Physostigmine
Physostigmine is a reversible acetylcholinesterase inhibitor that enters the central nervous system. This distinguishes it from predominantly peripheral anticholinesterases such as neostigmine. Its principal toxicologic application is reversal of selected antimuscarinic syndromes, while other motility or neuromuscular applications in veterinary medicine have a more limited and largely historical evidence base.
Group
Central and peripheral acetylcholinesterase inhibitor
Mechanism of Action
Physostigmine temporarily inhibits acetylcholinesterase, increasing the amount and duration of acetylcholine at cholinergic synapses. Because it crosses the blood–brain barrier, it can restore cholinergic signaling in both central and peripheral antimuscarinic intoxication. Increased acetylcholine also enhances nicotinic neuromuscular transmission and muscarinic smooth-muscle activity, accounting for additional peripheral effects.
Dose Rates
Dogs
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Anticholinergic intoxication | 0.02 mg/kg | IV | Every 12 h | |
| Ivermectin CNS depression diagnostic adjunct | 1 mg/animal | IV | Every 12 h | Transient response may last 30-90 minutes; not definitive antidotal therapy and may provoke seizure-like activity in less-depressed dogs. |
| Narcolepsy diagnostic challenge | 0.025 mg/kg | IV | Observe response to a food/stimulus test after 9-15 minutes; higher sequential challenges are separate protocols. | |
| Narcolepsy diagnostic challenge | 0.05 mg/kg | IV | Observe response to a food/stimulus test after 9-15 minutes; higher sequential challenges are separate protocols. |
Cats
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Anticholinergic intoxication | 0.02 mg/kg | IV | Every 12 h |
Horses
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Narcolepsy diagnostic challenge | 0.05–0.1 mg/kg | IV | Slow administration; colic/cholinergic signs possible and a negative challenge does not exclude narcolepsy. | |
| Narcolepsy diagnostic challenge | 0.06–0.08 mg/kg | IV | Slow administration; colic/cholinergic signs possible and a negative challenge does not exclude narcolepsy. |
Cattle
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Larkspur poisoning adjunct | 0.04–0.08 mg/kg | IV | As needed | Historical serial-injection report; monitor cardiac and cholinergic effects. |
Indications
- Specialist treatment of selected central and peripheral antimuscarinic intoxications, including suitable atropine-like drug exposures.
- Historical reversal of selected nondepolarizing neuromuscular blockade, with more limited veterinary use than peripheral reversal agents.
- Historical treatment of selected functional ileus or urinary retention, with limited controlled clinical evidence.
Contraindications
- Avoid concurrent choline esters such as bethanechol.
Interactions
- Other cholinergic drugs amplify toxicity.
Adverse effects
- Diarrhea, secretions, bradycardia, miosis, bronchoconstriction and weakness.
Toxicity
Atropine can counter excessive muscarinic effects. Severe cholinergic toxicity can compromise breathing; discontinue exposure, support ventilation/airway clearance and treat muscarinic effects with atropine. Additional antidotal measures require a specific toxicologic plan.
Preparations
| Preparation | Form | Strength | Route |
|---|---|---|---|
| Physostigmine injection 1 mg/mL | Injection | 1 mg / mL | IV |
Monitoring and Administration
Monitor rhythm, heart rate and gastrointestinal effects. For prolonged anticholinesterase treatment, alternatives with fewer central effects may be preferable.