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| Trade names | Adenocard; Adenocor; Adenic; Adenoco; Adeno-Jec; Adenoscan; Adenosin; Adrekar; Krenosin |
| Other names | SR-96225 (developmental code name) |
| AHFS/Drugs.com | Monograph |
| Pregnancy category |
(adenosine may be safe to the fetus in pregnant women) |
| Routes of administration | Intravenous |
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| Sourcetissues | Primarily liver |
| Metabolism | Rapidly converted to inosine and adenosine monophosphate |
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| Pharmacokinetic data | |
| Bioavailability | Rapidly cleared from circulation via enzyme degradation |
| Protein binding | No |
| Metabolism | Rapidly converted to inosine and adenosine monophosphate |
| Eliminationhalf-life | cleared plasma <30 seconds; half-life <10 seconds |
| Excretion | can leave cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid |
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| ECHA InfoCard | 100.000.354 |
| Chemical and physical data | |
| Formula | C10H13N5O4 |
| Molar mass | 267.245 g·mol−1 |
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Adenosine (symbolA) is anorganic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of anadenine attached to aribose via a β-N9-glycosidic bond. Adenosine is one of the fournucleoside building blocks ofRNA (and its derivativedeoxyadenosine is a building block ofDNA), which are essential for all life on Earth. Its derivatives include the energy carriersadenosine mono-, di-, and triphosphate, also known as AMP/ADP/ATP.Cyclic adenosine monophosphate (cAMP) is pervasive insignal transduction. Adenosine is used as an intravenous medication for somecardiac arrhythmias.
Adenosyl (abbreviatedAdo or5'-dAdo) is the chemical group formed by removal of the 5′-hydroxy (OH) group. It is found inadenosylcobalamin (an active form ofvitamin B12[1]) and as a radical in theradical SAM enzymes.[2]
In individuals withsupraventricular tachycardia (SVT), adenosine is a first line treatment used to help identify and convert the rhythm.[3][4][5][6]
Certain SVTs can be successfully terminated with adenosine.[7] This includes anyre-entrant arrhythmias that require the AV node for the re-entry, e.g.,AV reentrant tachycardia (AVRT) andAV nodal reentrant tachycardia (AVNRT). In addition,atrial tachycardia can sometimes be terminated with adenosine.[8]
Fast rhythms of the heart that are confined to theatria (e.g.,atrial fibrillation andatrial flutter) orventricles (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.[8]
Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class Vantiarrhythmic agent. When adenosine is used tocardiovert an abnormal rhythm, it is normal for the heart to enter ventricularasystole for a few seconds. This can be disconcerting to a normally conscious patient, and is associated with angina-like sensations in the chest.[9]
Adenosine is used as an adjunct tothallium (Tl-201) ortechnetium (Tc-99m)myocardial perfusion scintigraphy (nuclear stress test) in patients unable to undergo adequate stress testing with exercise.[10]
When used to treat SVT, adenosine is administeredintravenously as a rapidbolus (typically 0.10–0.15 mg/kg initially) over 1-2 seconds, followed by a rapidsaline flush (often using a 2-way or 3-way stopcock). If the initial dose is ineffective, it may be repeated every 2 minutes with a slightly increased dose (0.05–0.1 mg/kg increments) every 2 minutes up to a maximum total dose of 0.3 mg/kg (not exceeding 12 mg). Due to adenosine's extremely short half-life (less than 10 seconds), it is often injected through acentral venous line or a large proximal peripheral vein; administration into lower extremities,PICC lines, or smaller veins may lead to therapeutic failure due to rapid metabolism before reaching the heart.[3] 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 ondipyridamole (Persantine) anddiazepam (Valium) because adenosine potentiates the effects of these drugs. The recommended dose is also reduced by half in patients presentingcongestive heart failure,myocardial infarction,shock,hypoxia, and/or chronic liver disease orchronic kidney disease, and inelderly patients.
Adverse effects associated with adenosine administration are primarily due to its activation of adenosine receptors on vascular tissue, resulting in vasodilation. Side effects of adenosine include skin flushing, lightheadedness, nausea, sweating, nervousness, numbness, and asense of impending doom. These effects are typically very short-lived due to adenosine's rapid metabolism and short half-life. Less common, but more serious, cardiovascular effects can occur, such as cardiac arrhythmias (including premature atrial and ventricular contractions and atrioventricular (AV) block), hypotension, cardiac ischemia, and prolonged asystole.[11]
Dipyridamole potentiates the action of adenosine, requiring the use of lower doses.
Methylxanthines (e.g.caffeine found in coffee,theophylline found in tea, ortheobromine found in chocolate) have apurine structure and bind to some of the same receptors as adenosine.[13] Methylxanthines act as competitive antagonists of adenosine and can blunt its pharmacological effects.[14] Individuals taking large quantities of methylxanthines may require increased doses of adenosine.
