tegaserod and Gastroparesis

Topics: Domperidone; Dopamine Antagonists; Gastrointestinal Agents; Gastroparesis; Humans; Indoles; Metoclopramide; Octreotide; Scleroderma, Systemic

Studies have shown that early enteral nutrition in critically ill patients reduces the incidence of morbidity and death. Nonetheless, intolerance to gastric enteral nutrition is common in these patients as a result of gastroparesis. The use of prokinetic agents such as metoclopramide, domperidone, cisapride, and erythromycin can improve gastric emptying, but these agents are not without deleterious adverse effects. Tegaserod, a selective serotonin type 4 receptor partial agonist, was recently approved for treatment of women with irritable bowel syndrome. On the basis of tegaserod's mechanism of action, it was hypothesized that tegaserod may accelerate the return of gastric function in intensive care unit patients with gastroparesis. It would thus provide an additional agent for the management of gastroparesis with a more favorable safety profile. We present 3 case reports of the successful use of tegaserod in intensive care unit patients with impaired gastric motility. To our knowledge, the use of tegaserod in this setting has not been reported or studied previously.

Topics: Aged; Critical Illness; Gastrointestinal Agents; Gastrointestinal Motility; Gastroparesis; Humans; Indoles; Male; Middle Aged; Serotonin Receptor Agonists

Serotonin (5-hydroxytryptamine [5-HT])1 receptor agonists, such as those used for treating migraine, can cause coronary artery contraction, coronary spasm, and even myocardial infarction. Tegaserod maleate is a relatively new 5-HT4 receptor agonist with moderate affinity for the 5-HT1 receptor. Currently, it is approved only for treatment of irritable bowel syndrome in women who have constipation as the primary symptom. However, it is also being administered as a promotility agent in patients with gastroparesis. Since tegaserod has affinity for the 5-HT1 receptor, it is plausible that tegaserod could cause the same types of cardiovascular adverse events seen with agents prescribed for management of migraine. We report the first case of a man who experienced a myocardial infarction after receiving only two 6-mg doses of tegaserod; we also provide a hypothesis regarding this event. When considering prescribing a drug with 5-HT1 receptor agonist activity, clinicians should review the patient's medical history specifically for the presence of underlying cardiovascular risk factors.

Topics: Diabetes Complications; Gastroparesis; Humans; Indoles; Male; Middle Aged; Myocardial Infarction; Risk Factors; Serotonin Receptor Agonists

The C57BLKS/J db/db mouse develops hyperglycemia and has delayed gastric emptying that is improved with tegaserod, a partial 5-HT4 agonist. Our aims here were to determine regional gastric contractility alterations in C57BLKS/J db/db mice and to determine the effects of serotonin and tegaserod. The contractile effects of bethanechol, serotonin, and tegaserod in fundic, antral, and pyloric circular muscle were compared in C57BLKS/J db/db mice and normal littermates. The effects of tetrodotoxin, atropine, and 5-HT receptor antagonists were studied. Contractions in response to bethanechol were decreased in the fundus, similar in the antrum, but increased in the pylorus in diabetic mice compared with controls. Serotonin and, to a lesser extent, tegaserod caused contractions that were more pronounced in the fundus than in the antrum and pylorus in both diabetic and normal mice. Serotonin-induced contractions were partially inhibited by atropine, the 5-HT4 antagonist GR113808, and the 5-HT2 antagonist cinanseron but not tetrodotoxin. Regional gastric contractility alterations are present in this diabetic gastroparesis mouse model. Fundic contractility was decreased, but pyloric contractility was increased in the pylorus to cholinergic stimulation in diabetic mice. Serotonin's contractile effect is mediated, in part, through muscarinic, 5-HT2, and 5-HT4 receptors. This study suggests that fundic hypomotility and pyloric hypercontractility, rather than antral hypomotility, play important roles for the gastric dysmotility that occurs in diabetes.

Topics: Animals; Bethanechol; Cholinergic Agonists; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Electric Stimulation; Enteric Nervous System; Female; Gastroparesis; In Vitro Techniques; Indoles; Mice; Mice, Inbred C57BL; Muscarinic Agonists; Muscle Contraction; Muscle, Smooth; Piperidines; Potassium; Receptors, Muscarinic; Serotonin; Serotonin Receptor Agonists; Stomach

Topics: Attitude of Health Personnel; Gastrointestinal Agents; Gastroparesis; Humans; Indoles; Male; Middle Aged; Myocardial Infarction