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

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-HT
4
agonist and D
2
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-HT
4
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-HT
3
antagonists prevent chemotherapy-
induced acute vomiting in most cases (Table 39-2). Optimal antiemetic effects
often are obtained with a 5-HT
3
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 NK
1
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-
HT
3
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-HT
1
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.