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Prokinetic Agents

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Chronic constipation is a common problem after SCI, with a prevalence of up to 80% of affected individuals (Krogh et al. 2002). The presence of constipation in patients with SCI with slow transit times has been well-documented (Geders et al. 1995).

Five studies exploring the use of cisapride for neurogenic bowel management have been removed from this review as the drug is no longer available.

Table 13: Treatment Studies Using Pharmacology for Neurogenic Bowel after SCI

Discussion

Prokinetic agents are presumed to promote transit through the GI tract, thereby decreasing the length of time needed for stool to pass through the intestines and increasing the amount of stool available for evacuation. Since constipation in patients with both acute and chronic SCI is considered primarily a consequence of prolonged colonic transit time, stimulating intestinal motility would appear to be a reasonable therapeutic approach. Segal et al. (1987) investigated the use of metoclopramide (a potent dopamine receptor antagonist with prokinetic properties) for enhancing gastric emptying in individuals with SCI. They found that impaired gastric emptying in patients with SCI can be significantly improved using metoclopramide. Improvement in constipation and increased frequency of bowel movement were also seen with the use of prucalopride – a novel, highly selective serotonin receptor agonist with enterokinetic properties that facilitates cholinergic and excitatory non-adrenergic, non-cholinergic neurotransmission (Krogh et al. 2002). Korsten et al. (2005) found that neostigmine (a reversible cholinesterase inhibitor) or the combination of neostigmine and glycopyrrolate administered intravenously improved stool expulsion over normal saline. Rosman et al. (2008) reported similar findings for the use of neostigmine and glycopyrrolate in combination over placebo. Finally, a study by Cardenas et al. (2007) reported an increase in the number of days with bowel movements in approximately one-fifth of the subjects given sustained-release fampridine (selective potassium channel blocker).

Conclusion

Prucalopride: There is level 1b evidence (from one RCT) (Krogh et al. 2002) that prucalopride increases stool frequency, improves stool consistency and decreases gastrointestinal GI transit time; higher doses (2mg/day) were associated with moderate/severe abdominal pain.

Metoclopramide: There is level 2 evidence (from one prospective controlled trial; N=20) (Segal et al. 1987) that intravenous administration of metoclopramide decreases time of gastric emptying.

Neostigmine: There is level 1b evidence (from one RCT) (Korsten et al. 2005) that neostigmine, administered with or without glycopyrrolate, leads to a greater expulsion of stool. There is level 1 evidence that neostigmine with glycopyrrolate decreases total bowel evacuation times and improves bowel evacuation.

Fampridine: There is level 1b evidence (from one RCT) (Cardenas et al. 2007) that fampridine can increase the number of days with bowel movements.

  • In very small studies prucalopride, metoclopramide, neostigmine, and fampridine have been found to improve constipation in individuals with SCI.

    Prucalopride is not currently available the United States but is available in Canada and Europe. More research is required on prokinetic agents prior to their regular use in neurogenic bowel dysfunction.