Dipyridamole is a drug

Medication

A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...

 that inhibits thrombus

Thrombus

A thrombus , or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system...

 formation when given chronically and causes vasodilation

Vasodilation

Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...

 when given at high doses over a short time.

Mechanism and effects

• It acts as a thromboxane synthase inhibitor, therefore lowering the levels of TXA2 and thus stops the effects of TXA2 (platelet aggregation, bronchioconstriction and vasoconstriction).
• It inhibits the cellular reuptake of adenosine into platelets, red blood cell
  Red blood cell
  Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
  
  s and endothelial cells leading to increased extracellular concentrations of adenosine.
• It also inhibits the enzyme
  Enzyme
  Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
  
   adenosine deaminase
  Adenosine deaminase
  Adenosine deaminase is an enzyme involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues.-Reactions:...
  
  , which normally breaks down adenosine into inosine
  Inosine
  Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring via a β-N9-glycosidic bond....
  
  . This inhibition leads to further increased levels of extracellular adenosine.
• Dipyridamole also inhibits the phosphodiesterase
  Phosphodiesterase
  A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
  
   enzymes that normally break down cAMP
  Cyclic adenosine monophosphate
  Cyclic adenosine monophosphate is a second messenger important in many biological processes...
  
   (increasing cellular cAMP levels and blocking the platelet response to ADP) and/or cGMP
  Cyclic guanosine monophosphate
  Cyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate . cGMP acts as a second messenger much like cyclic AMP...
  
   (resulting in added benefit when given together with NO or statins).

Medical uses

• Dipyridamole has been shown to lower pulmonary hypertension without significant drop of systemic blood pressure
• It inhibits formation of pro-inflammatory cytokines (MCP-1, MMP-9) in vitro and results in reduction of hsCRP in patients.
• It inhibits proliferation of smooth muscle cells in vivo and has shown to prevent AV-shunt failure in dialysis patients.
• It increases the release of t-PA from brain microvascular endothelial cells
• It results in an increase of 13 - HODE and decrease of 12 - HETE in the subendothelial matrix (SEM) and reduced thrombogenicity of the SEM.
• Pretreatment it reduced reperfusion injury in volunteers.
• It has been shown to increase myocardial perfusion and left ventricular function in patients with ischemic cardiomyopathy.
• It results in a reduction of the number of thrombin and PECAM-1 receptors on platelets in stroke patients.
• cAMP impairs platelet aggregation and also causes arteriolar
  Arteriole
  An arteriole is a small diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries.Arterioles have muscular walls and are the primary site of vascular resistance...
  
   smooth muscle
  Smooth muscle
  Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
  
   relaxation. Chronic therapy did not show significant drop of systemic blood pressure.
• It inhibits the replication of mengovirus
  Mengovirus
  Mengovirus, also known as Columbia SK virus, mouse Elberfield virus and Encephalomyocarditisvirus , belongs to the genus Cardiovirus which is a member of the Picornaviridae. Its genome is a single stranded positive-sense RNA molecule, making the Mengoviruses a class IV virus under the Baltimore...
  
   RNA.
• It can be used for myocardial stress testing as an alternative to exercise-induced stress methods such as treadmills.

Use in individuals with a history of stroke

Modified release dipyridamole is used in conjunction with aspirin

Aspirin

Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

 (under the trade names Aggrenox in the USA or Asasantin Retard in the UK) in the secondary prevention of stroke

Stroke

A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

 and transient ischaemic attack. This practice has been confirmed by the ESPRIT trial. Dipyridamole absorption is pH

PH

In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...

-dependent and concomitant treatment with gastric acid suppressors (such as a proton pump inhibitor

Proton pump inhibitor

Proton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...

) will inhibit the absorption of liquid & plain tablets. Modified release preparations are buffered and absorption is not affected.

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.

A triple therapy of aspirin, clopidogrel

Clopidogrel

Clopidogrel is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. The drug works by irreversibly...

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

• 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
  Stenosis
  A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure.It is also sometimes called a stricture ....
  
   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
  Electrocardiogram
  Electrocardiography is a transthoracic interpretation of the electrical activity of the heart over a period of time, as detected by electrodes attached to the outer surface of the skin and recorded by a device external to the body...
  
   and echocardiography
  Echocardiography
  An echocardiogram, often referred to in the medical community as a cardiac ECHO or simply an ECHO, is a sonogram of the heart . Also known as a cardiac ultrasound, it uses standard ultrasound techniques to image two-dimensional slices of the heart...
  
   when it causes ischemia.
• Flow heterogeneity (a necessary precursor to ischemia) can be detected with gamma camera
  Gamma camera
  A gamma camera, also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy...
  
  s and SPECT using nuclear imaging agents such as Thallium
  Thallium
  Thallium is a chemical element with the symbol Tl and atomic number 81. This soft gray poor metal resembles tin but discolors when exposed to air. The two chemists William Crookes and Claude-Auguste Lamy discovered thallium independently in 1861 by the newly developed method of flame spectroscopy...
  
  -201 and Tc99m
  Technetium-99m
  Technetium-99m is a metastable nuclear isomer of technetium-99, symbolized as 99mTc. The "m" indicates that this is a metastable nuclear isomer, i.e., that its half-life of 6 hours is considerably longer than most nuclear isomers that undergo gamma decay...
  
  -Sestamibi
  Sestamibi
  Technetium sestamibi is a pharmaceutical agent used in nuclear medicine imaging. The drug is a coordination complex of the radioisotope technetium-99m with the ligand methoxyisobutylisonitrile . The generic drug became available late September 2008...
  
  . However relative differences in perfusion not necessarily imply absolute decrease in blood supply in the tissue supplied by a stenosed artery.

Other uses

Dipyridamole also has non-medicinal uses in a laboratory context, such as the inhibition of cardiovirus

Cardiovirus

Cardiovirus is a genus within the family Picornaviridae. The genus comprises two species: Encephalomyocarditis virus and Theilovirus...

 growth in cell culture

Cell culture

Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...

.

Overdose

Dipyridamole overdose can be treated with aminophylline

Aminophylline

Aminophylline is a bronchodilator. It is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate-Properties:...

 and reverses its hemodynamic

Hemodynamics

Hemodynamics, meaning literally "blood movement" is the study of blood flow or the circulation.All animal cells require oxygen for the conversion of carbohydrates, fats and proteins into carbon dioxide , water and energy in a process known as aerobic respiration...

effects (vasodilation). Symptomatic treatment is recommended, possibly including a vasopressor drug. Gastric lavage should be considered. Administration of xanthine derivatives (e.g., aminophylline) may reverse the hemodynamic effects of dipyridamole overdose. Since dipyridamole is highly protein bound, dialysis is not likely to be of benefit.