Pharmacology for Anaesthesia and Intensive Care

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11 Muscle relaxants and anticholinesterases

Neostigmine

Neostigmine is a quaternary amine.

Presentation and uses

Neostigmine is available as tablets and in solution for intravenous injection (and in

combination with glycopyrrolate). It is used to reverse the effects of non-depolarizing

muscle relaxants (0.05 mg.kg−^1 intravenously), in the treatment of myasthenia gravis

(15–30 mg orally where effects last up to 4 hours) and in urinary retention.

Effects


Cardiovascular – if administered alone it will precipitate a bradycardia. It has a

limited role in the treatment of supraventricular tachycardia.


Respiratory – it may precipitate bronchospasm in asthmatics.


Gut–it increases salivation and intestinal motility, which may result in abdominal

cramps.

Kinetics

Neostigmine is poorly absorbed from the gut and has a low oral bioavailability. It is

minimally protein bound, has a low volume of distribution and is partially metabo-

lized in the liver. Approximately 55% is excreted unchanged in the urine.

Pyridostigmine

Pyridostigmineis also a quaternary amine used mainly in the treatment of myas-

thenia gravis, where it is preferred to neostigmine because it has a longer duration

of action and has fewer autonomic effects.

Kinetics

Pyridostigmine has a slower onset of action than neostigmine and its duration of

action is longer. It relies on renal elimination more than neostigmine (75% excreted

unchanged).

Like neostigmine it does not cross the blood–brain barrier.

Physostigminehas a tertiary amine structure and it, therefore, has different prop-

erties. It is well absorbed from the gut and crosses the blood–brain barrier. In the

past it has been used in the treatment of anticholinergic poisoning.

Organophosphorous compounds

Organophosphorous compounds are highly toxic and are mainly used as insecti-

cides (e.g. tetraethylpyrophosphate (TEPP)), or nerve gases (sarin (GB)). However,

ecothiopate iodide has been used to treat glaucoma by relaxing the ciliary muscle

and thereby improving drainage channels of the trabecular meshwork.

These agents are highly lipid-soluble and are, therefore, rapidly absorbed across

skin.