Nondepolarizing Neuromuscular Antagonist
Action And Clinical Pharmacology: Edrophonium chloride is an anticholinesterase agent which antagonizes the action of nondepolarizing neuromuscular blocking drugs. Edrophonium chloride inactivates the enzyme acetylcholinesterase by combining with it in a reversible manner. The inactivation of the enzyme prevents the hydrolysis of acetylcholine and allows the accumulation of the neurotransmitter. The accumulation of acetylcholine at cholinergic receptor sites leads to the resumption of normal cholinergic transmission at the myoneural junction.
At equiantagonistic doses, the duration of action of edrophonium chloride is comparable to that of neostigmine methylsulfate but shorter than that of pyridostigmine bromide. The onset of action of edrophonium chloride is more rapid than that of either neostigmine methylsulfate or pyridostigmine bromide.
Indications And Clinical Uses: To reverse the neuromuscular blocking action of nondepolarizing skeletal muscle relaxants such as tubocurarine, atracurium, vecuronium, metocurine, or pancuronium. It is not effective against depolarizing agents such as succinylcholine or decamethonium.
Edrophonium may also be used adjunctively in the treatment of respiratory depression caused by curare overdosage.
Contra-Indications: In patients with known hypersensitivity to anticholinesterase agents, or in patients having intestinal or urinary obstruction of mechanical type. tag_WarningWarnings
Manufacturers’ Warnings In Clinical States: Whenever anticholinesterase drugs are used, atropine sulfate (1 mg) should be available for immediate use to counteract severe cholinergic reactions which may occur in hypersensitive individuals.
Edrophonium should be used with caution in patients with bronchial asthma or cardiac dysrhythmias. Transient bradycardia which sometimes occurs can be relieved by atropine sulfate.
Isolated instances of cardiac and respiratory arrest following administration have been reported. It is postulated that these are vagotonic effects. Special care should be taken in digitalized patients and in jaundiced subjects; cardiac arrest with cholinesterase inhibitors occurred in such subjects.
Precautions: Patients may develop “anticholinesterase insensitivity” for brief or prolonged periods. During these times patients should be carefully monitored and may need respiratory assistance. The dosage of anticholinesterase drugs should be reduced or withheld until subjects again become sensitive to them.
As with any antagonist of nondepolarizing muscle relaxants, adequate recovery of voluntary respiration and neuromuscular transmission must be obtained prior to discontinuation of respiratory assistance.
Edrophonium should not be given prior to the administration of any nondepolarizing muscle relaxant.
Caution should be exercised in anephric patients since a major portion of administered drug is excreted in the urine.
Caution should also be exercised when edrophonium is given to patients with symptoms of myasthenic weakness who are also on anticholinesterase drugs. Since symptoms of anticholinesterase overdose (cholinergic crisis) may mimic underdosage (myasthenic weakness), their condition may be worsened by the use of edrophonium.
Pregnancy and Women of Childbearing Potential: The safety of edrophonium on reproductive capacity and pregnancy has not been established. Thus, edrophonium should be used in women of childbearing potential and during pregnancy only when the potential benefits are expected to outweigh the expected risks.
Lactation: It is not known whether edrophonium is secreted in human milk.
Children: Limited experience suggests that the onset of antagonism of nondepolarizing neuromuscular blocking drugs in children may be different than in adults. Thus, the adequacy of neuromuscular function must be assessed clinically.
Adverse Reactions: Awareness of the possibility of severe cholinergic reactions is essential, particularly in hyperreactive individuals.
Reactions common to anticholinesterase agents such as edrophonium are: Cardiovascular: arrhythmias (especially bradycardia), fall in cardiac output leading to hypotension.
Respiratory: increased tracheobronchial secretions, laryngospasm, bronchiolar constriction, respiratory muscle paralysis, and central respiratory paralysis.
CNS: convulsions, dysarthria, dysphonia and dysphagia.
Musculoskeletal: weakness and fasciculations.
Eye: increased lacrimation, pupillary constriction, spasm of accommodation, diplopia and conjuctival hyperemia.
Gastrointestinal: nausea, vomiting, increased peristalsis, increased gastric and intestinal secretions, diarrhea, abdominal cramps.
Miscellaneous: increased urinary frequency and incontinence, diaphoresis.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: With an overdose of cholinesterase inhibitors muscarine-like symptoms (nausea, vomiting, diarrhea, sweating, increased bronchial and salivary secretions, bradycardia) often appear (cholinergic crisis).
Obstruction of the airway by bronchial secretions can be an important complication and may be managed with suction (especially if tracheostomy has been performed) and by the use of atropine. Some experts have advocated a wide range of dosages of atropine for the control of edrophonium induced bronchial secretions. If the secretions are copious, up to 1.2 mg i.v. may be given initially and repeated as required.
An overdose of edrophonium should be counteracted by the following steps: Administration of i.v. atropine sulfate, 0.4 to 0.5 mg, repeated as required. Because of the short duration of action of edrophonium, the atropine requirement seldom exceeds 2 mg; maintenance of adequate respiratory exchange by assuring an open airway and by the use of assisted respiration augmented by oxygen; monitoring of cardiac function until complete stabilization is achieved; pralidoxime chloride (a cholinesterase reactivator) may be given by slow i.v. infusion (50 to 100 mg/minute). The maximal dose should not exceed 2 g. Higher doses of pralidoxime may in themselves cause neuromuscular blockade and inhibit acetylcholinesterase; if convulsions or shock occur, appropriate measures should be instituted.
Dosage And Administration: The dose of edrophonium should depend on the expected duration of action of the nondepolarizing neuromuscular blocking agent and on the degree of spontaneous recovery. Edrophonium can be administered at a dose of 0.05 mL/kg body weight (0.5 mg/kg) usually by slow i.v. injection to ensure that the emergence of cholinergic reactions are detected. The maximum recommended dose is 0.1 mL/kg (1 mg/kg). Because edrophonium has a brief duration of action, it should not be administered prior to the nondepolarizing neuromuscular blocking agent. It should be administered at a point of at least 5% spontaneous recovery of twitch height (95% block).
To counteract curare overdosage: The effect of each dose of edrophonium on respiration should be carefully monitored before being repeated. Assisted ventilation should always be employed.
Availability And Storage: Each mL of sterile solution contains: edrophonium chloride 10 mg. Nonmedicinal ingredients: citric acid (anhydrous), phenol, sodium citrate and sodium sulfite. pH adjusted to approximately 5.4. Multiple dose vials of 15 mL, cartons of 5.
ENLON® Zeneca Edrophonium Chloride Nondepolarizing Neuromuscular Antagonist