UNDER REVIEW (September 2016)
Mechanism of Action:
Neostigmine is a reversible, medium-acting anticholinesterase drug (therapeutic effect up to 4 hours). Anticholinesterases competitively inhibit the action of acetylcholinesterase (AChE), which destroys the neurotransmitter acetylcholine following its release from cholinergic nerve endings. By interfering with the breakdown of acetylcholine, neostigmine indirectly (via action of ACh) stimulates both nicotinic and muscarinic receptors. Because neostigmine increases the effective concentration of acetylcholine, it causes such body changes as contraction of the pupils, increased activity of intestinal muscles, and increased secretion by the salivary and sweat glands. Neostigmine is a parasympathomimetic, ie it mimics the effects of stimulation of the parasympathetic nervous system.
Lecture and CAL materials:
- Lecture: Drugs and the Neuromuscular Junction
- Lecture: Drugs and the Parasympathetic Nervous System
- CAL: Enzymes as Drug Targets
- CAL: Suxamethonium
- CAL: Synaptic Transmission in the CNS
Drug specifics
| Alternative drug name | neostigmine metilsulfate (injection), neostigmine bromide (tablets) |
| Effects | Eye: Neostigmine, a parasympathomimetic, causes decreased fluid pressure in the eye. It is useful in treating certain types of glaucoma. Neuromuscular Block: Neostigmine inhibits AChE increasing the availability of acetylcholine molecules in the synaptic cleft. This increases the probability that any vacant nAChRs will be occupied by ACh, enhancing neuromuscular transmission. Hence, neostigmine is given IV to reverse the effects of non-depolarising muscle relaxants (e.g. atracurium), which are competitive antagonists of ACh at the receptor. Oral neostigmine is also useful in improving muscle tone in individuals with myasthenia gravis (autoimmune attack on nAChRs make the post-synaptic membrane less sensitive to ACh). Anticholinesterase inhibitors like neostigmine improve transmission by helping accumulation of ACh. |
| Adverse actions | Eye: Refer to eBNF. Neuromuscular Block: Predictable (Type A) effects of a drug that enhances parasympathetic activity - slowing of the heart rate (bradycardia); hypotension; increased gastric motility (hence gastrointestinal effects). Simultaneous administration of an antimuscarinic drug such as atropine or propantheline may be required to prevent colic, excessive salivation, or diarrhoea. |
| Dose | Eye: Refer to eBNF, Neuromuscular Block: Refer to eBNF. |
| Interactions | Eye: Refer to eBNF, Neuromuscular Block: Refer to eBNF. |
| Contraindications | not specified |
| Comments | Eye: Anticholinesterases are important as first-line treatment for ocular myasthenia gravis. They are used as adjuncts to immunosuppressant therapy for generalised myasthenia gravis. Neuromuscular Block: Neostigmine is routinely in anesthesia at the end of an operation to reverse the effects of non-depolarising muscle relaxants such as vecuronium. It can also be used for urinary retention resulting from general anaesthetics and to treat curariform drug toxicity. Edrophonium, a short-acting cholinesterase is too short acting for therapeutic purposes (would have to be repeated multiple times), but is used in diagnosing myasthenia gravis. |
| Contributors |
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