Pharmacology for Anaesthesia and Intensive Care

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Section IICoredrugs in anaesthetic practice

Edrophonium N

Neostigmine

Pyridostigmine

Physostigmine

CH 3

CH 3

CH 3

N

CH 3 — N

CH 3

(CH 3 ) 3 — N O— C — N(CH 3 ) 2

C 2 H 5 OH

O

——

O— C — N(CH 3 ) 2

O

——

O— C — N — CH 3

OH

—— —

—

CH 3

N

—

Figure 11.8.Chemical structure of some anticholinesterases.

Mechanism of action

Both ACh and the carbamate esters are hydrolyzed when they react with AChE.

However, ACh acetylates AChE while the carbamate esters produce a carbamylated

enzyme (Figure11.9). The later has a much slower rate of hydrolysis and so is unable

to work for longer, hence, it stops AChE hydrolyzing ACh. The carbamate esters are

also known as acid-transferring or time-dependent AChE inhibitors. Neostigmine

also inhibits plasma cholinesterase and as such may prolong the actions of suxam-

ethonium.

N

O

CN

O

H

Anionic site ( ) Esteratic site AChE

Figure 11.9.Neostigmine forms a carmabylated enzyme complex.