Intestinal Motility Disorders

Background

The phrase "intestinal motility disorders" applies to abnormal intestinal contractions, such as spasms and intestinal paralysis, and is used to describe a variety of disorders in which the gut has lost its ability to coordinate muscular activity because of endogenous or exogenous causes.^{[1, 2, 3]} Intestinal motility disorders can be categorized as upper gastrointestinal (GI) or lower GI motility disorders.

Upper GI motility disorders include the following^[4] :

• Achalasia: Loss of esophageal peristalsis, with failure of the lower esophageal sphincter (LES) to relax
• Gastroesophageal reflux disease (GERD): Reflux of gastric contents from the stomach into the esophagus, causing symptoms or resulting in mucosal damage
• Gastroparesis: Delayed gastric emptying without evidence of mechanical obstruction, resulting in upper GI symptoms such as nausea, vomiting, early satiety, and abdominal pain
• Biliary dyskinesia: Gallbladder motility disorder that results in abdominal pain in the absence of gallsones, sludge, or microlithiasis

Lower GI motility disorders include the folllowing^{[4, 5]} :

• Irritable bowel syndrome (diarrhea-predominant, constipation-predominant, and mixed): Chronic abdominal pain with change in bowel habits (according to Rome criteria) without an organic cause or the symptoms
• Colonic inertia: Delayed passage of stool through the colon without abnormalities in the defecation process, which results in constipation
• Intestinal pseudo-obstruction (Ogilvie syndrome): Acute severe colonic dilatation without an anatomic obstruction or process
• Pelvic floor dyssynergia: A functional obstruction from impaired relaxation of the puborectalis muscle, the external anal sphincter, or both, resulting in a decrease in the anorectal angle and causing difficulty in evacuation of stool
• Hirschsprung disease: Also known as congenital aganglionic megacolon, in which the distal section of the colon that is missing ganglion cells fails to relax, causing a functional obstruction
• Fecal incontinence: Involuntary leakage of stool

Upper intestinal motlity disorders may manifest as the following:

• Abdominal distention
• Severe abdominal colicky pain
• GERD
• Intractable or recurrent nausea or vomiting

Lower intestinal motility disorders may manifest as the following:

• Recurrent obstruction
• Severe abdominal colicky pain
• Severe constipation
• Diarrhea
• Stool incontinence

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Pathophysiology

Coordinated movements of the stomach and intestines are required to digest and propel intestinal contents along the digestive tract. The complex patterns of contraction and relaxation necessary for proper motility of the gastrointestinal (GI) tract are generated in the nerves and muscles within the GI walls.

Every day, at any time, many factors can influence GI motility (eg, physical exercise, emotional distress). The pathogenesis of primary intestinal motility disorders probably is multifactorial, but neither biochemical abnormality nor structural abnormality has been demonstrated commonly, except in some forms of intestinal pseudo-obstruction. More recently, there is evidence that low-grade mucosal inflammation and immune activation (particularly with mast cell involvement) in association with impaired epithelial barrier function and aberrant neuronal sensitivity may play a role in functional GI disorders.^[6]

Although the overall structural organization is similar throughout the digestive tract, each part has distinct motor activities. The musculature of the digestive tract has either extrinsic innervation (both sympathetic and parasympathetic) or intrinsic innervation (Auerbach plexus or myenteric plexus).

Intrinsic innervation is fundamental to coordinating GI motor activity. A neural network branching between longitudinal and circular muscle layers of the GI tract constitutes intrinsic innervation. Another nervous intrinsic plexus in the GI tract (Meissner plexus or submucosal plexus) helps to modify mucosal absorption and secretion without influencing motility.

Random, unorganized motor activity with occasional peristaltic and antiperistaltic complexes occurs during feeding, and this allows gastric remixing of foods. After this, another motor activity occurs, which is more regular, and this begins the peristaltic waves (ie, contractions of the circular musculature of the small intestine) that allow progression of undigested food through the intestines.

These events happen because the gastric pacemaker area, which originates electric slow waves with a frequency of 3 cycles per minute, occurs at the junction between the body and the antrum of the stomach. These electric waves, called migrating myoelectric complexes, determine the frequency of muscular contractions in the antral and pyloric areas through electromechanical coupling.

