Medical Applications and Usage Instructions for Dipyridamole

Dipyridamole, sold under the brand name Persantine among others, is an antiplatelet drug of the nucleoside transport inhibitor and PDE3 inhibitor class that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a short time.

Figure1: Single-Crystal Structure of Dipyridamole

Introduction

Figure2: Image of Dipyridamole

Dipyridamole is used to dilate blood vessels in patients with peripheral arterial and coronary artery disease, and it can also be used for myocardial stress testing as an alternative to exercise-induced methods. The drug has been shown to lower pulmonary hypertension without significantly dropping systemic blood pressure, a characteristic maintained during chronic therapy. Its mechanism involves elevating cyclic adenosine monophosphate, which impairs platelet aggregation and induces arteriolar smooth muscle relaxation. Furthermore, Dipyridamole inhibits the proliferation of smooth muscle cells in vivo and modestly improves the unassisted patency of synthetic arteriovenous hemodialysis grafts. Beyond its cardiovascular applications, Dipyridamole also inhibits the replication of mengovirus RNA and is being investigated as an experimental agent for restless leg syndrome, where it is conditionally recommended as a second-line treatment by the American Academy of Sleep Medicine. [1]

Medical uses

The fixed-dose combination of dipyridamole and aspirin is FDA-approved for the secondary prevention of stroke, offering a bleeding risk equivalent to aspirin alone; however, dipyridamole absorption is pH-dependent, and concomitant use of gastric acid suppressants like proton pump inhibitors can impair its bioavailability from liquid and plain tablet formulations. Although not licensed as monotherapy for stroke prophylaxis, a Cochrane review indicates that dipyridamole may reduce the risk of subsequent vascular events following cerebral ischemia. Furthermore, while a triple therapy regimen of aspirin, clopidogrel, and dipyridamole has been clinically investigated, it demonstrated an elevated risk of adverse bleeding events.

Mechanism of Action

Due to its action as a phosphodiesterase inhibitor, dipyridamole potentiates the effects of adenosine by blocking the nucleoside transporter (ENT1) responsible for adenosine uptake into erythrocytes and endothelial cells. According to the 2016 guidelines from the Association of Anaesthetists of Great Britain and Ireland, dipyridamole is not considered a bleeding risk during neuroaxial anesthesia or deep nerve blocks; therefore, dipyridamole does not require discontinuation prior to such procedures and may be continued even with indwelling nerve block catheters. Dipyridamole exerts its pharmacological effects through two distinct mechanisms: first, it inhibits phosphodiesterase enzymes that degrade cAMP and/or cGMP, thereby elevating cellular levels of these cyclic nucleotides and suppressing platelet aggregation in response to ADP; second, it blocks the cellular reuptake of adenosine by platelets, erythrocytes, and endothelial cells, resulting in increased extracellular adenosine concentrations. [1]

Safety Information

Dipyridamole overdose can be treated with aminophylline:  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 may cause side effects such as headache, nausea, rash, palpitations, and dizziness. The headache results from its vasodilatory effect on cerebral vessels, which increases intracranial pressure. Nausea occurs due to gastrointestinal smooth muscle spasms induced by the drug. The rash, often presenting as erythematous papules or urticarial lesions, is attributed to enhanced cutaneous microcirculation and release of inflammatory factors. Palpitations are triggered by increased myocardial contractility and heart rate. Dizziness arises from excessive peripheral vasodilation and consequent hypotension. Patients should be closely monitored during treatment, and any abnormalities should prompt immediate discontinuation and medical consultation. [2]

Interactions with Other Medicines

Concomitant use of dipyridamole with aspirin or other nonsteroidal anti-inflammatory drugs may produce synergistic therapeutic effects, while coadministration with adrenergic receptor agonists such as norepinephrine can lead to sharp increases in blood pressure. Prior to initiating dipyridamole therapy, patients should undergo comprehensive physical examination with evaluation of medical history and concurrent medications to rule out contraindications. Close monitoring for potential adverse reactions is essential throughout treatment to facilitate timely intervention and regimen adjustment.

Reference

[1] Brown DG. "A review of traditional and novel oral anticoagulant and antiplatelet therapy for dermatologists and dermatologic surgeons". Journal of the American Academy of Dermatology. 2015, 72 : 524–534.

[2] Gamboa A. "Role of adenosine and nitric oxide on the mechanisms of action of dipyridamole". Stroke. 2005, 36 : 2170.