Edrophonium uses, brand name, side effects and action

Description of Edrophonium

Edrophonium is a rapid-acting, short-duration, parenteral cholinesterase inhibitor. It is the drug of choice for diagnosing myasthenia gravis because of its rapid onset of action and reversibility. Other uses include assessing cholinesterase inhibitor therapy, differentiating cholinergic and myasthenic crises, and reversing the effects of nondepolarizing neuromuscular blockers after surgery. Edrophonium has been used to terminate paroxysmal atrial tachycardia, but alternative therapies have replaced edrophonium for this use. In combination with atropine sulfate, edrophonium is used adjunctively to treat respiratory depression associated with curare overdosage. Edrophonium was approved by the FDA in 1951.

Mechanism of Action of Edrophonium 

Edrophonium competes with acetylcholine for its binding site on acetylcholinesterase. By interfering with enzymatic destruction of acetylcholine, edrophonium potentiates the action of acetylcholine on both the skeletal muscle (nicotinic receptor) and the GI tract (muscarinic receptor). It also can stimulate cholinergic responses in the eyes (causing miosis) if directly applied. Different muscle groups exhibit different levels of response to cholinesterase inhibitors, and doses that stimulate one muscle group can weaken, through overdose, another.
 
Specific responses to cholinesterase inhibitors include: increased skeletal muscle tone (nicotinic); increased gastric motility and GI tone (muscarinic); bradycardia (muscarinic); ureteral constriction (muscarinic); stimulation of the sweat and salivary glands (muscarinic); and constriction of the bronchi (muscarinic). Few of these actions are seen with edrophonium, however, due to its short duration of action.
 
In myasthenia gravis, edrophonium increases the amount of acetylcholine in the neuromuscular junction, which is deficient of acetylcholine receptors at the motor endplate. This action allows for a greater number of the depleted acetylcholine receptors to be bound with acetylcholine. This binding can be clinically evaluated as an increase in the patient’s muscular strength and can establish the diagnosis of myasthenia gravis in 90—95% of those suspected of having the disease. Edrophonium is not used in the treatment of myasthenia gravis, however, due to its short duration of action.

Pharmacokinetics

Edrophonium is administered parenterally. The distribution of edrophonium is poorly understood, but the drug does not cross the placenta. Similarly, the metabolic fate and excretion of edrophonium are not known. Duration of action ranges from 5—10 minutes when given IV and 5—30 minutes when given IM.

Route-Specific Pharmacokinetics
Intravenous Route
Edrophonium has a rapid onset of action, occurring 30—60 seconds after IV administration.

Intramuscular Route
Edrophonium has a rapid onset of action, occurring 2—10 minutes after IM administration.

Special Populations
Pediatrics
Edrophonium was studied in 14 infants and 12 children during a steady-state infusion of d-tubocurarine during surgery. The ED₅₀ dose (dose producing 50% antagonism of 90% neuromuscular depression) of edrophonium was 0.145 mg/kg in infants and 0.233 mg/kg in children. The ED₅₀ dose, time to peak antagonism and duration of antagonism were similar between the pediatric groups and adults. Clearance in infants was 17.8 mL/kg/min and 14.2 mL/kg/min in children. Total clearance was significantly greater in infants than adults (8.3 ± 2.9 mL/kg/min). Elimination half-life was 73 ± 30 minutes in infants, 99 ± 31 minutes in children and 126 ± 59 minutes in adults. Volume of distribution in infants and children was 1.18 ± 0.20 L/kg and 1.22 ± 0.74 L/kg, respectively, compared with 0.90 ± 0.13 L/kg in adults.

• Edrophonium Chloride

• Enlon
• Reversol

• Cholinesterase Inhibitor
• Diagnostic Agent, Myasthenia Gravis

• Myasthenia gravis; Diagnosis: Adult
• Myasthenia gravis; Diagnosis: Pediatric
• Reversal of neuromuscular blockade, Nondepolarizing: Adult
• Reversal of neuromuscular blockade, Nondepolarizing: Pediatric

• Cardiovascular: Bradyarrhythmia, Hypotension
• Dermatologic: Sweating
• Gastrointestinal: Abnormal gastric secretion, Diarrhea, Dysphagia, Excessive salivation, Nausea, Vomiting
• Neurologic: Seizure
• Ophthalmic: Excessive tear production
• Renal: Increased frequency of urination

• Cardiovascular: Cardiac arrest
• Respiratory: Bronchospasm, Respiratory tract paralysis

• Inspect product visually for particulate matter and discoloration prior to administration
• Intravenous: When used as a curare antagonist, administer IV slowly over a period of 30 to 45 seconds
• Intramuscular: The IM route may be used in pediatric patients if IV injection is not feasible

• Enlon: Injection Solution: 10 MG/1 ML

• Important Note: Atropine sulfate should be readily available prior to the administration of edrophonium for reversal of severe cholinergic reactions .
• Myasthenia gravis; Diagnosis: 2 mg IV over 15 to 30 seconds, if no reaction in 45 seconds, give additional 8 mg
• Myasthenia gravis; Diagnosis: 10 mg IM in adults with inaccessible veins
• Reversal of neuromuscular blockade, Nondepolarizing: 10 mg IV over 30 to 45 seconds; may be repeated as needed until a cholinergic response is detected; MAX 40 mg

• Important Note: Atropine sulfate should be readily available prior to the administration of edrophonium for reversal of severe cholinergic reactions .
• Myasthenia gravis; Diagnosis: (infants) 0.5 mg IV
• Myasthenia gravis; Diagnosis: (34 kg or less) 1 mg IV, if no reaction in 45 seconds, may repeat at a rate of 1 mg every 30 to 45 seconds to maximum cumulative dose of 5 mg
• Myasthenia gravis; Diagnosis: (34 kg or less) 2 mg IM
• Myasthenia gravis; Diagnosis: (greater than 34 kg) 2 mg IV, if no reaction in 45 seconds, may repeat at a rate of 1 mg every 30 to 45 seconds to maximum cumulative dose of 10 mg
• Myasthenia gravis; Diagnosis: (greater than 34 kg) 5 mg IM
• Reversal of neuromuscular blockade, Nondepolarizing: doses ranging from 0.1 mg/kg to 1.43 mg/kg have been used during studies
• Reversal of neuromuscular blockade, Nondepolarizing: (infants) 145 mcg/kg IM
• Reversal of neuromuscular blockade, Nondepolarizing: (children) 233 mcg/kg IM