DESCRIPTION

Physostigmine is used to reverse anticholinergic toxicity.

FORMS AND USES

• Used primarily to diagnose anticholinergic toxicity.
• Physostigmine salicylate (Antilirium) is provided in 2-ml ampules containing 1 mg/ml physostigmine salicylate; the vehicle contains sodium bisulfite 0.1% and benzyl alcohol 2.0%.

MECHANISM OF ACTION

• Physostigmine is a cholinergic agonist that reversibly binds to acetylcholinesterase, increasing the concentration and duration of action of acetylcholine at the nerve receptor.
• Tertiary amine structure permits penetration into the CNS, thereby allowing reversal of central anticholinergic effects (hallucinosis).
• Because of actions on the reticular activating system, it produces analeptic effects and may result in partial, nonspecific arousal of obtunded patients.
• The onset of action after intravenous administration is 3 to 8 minutes; the duration of action is 15 to 40 minutes.

DRUG AND DISEASE INTERACTIONS

• Synergistic cholinergic effects may develop in patients already taking carbamate or anticholinesterase agents (edrophonium, neostigmine, and pyridostigmine).
• Synergistic effect with other cholinergic agents such as organophosphate or carbamate insecticides.
• Use in tricyclic antidepressant overdose has been reported to result in seizures and asystole even when physostigmine is given properly in moderate doses.
• Geriatric patients have increased susceptibility to arrhythmias and greater likelihood of underlying renal failure and drug interactions.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category C. Studies have shown that the drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
• The appropriate use of physostigmine in pregnant women has not been defined; in general, its use is discouraged due to low mortality of anticholinergic toxicity.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

• To differentiate between anticholinergic and other organic causes of altered mental status with hallucinations and psychosis, through use of the "physostigmine challenge test."
  • If dramatic reversal of anticholinergic effects is produced, it may be possible to avoid CT and lumbar puncture for evaluation of altered mental status.
• To reverse neuromuscular blockade after general anesthesia.
• To treat paraplegic anejaculation.
• To produce miosis through an ophthalmic preparation.

CONTRAINDICATIONS

• Known hypersensitivity to cholinergic agonists or sulfites precludes use of physostigmine.
• Ventricular dysrhythmia may occur with use of physostigmine in a known or suspected tricyclic antidepressant overdose.
• Underlying health problems such as asthma, heart disease, diabetes, inflammation of iris or ciliary body contraindicate use of physostigmine.
• Physostigmine is generally contraindicated in patients with significant cardiac conduction disturbances of anticholinergic overdoses.
• Physostigmine should not be used to reverse depolarizing blockers (e.g., succinylcholine, decamethonium) because blockade may be potentiated.

ADVERSE EFFECTS

• Acute overdose or oversensitivity reactions to physostigmine
  • Muscarine-like sympathetic (cholinergic) effects, including nausea, vomiting, diarrhea, sweating, increased bronchial and salivary secretions, bradycardia, and hypotension
  • Airway obstruction by secretions

Vital Signs

Bradycardia and increased respiratory rate secondary to pulmonary secretions

HEENT

Increased salivation and lacrimation; diplopia and pupillary constriction

Dermatologic

Diaphoresis

Cardiovascular

Tachydysrhythmia such as atrial fibrillation, ventricular tachycardia, and (rarely) asystole; cardiac standstill possible

Pulmonary

Increased pulmonary secretions, laryngospasm, bronchoconstriction, and central or peripheral paralysis of respiration

Gastrointestinal

Nausea, vomiting, diarrhea, abdominal cramps, and increased salivation and intestinal secretion

Musculoskeletal

Weakness or fasciculation

Neurologic

Seizures, dysarthria, dysphonia, and dysphagia

Section Outline:

• CONTRAINDICATIONS
• ADVERSE EFFECTS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Musculoskeletal
  • Neurologic

• Patient preparation
  • Patient should have intravenous access and continuous cardiac monitoring prior to and during physostigmine administration.
  • Atropine should be immediately available should excessive muscarinic side effects develop.
  • Physostigmine challenge test is used to diagnose the presence of anticholinergic syndrome. Baseline assessment of hallucinosis and presence of anticholinergic signs should be recorded.
• Dose
  • Adult dose is 1.0 to 2.0 mg; 2.0 mg is the most commonly used initial dose.
  • Pediatric dose is 0.02 mg/kg up to 2.0 mg; physostigmine should be administered by slow intravenous push over 5 minutes.
  • May be repeated once after 5- to 10-minute interval if needed.
• If symptoms and signs are truly the result of anticholinergic toxicity, reversal or attenuation of anticholinergic effects should be noted about 5 minutes after administration of physostigmine.
• If reversal of anticholinergic effects occurs, these effects may relapse approximately 30 minutes later.
• To reverse neuromuscular blockade, the patient should receive 0.5 to 1 mg, slow intravenous push, repeated as needed at intervals of 10 to 30 minutes.

• The use of physostigmine when there is no true need is common.
• Physostigmine is primarily a diagnostic tool; because of its short half-life, anticholinergic effects often recur. Fortunately most anticholinergic syndromes can be managed with supportive care.
• Mistaking nonspecific arousal for reversal of anticholinergic effects can lead to giving more physostigmine to a patient without true anticholinergic activity; this increases the risk of cholinergic crisis.
• Reversal of the central anticholinergic syndrome usually results in return to completely normal mentation for the duration of action. Partial response indicates the presence of another toxin or etiology that is not anticholinergic.
• Overly rapid administration is more likely to result in seizure or cardiac dysrhythmia, including asystole.
• Some patients exhibit an increased sensitivity to cholinergic agents and develop cholinergic crisis from very small doses.
• Sodium bisulfite, used as a preservative, may cause allergic reactions.
• Inadequate or excessive atropinization should be avoided in treating cholinergic crisis.

Poisoning by drugs affecting the autonomic nervous system: parasympatholytics (anticholinergics and antimuscarinics) and spasmolytics.

See Also: SECTION II, Anticholinergic Syndrome, Bradycardia Toxidrome, Hypotension, and Seizures (Unexplained) chapters; and SECTION III, Atropine chapter.

RECOMMENDED READING

Gilman AG, Fall TW, Nies AS, et al., eds. Goodman and Gilman's the pharmacological basis of therapeutics, 8th ed. New York: Pergamon, 1990.

Pentel P, Peterson CD. Asystole complicating physostigmine treatment of tricyclic antidepressant overdose. Ann Emerg Med 1980;9:588-590.

Author: Steven A. Seifert

Reviewer: Katherine M. Hurlbut