Adverse Effects of Drugs on Diarrhea Due to Changes in Motility

An increase in bowel frequency, or diarrhea, can occur if the amount of fluid in the lumen increases or if propulsive muscular contraction of the gut wall is enhanced. Parasympathetic cholinergic (muscarinic) stimulation increases motility, for example drugs such as the anticholinesterase neostigmine, used to treat myasthenia gravis. This is overcome in practice by giving atropine or another antimuscarinic agent to block the parasympathetic effects, but not those at skeletal muscle.

Prostaglandins alter gut motility. The synthetic prostaglandin misoprostol, used in peptic ulcer and in non-steroidal induced disease, can cause dose-related borborygmi and diarrhea, the effect being direct upon the enteric musculature.

Mefenamic acid, a non-steroidal anti-inflammatory drug used (among other conditions) in the treatment of period pain, may also cause diarrhoea, perhaps related to steatorrhoea or to colitis. The mechanism is unclear as inhibition of prostaglandin synthesis would be expected to cause constipation.

Other non-steroidal agents, including those used to treat ulcerative colitis, are prone to cause gastrointestinal adverse effects. Abdominal discomfort and nausea are not uncommon class effects. The 5aminosalicylate olsalazine, consisting of two 5-aminosalicylate moieties linked by a diazo-bond which is cleaved in the lower bowel, can cause watery diarrhea. The same can occur, but less frequently, with the simple molecule present in coated mesalazine tablets. Sulphasalazine and other aminosalicylates can in addition (rarely) cause an inflammatory hypersensitivity reaction with bloody diarrhoea which is indistinguishable from non-specific colitis. Both the watery diarrhea and the hypersensitivity-associated diarrhea can pose diagnostic problems in patients with ulcerative colitis. In the first instance, the treatment should be stopped and corticosteroids substituted in those with overt inflammatory reactions.

The antibiotic erythromycin can cause diarrhea by a specific action related to its ability to bind to motilin receptors in the gut, an effect which may prove to be exploitable in managing the gut paresis of patients with diabetes mellitus when other treatments fail. Selective serotonin re-uptake inhibitors, such as fluvoxamine and fluoxetine, can all induce diarrhea, presumably as a direct result of increased tissue serotonin concentration.