Physostigmine (Eserine)

Mechanism

Pharmacological Group and Molecular Target

Reversible inhibitor of the enzyme acetylcholinesterase with a tertiary amine structure.

Detailed Mechanism of Action

Many commonly used xenobiotics (such as atropine, first-generation antihistamines, tricyclic antidepressants or datura alkaloids) competitively block central and peripheral muscarinic receptors, triggering acute anticholinergic syndrome (fever, anhidrosis, mydriasis, tachycardia, hyperactive delirium with visual hallucinations and urinary retention).

Physostigmine is a non-ionized tertiary amine alkaloid. Lacking a net electrical charge, it rapidly crosses the blood-brain barrier. Once in the brain tissue, it reversibly blocks the enzyme acetylcholinesterase, preventing the degradation of acetylcholine in the synapses of the CNS. This increases endogenous levels of acetylcholine, which effectively competes with and displaces exogenous muscarinic blockers, reversing the central delirium and peripheral symptoms of the syndrome.

Indicators and dose

Specific Clinical Indications

• Reversal of refractory severe central anticholinergic syndrome characterized by uncontrollable extreme psychomotor agitation with benzodiazepines or delirium with risk of self-harm or secondary malignant hyperthermia.

Dosage Scheme and Infusion Protocols

• Standard Dose (Adults): 0.5 mg to 2 mg by slow intravenous route administered in a time not less than 5 minutes strictly. An excessive rate of administration can cause immediate convulsions and cholinergic crises.
• Rescue antidote ready at the bedside: During physostigmine administration, it is mandatory to have a 1 mg Atropine syringe ready for IV use immediately for any sign of cholinergic overdose (severe bradycardia, bronchorrhea, seizures).

Security

Contraindications and Precautions

Catastrophic Danger of Cardiac Asystole in Tricyclic Overdose

The administration of physostigmine is strictly contraindicated in patients with suspected or confirmed overdose of tricyclic antidepressants (such as amitriptyline). Tricyclic antidepressants block voltage-gated cardiac sodium channels (prolonging the QRS complex on the ECG). Physostigmine, by increasing cholinergic tone and concurrent sinus bradycardia, acts synergistically with sodium channel blockade, immediately inducing complete atrioventricular block, refractory asystole and irreversible cardiovascular collapse. Do not use if there is QRS prolongation >100 ms or evidence of cardiac involvement on the ECG.