Cholinesterase Inhibitors: Physostigmine

PHYSOSTIGMINE

Physical Structure

Physostigmine, a tertiary amine, has a carbamate group but no quaternary ammonium. Therefore, it is lipid soluble and is the only clinically available cholinesterase inhibitor that freely passes the blood– brain barrier.

Dosage & Packaging

The dose of physostigmine is 0.01–0.03 mg/kg. It is packaged as a solution containing 1 mg/mL.

Clinical Considerations

The lipid solubility and central nervous system penetration of physostigmine limit its usefulness as a reversal agent for nondepolarizing blockade, but make it effective in the treatment of central anticholinergic toxicity caused by overdoses of atro-pine or scopolamine. In addition, it reverses some of the central nervous system depression and delirium associated with use of benzodiazepines and volatile anesthetics. Physostigmine (0.04 mg/kg) has been shown to be effective in preventing postoperative shivering. It reportedly partially antagonizes mor-phine-induced respiratory depression, presumably because morphine reduces acetylcholine release in the brain. These effects are transient, and repeated doses may be required. Bradycardia is infrequent in the recommended dosage range, but atropine should be immediately available. Because glycopyrrolate does not cross the blood–brain barrier, it will not reverse the central nervous system effects of phy-sostigmine. Other possible muscarinic side effects include excessive salivation, vomiting, and convul-sions. In contrast to other cholinesterase inhibitors, physostigmine is almost completely metabolized by plasma esterases, so renal excretion is not important.