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