US Pharm. 2019;44(2):32-34.

Gastroparesis is a chronic disorder that affects a significant subset of the population. Ordinarily, strong muscular contractions move food through the digestive tract. In gastroparesis, this mechanism is disrupted, and undigested food stays in the abdomen for a long time and makes a person feel nauseous with the urge to vomit. Gastroparesis can also cause a lack of appetite, which may lead to malnutrition, and patients who are not eating can expect discomfort, bloating, and heartburn.1

The pathophysiology behind gastroparesis is varied and depends on disease etiology. Vagal and/or autonomic neuropathy play an important role in the development of diabetic gastroparesis, and it is estimated to occur in up to 20% to 40% of patients with diabetes. Gastroparesis can cause problems with blood sugar levels and nutrition. Sometimes, it is a complication of diabetes, and some people may develop gastroparesis after surgery. Although there is no cure for gastroparesis, changes to the diet, along with medication, can offer some relief.1,2

Certain medications, such as some antidepressants, opioid pain relievers, and high blood pressure and allergy medications, can lead to slow gastric emptying and cause similar symptoms. For people who already have gastroparesis, these medications may make their condition worse. Women are more likely to develop gastroparesis than men, and it is reported that many people with gastroparesis do not have any noticeable signs or symptoms.1 In this article, we briefly review the symptoms, causes, complications, and management of gastroparesis.

Symptoms

Signs and symptoms of gastroparesis include a feeling of fullness after eating just a few bites, vomiting undigested food eaten a few hours earlier, acid reflux, abdominal bloating, abdominal pain, changes in blood sugar levels, lack of appetite, and weight loss.3

Causes and Risk Factors

There are several risk factors that are considered to play a role in the condition’s cause, such as vagus-nerve damage. The vagus nerve is the longest cranial nerve in the body and is responsible for many functions. It is especially essential for proper operation of the digestive tract. If the vagus nerve is damaged, transfer of food from the abdomen to the small intestine is reduced because the muscles will not operate properly.4

Type 1 and type 2 diabetes are known to damage the vagus nerve. Some autoimmune diseases and virus infections (e.g., HIV) are also believed to have a negative impact on the vagus nerve. In certain cases, the vagus nerve stops working properly due to drinking excessive alcohol. Surgical complications could also affect the vagus nerve.4

Other factors that can increase the risk of gastroparesis include abdominal or esophageal surgery, infection (usually a virus), certain medications that slow the rate of stomach emptying (such as narcotic pain medications), nervous system diseases (such as Parkinson’s disease or multiple sclerosis) and hypothyroidism.4 Complications resulting from gastroparesis are shown in TABLE 1.

Treatment of gastroparesis depends on the cause, the severity of symptoms and complications, and how well patients respond to different treatments. As a result, the main goals of treatment for gastroparesis are alleviation of symptoms, correction of malnutrition, and resumption of adequate oral intake of liquids and solids. Patients with severe nausea and vomiting might require hospitalization for IV fluid and electrolyte replacement, and IV-administered prokinetic and/or antiemetic drugs might be needed initially.5

Sometimes, treating the cause may stop the problem. If diabetes is causing gastroparesis, patients must control their blood glucose levels. Acute hyperglycemia may impair gastric motor function as well as inhibit the action of prokinetic drugs, such as erythromycin. In patients with type 1 diabetes, gastroparesis can be an indication for insulin-pump therapy.5

Most physicians recommend that patients have a low-fat and low-fiber diet, eat smaller portions frequently during the day, chew food properly, eat well-cooked food, avoid alcohol and carbonated water, and drink plenty of water.

Medication Therapy

Initial management of gastroparesis consists of dietary modification, optimization of glycemic control and hydration, and in patients with continued symptoms, pharmacologic therapy with prokinetics and antiemetics.

Metoclopramide: This first-line therapy for gastroparesis is a dopamine 2 receptor antagonist, a 5-HT4 agonist, and a weak 5-HT3 receptor antagonist. It improves gastric emptying by enhancing gastric antral contractions and decreasing postprandial fundus relaxation.6

Metoclopramide is also used short-term to treat heartburn caused by gastroesophageal reflux in people who have used other medications without symptom relief. Dosage is 10 mg to 15 mg orally up to four times a day, 30 minutes before each meal and at bedtime. Depending upon symptoms being treated and clinical response, dosage will be different. It is commonly used to treat and prevent nausea and vomiting.6

Erythromycin: This macrolide antibiotic has been available since the 1950s. It is rarely used as an antibiotic today and is primarily prescribed for its “prokinetic” effect on the gastrointestinal (GI) tract. It has been used successfully off-label for the treatment of gastroparesis and other GI hypomotility disorders. When erythromycin was used as an antibiotic, patients often complained that it caused abdominal pain. Researchers eventually determined that erythromycin stimulates motilin receptors in the GI tract. Motilin receptors stimulate GI contractions and result in increased GI motility. This medicine also increases stomach-muscle contraction and may improve gastric emptying.7

Both oral and IV erythromycin have been used for its prokinetic effect. The IV form is generally reserved for acute conditions. The oral form is usually given in lower dosages than required for antibiotic effects (i.e., 150 mg-250 mg orally 3 to 4 times a day given 30 minutes before a meal). The oral form has been shown to work rapidly and can be substituted when the IV form is unavailable.7

