physostigmine (Antilirium, Isopto Eserine)

Introduction

Tradenames: Antilirium, Isopto Eserine.

Indications

• reversal of toxic CNS effects caused by anticholinergic agents*
• ointment used as a miotic agent in treatment of glaucoma

* bicarbonate is 1st line for tricyclic antidepressant overdose

Contraindications

• tricyclic antidepressant overdose (may precipitate asystole)

pregnancy category = c

safety in lactation = ?

Dosage

• 0.5-2 mg IM or IV (slowly, < 1 mg/min)
• repeat in 10-30 minutes if desired response not obtained
• ophthalmic ointment QHS

Injection: (as salicylate): 1 mg/mL (2 mL).

Ointment: (as sulfate) 0.025% (3.5 g)

Pharmacokinetics

• readily absorbed from GI tract, mucus membranes & subcutaneous tissue
• freely crosses blood-brain barrier after IM or IV administration
• onset of action is 3-8 minutes
• duration of action is 30 minutes to 5 hours
• inactivated via hydrolysis by cholinesterase
• elimination 1/2life is 15-40 minutes

elimination via plasma

Adverse effects

• ophthalmic agent
  • common (> 10%)
    • lacrimation, sweating, excessive miosis, blurred vision, eye pain
  • less common (1-10%)
    • burning, headache, browache, redness
• systemic agent
  • common (> 10%)
    • nausea, sweating, lacrimation, salivation, diarrhea, epigastric pain
  • less common (1-10%)
    • frequent urge to urinate, restlessness, miosis, nervousness, palpitations, bradycardia, hallucinations, seizures, muscle twitching, dyspnea, bronchospasm, respiratory tract paralysis, pulmonary edema
  • other
    • nausea/vomiting
    • epigastric pain
    • dyspnea
    • CNS stimulation
    • irregular pulse
    • weakness
    • seizures (rare)

• drug adverse effects of cholinesterase inhibitors

Mechanism of action

• reversible inhibitor of cholinesterase
• produces generalized cholinergic responses:
  • miosis
  • increased tone of intestinal musculature
  • bronchial constriction
  • increased secretion of salivary & sweat glands

More general terms

• carbamate
• alkaloid
• cholinesterase inhibitor

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5983
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6150
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=656508
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4811
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5992
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=111151
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=111150