Pilot study of pyridostigmine in constipated patients with autonomic neuropathy.
BACKGROUND
The effects of cholinesterase inhibitors, which increase colonic motility in health, on chronic constipation are unknown. Our aims were to evaluate the efficacy of cholinesterase inhibitors for dysautonomia and chronic constipation and to assess whether acute effects could predict the long term response.


METHODS
In this single-blind study, 10 patients with autonomic neuropathy and constipation were treated with placebo (2 weeks), followed by an escalating dose of pyridostigmine to the maximum tolerated dose (i.e., 180-540 mg daily) for 6 weeks. Symptoms and gastrointestinal transit were assessed at 2 and 8 weeks. The acute effects of neostigmine on colonic transit and motility were also assessed.


RESULTS
At baseline, 4, 6, and 3 patients had delayed gastric, small intestinal, and colonic transit respectively. Pyridostigmine was well tolerated in most patients, improved symptoms in 4 patients, and accelerated the geometric center for colonic transit at 24 h by > or =0.7 unit in 3 patients. The effects of i.v. neostigmine on colonic transit and compliance predicted (P < 0.05) the effects of pyridostigmine on colonic transit.


CONCLUSIONS
Pyridostigmine improves colonic transit and symptoms in some patients with autonomic neuropathy and constipation. The motor response to neostigmine predicted the response to oral pyridostigmine.
Bharucha
Adil E
AE
Clinical and Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic, 200 First St. S.W., Rochester, MN 55905, USA. bharucha.adil@mayo.edu
Low
Phillip A
PA
Camilleri
Michael
M
Burton
Duane
D
Gehrking
Tonette L
TL
Zinsmeister
Alan R
AR
D000293:Adolescent; D000328:Adult; D000368:Aged; D001341:Autonomic Nervous System / Q000187:drug effects; D001342:Autonomic Nervous System Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D003248:Constipation / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009388:Neostigmine / Q000008:administration & dosage / Q000627:therapeutic use; D010865:Pilot Projects; D011729:Pyridostigmine Bromide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016037:Single-Blind Method
D002800:Cholinesterase Inhibitors; D009388:Neostigmine; D011729:Pyridostigmine Bromide