Adenosine
Encyclopedia
Adenosine is a purine
nucleoside
comprising a molecule
of adenine
attached to a ribose
sugar molecule (ribofuranose) moiety via a β-N9-glycosidic bond
.
Adenosine plays an important role in biochemical
processes, such as energy transfer—as adenosine triphosphate
(ATP) and adenosine diphosphate
(ADP)—as well as in signal transduction
as cyclic adenosine monophosphate
, cAMP. It is also an inhibitory neurotransmitter, believed to play a role in promoting sleep and suppressing arousal, with levels increasing with each hour an organism is awake.
Adenosine is often abbreviated Ado.
Extracellular adenosine concentrations from normal cells are approximately 300 nM; however, in response to cellular damage (e.g. in inflammatory or ischemic tissue), these concentrations are quickly elevated (600–1,200 nM). Thus, in regard to stress or injury, the function of adenosine is primarily that of cytoprotection preventing tissue damage during instances of hypoxia
, ischemia
, and seizure activity. Activation of A2A receptors produces a constellation of responses that in general can be classified as anti-inflammatory.
activity. The A2A and A2B receptors couple to Gs and mediate the stimulation of adenylate cyclase, while the A1 and A3 adenosine receptors couple to Gi which inhibits adenylate cyclase activity. Additionally, A1 receptors couple to Go, which has been reported to mediate adenosine inhibition of Ca2+ conductance, whereas A2B and A3 receptors also couple to Gq and stimulate phospholipase activity.
agent at the A(2A) receptor. Topical treatment of adenosine to foot wounds in diabetes mellitus
has been shown in lab animals to drastically increase tissue repair and reconstruction. Topical administration of adenosine for use in wound healing deficiencies and diabetes mellitus in humans is currently under clinical investigation.
Methotrexate
's anti-inflammatory effect may be due to its stimulation of adenosine release.
in the Atrioventricular (AV) node
. This is mediated via the A1 receptor, inhibiting adenylyl cyclase, reducing cAMP and so causing cell hyperpolarization by increasing outward K+ flux. It also causes endothelial dependent relaxation of smooth muscle as is found inside the artery walls. This causes dilation of the "normal" segments of arteries; i.e. where the endothelium
is not separated from the tunica media by atherosclerotic plaque. This feature allows physicians to use adenosine to test for blockages in the coronary arteries, by exaggerating the difference between the normal and abnormal segments.
In individuals suspected of suffering from a supraventricular tachycardia
(SVT), adenosine is used to help identify the rhythm. Certain SVTs can be successfully terminated with adenosine. This includes any re-entrant arrhythmias that require the AV node for the re-entry (e.g., AV reentrant tachycardia (AVRT), AV nodal reentrant tachycardia
(AVNRT). In addition, atrial tachycardia
can sometimes be terminated with adenosine.
Adenosine has an indirect effect on atrial tissue causing a shortening of the refractory period. When administered via a central lumen catheter, adenosine has been shown to initiate atrial fibrillation
because of its effect on atrial tissue. In individuals with accessory pathways, the onset of atrial fibrillation can lead to a life-threatening ventricular fibrillation
.
Fast rhythms of the heart that are confined to the atria
(e.g., atrial fibrillation
, atrial flutter
) or ventricles
(e.g., monomorphic ventricular tachycardia) and do not involve the AV node as part of the re-entrant circuit are not typically converted by adenosine. However, the ventricular response rate is temporarily slowed with adenosine in such cases.
Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class IV antiarrhythmic agent. When adenosine is used to cardiovert
an abnormal rhythm, it is normal for the heart to enter ventricular asystole
for a few seconds. This can be disconcerting to a normally conscious patient, and is associated with angina-like sensations in the chest.
By nature of caffeine
's purine
structure it binds to some of the same receptors as adenosine. The pharmacological effects of adenosine may therefore be blunted in individuals who are taking large quantities of methylxanthines (e.g., caffeine
, found in coffee and tea, or theobromine
, as found in chocolate).
(CNS).
Caffeine
's stimulatory effects, on the other hand, are primarily (although not entirely) credited to its inhibition of adenosine by binding to the same receptors, and therefore effectively blocking adenosine receptors in the CNS. This reduction in adenosine activity leads to increased activity of the neurotransmitter
s dopamine
and glutamate.
