EDROPHONIUM CHLORIDE

Chemistry - A synthetic quanternary ammonium cholinergic (parasympathomimetic) agent, edrophonium chloride occurs as a white crystalline powder having a bitter taste. Approximately 2grams are soluble in one ml of water. The injection has a pH of approximately 5.4.

Storage, Stability, Compatibility

Edrophonium chloride injection should be stored at roomtemperature. It is reportedly compatible at Y-site injections with Heparin Sodium, Hydrocortisonesodium succinate, potassium chloride and vitamin B complex with C. Compatibility is dependentupon factors such as pH, concentration, temperature and diluents used. It is suggested to consultspecialized references (e.g., Handbook on Injectable Drugs by Trissel; see bibliography) for morespecific information.

Pharmacology - EDROPHONIUM CHLORIDE

Edrophonium is an anticholinesterase agent that is very short acting. It brieflyattaches to acetylcholinesterase, thereby inhibiting its hydrolytic activity on acetylcholine. Asacetylcholine accumulates, the following signs and symptoms may be noted: miosis, increasedskeletal and intestinal muscle tone, bronchoconstriction, ureter constriction, salivation, sweating (inanimals with sweat glands), and bradycardia.
Uses, Indications - The primary use for edrophonium is in the diagnosis of myasthenia gravis. It isalso used for the reversal of nondepolarizing agents (e.g., vecuronium, pancuronium, metocurine, atracurium, gallamine or tubocurarine). Because of its short duration of action, its clinicalusefulness for this indication is questionable as longer acting drugs such as neostigmine orpyridostigmine may be more useful. Edrophonium may also be useful in the diagnosis andtreatment of some supraventricular arrhythmias, particularly when other more traditional treatmentsare ineffective and in a controlled intensive care-type setting.

Pharmacokinetics - EDROPHONIUM CHLORIDE

Edrophonium is only effective when given parenterally. After IV administration, it begins to have effects on skeletal muscle within one minute and effects may persist for up to 10 minutes. Myasthenic patients may have effects persisting longer after the first dose.
Edrophonium's exact metabolic fate and excretion characteristics have not been well described.

Contraindications, Precautions, Reproductive Safety

Edrophonium is considered relativelycontraindicated in patients with bronchial asthma, or mechanical urinary or intestinal tract obstruction. It should be used with caution (with adequate monitoring and treatment available) inpatients with bradycardias or atrioventricular block. Some human patients are documented to behypersensitive to the drug and exhibit severe cholinergic reactions.
Edrophonium's safety profile during pregnancy is not established; use only when necessary. It isunknown whether edrophonium enters maternal milk. While no problems have been documented innursing humans or animals, its safety has not been established.

Adverse Effects, Warnings

Adverse effects associated with edrophonium are generally doserelated and cholinergic in nature. Although usually mild and easily treated with a "tincture of time", severe adverse effects are possible with large overdoses (see below).
Overdosage, Acute Toxicity - Overdosage of edrophonium may induce a cholinergic crisis.
Symptoms of cholinergic toxicity can include GI effects (nausea, vomiting, diarrhea), salivation, sweating (in animals able to do so), respiratory effects (increased bronchial secretions, bronchospasm, pulmonary edema, respiratory paralysis), ophthalmic effects (miosis, blurred vision, lacrimation), cardiovascular effects (bradycardia or tachycardia, cardiospasm, hypotension, cardiacarrest), muscle cramps and weakness.
Treatment of edrophonium overdosage, consists of both respiratory and cardiac supportive therapyand atropine if necessary. Refer to the atropine monograph for more information on its use forcholinergic toxicity.

Drug Interactions

Edrophonium's cardiac effects may be increased in patients receivingdigoxin; excessive slowing of heart rate may occur. Drugs that possess some neuromuscularblocking activity (e.g., aminoglycoside antibiotics, some antiarrhythmic and anesthetic drugs)may necessitate increased dosages of edrophonium in treating or diagnosing myasthenic patients.
Edrophonium may prolong the Phase I block of depolarizing muscle relaxants (e.g., succinylcholine, decamethonium). Pyridostigmine antagonizes the actions of non-depolarizing neuromuscular blocking agents (pancuronium, tubocurarine, gallamine, vecuronium, atracurium, etc.). Atropine will antagonize the muscarinic effects of edrophonium, but concurrentuse should be used cautiously as atropine can mask the early symptoms of cholinergic crisis.
Theoretically, dexpanthenol may have additive effects when used with edrophonium.