Chapter 039. Nausea, Vomiting, and Indigestion (Part 5)

Gastrointestinal Motor StimulantsDrugs that stimulate gastric emptying are indicated for gastroparesis (Table 39-2). Metoclopramide, a combined 5-HT4 agonist and D2 antagonist, exhibits efficacy in gastroparesis, but antidopaminergic side effects limit its use in 25% of patients. Erythromycin, a macrolide antibiotic, increases gastroduodenal motility by action on receptors for motilin, an endogenous stimulant of fasting motor activity. Intravenous erythromycin is useful for inpatients with refractory gastroparesis; however, oral forms also have some utility. Domperidone, a D 2 antagonist not available in the United States, exhibits prokinetic and antiemetic effects but does not cross into most other brain regions; thus, anxiety...
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Chapter 039. Nausea, Vomiting, and Indigestion (Part 5) Chapter 039. Nausea, Vomiting, and Indigestion (Part 5) Gastrointestinal Motor Stimulants Drugs that stimulate gastric emptying are indicated for gastroparesis (Table39-2). Metoclopramide, a combined 5-HT4 agonist and D2 antagonist, exhibitsefficacy in gastroparesis, but antidopaminergic side effects limit its use in 25% ofpatients. Erythromycin, a macrolide antibiotic, increases gastroduodenal motilityby action on receptors for motilin, an endogenous stimulant of fasting motoractivity. Intravenous erythromycin is useful for inpatients with refractorygastroparesis; however, oral forms also have some utility. Domperidone, a D 2antagonist not available in the United States, exhibits prokinetic and antiemeticeffects but does not cross into most other brain regions; thus, anxiety and dystonicreactions are rare. The main side effects of domperidone relate to induction ofhyperprolactinemia via effects on pituitary regions served by a porous blood-brainbarrier. The 5-HT4 agonist tegaserod potently stimulates gastric emptying inpatients with gastroparesis; however, its effects on symptoms of gastric retentionare unproven. Patients with refractory upper gut motility disorders pose significantchallenges. Liquid suspensions of prokinetic drugs may be beneficial, as liquidsempty from the stomach more rapidly than pills. Metoclopramide can beadministered subcutaneously in patients unresponsive to oral drugs. Intestinalpseudoobstruction may respond to the somatostatin analogue octreotide, whichinduces propagative small intestinal motor complexes. Pyloric injections ofbotulinum toxin are reported in uncontrolled studies to benefit patients withgastroparesis. Placement of a feeding jejunostomy reduces hospitalizations andimproves overall health in some patients with gastroparesis who do not respond todrug therapy. Surgical options are limited for refractory cases, but postvagotomygastroparesis may improve with near-total resection of the stomach. Implantedgastric electrical stimulators may reduce symptoms, enhance nutrition, improvequality of life, and decrease health care expenditures in patients with medication-refractory gastroparesis. Selected Clinical Settings Cancer chemotherapeutic agents such as cisplatin are intensely emetogenic(Chap. 77). Given prophylactically, 5-HT3 antagonists prevent chemotherapy-induced acute vomiting in most cases (Table 39-2). Optimal antiemetic effectsoften are obtained with a 5-HT3 antagonist combined with a glucocorticoid. High-dose metoclopramide also exhibits efficacy in chemotherapy-evoked emesis, whilebenzodiazepines such as lorazepam are useful in reducing anticipatory nausea andvomiting. Therapy of delayed emesis 1–5 days after chemotherapy is lesssuccessful. Neurokinin NK1 antagonists (e.g., aprepitant) exhibit antiemetic andantinausea effects during both the acute and delayed periods after chemotherapy.Cannabinoids such as tetrahydrocannabinol, long advocated for cancer-associatedemesis, produce significant side effects and exhibit no more efficacy thanantidopaminergic agents. Most current drug regimens produce greater reductionsin vomiting than in nausea. The clinician should exercise caution in managing the pregnant patient withnausea. Studies of the teratogenic effects of available antiemetic agents provideconflicting results. Few controlled trials have been performed in nausea ofpregnancy, although antihistamines such as meclizine and antidopaminergics suchas prochlorperazine demonstrate efficacy greater than placebo. Some obstetriciansoffer alternative therapies such as pyridoxine, acupressure, or ginger. Controlling emesis in cyclic vomiting syndrome is a challenge. In manyindividuals, prophylactic treatment with tricyclic antidepressants, cyproheptadine,or β-adrenoceptor antagonists can reduce the frequency of attacks. Intravenous 5-HT3 antagonists combined with the sedating effects of a benzodiazepine such aslorazepam are a mainstay of treatment of acute symptom flares. Small studiesreport benefits with antimigraine therapies, including the serotonin 5-HT1 agonistsumatriptan as well as certain newer anticonvulsant drugs. Indigestion Mechanisms The most common causes of indigestion are gastroesophageal acid refluxand functional dyspepsia. Other cases are a consequence of a more serious organicillness. Gastroesophageal Acid Reflux Acid reflux can result from a variety of physiologic defects. Reduced loweresophageal sphincter (LES) tone is an important cause of reflux in sclerodermaand pregnancy; it may also be a factor in patients without other systemicconditions. Many individuals exhibit frequent t ...