(SVT), the initial dose is 6 mg, given as a rapid parenteral infusion. Due to adenosine's extremely short half-life, the IV line is started as proximal (near) to the heart as possible, such as the cubital fossa
. The IV push is often followed with an immediate flush of 10-20ccs of saline. If this has no effect (i.e. no evidence of transient AV block), a 12 mg dose can be given 1–2 minutes after the first dose. AHA 2010 IS NO LONGER RECOMMENDING A SECOND DOSE OF 12MG. PLEASE VIEW ALGORITHM AS CONFIRMATION. Some clinicians may prefer to administer a higher dose (typically 18 mg), rather than repeat a dose that apparently had no effect. When given to dilate the arteries, such as in a "stress test", the dosage is typically 0.14 mg/kg/min, administered for 4 or 6 minutes, depending on the protocol.
The recommended dose may be increased in patients on theophylline since methylxanthines prevent binding of adenosine at receptor sites. The dose is often decreased in patients on dipyridamole (Persantine) and diazepam (Valium) because adenosine potentiates the effects of these drugs. The recommended dose is also reduced by half in patients who are presenting congestive heart failure
, myocardial infarction
, shock, hypoxia
, and/or hepatic or renal insufficiency, and in elderly patients.
Carbamazepine may increase heart block.
Theophylline and caffeine (methylxanthines) competitively antagonize adenosine's effects; an increased dose of adenosine may be required.
Dipyridamole potentiates the action of adenosine, requiring the use of lower doses.
s for adenosine are:
In Wolff-Parkinson-White syndrome
, adenosine may be administered if equipment for cardioversion is immediately available as a backup.
, or nausea after administration of adenosine due to its vasodilatory effects. Metallic taste is a hallmark side effect of adenosine administration. These symptoms are transitory, usually lasting less than one minute. It is classically associated with a sense of "impending doom", more prosaically described as apprehension. This lasts a few seconds after administration of a bolus dose, during transient asystole
induced by intravenous administration. In some cases adenosine can make patients' limbs feel numb for about 2–5 minutes after administration intravenously depending on the dosage (usually above 12 mg).
(AMP), though it is possible other pathways exist.
When adenosine enters the circulation, it is broken down by adenosine deaminase
, which is present in red cell
s and the vessel wall.
Dipyridamole
, an inhibitor of adenosine deaminase
, allows adenosine to accumulate in the blood stream. This causes an increase in coronary vasodilatation.
Adenosine deaminase deficiency
is a known cause of immunodeficiency.
of the dengue virus
by terminating its RNA chain synthesis. This suppresses peak viremia
, rise in cytokine
s and prevented infected animal from death raising the possibility of a new treatment for this flavivirus
. The 7-deaza-adenosine analog has been shown to inhibit the replication of the hepatitis C virus
. Such adenosine analogs are potentially clinically useful since they can be taken orally.
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
nucleoside
Nucleoside
Nucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage...
comprising a molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
of adenine
Adenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
attached to a ribose
Ribose
Ribose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....
sugar molecule (ribofuranose) moiety via a β-N9-glycosidic bond
Glycosidic bond
In chemistry, a glycosidic bond is a type of covalent bond that joins a carbohydrate molecule to another group, which may or may not be another carbohydrate....
.
Adenosine plays an important role in biochemical
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
processes, such as energy transfer—as adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
(ATP) and adenosine diphosphate
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
(ADP)—as well as in signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
as cyclic adenosine monophosphate
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
, cAMP. It is also an inhibitory neurotransmitter, believed to play a role in promoting sleep and suppressing arousal, with levels increasing with each hour an organism is awake.
Adenosine is often abbreviated Ado.
Pharmacological effects
Adenosine is an endogenous purine nucleotide that modulates many physiological processes. Cellular signaling by adenosine occurs through four known adenosine receptor subtypes (A1, A2A, A2B, and A3).Extracellular adenosine concentrations from normal cells are approximately 300 nM; however, in response to cellular damage (e.g. in inflammatory or ischemic tissue), these concentrations are quickly elevated (600–1,200 nM). Thus, in regard to stress or injury, the function of adenosine is primarily that of cytoprotection preventing tissue damage during instances of hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
, ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
, and seizure activity. Activation of A2A receptors produces a constellation of responses that in general can be classified as anti-inflammatory.
