PHYSOSTIGMINE
DESCRIPTION:
NEOSTIGMINE (Physostigmine Salicylate) is a derivative of the Calabar bean, and
its active moiety, physostigmine, is also known as eserine.
It is soluble in water and a 0.5% aqueous solution has a pH of 5.8.
NEOSTIGMINE Injection is available in 2 ml ampuls, each ml containing 1 mg of
Physostigmine Salicylate in a vehicle composed of sodium bisulfite 0.1%, benzyl
alcohol 2.0% as a preservative in water for injection.
ACTIONS/CLINICAL PHARMACOLOGY:
NEOSTIGMINE is a reversible anticholinesterase which effectively increases the
concentration of acetylcholine at the sites of cholinergic transmission. The
action of acetylcholine is normally very transient because of its hydrolysis by
the enzyme, acetylcholinesterase. NEOSTIGMINE inhibits the destructive action of
acetylcholinesterase and thereby prolongs and exaggerates the effect of the
acetylcholine.
NEOSTIGMINE contains a tertiary amine and easily penetrates the blood-brain
barrier, while an anticholinesterase, such as neostigmine, which has a
quaternary ammonium ion is not capable of crossing the barrier. NEOSTIGMINE can
reverse both central and peripheral anticholinergia. The anticholinergic
syndrome has both central and peripheral signs and symptoms. Central toxic
effects include anxiety, delirium, disorientation, hallucinations, hyper-
activity and seizures. Severe poisoning may produce coma, medullary paralysis
and death. Peripheral toxicity is characterized by tachycardia, hyperpyrexia,
mydriasis, vasodilatation, urinary retention, diminution of gastrointestinal
motility, decrease of secretion in salivary and sweat glands, and loss of
secretions in the pharynx, bronchi, and nasal passages.
Dramatic reversal of the effects of anticholinergic symptoms can be expected in
minutes after the intravenous administration of NEOSTIGMINE, if the diagnosis is
correct and the patient has not suffered anoxia or other insult. The duration of
action of NEOSTIGMINE is relatively short, approx. 45 to 60 minutes.
Numerous drugs and some plants produce the anticholinergic syndrome either
directly or as a side effect; this undesirable or potentially dangerous
phenomenon may be brought about by either therapeutic doses or overdoses of the
drugs. Such drugs include among others, atropine, other derivatives of the
belladonna alkaloids, tricyclic antidepressants, phenothiazines, and
antihistamines.
INDICATIONS AND USAGE:
To reverse the effect upon the central nervous system, caused by clinical or
toxic dosages of drugs capable of producing the anticholinergic syndrome.
CONTRAINDICATIONS:
NEOSTIGMINE should not be used in the presence of asthma, gangrene, diabetes,
cardiovascular disease, mechanical obstruction of the intestine or urogenital
tract or any vagotonic state, and in patients receiving choline esters or
depolarizing neuromuscular blocking agents (decamethonium succinylcholine).
For post-anesthesia, the concomitant use of atropine with the physostigmine
salicylate is not recommended, since the atropine antagonizes the action of
physostigmine.
WARNINGS:
Contains sodium bisulfite, a sulfite that may cause allergic-type reactions
including anaphylactic symptoms and life-threatening or less severe asthmatic
episodes in certain susceptible people. The overall prevalence of sulfite
sensitivity in the general population is unknown and probably low. Sulfite
sensitivity is seen more frequently in asthmatic than in non- asthmatic people.
If excessive symptoms of salivation, emesis, urination and defecation occur, the
use of NEOSTIGMINE should be terminated. If excessive sweating or nausea occur,
the dosage should be reduced.
Intravenous administration should be at a slow, controlled rate, no more than 1
mg per minute (see dosage). Rapid administration can cause bradycardia,
hypersalivation leading to respiratory difficulties and possible convulsions.
An overdosage of NEOSTIGMINE can cause a cholinergic crisis.
PRECAUTIONS:
Because of the possibility of hypersensitivity in an occasional patient,
atropine sulfate injection should always be at hand since it is an antagonist
and antidote for physostigmine.
USAGE IN PREGNANCY: Safe use in pregnancy and lactation has not been
established; therefore, use in pregnant women, nursing mothers or women who may
become pregnant requires that possible benefits be weighed against possible
hazards to mother and child.
DRUG INTERACTIONS:
NEOSTIGMINE should not be used in the presence of asthma, gangrene, diabetes,
cardiovascular disease, mechanical obstruction of the intestine or urogenital
tract or any vagotonic state, and in patients receiving choline esters or
depolarizing neuromuscular blocking agents (decamethonium succinylcholine).
For post-anesthesia, the concomitant use of atropine with the physostigmine
salicylate is not recommended, since the atropine antagonizes the action of
physostigmine.
(See Also CONTRAINDICATIONS)
ADVERSE REACTIONS:
Nausea, vomiting, and salivation can be offset by reducing dosage. Bradycardia
and convulsions can occur if intravenous administration is too rapid. See DOSAGE
AND ADMINISTRATION.
OVERDOSAGE:
Can cause a cholinergic crisis. Appropriate antidote is atropine sulfate.
DOSAGE AND ADMINISTRATION:
POST-ANESTHESIA CARE: 0.5 to 1.0 mg intramuscularly or intravenously.
INTRAVENOUS ADMINISTRATION SHOULD BE AT A SLOW CONTROLLED RATE OF NO MORE THAN 1
MG PER MINUTE. Dosage may be repeated at intervals of 10 to 30 minutes if
desired patient response is not obtained.
OVERDOSAGES OF DRUGS THAT CAUSE ANTICHOLINERGIA: 2.0 mg intramuscularly or
INTRAVENOUSLY AT SLOW CONTROLLED RATE (SEE ABOVE). Dosage may be repeated if
life-threatening signs, such as arrhythmia, convulsions or coma occur.
PEDIATRIC DOSAGE: Recommended dosage is 0.02 mg/kg, intramuscularly or by slow
intravenous injection, no more than 0.5 mg per minute. If the toxic effects
persist, and there is no sign of cholinergic effects, the dosage may be repeated
at 5 to 10 minute intervals until a therapeutic effect is obtained or a maximum
dose of 2 mg is attained.
IN ALL CASES OF POISONING, THE USUAL SUPPORTIVE MEASURES SHOULD BE UNDERTAKEN.
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