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Overdosage of Prostigmin (neostigmine) can cause cholinergic crisis, which is characterized by increasing muscle weakness, and through involvement of the muscles of respiration, may result in death. Myasthenic crisis, due to an increase in the severity of the disease, is also accompanied by extreme muscle weakness and may be difficult to distinguish from cholinergic crisis on a symptomatic basis. However, such differentiation is extremely important because increases in the dose of Prostigmin (neostigmine) or other drugs in this class, in the presence of cholinergic crisis or of a refractory or “insensitive” state, could have grave consequences. The two types of crises may be differentiated by the use of Tensilon® (edrophonium chloride) as well as by clinical judgment.
Treatment of the two conditions differs radically. Whereas the presence of myasthenic crisis requires more intensive anticholinesterase therapy, cholinergic crisis calls for the prompt withdrawal of all drugs of this type. The immediate use of atropine in cholinergic crisis is also recommended.
Atropine may also be used to abolish or minimize gastrointestinal side effects or other muscarinic reactions; but such use, by masking signs of overdosage, can lead to inadvertent induction of cholinergic crisis.
The LD50 of neostigmine methylsulfate in mice is 0.3 ± 0.02 mg/kg intravenously, 0.54 ± 0.03 mg/kg subcutaneously, and 0.395 ± 0.025 mg/kg intramuscularly; in rats the LD50 is 0.315 ± 0.019 mg/kg intravenously, 0.445 ± 0.032 mg/kg subcutaneously, and 0.423 ± 0.032 mg/kg intramuscularly.
Prostigmin (neostigmine) is contraindicated in patients with known hypersensitivity to the drug. Because of the presence of the bromide ion, it should not be used in patients with a previous history of reaction to bromides. It is contraindicated in patients with peritonitis or mechanical obstruction of the intestinal or urinary tract.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 3/26/2009
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