Ach is rapidly inactivated by ChE and endplate returns to its resting potential. However, if there is prolonged depolarization induced by these drugs, there is no further generation of action potential after the initial twitch and there is loss of electrical excitability at the motor endplate.
Directly acting muscle relaxant: They exert direct action on the skeletal muscle, by interfering with the release of Ca2+ from the sarcoplasmic reticulum, they interfere with the excitation-contraction coupling (Bhattacharya 2003).
Treatment of respiratory paralysis arising from an adverse reaction or overdose of a neuromuscular blocking agent should be by positive pressure artificial respiration with oxygen and maintenance of a patient airway until the recovery of normal respiration is assured. With the competitive blocking agents, this may be hastened by the administration of neostigmine methyl sulphate (0.5 to 2mg, intravenously) or edrophonium (10mg intravenously, repeated as required.) (Hardman 1996).
Neostigmine is a quaternary ammonium compound that inhibits cholinesterase activity and thus prolongs and intensifies the physiological actions of acetylcholine. It probably also has direct effects on skeletal muscle fibres. To reverse neuromuscular blockade produced by competitive neuromuscular blockers, the usual adult dose in the UK is 50 to 70micrograms/kg given by intravenous injection over a period of 60 seconds; in the USA lower doses of 0.5 to 2mg are used. Additional neostigmine may be given until the muscle power is normal but a total of 5mg should not be exceeded. Similar doses may be used in children; the BNFC recommends a dose of 50 to 80micrograms/kg in neonates and children, to a maximum of 2.5mg in those under 12 years of age. The patient should be well ventilated until complete recovery of normal respiration is assured. To counteract any muscarinic effects in adults 0.6 to 1.2mg of atropine sulfate is given by intravenous injection with or before the dose of neostigmine; neonates and children up to 18 years of age may be given 20micrograms/kg of atropine sulfate (to a maximum of 600micrograms in those aged 1 month and over). It has been suggested that in the presence of bradycardia atropine sulfate should be given several minutes before neostigmine. Glycopyrronium bromide has been used as an alternative to atropine sulfate.
The adverse effects of neostigmine are chiefly due to