Gastroparesis: MANAGEMENT OF GASTROPARESIS ASSOCIATED WITH GASTROINTESTINAL SYMPTOMS Part 3

Treatment of symptomatic gastroparesis Erythromycin is the most potent drug when given intravenously (in doses of approximately 3 mg/kg or less) and may be particularly useful in the initial phase of management. When used orally, erythromycin may have greater efficacy when given as a suspension, rather than as a tablet, but is still probably less effective than when given intravenously. It is uncertain whether tachyphylaxis to the effects of erythromycin occurs as a result of downregulation of motilin receptors. It has recently been demonstrated, in healthy subjects and in patients with diabetes, that the response to erythromycin is markedly attenuated during hyperglycemia; it is uncertain whether this effect occurs with other prokinetic drugs. The drug of first choice for oral administration is probably cisapride, which appears to have the most diffuse gastrointestinal effects. While cisapride has been well tolerated in clinical trials, there have been recent reports of cardiac arrhythmias, including deaths. It has been established that cisapride has the potential to induce cardiac adverse effects as a result of prolongation of the cardiac action potential (leading to lengthening of the electrocardiographic Q-T interval and torsades de pointes); these effects are likely to be related to class III antiarrhythmic properties, rather than 5-hydroxytryptamine (HT)4-recep-tor activation. Other substituted benzamides, including metoclopramide and prucalopride, do not have class III antiarrhythmic effects. The clinical relevance of the cardiac effects of cisapride is still uncertain, particularly because the majority of patients who have died while taking cisapride had other risk factors and were taking the drug in relatively high doses (approximately 80 mg/day orally). However, the potential for cardiotoxicity dictates that the use of cisapride should be more circumspect than previously recommended, particularly in some populations, and has led to restrictions in its use in some countries. It is likely that the use of cisapride in the treatment of gastroesophageal reflux disease will decrease in the future, because there are other effective therapeutic approaches, but this may not apply to severe, symptomatic gastroparesis. Neonates, children and people with idiopathic, congenital or acquired long Q-T syndrome may be at particular risk for cardiac toxicity. Drugs that inhibit cisapride metabolism, such as ketoconazole, erythromycin and clarithromycin, or those that may prolong the Q-T interval, should not be used concurrently. Before initiating therapy with cisapride, it may be appropriate to perform an electrocardiogram (a Q-T interval greater than 450 ms is probably a contraindication to its use) and electrolyte screen. It would not be surprising if there were an increase in the use of domperidone, which has been shown to improve quality of life in patients with gastroparesis, and is better tolerated than metoclopramide because of the reduced risk of central nervous system side effects. If symptoms are refractory to prokinetic therapy, a feeding jejunostomy may be required to maintain nutrition. In most cases, surgery is not recommended because it may be associated with deterioration. If surgery is performed, it should be done in specialized centres. In patients with diabetes, there is anecdotal evidence that pancreatic transplantation may improve both gastric emptying and symptoms. Find very low prices on non-prescription drugs – cialis professional 20 mg for smart customers.

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