Pharmacodynamics

ENLON-PLUS (edrophonium chloride, USP and atropine sulfate, USP) Injection is a combination of an anticholinesterase agent, which antagonizes the action of nondepolarizing neuromuscular blocking drugs, and a parasympatholytic (anticholinergic) drug, which prevents the muscarinic effects caused by inhibition of acetylcholine breakdown by the anticholinesterase. Edrophonium chloride antagonizes the effect of nondepolarizing neuromuscular blocking agents primarily by inhibiting or inactivating acetylcholinesterase. By inactivating the acetylcholinesterase enzyme, acetylcholine is not hydrolyzed as rapidly by acetylcholinesterase and is thereby allowed to accumulate. The greater quantity of acetylcholine reaching the sites of nicotinic cholinergic postjunctional receptors improves transmission of impulses across the myoneural junction. The concomitant, unavoidable accumulation of acetylcholine at the sites of muscarinic cholinergic transmission occurring at the parasympathetic, postganglionic receptors of the autonomic nervous system, may cause bradycardia, bronchoconstriction, increased secretions, and other parasympathomimetic side effects. The magnitude of these muscarinic side effects can be expected to vary from patient to patient depending upon the amount of vagal nerve activity present. Atropine sulfate counteracts these side effects.

Intravenous edrophonium chloride in doses of 0.5 to 1.0 mg/kg promptly antagonizes the effects of nondepolarizing muscle relaxants reaching the maximum antagonism within 1.2 minutes. A plateau of maximal antagonism is sustained for 70 minutes¹. Intravenous atropine sulfate has an immediate effect on heart rate which reaches a peak in 2 to 16 minutes and lasts 170 minutes after an average 0.02 mg/kg dose.

Edrophonium Chloride

Edrophonium chloride given intravenously shows first order elimination in a two compartment open pharmacokinetic model³. Onset of reversal of muscle relaxant induced depression in twitch tension occurs within three minutes. Edrophonium is primarily renally excreted with 67% of the dose appearing in the urine⁴. Hepatic metabolism and biliary excretion have also been demonstrated in animals^4,8. While infants and children have been shown to have a reduced plasma half-life and an increased clearance of edrophonium, doses in children are not significantly different from adults on a mg/kg basis although they are more variable in effect. Conversely, elderly subjects (>75 years old) have a prolonged plasma half-life and a reduced clearance. Studies have shown that in spite of these changes the onset and duration of action is unchanged in these patients.

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