Migrating myoelectric complexes regulate gastric emptying and move gastric contents distally. Every 90 minutes, a cluster of migrating myoelectric complexes arises in the stomach and migrates distally beyond the ileum. Vagal function and the release of nitric oxide, vasoactive intestinal polypeptide, motilin, and nutrients of the meal and other enterohormones also affect GI motility.

Knowles and Martin attempted to define a novel classification for intestinal motility disorders,^[7] in which these conditions are categorized as well-defined entities, entities with a variable dysfunction-symptom relation, questionable entities, and entities associated with behavioral disorders.

Well-defined entities in the Knowles-Martin classification include the following:

• Delayed colonic transit: Slow transit constipation (eg, enteric neuropathy, enteric myopathy, Parkinson disease, endocrine disorders, spinal injury); the impairment of gastric motility in Parkinson disease patients, particularly in those with motor complications (42%), may be due in part to the effect of L-dopa on gastric dopaminergic receptors^[8] ; in patients with spina bifida and spinal cord injuries, altered histology of the enteric nervous system as well as myenteric plexus neuronal loss and decreased nerve fiber density may play a major role in intestinal motility^[9]
• Dilated colon (diffuse or segmental) - Ogilvie syndrome, megacolon
• Absent rectoanal inhibitory reflex: Hirschsprung disease

Entities with a variable dysfunction-symptom relation include the following:

• Abnormally low anal canal pressure fecal incontinence (eg, diabetes mellitus, spinal injury)

Questionable entities include the following:

• Accelerated transit bile salts
• Short bowel
• Rare endocrine and metabolic disorders

Entities associated with behavioral disorders include the following:

• Impaired pelvic floor relaxation, prolonged storage in the rectosigmoid, outlet delay, anismus
• Avoidance of defecation, functional fecal retention (eg, poor pelvic floor training, poor diet, fear of pain, learned suppression)

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Etiology

Causes of intestinal motility disorders appear to be multifactorial, and only a few have been detected.

Achalasia

Studies on primary achalasia suggest it is primarily an autoimmune disorder. Worldwide, the most common cause of secondary achalasia is Trypanosoma cruzi infection (Chagas disease); another cause is iatrogenic (ie, surgical error in forming fundoplication or gastric banding).^[10] Systemic diseases that infiltrate the lower esophageal sphincter can cause a pseudoachalasia, such as tumors of the gastroesophageal junction or gastric cardia and amyloidosis.

Gastroesophageal reflux disease

Many different factors can attribute to gastroesophageal reflux disease (GERD). These include but are not limited to transient lower esophageal relaxations, weak lower esophageal sphincter, delayed gastric emptying, increased gastric acid production, hiatal hernia, and obesity.^[11]

Gastroparesis

The most common etiologies of gastroparesis noted in tertiary care centers include idiopathic (36%), diabetes mellitus (29%), and postsurgical (13%).^[12] Less common etiologies include postviral and opioid-induced gastroparesis. Rare causes include paraneoplastic syndrome, Parkinson disease, amyloidosis, and scleroderma.

Biliary dyskinesia

The exact etiology of biliary dyskinesia is unknown.

Irritable bowel syndrome

The causes of irritable bowel syndrome (IBS) remain unknown. According to some reports, the small intestine and colon of patients with IBS are more sensitive and reactive to mild stimuli than usual. IBS may be related to the immature status of muscles and nerves in the intestinal wall of affected persons.

Colonic inertia

The underlying etiology of colonic inertia appears to be dysfunction of the enteric nerve plexus. It has been suggested that patients have a decreased number or complete absence of interstitial cells of Cajal.^[13]

Intestinal pseudo-obstruction (Ogilvie syndrome)

The exact etiology of acute colonic pseudo-obstruction is unknown. It has been hypothesized that a dysregulation of nerve impulses in the enteric nervous system results in a large bowel obstruction without an actual physical obstruction. The inciting event is most commonly postsurgical, cardiopulmonary conditions, metabolic disorders, and trauma, among many other reported causes.^[14]

Pelvic floor dyssynergia

Pelvic floor dyssynergia and pelvic floor dysfunction are caused by impaired relaxation of the external anal sphincter, impaired relaxation of the puborectalis muscle, or decreased propulsion of stool through the colon. Similar to other motility disorders, there is an underlying dysfunction of nerve conduction. Defecation specifically involves coordination of the enteric, parasympathetic, and sympathetic nervous systems.

