Prokinetic agents in the surgical patient.

Surgeons may be confronted by several conditions that benefit from therapy with prokinetic agents. Prokinetic agents enhance contractile force, coordinate contractile activity, and accelerate transit in the gastrointestinal tract. Although some of these drugs may also have antiemetic effects, these are not the focus of this review. The number of available prokinetic agents has increased markedly in the last few years (Table I). This, coupled with advances in understanding the pathophysiology of motility disorders, has led to many new therapeutic options in the management of these disorders. The purpose of this paper is to review the pharmacology and physiologic effects of the common prokinetic agents and to discuss their use in motility disorders of relevance to surgeons. PHARMACOLOGY OF PROKINETIC AGENTS Several general observations can be made about prokinetic agents. 1 Since receptors in the various neuronal systems are ubiquitous, the usefulness of several of these agents has been limited by central nervous system and cardiovascular side effects. Tolerance has also been a problem for many of these drugs, making long-term efficacy elusive. As some of these agents are somewhat site specific (Table II), therapy needs to be tailored to specific target organs within the gastrointestinal tract. Another difficulty in management is that gastrointestinal dysmotility syndromes are, in general, poorly defined, and, thus, available information on prokinetics derived from such patients is difficult to interpret. Nevertheless, our understanding of the pharmacology and potential clinical usefulness of these agents has progressed rapidly in the past decade. Cholinergic Agonists Cholinergic agonists, such as bethanechol (Urecholine) and neostigmine (Prostigmin), were the original prokinetic agents. Bethanechol, an ester derivative of choline, primarily has a parasympathomimetic effect from stimulation of muscarinic M2-type receptors on the smooth muscle cell. Neostigmine is a cholinesterase inhibitor. Not surprisingly, cholinergic agonists are associated with a significant incidence of side effects (10% to 15%) owing to their nonspecificity, and their use has virtually disappeared with the availability of newer agents. Adverse affects include abdominal cramping, blurred vision, fatigue, bladder cramps, increased micturition, and stimulation of acid secretion. Their use is contraindicated for patients with hyperthyroidism, peptic ulcer disease, and asthma. Bethanechol increases lower esophageal sphincter (LES) pressure, as well as increasing the amplitude and velocity of esophageal contraction. 2 Although it increases the amplitude of contractions throughout the gastrointestinal tract, it does not appear to coordinate contractions or accelerate transit in the stomach and small intestine. 3,4 Neostigmine stimulates contractility in the small intestine and colon. Evidence for the effectiveness of cholinergic agonists in motility disorders is, in general, inconsistent, although beneficial effects of bethanechol in gastroesophageal reflux disease (GERD) and gastroparesis have been claimed. 3,4 The recommended dose is 25 mg QID, 1 half hour before meals and at bedtime. Bethanechol is effective when given either subcutaneously or orally. Neostigmine (0.5 mg intramuscularly TID) has been used for postoperative ileus without apparent benefit. 5