Adenosine receptors
The different adenosine receptor subtypes (A1, A2A, A2B, and A3) are all seven transmembrane spanning G-protein coupled receptors. These four receptor subtypes are further classified based on their ability to either stimulate or inhibit adenylate cyclaseAdenylate cyclase
Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....
activity. The A2A and A2B receptors couple to Gs and mediate the stimulation of adenylate cyclase, while the A1 and A3 adenosine receptors couple to Gi which inhibits adenylate cyclase activity. Additionally, A1 receptors couple to Go, which has been reported to mediate adenosine inhibition of Ca2+ conductance, whereas A2B and A3 receptors also couple to Gq and stimulate phospholipase activity.
Anti-inflammatory properties
Adenosine is believed to be an anti-inflammatoryAnti-inflammatory
Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....
agent at the A(2A) receptor. Topical treatment of adenosine to foot wounds in diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
has been shown in lab animals to drastically increase tissue repair and reconstruction. Topical administration of adenosine for use in wound healing deficiencies and diabetes mellitus in humans is currently under clinical investigation.
Methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
's anti-inflammatory effect may be due to its stimulation of adenosine release.
Action on the heart
When administered intravenously, adenosine causes transient heart blockHeart block
A heart block can be a blockage at any level of the electrical conduction system of the heart .* Blocks that occur within the sinoatrial node are described as SA nodal blocks....
in the Atrioventricular (AV) node
Atrioventricular node
The atrioventricular node is a part of the electrical control system of the heart that coordinates heart rate. It electrically connects atrial and ventricular chambers...
. This is mediated via the A1 receptor, inhibiting adenylyl cyclase, reducing cAMP and so causing cell hyperpolarization by increasing outward K+ flux. It also causes endothelial dependent relaxation of smooth muscle as is found inside the artery walls. This causes dilation of the "normal" segments of arteries; i.e. where the endothelium
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
is not separated from the tunica media by atherosclerotic plaque. This feature allows physicians to use adenosine to test for blockages in the coronary arteries, by exaggerating the difference between the normal and abnormal segments.
In individuals suspected of suffering from a supraventricular tachycardia
Supraventricular tachycardia
Supraventricular tachycardia is a general term that refers to any rapid heart rhythm originating above the ventricular tissue. Supraventricular tachycardias can be contrasted to the potentially more dangerous ventricular tachycardias - rapid rhythms that originate within the ventricular...
(SVT), adenosine is used to help identify the rhythm. Certain SVTs can be successfully terminated with adenosine. This includes any re-entrant arrhythmias that require the AV node for the re-entry (e.g., AV reentrant tachycardia (AVRT), AV nodal reentrant tachycardia
AV nodal reentrant tachycardia
AV nodal reentrant tachycardia , or atrioventricular nodal reentrant tachycardia, is a type of tachycardia of the heart. It is a type of supraventricular tachycardia , meaning that it originates from a location within the heart above the bundle of His. AV nodal reentrant tachycardia is the most...
(AVNRT). In addition, atrial tachycardia
Atrial tachycardia
Atrial tachycardia is a type of atrial arrhythmia in which the heart's electrical impulse comes from an ectopic atrial pacemaker rather than from the SA node. Atrial tachycardias are characterized by very regular rates ranging from 140–220 bpm....
can sometimes be terminated with adenosine.
Adenosine has an indirect effect on atrial tissue causing a shortening of the refractory period. When administered via a central lumen catheter, adenosine has been shown to initiate atrial fibrillation
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
because of its effect on atrial tissue. In individuals with accessory pathways, the onset of atrial fibrillation can lead to a life-threatening ventricular fibrillation
Ventricular fibrillation
Ventricular fibrillation is a condition in which there is uncoordinated contraction of the cardiac muscle of the ventricles in the heart, making them quiver rather than contract properly. Ventricular fibrillation is a medical emergency and most commonly identified arrythmia in cardiac arrest...
.
Fast rhythms of the heart that are confined to the atria
Atrium (anatomy)
In anatomy, the atrium , sometimes called auricle , refers to a chamber or space. For example, the term is used for a portion of the lateral ventricle in the brain and the blood collection chamber of the heart...
