Competitive NMJ blockers

These act as antagonists at the NMJ nicotinic receptors, ie compete with acetylcholine for the receptors.

Indications

dogs for thoracic / upper abdominal ops (pancuronium, atracurium, vecuronium) to allow better access for surgeon
(horses for thoracic ops (rare)(atracurium)
(experimental animals)

Pancuronium is cheap, duration 20 - 40 mins: atracurium is possibly best, duration 15 - 20 mins, used in sick animals - broken down by Hofmann degradation in the plasma so no liver function required. Vecuronium is short acting - 10 mins. Obselete drugs not used any more include tubocurarine (releases histamine in dogs), gallamine, alcuronium (drops blood pressure), fazadinium etc. New drugs such as mivacurium and rocuronium have not worked into veterinary use yet - no obvious advantages.

Drug interactions

potentiated by inhalation anaesthetics (unknown mechanism) and aminoglycoside antibiotics, high magnesium, low calcium - reduced acetylcholine release

Precautions

artificial ventilation and adequate anaesthesia required

Clinical use

Given iv after the animal has lost consciousness from the anaesthetic. Paralysis usually takes 1 - 2 minutes and the animal must be ventilated (by mask). Alternatively, they can be given after the animal has been anaesthetised and intubated.
At the end of the procedure neuromuscular blockade is reversed using anticholinesterases - neostigmine (rarely edrophonium) and atropine to block the muscarinic effects (except horses). Neostigmine blocks the breakdown of acetylcholine which then competes with the neuromuscular blocker for the nicotinic receptors. Increased acetylcholine in other parts of the body can cause unwanted effects such as gut spasm, possible rupture of enterotomy wounds and colic in horses.
The shorter acting atracurium and vecuronium tend to be used to avoid having to reverse blockade; the animal is ventilated until the block wears off. This approach is used in human anaesthesia and neostigmine and edrophonium are becoming difficult to obtain in NZ.
Neostigmine and edrophonium are sometimes used to diagnose myaesthenia gravis, the longer acting pyridostigmine to treat it.

Experimental drugs

You may see a bungarotoxin (from kraits) mentioned in the literature. It binds irreversibly to nicotinic NMJ receptors and is used to characterise the receptors. It is not used clinically and you are unlikely to come across snake bites in NZ.

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