Physostigmine Salicylate — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	IV	0.02-0.06 mg/kg (slow IV)	Repeat as needed every 10-15 minutes for anticholinergic toxicity, up to a maximum total dose of 0.15 mg/kg	Duration: As needed for reversal of toxicity Notes: Administer slowly to avoid bradycardia and seizures. Use with atropine at the ready for cholinergic crisis.
Dog	Ophthalmic (topical)	1-2 drops of 0.25-0.5% solution	q6-8h	Duration: For glaucoma, as directed by veterinarian Notes: Monitor intraocular pressure and pupillary response.
Cat	IV	0.02-0.04 mg/kg (slow IV)	Repeat as needed every 10-15 minutes for anticholinergic toxicity	Duration: As needed Notes: Use cautiously in cats due to increased sensitivity to cholinergic effects.
Cat	Ophthalmic (topical)	1-2 drops of 0.25% solution	q6-8h	Duration: For glaucoma, as directed Notes: Monitor for systemic effects.
Horse	IV	0.01-0.02 mg/kg (slow IV)	Repeat as needed for anticholinergic toxicity	Duration: As needed Notes: Monitor for colic and bradycardia.
Horse	Ophthalmic (topical)	1-2 drops of 0.25-0.5% solution	q6-8h	Duration: For glaucoma, as directed Notes: Use with caution in horses with asthma.
Cattle	IV	0.02-0.04 mg/kg (slow IV)	Repeat as needed for anticholinergic toxicity	Duration: As needed Notes: Not commonly used; ensure accurate dosing to avoid toxicity.
Small Ruminants	IV	0.02-0.04 mg/kg (slow IV)	Repeat as needed	Duration: As needed Notes: Limited data; use cautiously.
Rabbit	IV	0.02-0.04 mg/kg (slow IV)	Repeat as needed	Duration: As needed Notes: Limited data; use cautiously.
Birds/Poultry	IV	0.01-0.02 mg/kg (slow IV)	Repeat as needed	Duration: As needed Notes: Limited data; use cautiously.

Clinical Indications & Species Uses

General Indications

Reversal of central anticholinergic syndrome
Treatment of glaucoma (topical)
Diagnostic agent for myasthenia gravis (short-acting)

Dog (Canine)

Reversal of central anticholinergic syndrome (e.g., atropine, diphenhydramine, tricyclic antidepressants)
Treatment of glaucoma (topical use)
Diagnosis and treatment of myasthenia gravis (as an adjunct, though not first-line)
Treatment of ileus (non-obstructive) in some cases

Cat (Feline)

Reversal of central anticholinergic syndrome
Treatment of glaucoma (topical use)
Diagnosis of myasthenia gravis (short-acting diagnostic agent)

Horse (Equine)

Reversal of anticholinergic toxicity (e.g., atropine overdose)
Treatment of glaucoma (topical use)
Treatment of postoperative ileus (in some cases)

Cattle (Bovine)

Reversal of anticholinergic toxicity (e.g., organophosphate poisoning? Not primary; but for atropine toxicity)

Small Ruminants (Sheep / Goat)

Reversal of anticholinergic toxicity (rarely)

Rabbit & Small Mammals

Reversal of anticholinergic toxicity (rarely)

Avian & Poultry

Reversal of anticholinergic toxicity (rarely)

Exotic & Other Species

Reversal of anticholinergic toxicity (rarely)

Pharmacology & Mechanism of Action

Drug Class: Cholinesterase Inhibitor | Pharmacological Group: Parasympathomimetic (Anticholinesterase)

Mechanism of Action: Physostigmine is a reversible carbamate acetylcholinesterase inhibitor. It binds to the esteratic site of acetylcholinesterase, preventing the hydrolysis of acetylcholine, thereby increasing the concentration and duration of action of acetylcholine at cholinergic synapses. This results in enhanced stimulation of muscarinic and nicotinic receptors, leading to parasympathomimetic effects. Unlike quaternary ammonium cholinesterase inhibitors, physostigmine is a tertiary amine that can cross the blood-brain barrier, thus also increasing acetylcholine in the central nervous system.

Pharmacodynamics: Physostigmine produces dose-dependent parasympathomimetic effects including miosis, bradycardia, increased gastrointestinal motility and secretions, bronchoconstriction, salivation, lacrimation, and urination. Central effects include arousal, increased alertness, and reversal of central anticholinergic syndrome. In the eye, it causes pupillary constriction and reduces intraocular pressure by improving aqueous humor outflow. Its effects are reversible and short-lived due to rapid metabolism.

⚡ Pharmacokinetics Summary

Absorption: Physostigmine is well absorbed after oral, parenteral, and ophthalmic administration. Onset of action after IV administration is rapid (within minutes). Oral absorption is variable due to first-pass metabolism.

Distribution: Widely distributed throughout the body. As a tertiary amine, it crosses the blood-brain barrier and the placenta. It is also distributed into ocular tissues after topical application.

Metabolism: Rapidly hydrolyzed by plasma esterases and metabolized in the liver. The major metabolite is eseroline, which is inactive.

Excretion: Excreted primarily in the urine as metabolites and small amounts of unchanged drug. Biliary excretion also occurs.

Half-Life: Short; approximately 15-40 minutes in dogs and cats. In horses, the half-life is approximately 30 minutes.