(e.g., atrial fibrillation
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
, atrial flutter
Atrial flutter
Atrial flutter is an abnormal heart rhythm that occurs in the atria of the heart. When it first occurs, it is usually associated with a fast heart rate or tachycardia , and falls into the category of supra-ventricular tachycardias. While this rhythm occurs most often in individuals with...
) or ventricles
Ventricle (heart)
In the heart, a ventricle is one of two large chambers that collect and expel blood received from an atrium towards the peripheral beds within the body and lungs. The Atria primes the Pump...
(e.g., monomorphic ventricular tachycardia) and do not involve the AV node as part of the re-entrant circuit are not typically converted by adenosine. However, the ventricular response rate is temporarily slowed with adenosine in such cases.
Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class IV antiarrhythmic agent. When adenosine is used to cardiovert
Cardioversion
Cardioversion is a medical procedure by which an abnormally fast heart rate or cardiac arrhythmia is converted to a normal rhythm, using electricity or drugs. Synchronized electrical cardioversion uses a therapeutic dose of electric current to the heart, at a specific moment in the cardiac cycle...
an abnormal rhythm, it is normal for the heart to enter ventricular asystole
Asystole
In medicine, asystole is a state of no cardiac electrical activity, hence no contractions of the myocardium and no cardiac output or blood flow...
for a few seconds. This can be disconcerting to a normally conscious patient, and is associated with angina-like sensations in the chest.
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
's purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
structure it binds to some of the same receptors as adenosine. The pharmacological effects of adenosine may therefore be blunted in individuals who are taking large quantities of methylxanthines (e.g., caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
, found in coffee and tea, or theobromine
Theobromine
Theobromine , also known as xantheose, is a bitter alkaloid of the cacao plant, with the chemical formula C7H8N4O2. It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola nut...
, as found in chocolate).
Action in the central nervous system
Generalized, adenosine has an inhibitory effect in the central nervous systemCentral nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS).
Caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
's stimulatory effects, on the other hand, are primarily (although not entirely) credited to its inhibition of adenosine by binding to the same receptors, and therefore effectively blocking adenosine receptors in the CNS. This reduction in adenosine activity leads to increased activity of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
and glutamate.
Dosage
When given for the evaluation or treatment of a supraventricular tachycardiaSupraventricular tachycardia
Supraventricular tachycardia is a general term that refers to any rapid heart rhythm originating above the ventricular tissue. Supraventricular tachycardias can be contrasted to the potentially more dangerous ventricular tachycardias - rapid rhythms that originate within the ventricular...
(SVT), the initial dose is 6 mg, given as a rapid parenteral infusion. Due to adenosine's extremely short half-life, the IV line is started as proximal (near) to the heart as possible, such as the cubital fossa
Cubital fossa
The cubital fossa is the triangular area on the anterior view of the elbow of a human or other hominid animal. It is colloquially known as the "elbow pit".-Boundaries:...
. The IV push is often followed with an immediate flush of 10-20ccs of saline. If this has no effect (i.e. no evidence of transient AV block), a 12 mg dose can be given 1–2 minutes after the first dose. AHA 2010 IS NO LONGER RECOMMENDING A SECOND DOSE OF 12MG. PLEASE VIEW ALGORITHM AS CONFIRMATION. Some clinicians may prefer to administer a higher dose (typically 18 mg), rather than repeat a dose that apparently had no effect. When given to dilate the arteries, such as in a "stress test", the dosage is typically 0.14 mg/kg/min, administered for 4 or 6 minutes, depending on the protocol.
The recommended dose may be increased in patients on theophylline since methylxanthines prevent binding of adenosine at receptor sites. The dose is often decreased in patients on dipyridamole (Persantine) and diazepam (Valium) because adenosine potentiates the effects of these drugs. The recommended dose is also reduced by half in patients who are presenting congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
, myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
, shock, hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
, and/or hepatic or renal insufficiency, and in elderly patients.
Drug interactions
Dopamine may precipitate toxicity in the patient.Carbamazepine may increase heart block.
Theophylline and caffeine (methylxanthines) competitively antagonize adenosine's effects; an increased dose of adenosine may be required.
Dipyridamole potentiates the action of adenosine, requiring the use of lower doses.
