Pyridostigmine in autonomic disorders

Pyridostigmine is a reversible inhibitor of acetylcholinesterase. Apart from cholinergic effects due to increasing acetylcholine on end-organ synapses, it has been shown to enhance ganglionic neurotransmission with resulting increase of norepinephrine and therefore sympathetic adrenergic tone “on demand” upon standing whereas the effect is silent under conditions of low sympathetic activation such as the supine position. The efficacy of pyridostigmine in orthostatic hypotension (OH) without inducing supine hypertension has been demonstrated in a double-blind randomized controlled trial. Since the effects are modest, pyridostigmine may be most suitable for patients with mild OH or in combination. Pyridostigmine can also improve orthostatic symptoms in patients with postural orthostatic tachycardia syndrome. Pyridostigmine can increase gastrointestinal motility and should be used with caution in patients with increased colonic motility who are prone to diarrhea; on the other hand, it can be beneficial in cases with slow transit constipation, gastrointestinal pseudoobstruction, and gastroparesis.