Dipyridamole

• 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 proliferation of smooth muscle cells in vivo and modestly increases unassisted patency of synthetic arteriovenous hemodialysis grafts.{{cite journal | vauthors = Dixon BS, Beck GJ, Vazquez MA, Greenberg A, Delmez JA, Allon M, Dember LM, Himmelfarb J, Gassman JJ, Greene T, Radeva MK, Davidson IJ, Ikizler TA, Braden GL, Fenves AZ, Kaufman JS, Cotton JR, Martin KJ, McNeil JW, Rahman A, Lawson JH, Whiting JF, Hu B, Meyers CM, Kusek JW, Feldman HI | title = Effect of dipyridamole plus aspirin on hemodialysis graft patency | journal = The New England Journal of Medicine | volume = 360 | issue = 21 | pages = 2191–2201 | date = May 2009 | pmid = 19458364 | pmc = 3929400 | doi = 10.1056/nejmoa0805840 }}
• Cyclic adenosine monophosphate 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.Dipyridamole in the laboratory: {{cite journal | vauthors = Fata-Hartley CL, Palmenberg AC | title = Dipyridamole reversibly inhibits mengovirus RNA replication | journal = Journal of Virology | volume = 79 | issue = 17 | pages = 11062–11070 | date = September 2005 | pmid = 16103157 | pmc = 1193570 | doi = 10.1128/JVI.79.17.11062-11070.2005 }}
• It can be used for myocardial stress testing as an alternative to exercise-induced stress methods such as treadmills.
• It is an experimental agent used for the treatment of restless leg syndrome, conditionally recommended by the American Academy of Sleep Medicine as a second-line treatment (conditional recommendation, low certainty of evidence).{{cite journal | vauthors = Winkelman JW, Berkowski JA, DelRosso LM, Koo BB, Scharf MT, Sharon D, Zak RS, Kazmi U, Falck-Ytter Y, Shelgikar AV, Trotti LM, Walters AS | title = Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline | journal = Journal of Clinical Sleep Medicine | volume = 21 | issue = 1 | pages = 137–152 | date = January 2025 | pmid = 39324694 | pmc = 11701286 | doi = 10.5664/jcsm.11390 | title-link = doi | doi-access = free }}

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.{{cite journal | vauthors = Russell TL, Berardi RR, Barnett JL, O'Sullivan TL, Wagner JG, Dressman JB | title = pH-related changes in the absorption of dipyridamole in the elderly | journal = Pharmaceutical Research | volume = 11 | issue = 1 | pages = 136–43 | date = January 1994 | pmid = 7908130 | doi = 10.1023/a:1018918316253 | hdl = 2027.42/41435 | s2cid = 12877330 | hdl-access = free }}{{cite journal | vauthors = Derendorf H, VanderMaelen CP, Brickl RS, MacGregor TR, Eisert W | title = Dipyridamole bioavailability in subjects with reduced gastric acidity | journal = Journal of Clinical Pharmacology | volume = 45 | issue = 7 | pages = 845–50 | date = July 2005 | pmid = 15951475 | doi = 10.1177/0091270005276738 | s2cid = 36579161 }}{{Cite web |url= http://emc.medicines.org.uk/medicine/304/SPC/Persantin+Retard+200mg/#EXCIPIENTS |title=Persantin Retard 200mg - Summary of Product Characteristics (SPC) | work = Electronic Medicines Compendium (EMC) |access-date=6 February 2010 |archive-url=https://web.archive.org/web/20090705233529/http://emc.medicines.org.uk/medicine/304/SPC/Persantin%20Retard%20200mg/#EXCIPIENTS |archive-date=5 July 2009 |url-status=dead }}{{Cite book| vauthors = Stockley I |year=2009 |title= Stockley's Drug Interactions |publisher = The Pharmaceutical Press|isbn=978-0-85369-424-3}}

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.{{cite journal | vauthors = De Schryver EL, Algra A, van Gijn J | title = Dipyridamole for preventing stroke and other vascular events in patients with vascular disease | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD001820 | date = July 2007 | pmid = 17636684 | doi = 10.1002/14651858.CD001820.pub3 | veditors = Algra A }}

A triple therapy of aspirin, clopidogrel, and dipyridamole has been investigated, but this combination led to an increase in adverse bleeding events.{{cite journal | vauthors = Sprigg N, Gray LJ, England T, Willmot MR, Zhao L, Sare GM, Bath PM | title = A randomised controlled trial of triple antiplatelet therapy (aspirin, clopidogrel and dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility | journal = PLOS ONE | volume = 3 | issue = 8 | pages = e2852 | date = August 2008 | pmid = 18682741 | pmc = 2481397 | doi = 10.1371/journal.pone.0002852 | veditors = Berger JS | doi-access = free | bibcode = 2008PLoSO...3.2852S }}

Due to its action as a phosphodiesterase inhibitor, dipyridamole is likely to potentiate the effects of adenosine. This occurs by blocking the nucleoside transporter (ENT1) through which adenosine enters erythrocyte and endothelial cells.{{cite journal | vauthors = Gamboa A, Abraham R, Diedrich A, Shibao C, Paranjape SY, Farley G, Biaggioni I | title = Role of adenosine and nitric oxide on the mechanisms of action of dipyridamole | journal = Stroke | volume = 36 | issue = 10 | pages = 2170–5 | date = October 2005 | pmid = 16141426 | doi = 10.1161/01.STR.0000179044.37760.9d | s2cid = 1877425 }}

According to Association of Anaesthetists of Great Britain and Ireland 2016 guidelines, dipyridamole is considered to not cause risk of bleeding when receiving neuroaxial anaesthesia and deep nerve blocks. It does not therefore require cessation prior to anaesthesia with these techniques, and can continue to be taken with nerve block catheters in place.AAGBI Guidelines Neuraxial and Coagulation June 2016

Dipyridamole overdose can be treated with aminophylline{{rp|6}} or caffeine which reverses its dilating effect on the blood vessels. Symptomatic treatment is recommended, possibly including a vasopressor drug. Gastric lavage should be considered. Since dipyridamole is highly protein bound, dialysis is not likely to be of benefit.

Dipyridamole has two known effects, acting via different mechanisms of action:

• Dipyridamole inhibits the phosphodiesterase enzymes that normally break down cAMP (increasing cellular cAMP levels and blocking the platelet aggregation, response{{cite journal | vauthors = Brown DG, Wilkerson EC, Love WE | title = A review of traditional and novel oral anticoagulant and antiplatelet therapy for dermatologists and dermatologic surgeons | journal = Journal of the American Academy of Dermatology | volume = 72 | issue = 3 | pages = 524–534 | date = March 2015 | pmid = 25486915 | doi = 10.1016/j.jaad.2014.10.027 }} to ADP) and/or cGMP.
• Dipyridamole inhibits the cellular reuptake of adenosine into platelets, red blood cells, and endothelial cells, leading to increased extracellular concentrations of adenosine.

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