Contraindications
Common ContraindicationContraindication
In medicine, a contraindication is a condition or factor that serves as a reason to withhold a certain medical treatment.Some contraindications are absolute, meaning that there are no reasonable circumstances for undertaking a course of action...
s for adenosine are:
- 2nd or 3rd degree heart blockHeart blockA heart block can be a blockage at any level of the electrical conduction system of the heart .* Blocks that occur within the sinoatrial node are described as SA nodal blocks....
(without a pacemaker) - Sick sinus syndromeSick sinus syndromeSick sinus syndrome, also called sinus node dysfunction, is a group of abnormal heart rhythms presumably caused by a malfunction of the sinus node, the heart's primary pacemaker...
(without a pacemaker) - Long QT syndromeLong QT syndromeThe long QT syndrome is a rare inborn heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsade de pointes . These episodes may lead to palpitations, fainting and sudden death due to ventricular fibrillation...
- Severe hypotension
- Decompensated heart failure
- AsthmaAsthmaAsthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, traditionally an absolute CI this is being contended and it is now considered relative (however, selective adenosine agonists are being investigated for use in treatment of asthma) - Poison/drug-induced tachycardia
In Wolff-Parkinson-White syndrome
Wolff-Parkinson-White syndrome
Wolff–Parkinson–White syndrome is a disorder of the heart in which the ventricles of the heart contract prematurely due to an accessory pathway known as the bundle of Kent. This accessory pathway is an abnormal electrical communication from the atria to the ventricles...
, adenosine may be administered if equipment for cardioversion is immediately available as a backup.
Side effects
Many individuals experience facial flushing, a temporary rash on the chest, lightheadedness, diaphoresisDiaphoresis
Diaphoresis is excessive sweating commonly associated with shock and other medical emergency conditions.Diaphoretic is the state of perspiring profusely, or something that has the power to cause increased perspiration....
, or nausea after administration of adenosine due to its vasodilatory effects. Metallic taste is a hallmark side effect of adenosine administration. These symptoms are transitory, usually lasting less than one minute. It is classically associated with a sense of "impending doom", more prosaically described as apprehension. This lasts a few seconds after administration of a bolus dose, during transient asystole
Asystole
In medicine, asystole is a state of no cardiac electrical activity, hence no contractions of the myocardium and no cardiac output or blood flow...
induced by intravenous administration. In some cases adenosine can make patients' limbs feel numb for about 2–5 minutes after administration intravenously depending on the dosage (usually above 12 mg).
Metabolism
Adenosine used as a second messenger can be the result of de novo purine biosynthesis via adenosine monophosphateAdenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...
(AMP), though it is possible other pathways exist.
When adenosine enters the circulation, it is broken down by 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 is present in red 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 the vessel wall.
Dipyridamole
Dipyridamole
Dipyridamole is a drug that inhibits thrombus formation when given chronically and causes vasodilation when given at high doses over a short time.-Mechanism and effects:...
, an inhibitor of 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:...
, allows adenosine to accumulate in the blood stream. This causes an increase in coronary vasodilatation.
Adenosine deaminase deficiency
Adenosine deaminase deficiency
Adenosine deaminase deficiency, also called ADA deficiency or ADA-SCID, is an autosomal recessive metabolic disorder that causes immunodeficiency. It occurs in fewer than one in 100,000 live births worldwide....
is a known cause of immunodeficiency.
Analogs and viruses
The adenosine analog, NITD008 has been reported to directly inhibit the recombinant an RNA-dependent RNA polymeraseRNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
of the dengue virus
Dengue virus
Dengue virus in one of four serotypes is the cause of dengue fever. It is a mosquito-borne single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus...
by terminating its RNA chain synthesis. This suppresses peak viremia
Viremia
Viremia is a medical condition where viruses enter the bloodstream and hence have access to the rest of the body. It is similar to bacteremia, a condition where bacteria enter the bloodstream.- Primary versus Secondary :...
, rise in cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s and prevented infected animal from death raising the possibility of a new treatment for this flavivirus
Flavivirus
Flavivirus is a genus of the family Flaviviridae. This genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, and several other viruses which may cause encephalitis....
. The 7-deaza-adenosine analog has been shown to inhibit the replication of the hepatitis C virus
Hepatitis C virus
Hepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...
. Such adenosine analogs are potentially clinically useful since they can be taken orally.