Adenosine - Antiarrhythmic Cardiovascular Poison

Adenosine

Adenosine (9-beta- D-ribofuranosyladenine) is a nucleotide found in all cells, and is released from myocardial cells under various physiological and pathological conditions. It is primarily formed as a degradation product of adenosine triphosphate (ATP). As an intermediate metabolite in several biochemical pathways, adenosine contributes to the regula-tion of numerous physiologic processes, including platelet function, coronary and systemic vascular tone, and lipolysis in adipocytes.

Adenosine, an endogenous coronary vasodilator, is used in a continuous infusion (0.140 mg/kg/min for 6 minutes) as a pharmacologic agent for thallium stress testing. Adenosine causes more vasodilation in normal coronary arteries, leading to increased thallium uptake in normal myocardium versus ischaemic areas. It is effective in the treatment of re-entrant supraventricular tachycardia when administered as a rapid IV bolus. Adenosine has a half-life of just a few seconds and is metabolised to inosine.

Adenosine acts by decreasing spontaneous depolarisation in the sinus node and conduction velocity in the A-V node. Its direct negative chronotropic and dromotropic properties are the basis for its wide therapeutic application in patients with supraventricular tachycardia.

The duration of electrophysiologic and clinical effects with adenosine is extremely short, usually less than 10 seconds, due to rapid cellular uptake and metabolism. Total clearance from plasma occurs in less than 30 seconds following intravenous administration. Adenosine is rapidly cleared from the plasma by cellular uptakes, particularly by erythrocytes, vascular endothelial cells, and cardiomyocytes. Within cells, adenosine is rapidly degraded to inosine by adenosine deaminase and subsequently to hypoxanthine. It is also metabolised to adenosine monophosphate (AMP) by adenosine kinase.

Adverse Effects and Clinical (Toxic) Features

·      Cutaneous flushing, dyspnoea, chest pain, nausea, vomiting, vertigo, headache, hypotension, and proarrhythmias. Occasionally there may be minimal cardiac adverse effects including atrial fibrillation, atrial flutter, bradycardia, and angina-like chest pain at doses as high as 23 milligrams. Sometimes adenosine may induce prolonged bradysystole and convulsions.

·      Infusion of adenosine causes angina-like chest pain in susceptible persons without ECG signs of ischaemia. In controlled US trials, some patients developed dyspnoea following intravenous adenosine administration. It is thought that adenosine can produce bronchoconstric-tion by enhancing IgE-dependant release of pre-formed mediators from mast cells. Until further data are avail-able, adenosine should be used with caution in asthmatic patients.

·      Adenosine triphosphate: May be associated with ahigher incidence of adverse effects than adenosine. A high frequency of cardiac adverse effects have been observed, including sinus bradycardia, sinus arrest, sinus tachycardia, and varying degrees of atrioventricular (AV) block upon termination of the tachycardia. Noncardiac adverse effects include flushing, malaise, hyperpnoea, headaches, retching, vomiting, seizures (rare), and coughing.

Drug Interactions

·              Dipyridamole is a competitive inhibitor of adenosine’stransport into cells and can potentiate the effects of thedrug. Significantly lower doses of adenosine should be administered to patients receiving dipyridamole.

·              Adenosine may not be effective in patients receiving meth- ylxanthines; methylxanthines are competitive antagonists of adenosine and can completely block the electrophysi-ologic effects of the drug.

·              If adenosine is used to treat patients with toxic concentra-tions of calcium channel blockers, prolonged bradycardia may occur.

Treatment

·      Continuous electrocardiogram monitoring is recommended, especially in patients capable of rapid atrioventricular (AV) conduction.

·      The duration of electrophysiologic and clinical effects with adenosine is extremely short, usually less than 10 seconds, due to rapid cellular uptake and metabolism. Laboratory measures are not likely to be useful in an intoxication.

·      External pacing.

·      Theophylline for prolonged chest pain (in patients with ischaemic heart disease).

·      Symptomatic and supportive measures.

·              The incidence of adverse effects with adenosine triphos-phate can be reduced with the use of smaller initial doses (10 mg). Pretreatment with inosine may also alleviate the adverse effects of ATP.