Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Aventis Pharma Limited, 410 Thames Valley Park Drive, Reading, Berkshire, RG6 1PT, UK Trading as: Sanofi, 410 Thames Valley Park Drive, Reading, Berkshire, RG6 1PT, UK
Pharmacotherapeutic group: Other Cardiac Preparations
ATC code: C01EB10
Endogenous nucleoside with peripheral vasodilator/antiarrhythmic effect.
Adenosine is a potent vasodilator in most vascular beds, except in renal afferent arterioles and hepatic veins where it produces vasoconstriction. Adenosine exerts its pharmacological effects through activation of purine receptors (cell-surface A1 and A2 adenosine receptors). Although the exact mechanism by which adenosine receptor activation relaxes vascular smooth muscle is not known, there is evidence to support both inhibition of the slow inward calcium current reducing calcium uptake, and activation of adenylate cyclase through A2 receptors in smooth muscle cells. Adenosine may reduce vascular tone by modulating sympathetic neurotransmission. The intracellular uptake of adenosine is mediated by a specific transmembrane nucleoside transport system. Once inside the cell, adenosine is rapidly phosphorylated by adenosine kinase to adenosine monophosphate, or deaminated by adenosine deaminase to inosine. These intracellular metabolites of adenosine are not vasoactive.
Intracoronary Doppler flow catheter studies have demonstrated that intravenous Adenoscan at 140 µg/kg/min produces maximum coronary hyperaemia (relative to intracoronary papaverine) in approximately 90% of cases within 2–3 minutes of the onset of the infusion. Coronary blood flow velocity returns to basal levels within 1–2 minutes of discontinuing the Adenoscan infusion.
The increase in blood flow caused by Adenoscan in normal coronary arteries is significantly more than that in stenotic arteries. Adenoscan redirects coronary blood flow from the endocardium to the epicardium and may reduce collateral coronary blood flow thereby inducing regional ischaemia.
Continuous infusion of adenosine in man has been shown to produce a mild dose-dependent fall in mean arterial pressure and a dose-related positive chronotropic effect, most likely caused by sympathetic stimulation. The onset of this reflex increase in heart rate occurs later than the negative chronotropic/dromotropic effect. This differential effect is mostly observed after bolus injection thus explaining the potential use of adenosine as a treatment for supraventricular arrhythmias when administered as a bolus or as a coronary vasodilator when administered as an infusion.
Although Adenoscan affects cardiac conduction, it has been safely and effectively administered in the presence of other cardioactive or vasoactive drugs such as beta-adrenergic blocking agents, calcium channel antagonists, nitrates, ACE inhibitors, diuretics, digitalis or anti-arrhythmics.
Literature review identified three studies where intravenous adenosine infusion was used in conjunction with radionuclide myocardial perfusion imaging at a dose of 0.14 mg/kg body weight/min for 2–4 minutes in paediatric patients aged 1 month to 18 years. The largest study included 47 patients aged 1 month to 18 years of age and reported 87% sensitivity (CI 52–97%) and 95% specificity (CI 79–99%) for cardiovascular magnetic resonance imaging under pharmacological stress with intravenous adenosine in a dose of 0.14 mg/kg/min for 3 minutes. No adverse events were reported in the study.
However, the currently available data is considered very limited to support the use of adenosine for diagnostic purposes in the paediatric population.
It is impossible to study adenosine in classical pharmacokinetic studies. It is present in various forms in all the cells of the body where it plays an important role in energy production and utilisation systems. An efficient salvage and recycling system exists in the body, primarily in erythrocytes and blood vessel endothelial cells.
The half-life in vitro is estimated to be less than 10 seconds. The in vivo half-life may be even shorter.
Since neither the kidney nor the liver are involved in the degradation of exogenous adenosine, the efficacy of Adenoscan should be unaffected by hepatic or renal insufficiency.
Because adenosine is naturally present in all living cells, studies in animals to evaluate the carcinogenic potential of Adenoscan (adenosine) have not been performed.
No controlled reproductive studies were conducted in animals with adenosine.
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