indication

Used as an adjunct with succinylcholine (or suxamethonium chloride) to prolong muscle relaxation and to prevent succinylcholine-induced muscle fasciculations.

pharmacology

Hexafluronium bromide is a cholinesterase antagonist that can be used to prolong the relaxation effects of succinylcholine or suxamethonium chloride. Suxamethonium acts as a depolarizing muscle relaxant. It imitates the action of acetylcholine at the neuromuscular junction and is degraded by pseudocholinesterase, a plasma cholinesterase. The prolonged stimulation of the acetylcholine receptor results first in disorganized muscle contractions, then in profound relaxation. Cholinesterases catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation. There are two types of cholinesterase acetylcholinesterase and pseuodocholinesterase. The first hydrolyses acetylcholine more quickly; the latter hydrolyses butyrylcholine and succinylcholine more quickly. An absence or mutation of the pseudocholinesterase enzyme leads to a medical condition known simply as pseudocholinesterase deficiency. This is a silent condition that only manifests itself when people who have the deficiency receive the muscle relaxants succinylcholine or mivacurium during a surgery.

mechanism of action

Hexafluronium bromide is a non-competitive reversible inhibitor of human plasma cholinesterase or pseudocholinesterase. Hexafluornium probably binds to anionic side receptors near the active center, causing a conformational change in the enzyme, preventing acylation of the esteratic site. The esteratic site on cholistereases is where acetylcholine is hydrolyzed to acetic acid and choline.

toxicity

LD₅₀ = 280 mg/kg (mouse, oral)