Pyridostigmine is used mainly to improve muscle strength in the symptomatic treatment of myasthenia gravis. Because of its longer duration of action, smoother and steadier effects, and reportedly lower incidence of adverse muscarinic effects, most clinicians prefer pyridostigmine to neostigmine for oral therapy. In addition, pyridostigmine may be more effective than neostigmine in relieving ptosis, diplopia, dysarthria, and weakness in bulbar muscles. Pyridostigmine is not effective in patients who are resistant to other anticholinesterase drugs.
Pyridostigmine is used parenterally for symptomatic treatment of acute exacerbations of myasthenia gravis and when oral therapy is impractical. However, the injectable preparation that was used for this indication no longer is commercially available in the US, and the parenteral injection that is commercially available does not include this use in its prescribing information. Some clinicians prefer neostigmine to pyridostigmine for IM therapy since it has a shorter duration of action and therefore dosage can be adjusted more frequently as needed. Neostigmine is usually preferred for treatment of neonatal myasthenia gravis, although pyridostigmine has been used.
Parenteral pyridostigmine is useful for reversal of the effects of nondepolarizing neuromuscular blocking agents (e.g., tubocurarine, metocurine, gallamine [no longer commercially available in the US], pancuronium) after surgery. When used for this purpose, pyridostigmine has been reported to produce less oropharyngeal secretion, bradycardia, and cardiac arrhythmia than neostigmine. Anticholinesterase drugs do not antagonize the phase I block of depolarizing neuromuscular blocking agents such as succinylcholine; therefore, pyridostigmine should not be given in an attempt to reverse the neuromuscular block produced by these agents.
Chemical Warfare Agent Poisoning
Pyridostigmine bromide is used in military combat personnel for preexposure prophylaxis against the lethal effects of soman nerve agent poisoning. Pyridostigmine is used in conjunction with standard treatment of nerve agent poisoning (i.e., atropine and pralidoxime chloride) and other protective measures such as specifically designed masks, hoods, and overgarments. Use of pyridostigmine alone will not be protective against the effects of soman; efficacy of pyridostigmine is dependent on the rapid administration of atropine and pralidoxime following exposure to the nerve agent. Pyridostigmine is administered orally prior to an expected exposure to soman (i.e., when under the threat of a nerve agent attack); the drug must be discontinued immediately at the first indication of nerve agent poisoning. In addition, pyridostigmine should not be taken after exposure to soman. If pyridostigmine is taken immediately before exposure or at the same time as soman poisoning, the drug is not likely to be effective and may exacerbate the effects of a sublethal exposure to soman.
The most toxic of the known chemical warfare agents are the nerve agents. Most nerve agents are liquid at room temperature (although most are volatile at ambient temperatures, the term nerve gas is a misnomer); nerve agents are readily absorbed after inhalation of aerosols (e.g., following an explosion), ingestion, or dermal contact. Nerve agents (e.g., sarin, soman, tabun, VX [metylphosphonothionic acid]) are chemically similar to the organophosphate pesticides and exert their biologic effects by inhibiting acetylcholinesterase enzymes. Nerve agents alter cholinergic synaptic transmission at neuroeffector junctions (muscarinic effects), at skeletal myoneural junctions and autonomic ganglia (nicotinic effects), and in the CNS.
Pyridostigmine was approved for preexposure prophylaxis against effects of soman under the US Food and Drug Administration's (FDA's) animal efficacy rule that allows use of animal data of effectiveness for certain conditions when a drug cannot be ethically tested in humans. Studies in animals indicate that administration of pyridostigmine prior to exposure to soman reduces lethality of soman provided that atropine and pralidoxime are given immediately after exposure to the nerve agent. Administration of pyridostigmine in conjunction with atropine and pralidoxime increases survival after lethal exposures to soman above that provided by atropine and pralidoxime alone.