Caffeine acts by blocking binding of adenosine to theadenosine A1 receptor, which enhances release of the neurotransmitteracetylcholine.[15] Caffeine also increases cyclic AMP levels through nonselective inhibition of phosphodiesterase.[16] "Caffeine has a three-dimensional structure similar to that of adenosine," which allows it to bind and block its receptors.[17]
Alcohol can increase extracellular adenosine levels.[18][19]
Commoncontraindications for adenosine include
Adenosine is an endogenous purine nucleoside that modulates many physiological processes. Cellular signaling by adenosine occurs through four known adenosine receptor subtypes (A1,A2A,A2B, andA3).[21]
Extracellular adenosine concentrations from normal cells are approximately 300 nM; however, in response to cellular damage (e.g., in inflammatory orischemic 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 ofhypoxia,ischemia, and seizure activity. Activation of A2A receptors produces a constellation of responses that in general can be classified as anti-inflammatory.[22] Enzymatic production of adenosine can be anti-inflammatory orimmunosuppressive.[23][24][25]
All adenosine receptor subtypes (A1, A2A, A2B, and A3) areG-protein-coupled receptors. The four receptor subtypes are further classified based on their ability to either stimulate or inhibitadenylate cyclase activity. The A1 receptors couple to Gi/o and decrease cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates adenylate cyclase activity. In addition, 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 stimulatephospholipase activity.Researchers at Cornell University have recently shown adenosine receptors to be key in opening the blood-brain barrier (BBB).Mice dosed with adenosine have shown increased transport across the BBB of amyloid plaque antibodies and prodrugs associated with Parkinson's disease, Alzheimer's, multiple sclerosis, and cancers of the central nervous system.[26]
Adenosine is anendogenousagonist of theghrelin/growth hormone secretagogue receptor.[27] However, while it is able to increaseappetite, unlike other agonists of this receptor, adenosine is unable to induce the secretion ofgrowth hormone and increase its plasma levels.[27]
When it is administered intravenously, adenosine causes transientheart block in theatrioventricular (AV) node. This is mediated via theA1 receptor, inhibiting adenylyl cyclase, reducing cAMP and so causing cell hyperpolarization by increasing K+ efflux viainward rectifier K+ channels, subsequently inhibiting Ca2+ current.[28][29] 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 theendothelium is not separated from the tunica media byatherosclerotic 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.
The administration of adenosine also reduces blood flow to coronary arteries past the occlusion. Other coronary arteries dilate when adenosine is administered while the segment past the occlusion is already maximally dilated, which is a process calledcoronary steal. This leads to less blood reaching the ischemic tissue, which in turn produces the characteristic chest pain.
Adenosine used as asecond messenger can be the result ofde novopurine biosynthesis viaadenosine monophosphate (AMP), though it is possible other pathways exist.[30]
When adenosine enters the circulation, it is broken down byadenosine deaminase, which is present inred blood cells and the vessel wall.
Dipyridamole, an inhibitor ofadenosine nucleoside transporter, allows adenosine to accumulate in the blood stream. This causes an increase in coronaryvasodilatation.
Adenosine deaminase deficiency is a known cause of immunodeficiency.
The adenosine analogNITD008 has been reported to directly inhibit the recombinant RNA-dependentRNA polymerase of thedengue virus by terminating its RNA chain synthesis. This interaction suppresses peakviremia and rise incytokines and prevents lethality in infected animals, raising the possibility of a new treatment for thisflavivirus.[31] The 7-deaza-adenosine analog has been shown to inhibit the replication of thehepatitis C virus.[32]BCX4430 is protective againstEbola andMarburg viruses.[33] Such adenosine analogs are potentially clinically useful since they can be taken orally.
Adenosine is believed to be ananti-inflammatory agent at the A2A receptor.[34][35] Topical treatment of adenosine to foot wounds indiabetes 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.[36]
In general, adenosine has an inhibitory effect in thecentral nervous system (CNS).Caffeine's stimulatory effects are credited primarily (although not entirely) to its capacity to block adenosine receptors, thereby reducing the inhibitory tonus of adenosine in the CNS. This reduction in adenosine activity leads to increased activity of theneurotransmittersdopamine andglutamate.[37] Experimental evidence suggests that adenosine and adenosine agonists can activateTrk receptor phosphorylation through a mechanism that requires the adenosine A2A receptor.[38]
Adenosine has been shown to promote thickening of hair on people with thinning hair.[39][40] A 2013 study compared topical adenosine withminoxidil in maleandrogenetic alopecia, finding it was as potent as minoxidil (in overall treatment outcomes) but with higher satisfaction rate with patients due to "faster prevention of hair loss and appearance of the newly grown hairs" (further trials were called for to clarify the findings).[41]
Adenosine is a key factor in regulating the body'ssleep-wake cycle.[42] Adenosine levels build up in the brain during periods of wakefulness, causing a need to sleep when levels become too high, and lowers during periods of sleep, giving a sensation of restedness when waking. Higher adenosine levels correlate with a stronger feeling ofsleepiness, also known as sleep drive or sleep pressure.[43]Cognitive behavioral therapy for insomnia (CBT-I), which is considered one of the most effective treatments forinsomnia, utilizes short-termsleep deprivation to raise and regulate adenosine levels in the body, for the intended promotion of consistent and sustained sleep in the long term.[44]
A principal component ofcannabisdelta-9-tetrahydrocannabinol (THC) and theendocannabinoidanandamide (AEA) inducessleep inrats by increasing adenosine levels in thebasal forebrain. These components also significantly increaseslow-wave sleep during thesleep cycle, mediated byCB1 receptoractivation. These findings identify a potentialtherapeutic use ofcannabinoids to induce sleep in conditions where sleep may be severely attenuated.[45]
It also plays a role in regulation of blood flow to various organs throughvasodilation.[46][47][48]
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