Domperidone: This medication is used to treat nausea and vomiting as well as complaints of the stomach that occur with delayed emptying. It is used in patients whose symptoms fail to respond to metoclopramide or with side effects to metoclopramide. Domperidone is a dopamine 2 antagonist and is available for use only under a special program administered by the FDA. Each film-coated tablet contains 10-mg domperidone base. It should be taken 15 to 30 minutes before meals and, if necessary, before sleep. If taken after meals, absorption is somewhat delayed. Domperidone is taken by adults and adolescents aged 12 years or older.8

CisaprideThis 5-HT4 agonist stimulates antral and duodenal motility and accelerates gastric emptying of solids and liquids, which, in open-label trials, has been maintained for up to 1 year. Although cisapride is better tolerated than metoclopramide, its use has been associated with important drug interactions with medications metabolized by the cytochrome P450-3A4 isoenzyme (e.g., macrolide antibiotics, antifungals, and phenothiazines), resulting in cardiac arrhythmias. In the United States, prescriptions for cisapride can only be filled through an investigational limited-access program from the manufacturer after providing documentation as to the patient’s need for cisapride and assessment of risk factors for cardiac arrhythmias (e.g., a QTc >450 ms).9

Antiemetics: Antiemetics are medicines that help relieve nausea and vomiting. Prescription antiemetics include ondansetron, prochlorperazine, and promethazine. Over-the-counter antiemetic medications include bismuth subsaliclate and diphenhydramine. Antiemetics do not improve gastric emptying. In addition, they have not been studied in the management of patients with gastroparesis, and their use in gastroparesis is based on their efficacy in controlling nonspecific nausea and vomiting and in chemotherapy-induced emesis. Diphenhydramine 12.5 mg to 25 mg is given orally or IV every 6 to 8 hours as needed and in patients with persistent symptoms. Ondansetron, a 5-HT3 antagonist, is given 4 mg to 8 mg orally three times daily. Prolongation of the QT interval and central side effects have limited the use of phenothiazines, such as prochlorperazine, to patients who remain symptomatic despite antihistamines and 5-HT3 antagonists.1,4,10

Tricyclic AntidepressantsLow-dose nortriptyline, a tricyclic antidepressant with low anticholinergic effects, has been demonstrated to decrease symptoms of nausea, vomiting, and abdominal pain in patients with diabetic and idiopathic gastroparesis. Certain antidepressants, such as mirtazapine, may help relieve nausea and vomiting. These medicines may not improve gastric emptying.11

Pain Medicines: Pain medicines that are not narcotic may reduce pain in the abdomen due to gastroparesis.

Gastric Electrical Stimulation: This procedure may be considered for compassionate treatment in patients with refractory symptoms, particularly nausea and vomiting with persisting symptoms despite antiemetic and prokinetic drug therapy for at least 1 year. Gastric electrical stimulation has been demonstrated to improve symptom severity and gastric emptying in patients with diabetes but not idiopathic or postsurgical gastroparesis. In the U.S., the gastric electrical neurostimulator has been approved as a humanitarian exemption device for diabetic and idiopathic gastroparesis.12

REFERENCES

1. Camilleri M, Parkman HP, Shafi MA, et al. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013;108:18-37.
2. Wytiaz V, Homko C, Duffy F, et al. Foods provoking and alleviating symptoms in gastroparesis: patient experiences. Dig Dis Sci. 2015;60:1052-1058.
3. Homko CJ, Duffy F, Friedenberg FK, et al. Effect of dietary fat and food consistency on gastroparesis symptoms in patients with gastroparesis. Neurogastroenterol Motil. 2015;27:501-508.
4. Type 2 diabetes and gastroparesis. www.healthline.com/health/type-2-diabetes/gastroparesis. Accessed August 2018.
5. Parkman HP, Yates KP, Hasler WL, et al. Dietary intake and nutritional deficiencies in patients with diabetic or idiopathic gastroparesis. Gastroenterology. 2011;141:486-498.
6. Rao AS, Camilleri M. Review article: metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther. 2010;31:11-19.
7. Maganti K, Onyemere K, Jones MP. Oral erythromycin and symptomatic relief of gastroparesis: a systematic review. Am J Gastroenterol. 2003;98:259-263.
8. Sugumar A, Singh A, Pasricha PJ. A systematic review of the efficacy of domperidone for the treatment of diabetic gastroparesis. Clin Gastroenterol Hepatol. 2008;6:726-733.
9. Abell TL, Camilleri M, DiMagno EP, et al. Long-term efficacy of oral cisapride in symptomatic upper gut dysmotility. Dig Dis Sci. 1991;36:616-620.
10. Youssef AS, Parkman HP, Nagar S. Drug-drug interactions in pharmacologic management of gastroparesis. Neurogastroenterol Motil. 2015;27:1528-1541.
11. Prakash C, Lustman PJ, Freedland KE, Clouse RE. Tricyclic antidepressants for functional nausea and vomiting: clinical outcome in 37 patients. Dig Dis Sci. 1998;43:1951-1956.
12. Heckert J, Sankineni A, Hughes WB, et al. Gastric electric stimulation for refractory gastroparesis: a prospective analysis of 151 patients at a single center. Dig Dis Sci. 2016;61:168-175.