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

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Gastrointestinal Motor Stimulants Drugs 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) Gastrointestinal Motor Stimulants Drugs 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 and dystonic reactions are rare. The main side effects of domperidone relate to induction of
hyperprolactinemia via effects on pituitary regions served by a porous blood-brain barrier. The 5-HT4 agonist tegaserod potently stimulates gastric emptying in patients with gastroparesis; however, its effects on symptoms of gastric retention are unproven. Patients with refractory upper gut motility disorders pose significant challenges. Liquid suspensions of prokinetic drugs may be beneficial, as liquids empty from the stomach more rapidly than pills. Metoclopramide can be administered subcutaneously in patients unresponsive to oral drugs. Intestinal pseudoobstruction may respond to the somatostatin analogue octreotide, which induces propagative small intestinal motor complexes. Pyloric injections of botulinum toxin are reported in uncontrolled studies to benefit patients with gastroparesis. Placement of a feeding jejunostomy reduces hospitalizations and improves overall health in some patients with gastroparesis who do not respond to drug therapy. Surgical options are limited for refractory cases, but postvagotomy gastroparesis may improve with near-total resection of the stomach. Implanted gastric electrical stimulators may reduce symptoms, enhance nutrition, improve quality 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 effects often are obtained with a 5-HT3 antagonist combined with a glucocorticoid. High- dose metoclopramide also exhibits efficacy in chemotherapy-evoked emesis, while benzodiazepines such as lorazepam are useful in reducing anticipatory nausea and vomiting. Therapy of delayed emesis 1–5 days after chemotherapy is less successful. Neurokinin NK1 antagonists (e.g., aprepitant) exhibit antiemetic and antinausea effects during both the acute and delayed periods after chemotherapy. Cannabinoids such as tetrahydrocannabinol, long advocated for cancer-associated emesis, produce significant side effects and exhibit no more efficacy than antidopaminergic agents. Most current drug regimens produce greater reductions in vomiting than in nausea. The clinician should exercise caution in managing the pregnant patient with nausea. Studies of the teratogenic effects of available antiemetic agents provide conflicting results. Few controlled trials have been performed in nausea of pregnancy, although antihistamines such as meclizine and antidopaminergics such as prochlorperazine demonstrate efficacy greater than placebo. Some obstetricians offer alternative therapies such as pyridoxine, acupressure, or ginger. Controlling emesis in cyclic vomiting syndrome is a challenge. In many individuals, 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 as lorazepam are a mainstay of treatment of acute symptom flares. Small studies report benefits with antimigraine therapies, including the serotonin 5-HT1 agonist sumatriptan as well as certain newer anticonvulsant drugs. Indigestion Mechanisms The most common causes of indigestion are gastroesophageal acid reflux and functional dyspepsia. Other cases are a consequence of a more serious organic illness. Gastroesophageal Acid Reflux Acid reflux can result from a variety of physiologic defects. Reduced lower esophageal sphincter (LES) tone is an important cause of reflux in scleroderma and pregnancy; it may also be a factor in patients without other systemic conditions. Many individuals exhibit frequent transient LES relaxations during which acid bathes the esophagus. Overeating and aerophagia can transiently override the barrier function of the LES, whereas impaired esophageal body motility and reduced salivary secretion prolong acid exposure. The role of hiatal
hernias is controversial—although most reflux patients exhibit hiatal hernias, most individuals with hiatal hernias do not have excess heartburn.