Prokinetic agents: current aspects with focus on cisapride

Abstract

SUMMARY
Prokinetic agents are substances which, through various
mechanisms, stimulate gastrointestinal motor activity, e.g.
cholinergic agonists, macrolide antibiotics (such as erythromycin),
dopamine receptors antagonists (metoclopramide)
and substituted benzamides (domperidone and cisapride).
Cisapride is the only prokinetic agent which increases
the motility of both the small and large bowel. Since
1993 when it was introduced to the pharmaceutical market,
cisapride has been widely used with remarkable success in
a variety of gastrointestinal diseases such as: gastrooesophageal
reflux disease, gastric ulcer, chronic idiopathic
constipation, irritable bowel syndrome, intestinal pseudoobstruction.
Its major side-effects are gastrointestinal (abdominal
pain, diarrhoea) and cardiovascular. Although it
has always been considered an effective and rather safe medication,
the large number of reports referring to serious and
even fatal adverse effects on the cardiovascular system (QT
interval extension, torsades de pointes, ventricular fibrillation)
have prompted manufacturing company to withdraw
the drug from the U.S. market as of July 12, 2000, pending
further research.
Key words: prokinetic agents, gastrointestinal hypomotility,
pharmacodynamics, pharmacokinetics, drug interactions,
side-effects