Bioavailability: Oral bioavailability is low and variable due to extensive first-pass metabolism; parenteral administration provides complete bioavailability.

Protein Binding: Low; approximately 20-30% bound to plasma proteins.

Available Formulations & Strengths

Injectable Solution 1 mg/mL (as salicylate) (IV, IM, SC)

Ophthalmic Solution 0.25%, 0.5% (Ophthalmic)

Ophthalmic Ointment 0.25% (Ophthalmic)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to physostigmine or other cholinesterase inhibitors
Asthma or chronic obstructive pulmonary disease (due to bronchoconstriction)
Cardiovascular disease (bradycardia, hypotension, cardiac arrhythmias)
Gastrointestinal or urogenital obstruction (due to increased motility and secretions)
Concurrent use of depolarizing neuromuscular blocking agents (e.g., succinylcholine)
Peptic ulcer disease
Epilepsy or seizure disorders (may precipitate seizures)

Warnings & Clinical Precautions:

Use with extreme caution in animals with bradycardia, hypotension, or cardiac conduction disturbances.
May cause severe cholinergic toxicity if overdosed; have atropine available as an antidote.
In animals with myasthenia gravis, use only as a diagnostic aid; may cause cholinergic crisis if overdosed.
Ophthalmic use may cause systemic absorption; monitor for systemic effects, especially in small animals.
Use in pregnant or lactating animals only if clearly needed; safety not established.
Physostigmine is a tertiary amine and crosses the blood-brain barrier; central effects may include seizures and confusion.
In horses, monitor for signs of colic due to increased gastrointestinal motility.
In cattle and other ruminants, use with caution due to potential for bloat and respiratory issues.

Adverse Effects & Reactions

Common:

Miosis
Bradycardia
Salivation
Lacrimation
Urination
Defecation
Gastrointestinal cramps
Nausea and vomiting
Bronchoconstriction
Sweating (in horses)

Serious / Severe:

Seizures
Severe bradycardia or asystole
Hypotension
Respiratory depression or bronchospasm
Cholinergic crisis (muscle fasciculations, weakness, paralysis)
Pulmonary edema

Rare:

Allergic reactions
Cardiac arrhythmias
Central nervous system excitation or depression
Hypersalivation and excessive bronchial secretions

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Atropine and other anticholinergics	Antagonizes the effects of physostigmine; used as antidote for physostigmine toxicity.	High
Depolarizing neuromuscular blockers (e.g., succinylcholine)	May prolong or enhance neuromuscular blockade.	High
Non-depolarizing neuromuscular blockers (e.g., pancuronium)	May antagonize the neuromuscular blockade, potentially reversing paralysis.	Moderate
Other cholinesterase inhibitors (e.g., neostigmine, organophosphates)	Additive toxicity; increased risk of cholinergic crisis.	High
Beta-blockers	May exacerbate bradycardia and hypotension.	Moderate
Digoxin	May increase risk of bradyarrhythmias.	Moderate
Corticosteroids	May reduce the effect of physostigmine in myasthenia gravis.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Severe miosis
Bradycardia or heart block
Hypotension
Bronchoconstriction and respiratory distress
Excessive salivation, lacrimation, urination, defecation
Muscle fasciculations and weakness
Seizures
Coma
Pulmonary edema

Emergency Treatment Protocol: Immediate administration of atropine (0.02-0.04 mg/kg IV, half dose IM) to counteract muscarinic effects. Supportive care includes oxygen therapy, mechanical ventilation if needed, fluid therapy for hypotension, and anticonvulsants (e.g., diazepam) for seizures. Monitor cardiac and respiratory function closely. For severe cases, pralidoxime may be considered, but it is less effective for carbamate inhibitors. Symptomatic and supportive treatment is essential.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 3 days

Withdrawal times are not officially established for physostigmine in food animals. The values provided are conservative estimates based on its short half-life. However, due to limited data, it is recommended to consult regulatory guidelines and use a longer withdrawal period if possible. Extra-label use in food animals requires a veterinary prescription and adherence to AMDUCA.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), with excursions permitted between 15-30°C (59-86°F).

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light. Keep container tightly closed. Do not freeze. Store ophthalmic solutions upright and discard after 30 days of opening.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use (as an antidote and for glaucoma).

Extra-Label (Off-Label) Use: Physostigmine is not FDA-approved for veterinary species; its use in animals is extra-label. In the US, extra-label use is permitted under AMDUCA (Animal Medicinal Drug Use Clarification Act) for non-food animals and in food animals only with a valid veterinary-client-patient relationship and if no approved drug is available. For food animals, extended withdrawal times must be observed to ensure food safety.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Physostigmine salicylate is a valuable antidote for central anticholinergic syndrome, but its use in veterinary medicine is limited due to the availability of safer alternatives. It is primarily used in emergency settings for reversal of atropine or other anticholinergic toxicity, and as a diagnostic agent for myasthenia gravis (though edrophonium is more commonly used). Its short duration of action requires repeated dosing, and careful monitoring is essential to avoid cholinergic toxicity. In ophthalmic use, it is less preferred than other miotics due to systemic side effects and the need for frequent administration. Always have atropine available when administering physostigmine. Due to its narrow therapeutic index, accurate dosing and slow IV administration are critical. In food animals, extra-label use is discouraged due to lack of withdrawal data; consider alternative therapies.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)