Adenosine

Source: Wikipedia, the free encyclopedia.
Not to be confused with adenine.
Adenosine
Clinical data
Trade namesAdenocard; Adenocor; Adenic; Adenoco; Adeno-Jec; Adenoscan; Adenosin; Adrekar; Krenosin
Other namesSR-96225 (developmental code name)
AHFS/Drugs.comMonograph
Pregnancy
category
  • C

(adenosine may be safe to the fetus in pregnant women)

Routes of
administration		Intravenous
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityRapidly cleared from circulation via cellular uptake
Protein bindingNo
MetabolismRapidly converted to inosine and adenosine monophosphate
Elimination half-lifecleared plasma <30 seconds; half-life <10 seconds
Excretioncan leave cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid
Identifiers
  • (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
JSmol)
  • n2c1c(ncnc1n(c2)[C@@H]3O[C@@H]([C@@H](O)[C@H]3O)CO)N
  • InChI=1S/C10H13N5O4/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(18)6(17)4(1-16)19-10/h2-4,6-7,10,16-18H,1H2,(H2,11,12,13)/t4-,6-,7-,10-/m1/s1 checkY
  • Key:OIRDTQYFTABQOQ-KQYNXXCUSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Adenosine (

cardiac arrhythmias
.

Adenosyl (abbreviated Ado or 5'-dAdo) is the chemical group formed by removal of the 5′-hydroxy (OH) group. It is found in adenosylcobalamin (an active form of vitamin B12[1]) and as a radical in the radical SAM enzymes.[2]

Medical uses

Supraventricular tachycardia

In individuals with supraventricular tachycardia (SVT), adenosine is used to help identify and convert the rhythm.[3][4][5]

Certain SVTs can be successfully terminated with adenosine.

AV reentrant tachycardia (AVRT) and AV nodal reentrant tachycardia (AVNRT). In addition, atrial tachycardia can sometimes be terminated with adenosine.[7]

Fast rhythms of the heart that are confined to the

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.[7]

Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class V

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.[8]

Nuclear stress test

Adenosine is used as an adjunct to

myocardial perfusion scintigraphy (nuclear stress test) in patients unable to undergo adequate stress testing with exercise.[9]

Dosage

When given for the evaluation or treatment of a

antecubital fossa
. The IV push is often followed with a flush of 10–20 mL of normal saline. If this has no effect (i.e., no evidence of transient AV block), a dose of 12 mg can be given 1–2 minutes after the first dose. 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

elderly
patients.

Drug interactions

Dipyridamole potentiates the action of adenosine, requiring the use of lower doses.

Caffeine's principal mode of action is as an antagonist of adenosine receptors in the brain.[11]

Methylxanthines (e.g. caffeine found in coffee, theophylline found in tea, or theobromine found in chocolate) have a purine structure and bind to some of the same receptors as adenosine.[12] Methylxanthines act as competitive antagonists of adenosine and can blunt its pharmacological effects.[13]
Individuals taking large quantities of methylxanthines may require increased doses of adenosine.

Caffeine acts by blocking binding of adenosine to the adenosine A1 receptor, which enhances release of the neurotransmitter acetylcholine.[14] Caffeine also increases cyclic AMP levels through nonselective inhibition of phosphodiesterase.[15] "Caffeine has a three-dimensional structure similar to that of adenosine," which allows it to bind and block its receptors.[16]

Contraindications

Common contraindications for adenosine include

  • Asthma, traditionally considered an absolute contraindication. This is being contested, and it is now considered a relative contraindication (however, selective adenosine antagonists are being investigated for use in treatment of asthma)[17]

Pharmacological effects

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, and A3).[18]

Extracellular adenosine concentrations from normal cells are approximately 300 nM; however, in response to cellular damage (e.g., in inflammatory or

hypoxia, ischemia, and seizure activity. Activation of A2A receptors produces a constellation of responses that in general can be classified as anti-inflammatory.[19] Enzymatic production of adenosine can be anti-inflammatory or immunosuppressive.[20][21][22]

Adenosine receptors

Main article: Adenosine receptor

All adenosine receptor subtypes (A1, A2A, A2B, and A3) are

adenylate 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 stimulate phospholipase
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.[23]

Ghrelin/growth hormone secretagogue receptor

Adenosine is an

endogenous agonist of the ghrelin/growth hormone secretagogue receptor.[24] However, while it is able to increase appetite, unlike other agonists of this receptor, adenosine is unable to induce the secretion of growth hormone and increase its plasma levels.[24]

Mechanism of action

When it is administered intravenously, adenosine causes transient

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.

