The first-line medical therapy for patients with DGP is generally a combination of an antiemetic agent and a promotility drug (). Unfortunately, data from adequately powered clinical trials in patients with gastroparesis are limited, and no study has adequately stratified patients by etiologic subtypes. Thus, these drugs are used empirically.
Gastroparesis Treatment Guidelines
Antiemetics are helpful in relieving the DGP symptoms of nausea and vomiting, which are often the most disabling for patients and result in a substantial impact on quality of life.6
One class of antiemetics often used for managing these symptoms are the phenothiazines; these are dopamine-receptor antagonists that work at the level of the area postrema of the medulla oblongata. The most commonly prescribed phenothiazine agent for DGP is prochlorperazine, a neuroleptic with a potency 10 to 20 times that of chlorpromazine.7
Adverse effects include drowsiness, dry mouth, constipation, skin rashes, and tardive dyskinesia.
Other, less commonly used antiemetic agents include the antihistamines cyclizine and dimenhydrinate. Cyclizine is available as a tablet and also in injectable form, and dimenhydrinate is available as a tablet, liquid suspension, and suppository. The adverse effects include drowsiness, dry mouth, blurred vision, difficulty urinating, constipation, palpitations, dizziness, insomnia, and tremor. The serotonin receptor antagonists are occasionally used to treat DGP, although they are expensive and there are no data to support their use in this setting. They may be helpful when all other drugs have failed to provide symptom relief.
There are only a few prokinetic agents that are approved in the United States. Their expected effect includes increasing antral contractility, correcting gastric dysrhythmia, and improving antroduodenal coordination.
The only prokinetic agent that is approved in the United States specifically for DGP is metoclopramide, which is available in tablet, intravenous, and orally disintegrating tablet formulations. Metoclopramide is a 5-HT4
receptor agonist that releases acetylcholine from the myen-teric plexus. The net effect is to increase lower esophageal sphincter pressure and fundal tone, as well as increase the amplitude of antral contractions and facilitate antroduodenal coupling. Metoclopramide also has dopamine receptor antagonist properties and is a weak 5-HT3
receptor antagonist. Thus, metoclopramide acts both as a prokinetic agent and an antiemetic agent. Adverse events include drowsiness, fatigue, and lassitude, which occur in approximately 10% of patients receiving the most commonly prescribed dosage of 10 mg 3 times daily.8
Extrapyramidal symptoms, primarily acute dystonic reactions, can also occur. Such symptoms include involuntary movements of the limbs and facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of the tongue, bulbar type of speech, trismus, and dystonic reactions resembling tetanus.8
Other adverse events include both physical and mental restlessness, agitation, irritability, and an aggravation of underlying depression.8
In 2009, a black box warning was added for metoclopramide, against long-term (>3 months) or high-dose usage because of the risk of tardive dyskinesia.9
Due to these risks, it is critical that patients who are prescribed metoclopramide receive careful, scheduled follow-up.
The prokinetic agent domperidone is a benzimidazole derivative and is a specific dopamine antagonist with similar physiologic effects on the upper gastrointestinal tract as metoclopramide. Patterson and colleagues compared meto-clopramide with domperidone for the alleviation of DGP symptoms in 93 patients with insulin-dependent diabetes mellitus and found both agents to be equally effective.10
Several central nervous system–related adverse events were sig-nifcantly less common with domperidone. However, hyper-prolactinaemia, menstrual disturbance, breast engorgement, and galactorrhea can occur with domperidone because of its antidopaminergic effect. Unlike metoclopramide, domperi-done is not currently approved for use in the United States.
The macrolides, such as erythromycin and azithromycin, are antibiotics that also have motilin receptor agonist activity. Motilin is a hormone present in the endocrine cells of the distal stomach and duodenum. It increases lower esophageal sphincter pressure and is responsible for initiating the migrating motor complex (MMC). Erythromycin has been shown to increase the amplitude of antral peristalsis, trigger premature MMC phase III activity, and stimulate gastric emptying.11
Administration of erythromycin is generally short term because tolerance develops rapidly.12
Erythromycin is available as a tablet and liquid suspension, but it is more potent when administered intravenously. The most common adverse events include nausea, vomiting, and abdominal pain.