessed on: May 1, 2007.</ref> and reverses its [[hemodynamics|hemodynamic]] effects (vasodilation).
==References==
{{Reflist}}
* Dipyridamole in the laboratory: {{cite web | last = Fata-Hartley | first = Cori L. | coauthors=Ann C. Palmenberg | title = Dipyridamole reversibly inhibits mengovirus RNA replication
| url=http://jvi.asm.org/cgi/content/full/79/17/11062?view=long&pmid=16103157 | accessdate=2007-02-13 | doi=10.1128/JVI.79.17.11062-11070.2005 }}.
{{Antithrombotics}}
[[Category:Antiplatelet drugs]]
[[Category:Piperidines]]
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