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 called coronary steal. This leads to less blood reaching the ischemic tissue, which in turn produces the characteristic chest pain.

Metabolism

Adenosine used as a

purine biosynthesis via adenosine monophosphate (AMP), though it is possible other pathways exist.[27]

When adenosine enters the circulation, it is broken down by adenosine deaminase, which is present in red blood cells and the vessel wall.

vasodilatation
.

Adenosine deaminase deficiency is a known cause of immunodeficiency.

Research

Viruses

See also: Nucleoside analogue

The adenosine analog

Ebola and Marburg viruses.[30]
Such adenosine analogs are potentially clinically useful since they can be taken orally.

Anti-inflammatory properties

Adenosine is believed to be an

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.[33]

Central nervous system

In general, adenosine has an inhibitory effect in the central nervous system (CNS).

glutamate.[34] Experimental evidence suggests that adenosine and adenosine agonists can activate Trk receptor phosphorylation through a mechanism that requires the adenosine A2A receptor.[35]

Hair

Adenosine has been shown to promote thickening of hair on people with thinning hair.

androgenetic 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).[38]

Sleep

Adenosine is a key factor in regulating the body's

sleepiness, also known as sleep drive or sleep pressure.[40] Cognitive behavioral therapy for insomnia (CBT-I), which is considered one of the most effective treatments for insomnia, utilizes short-term sleep deprivation to raise and regulate adenosine levels in the body, for the intended promotion of consistent and sustained sleep in the long term.[41]

A principal component of

activation. These findings identify a potential therapeutic use of cannabinoids to induce sleep in conditions where sleep may be severely attenuated.[42]

Vasodilation

It also plays a role in regulation of blood flow to various organs through vasodilation.[43][44][45]

See also

References

  1. ISBN 3-540-33047-X
    .
  2. ISBN 0-7167-4339-6
    .
  3. S2CID 44107679
    .
  4. PMID 16525141
    .
  5. S2CID 21575090
    .
  6. PMID 19000353
    .
  7. ^
    PMID 30725774
    . Retrieved 2022-01-28.
  8. ISBN 0-7923-6170-9.[page needed
    ]
  9. PMID 1514488
    .
  10. ^ "2014 Guidelines" (PDF). regionsems.com. April 2016. Retrieved 10 April 2023.
  11. PMID 32166015
    .
  12. PMID 20164566
    .
  13. ^ "Vitamin B4". R&S Pharmchem. April 2011. Archived from the original on 2011-07-15.
  14. PMID 7752065
    .
  15. S2CID 235094871
    .
  16. ISBN 978-1-4641-8652-3
    .
  17. PMID 18311158
    .
  18. PMID 18758473
    .
  19. PMID 14698282
    .
  20. PMID 30513816
    .
  21. PMID 31878283
    .
  22. PMID 23601906
    .
  23. PMID 21917810
    .
  24. ^
    ISBN 978-3-642-18999-9
    .
  25. ^ "Аденозин в косметике - Польза антивозрастной корейской косметики". KIMITO (in Russian). 2021-03-18. Retrieved 2021-03-22.
  26. ISBN 978-0-07-176402-5
    .
  27. PMID 8020339
    .
  28. PMID 19918064
    .
  29. PMID 15388457
    .
  30. PMID 24590073
    .
  31. PMID 18461129
    .
  32. PMID 18846036
    .
  33. PMID 21044428
    .
  34. PMID 12151508
    .
  35. PMID 11248116
    .
  36. S2CID 12289511
    .
  37. PMID 22020741
    .
  38. PMID 24183218
    .
  39. PMID 35575450
    .
  40. ^ "Adenosine and Sleep". Sleep Foundation. 2022-06-07. Retrieved 2023-04-12.
  41. ISBN 9781416066453
    .
  42. PMID 14746372
    .
  43. S2CID 71178
    .
  44. PMID 9576114
    .
  45. PMID 1884445
    .
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