Adenosine is a purine nucleoside composed of a molecule of adenine attached to a ribose sugar molecule ( ribofuranose) moiety via a β-N9- glycosidic bond. Derivatives of adenosine are widely found in nature and play 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). Adenosine itself is a neuromodulator, believed to play a role in promoting sleep and suppressing arousal. Adenosine also plays a role in regulation of blood flow to various organs through vasodilation. In addition to adenosine's endogenous forms, it is also used as a medication, specifically, as an antiarrhythmic agent, to treat a number of forms of supraventricular tachycardia that do not improve with vagal maneuvers. Common side effects include chest pain, feeling faint, shortness of breath along with tingling of the senses . Serious side effects include a worsening dysrhythmia and low blood pressure. It appears to be safe in pregnancy.
Diagnosis of supraventricular tachycardiaWhen it is administered intravenously, adenosine causes transient heart block in the atrioventricular (AV) node. This is mediated via the A1 receptor, inhibiting adenylyl cyclase, reducing cAMP and so causing cell hyperpolarization by increasing K+ efflux via inward rectifier K+ channels, subsequently inhibiting Ca2+ current. 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. 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. This leads to less blood reaching the ischemic tissue, which in turn produces the characteristic chest pain. In individuals suspected of suffering from a supraventricular tachycardia (SVT), adenosine is used to help identify the rhythm.
Antiarrhythmic agentCertain 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. 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 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.
Nuclear stress testAdenosine is used as an adjunct to thallous (thallium) chloride TI 201 or Tc99m myocardial perfusion scintigraphy (nuclear stress test) in patients unable to undergo adequate stress testing with exercise.
DosageWhen given for the evaluation or treatment of a supraventricular tachycardia (SVT), the initial dose is 6 mg to 12 mg, depending on standing orders or provider preference,http://www.regionsems.com/wp-content/uploads/2016/04/2014-Guidelines.pdf 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 antecubital fossa. The IV push is often followed with an immediate flush of 10-20 ccs of 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. 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 presenting congestive heart failure, myocardial infarction, shock, hypoxia, and/or hepatic or renal insufficiency, and in elderly patients.
Drug interactionsDopamine may precipitate toxicity in a person. Carbamazepine may increase heart block. Dipyridamole potentiates the action of adenosine, requiring the use of lower doses. Methylxanthines (e.g., caffeine, found in coffee, or theophylline in tea, or theobromine, as found in chocolate) competitively antagonize adenosine's effects; an increased dose of adenosine may be required. By nature of caffeine's purine structure, it binds to some of the same receptors as adenosine. Therefore, with the proviso that theophylline and theobromine cross the blood-brain barrier very poorly (thus, have low CNS effects on the heart), the pharmacological effects of adenosine may be blunted in individuals taking large quantities of methylxanthines.
ContraindicationsCommon contraindications for adenosine are:
- Second- or third-degree heart block (without a pacemaker)
- Sick sinus syndrome (without a pacemaker)
- Long QT syndrome
- Severe hypotension
- Decompensated heart failure
- Asthma, traditionally considered an absolute contraindication. This is being contended and it is now considered a relative contraindication (however, selective adenosine antagonists are being investigated for use in treatment of asthma)
- Poison/drug-induced tachycardia