Mechanism of Action

Adenosine is a potent vasodilator in most vascular beds, except in renal afferent arterioles and hepatic veins where it produces vasoconstriction. Adenosine is thought to exert 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 also lessen 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.

Myocardial uptake of thallium-201 is directly proportional to coronary blood flow. Since Adenoscan (adenosine injection) significantly increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, Adenoscan (adenosine injection) causes relatively less thallium-201 uptake in vascular territories supplied by stenotic coronary arteries i.e., a greater difference is seen after Adenoscan (adenosine injection) between areas served by normal and areas served by stenotic vessels than is seen prior to Adenoscan.

Hemodynamics

Adenosine produces a direct negative chronotropic, dromotropic and inotropic effect on the heart, presumably due to A1-receptor agonism, and produces peripheral vasodilation, presumably due to A2-receptor agonism. The net effect of Adenoscan (adenosine injection) in humans is typically a mild to moderate reduction in systolic, diastolic and mean arterial blood pressure associated with a reflex increase in heart rate. Rarely, significant hypotension and tachycardia have been observed.

Pharmacokinetics

Intravenously administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. Intracellular adenosine is rapidly metabolized either via phosphorylation to adenosine monophosphate by adenosine kinase, or via deamination to inosine by adenosine deaminase in the cytosol. Since adenosine kinase has a lower Km and Vmax than adenosine deaminase, deamination plays a significant role only when cytosolic adenosine saturates the phosphorylation pathway. Inosine formed by deamination of adenosine can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid. Adenosine monophosphate formed by phosphorylation of adenosine is incorporated into the high-energy phosphate pool. While extracellular adenosine is primarily cleared by cellular uptake with a half-life of less than 10 seconds in whole blood, excessive amounts may be deaminated by an ecto-form of adenosine deaminase. As Adenoscan (adenosine injection) requires no hepatic or renal function for its activation or inactivation, hepatic and renal failure would not be expected to alter its effectiveness or tolerability.

Clinical Trials

In two crossover comparative studies involving 319 subjects who could exercise (including 106 healthy volunteers and 213 patients with known or suspected coronary disease), Adenoscan (adenosine injection) and exercise thallium images were compared by blinded observers. The images were concordant for the presence of perfusion defects in 85.5% of cases by global analysis (patient by patient) and up to 93% of cases based on vascular territories. In these two studies, 193 patients also had recent coronary arteriography for comparison (healthy volunteers were not catheterized). The sensitivity (true positive Adenoscan (adenosine injection) divided by the number of patients with positive (abnormal) angiography) for detecting angiographically significant disease ( ≥ 50% reduction in the luminal diameter of at least one major vessel) was 64% for Adenoscan (adenosine injection) and 64% for exercise testing, while the specificity (true negative divided by the number of patients with negative angiograms) was 54% for Adenoscan (adenosine injection) and 65% for exercise testing. The 95% confidence limits for Adenoscan (adenosine injection) sensitivity were 56% to 78% and for specificity were 37% to 71%.

Intracoronary Doppler flow catheter studies have demonstrated that a dose of intravenous Adenoscan (adenosine injection) of 140 mcg/kg/min produces maximum coronary hyperemia (relative to intracoronary papaverine) in approximately 95% of cases within two to three minutes of the onset of the infusion. Coronary blood flow velocity returns to basal levels within one to two minutes of discontinuing the Adenoscan (adenosine injection) infusion.

Last reviewed on RxList: 4/7/2011
This monograph has been modified to include the generic and brand name in many instances.