Dipyridamole, sold under the brand name Persantine among others, is an

antiplatelet drug An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effectiv ...

of the nucleoside transport inhibitor and

PDE3 inhibitor A PDE3 inhibitor is a drug which inhibits the action of the phosphodiesterase enzyme PDE3. They are used for the therapy of acute heart failure and cardiogenic shock. Medical uses Cardiac Amrinone, milrinone and enoximone are used clinically ...

class that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a short time.

Medical uses

* Dipyridamole is used to dilate blood vessels in people with

peripheral arterial disease Peripheral artery disease (PAD) is a vascular disorder that causes abnormal narrowing of arteries other than those that supply the heart or brain. PAD can happen in any blood vessel, but it is more common in the legs than the arms. When narr ...

and

coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...

. * Dipyridamole has been shown to lower

pulmonary hypertension Pulmonary hypertension (PH or PHTN) is a condition of increased blood pressure in the pulmonary artery, arteries of the lungs. Symptoms include dypsnea, shortness of breath, Syncope (medicine), fainting, tiredness, chest pain, pedal edema, swell ...

without significant drop of systemic

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

. * It inhibits proliferation of smooth muscle cells in vivo and modestly increases unassisted patency of synthetic arteriovenous hemodialysis grafts. *

Cyclic adenosine monophosphate Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger, or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of adenosine tri ...

impairs platelet aggregation and also causes arteriolar

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

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. * It is an experimental agent used for the treatment of

restless leg syndrome Restless legs syndrome (RLS), also known as Willis–Ekbom disease (WED), is a neurological disorder, usually chronic, that causes an overwhelming urge to move one's legs. There is often an unpleasant feeling in the legs that improves temporaril ...

, conditionally recommended by the

American Academy of Sleep Medicine The American Academy of Sleep Medicine (AASM) is a United States professional society for the medical subspecialty of sleep medicine which includes disorders of circadian rhythms. It was established in 1975. The organization's functions includ ...

as a second-line treatment (conditional recommendation, low certainty of evidence).

Stroke

A combination of dipyridamole and

aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

( acetylsalicylic acid/dipyridamole) is

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

-approved for the secondary prevention of

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

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 Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump. The body eventually synthesizes ne ...

) will inhibit the absorption of liquid and plain tablets. However, it is not licensed as monotherapy for stroke prophylaxis, although a

Cochrane review Cochrane is a British international charitable organisation formed to synthesize medical research findings to facilitate evidence-based choices about health interventions involving health professionals, patients and policy makers. It includes ...

suggested that dipyridamole may reduce the risk of further vascular events in patients presenting after cerebral

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...

. A triple therapy of

clopidogrel Clopidogrel, sold under the brand name Plavix among others, is an antiplatelet drug, antiplatelet medication used to reduce the risk of Cardiovascular disease, heart disease and stroke in those at high risk. It is also used together with aspi ...

, and dipyridamole has been investigated, but this combination led to an increase in adverse bleeding events.

Interactions

Due to its action as a phosphodiesterase inhibitor, dipyridamole is likely to potentiate the effects of

adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside build ...

. This occurs by blocking the nucleoside transporter (ENT1) through which adenosine enters

erythrocyte Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood ce ...

and

endothelial The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...

cells. According to

Association of Anaesthetists of Great Britain and Ireland The Association of Anaesthetists, in full the Association of Anaesthetists of Great Britain and Ireland (AAGBI), is a professional association for anaesthesiology, anaesthetists in the United Kingdom and Republic of Ireland, Ireland. It was f ...

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

Overdose

Dipyridamole

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

can be treated with aminophylline or

caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...

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.

Mechanisms of action

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 Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cytop ...

, response to ADP) and/or

cGMP CGMP is an initialism. It can refer to: *cyclic guanosine monophosphate (cGMP) * current good manufacturing practice (cGMP) *CGMP, Cisco Group Management Protocol, the Cisco version of Internet Group Management Protocol The Internet Group Manag ...

. * Dipyridamole inhibits the cellular reuptake of

into

platelets Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cyto ...

red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

s, and

endothelial cell The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...

s, leading to increased extracellular concentrations of adenosine.

References

{{Portal bar , Medicine Adenosine reuptake inhibitors Hydroxyethyl compounds Antiplatelet drugs PDE3 inhibitors 1-Piperidinyl compounds Pyrimidopyrimidines Management of stroke