Adenosine

Adenosine (ADO) is a medication used to treat a number of supraventricular tachycardia that do not improve with vagal maneuvers.[disambiguation needed]^[1] Common side effects include chest pain, feeling faint, shortness of breath and tingling.^[1] Serious side effects include a worsening dysrhythmia and low blood pressure.^[1] It appears to be safe in pregnancy.^[1]

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. 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 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.

Medical uses[edit]

Heart[edit]

When 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 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.^[5] 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.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 withaccessory pathways, the onset of atrial fibrillation can lead to a life-threatening ventricular fibrillation.

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.^[6]

Dosage[edit]By nature of caffeine's purine structure,^[7] it binds to some of the same receptors as adenosine.^[7] With the proviso that theophylline and theobromine cross the blood-brain barrier very poorly (thus, a low CNS effects on the heart), the pharmacological effects of adenosine may therefore be blunted in individuals taking large quantities of methylxanthines (e.g., caffeine, found in coffee, ortheophylline in tea, or theobromine, as found in chocolate).^{[8][citation needed]}

When given for the evaluation or treatment of a supraventricular tachycardia (SVT), the initial dose is 6 mg, given as a rapidparenteral 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 10-20 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.^{[dubious – discuss]} 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.