Physostigmine
Physostigmine salicylate
Also known as: Antilirium · Anticholium · Eserine salicylate · Physostigmine monosalicylate
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Audited v13 dosing evidence
Reviewed non-calculator evidenceReviewed non-calculator evidence (1)
Evidence only — not for automatic calculation
May ameliorate flaccid paralysis from ivermectin or levamisole toxicosis
TABLE 128.6. Agent: Physostigmine (ophthalmic drops). Dosage: 1 drop/50 g topically q1–2h to effect52. Species/Comments: May ameliorate flaccid paralysis from ivermectin or levamisole toxicosis.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Physostigmine is a reversible cholinesterase inhibitor used primarily in veterinary medicine for the adjunctive treatment of ivermectin toxicity, as a provocative agent for diagnosing narcolepsy/cataplexy in dogs and horses, and as an antidote for central anticholinergic toxicity.
Clinical Pearls:
- Unlike quaternary amine cholinesterase inhibitors (e.g., neostigmine, pyridostigmine), physostigmine is a tertiary amine.
- This structural difference allows it to readily cross the blood-brain barrier (BBB), making it uniquely effective for treating central anticholinergic toxicity.
- Because it enters the CNS, it carries a higher risk of central toxic effects (e.g., seizures) compared to its quaternary counterparts.
- Due to its narrow therapeutic index and potential for severe adverse effects, its use is generally reserved for life-threatening CNS toxicity.
Mechanism of action
Physostigmine reversibly inhibits the enzyme acetylcholinesterase → prevents the hydrolysis and destruction of acetylcholine (ACh) → increases the concentration of ACh at both muscarinic and nicotinic receptor sites.
Because it is a lipophilic tertiary amine, it crosses the blood-brain barrier and exerts its cholinergic effects both centrally and peripherally. This widespread cholinergic stimulation leads to miosis, bronchoconstriction, hypersalivation, and increased gastrointestinal motility.
Safety & warnings
Contraindications
- Prior hypersensitivity reactions to physostigmine or sulfites
- Bronchoconstrictive disease (asthma)
- Gangrene
- Diabetes mellitus
- Cardiovascular disease
- Mechanical obstruction of the GI or urinary tract
- Any vagotonic state
- Concurrent use of choline esters or depolarizing neuromuscular blocking agents
Adverse effects
- Miosis
- Bronchial constriction
- Hypersalivation
- Muscle weakness
- Sweating (in species with sweat glands)
- Seizures
- Bradycardia
- Tachycardia
- Asystole
- Nausea
- Vomiting
- Diarrhea
- Depolarizing neuromuscular block
- Pulmonary edema
- Respiratory paralysis
Precautions
WARNING: Toxic effects from this drug can be serious and life-threatening. Must be administered with direct patient supervision.
- Cholinergic Crisis Risk: Increased risk when used in the absence of anticholinergic toxicity or to treat tricyclic/tetracyclic antidepressant overdoses.
- Administration Rate: Rapid IV administration increases the potential for bradycardia, hypersalivation, or seizures. Must be given slowly.
- Antidote Availability: Atropine must be readily available when administering physostigmine.
- Neonatal Toxicity: The injection contains benzyl alcohol, which may be toxic to neonatal animals.
- Pregnancy: Weigh potential risks versus benefits. Teratogenic effects have been observed in mice.
Drug interactions
May cause additive adverse cholinergic effects.
May cause additive adverse cholinergic effects.
High doses of physostigmine may cause muscle fasciculations or depolarization block, which may be additive to the effects of succinylcholine-like neuromuscular blockers.
Monitoring
- Direct patient supervision is required
- Blood pressure
- ECG/Heart rhythm (especially if heart rate is abnormal)
- Signs of cholinergic crisis (salivation, lacrimation, urination, defecation, dyspnea, emesis)
Pharmacokinetics
Absorption
Rapidly absorbed from the GI tract (though no oral dosage form is available), subcutaneous tissue, or mucous membranes. Peak effects occur within 5 minutes after IV administration and about 25 minutes after IM dosing.
Distribution
Readily crosses the blood-brain barrier into the CNS due to its tertiary amine structure.
Metabolism
The majority of the administered drug is rapidly destroyed via hydrolysis by cholinesterases.
Elimination
Very small amounts can be eliminated unchanged into the urine. Duration of pharmacologic effects ranges from 30 minutes to 5 hours (average duration is 30-60 minutes).
Overdose
Overdoses or acute toxicity can be life-threatening and may result in a severe cholinergic crisis (seizures, bradycardia, asystole, respiratory paralysis).
- Supportive Care: Because of the short duration of effect, supportive care (including mechanical ventilation and repeated bronchial aspiration) may be sufficient in some cases.
- Antidote (Muscarinic): Administration of IV atropine is the primary treatment for cholinergic toxicity. Re-administration may be required.
- Antidote (Nicotinic): Pralidoxime (2-PAM) may be useful in reversing the ganglionic and skeletal muscle effects of physostigmine.
- Contact an animal poison control center for case management assistance.
Available products
Formulations
- Injection
Human-labeled
- Physostigmine Salicylate Injection: 1 mg/mL (contains benzyl alcohol 2% and 0.1% sodium metabisulfite) in 2 mL ampules
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store ampules below 40°C, preferably between 15-30°C. Protect from light and freezing. It should be administered IV undiluted and should not be added to IV solutions.
Client information
This medication is strictly for use in a clinical setting.
- Direct Supervision: It must be administered in a veterinary hospital where direct veterinary supervision and emergency monitoring are available.
- Not for Home Use: Due to the risk of severe and potentially life-threatening side effects, this drug is never dispensed for owners to administer at home.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.