Pharmacology for Anaesthesia and Intensive Care

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11 Muscle relaxants and anticholinesterases

N O

H

Anionic site ( ) Esteratic site AChE

Figure 11.7.Edrophonium forms an easily reversible enzyme complex.

Three groups are defined based on their mechanism of action:


Easily reversible inhibition


Formation of a carbamylated enzyme complex


Irreversible inactivation by organophosphorous compounds

Easily reversible inhibition

Edrophonium

Edrophonium is the only drug in this group. It is a phenolic quaternary amine.

Uses

Atan intravenous dose of 2–10 mg it rapidly distinguishes between a myasthenic

crisis (where muscle power is improved) and a cholinergic crisis (where the clinical

picture is worsened).

Mechanism of action

The quaternary amine group of edrophonium is attracted to the anionic site of AChE

while its hydroxyl group forms a hydrogen bond at the esteratic site and stabilizes the

complex (Figure11.7). ACh is now unable to reach the active site of AChE. However,

AChcompetes with edrophonium for AChE because a true covalent bond is not

formed between edrophonium and AChE. Edrophonium also causes increased ACh

release.

Kinetics

Owing to its quaternary amine structure edrophonium has a low lipid solubility and

is not absorbed following oral administration. For similar reasons, it does not cross

the BBB or the placenta. It has a faster onset of action than neostigmine. Up to 65%

is excreted unchanged in the urine, the rest undergoes glucuronidation in the liver

and subsequent excretion in the bile. It has only slight muscarinic side-effects but

may still cause a bradycardia and salivation.

Formation of a carbamylated enzyme complex

Neostigmine, pyridostigmine, physostigmine (Figure11.8).