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| __NOTOC__
| | #REDIRECT [[Adenosine#Pharmacology]] |
| {{drugbox
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| | IUPAC_name = (2R,3R,4R,5R)-2-(6-aminopurin-9-yl)- 5-(hydroxymethyl)oxolane-3,4-diol
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| | image = Adenosine_svg.png
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| | CAS_number = 58-61-7
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| | ATC_prefix = C01
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| | ATC_suffix = EB10
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| | ATC_supplemental =
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| | PubChem = 60961
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| | DrugBank = APRD00132
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| | smiles = Nc1ncnc2[n](cnc12)[C@@H]3O[C@H](CO)C(O)C3O
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| | C=10 | H=13 | N=5 | O=4
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| | molecular_weight = 267.242 g/mol
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| | bioavailability = Rapidly cleared from circulation via cellular uptake
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| | protein_bound = No
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| | metabolism = Rapidly converted to inosine and adenosine monophosphate
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| | elimination_half-life = cleared plasma <30 seconds - half life <10 seconds
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| | excretion = can leave cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid
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| | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
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| | pregnancy_US = <!-- A / B / C / D / X -->
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| | pregnancy_category = C
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| | legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
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| | legal_UK = <!-- GSL / P / POM / CD -->
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| | legal_US = <!-- OTC / Rx-only -->
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| | legal_status = Australia - Legal; UK - Legal; US - Rx only
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| | routes_of_administration = IV or injection
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| }}
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| {{SI}}
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| {{CMG}}
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| {{Editor Join}}
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| '''Adenosine''' is a [[nucleoside]] composed of [[adenine]] attached to a [[ribose]] ([[ribofuranose]]) moiety via a β-N<sub>9</sub>-[[glycosidic bond]].
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| Adenosine plays an important role in [[biochemistry|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.
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| ==Pharmacological effects==
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| Adenosine is an endogenous purine nucleoside that modulates many physiologic processes. Cellular signaling by adenosine occurs through four known adenosine receptor subtypes (A1, A2A, A2B, and A3).
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| 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 regards 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.
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| ===Adenosine receptors===
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| {{Main|Adenosine receptor}}
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| 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 cyclase]] activity. The A2A and A2B receptors couple to Gάs and mediate the stimulation of adenylate cyclase, while the A1 and A3 adenosine receptors couple to Gάi which inhibits adenylate cyclase activity. Additionally, A1 receptors couple to Gάo, which has been reported to mediate adenosine inhibition of Ca2+ conductance, whereas A2B and A3 receptors also couple to Gάq and stimulate phospholipase activity.
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| ===Anti-inflammatory Properties===
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| Adenosine is a potent anti-inflammatory agent, acting at its four G-protein coupled receptors. 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.
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| ===Action on the heart===
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| When administered intravenously, adenosine causes transient [[heart block]] in the [[AV node]]. This is mediated via the [[A1 receptor]], inhibiting adenyl 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 dilatation 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.
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| 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 arrhythmia]]s 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.
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| 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]].
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| Fast rhythms of the heart that are confined to the [[atrium (anatomy)|atria]] (e.g., [[atrial fibrillation]], [[atrial flutter]]) or [[Ventricle (heart)|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.
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| Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class V [[antiarrhythmic agents|antiarrhythmic agent]]. When adenosine is used to [[cardioversion|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.<ref>{{cite book |title=Coronary Pressure |last=Pijls |first=Nico H. J. |coauthors=Bernard De Bruyne |year=2000 |publisher=Springer |isbn=0792361709 }}</ref>
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| [[Image:Caffeine and adenosine_svg.png|thumb|left|350px|[[Caffeine]]'s principal mode of action is as an [[Receptor antagonist|antagonist]] of adenosine receptors in the brain. They are presented here side by side for comparison.]]
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| 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 [[methylxanthine]]s (e.g., [[caffeine]] (found in coffee) and [[theophylline]] (found predominantly in tea).
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| ===Action in CNS===
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| Generalized, adenosine has an inhibitory effect in the [[central nervous system]] (CNS).
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| 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]].
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| ===Dosage===
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| When given for the evaluation or treatment of an SVT, the initial dose is 6 mg, given as a fast [[intravenous|IV]]/Intraosseous [[IO]] push. Due to adenosine's extremely short half-life, the IV line is started as proximal to the heart as possible, such as the antecubital fossa. The IV push is often followed with an immediate flush of 5-10ccs of saline. If this has no effect (e.g., no evidence of transient AV block), a 12mg dose can be given 1-2 minutes after the first dose. If the 12mg dose has no effect, a second 12mg dose can be administered 1-2 minutes after the previous dose. 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.
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| 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 (medical)|shock]], [[hypoxia]], and/or hepatic or renal insufficiency, and in [[elderly]] patients.
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| ===Drug Interactions===
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| Dopamine may precipitate toxicity in the patient.
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| Carbamazepine may increase heart block.
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| Theophylline and caffeine (methylxanthines) antagonize adenosine's effects; may require increased dose of adenosine.
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| ===Contraindications===
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| [[Contraindication]]s for adenosine are e.g.:
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| *Poison/Drug induced tachycardia,
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| *[[Asthma]] (relative contraindication),
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| *2nd or 3rd degree [[heart block]],
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| *[[Atrial fibrillation]],
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| *[[atrial flutter]],
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| *[[Ventricular tachycardia]],
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| *[[Sick sinus syndrome]],
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| *[[Stokes-Adams Attack]],
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| *[[Wolf-Parkinson-White syndrome]],
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| *[[bradycardia]] with [[Premature Ventricular Contraction]]s (PVCs).
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| In Wolf-Parkinson-White syndrome adenosine may be administered if equipment for cardioversion is immediately available as a backup.
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| ===Side effects===
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| Many individuals experience facial flushing, lightheadedness, [[diaphoresis]], or nausea after administration of adenosine. These symptoms are transitory, usually lasting less than one minute.
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| ==Metabolism==
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| When adenosine enters the circulation, it is broken down by adenosine deaminase, which is present in [[red cell]]s and the vessel wall.
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| [[Dipyridamole]], an inhibitor of [[adenosine deaminase]], allows adenosine to accumulate in the blood stream. This causes an increase in coronary vasodilatation.
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| == See also ==
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| * [[Adenosine receptor]]s
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| ==References==
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| {{reflist}}
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| == External links ==
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| *[http://www.compchemwiki.org/index.php?title=Adenosine Computational Chemistry Wiki]
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| *[http://www.sfn.org/index.cfm?pagename=brainBriefings_adenosineAndSleep Adenosine and Sleep]
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| {{Nucleic acids}}
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| {{Antiarrhythmic agents}}
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| [[Category:Antiarrhythmic agents]]
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| [[Category:Nucleosides]]
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