Hirschsprung disease

Hirschsprung disease is a congenital disorder that results from absence of ganglion cells in a portion of the colon, most commonly the rectosigmoid colon. This is caused by a failure of neural crest cells to migrate during fetal development. Several genetic mutations have also been found to be associated with Hirschsprung disease.^[15]

Fecal incontinence

Aging, dementia, stroke, Parkinson disease, spinal cord injuries, rectal tears during birthing, diabetes, surgical complications, and neuromuscular disorders (eg, myasthenia gravis) may cause fecal incontinence.

Occasionally, fecal incontinence may occur after ingestion of certain foods. Sugars, insoluble fibers, and starches (except rice) are broken down in the intestines, forming a variable amount of gas that must be expelled. Most people who have lactase deficiency cannot digest lactose, a sugar common in several foods (eg, milk, cakes). People who have lactose deficiency may experience uncontrolled liquid diarrhea after lactose ingestion.

Constipation

Constipation commonly has several causes, either primary or secondary. The most frequent of these are the following:

• Diet that is very poor in fiber and high in animal fats and refined sugars
• Pregnancy
• Psychological constipation related to lifestyle changes (eg, travel, a new job, or divorce), in which the patient ignores the urge to defecate
• Hypothyroidism
• Electrolyte imbalance, especially if it involves Ca⁺⁺ or K⁺
• Tumors producing mechanical compression on an intestinal tract, either internally or externally
• Nervous system injuries
• Intoxication from lead, mercury, phosphorus, or arsenic
• Constipation also may be secondary to rhagades (anal fissures) and piles.

Genetic factors

In a retrospective study investigating the association between mitochondrial disorders and chronic intestinal pseudo-obstruction (CIP) in 80 patients, Amiot et al determined that 15 patients (19% of the study cohort) had mitochondrial defects, including mutations in the thymidine phosphorylase gene (5 patients), the DNA polymerase-gamma gene (5 patients), and tRNA(leu(UUR)) (2 patients); 3 of the patients had no identifiable genetic defects.^[16] Extradigestive symptoms occurred in all 15 patients.

Unlike other CIP patients, patients in whom the condition was associated with a mitochondrial defect tend to require frequent and long-term parenteral nutrition.^[16] Because of the frequent occurrence of digestive and neurologic complications, these patients also had a high incidence of premature death. The authors suggested that mitochondrial defects are an important cause of CIP and recommended that CIP patients be tested for such defects, particularly those with severe CIP who experience associated neurologic symptoms.

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Epidemiology

According to some epidemiologic reports, as many as 30 million Americans have intestinal motility disorders. Available data from the medical literature indicate that worldwide, 30%-45% of all gastrointestinal conditions are referable to intestinal motility disorders.

When intestinal motility disorders are idiopathic and not related to either malignancies or systemic diseases, morbidity is minimal and mortality from complications is low (1%-1.5%); complications usually occur in patients with intestinal pseudo-obstruction.

Persons of any age group may be affected, depending on the specific intestinal motility disorder. For example, IBS occurs more frequently in people aged 20-40 years, whereas intestinal pseudo-obstruction may occur in either newborns or elderly patients. Most patients are female, with a female-to-male ratio of 2.8:1. Primary intestinal motility disorders are most common in white persons and are usually thought to be related to diet.

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Prognosis

Primary intestinal motility disorders or disorders that are not secondary to malignancy or debilitating pathology have a good prognosis. According to many reports, the prognosis is excellent for patients with irritable bowel syndrome and mild fecal incontinence.

The prognosis is worse for patients with intestinal pseudo-obstruction, which has a high mortality.

Complications

Complications of intestinal motility disorders vary greatly, depending on the specific type of disorder under consideration.

Intestinal pseudo-obstruction is often associated with a high mortality (15%-30%), in most cases due to delayed diagnosis.

Constipation may have a severe complication, impaction. If this condition is not recognized early, the patient may die. Impaction is the collection of dry and hardened feces in the rectum or colon. Symptoms of impaction may be similar to those of constipation or may be unrelated to the gastrointestinal system.

If abdominal distention occurs, movements of the diaphragm are compromised and cause insufficient aeration with subsequent hypoxia and left ventricular dysfunction. In addition, hypoxia can precipitate angina or tachycardia. When a vasovagal response begins, the patient may have hypotension. Patients with impaction may experience vomiting, diarrhea, and resultant dehydration. They may present in an acutely confused and disoriented state, with tachycardia, fever, and altered blood pressure.

Irritable bowel syndrome is not usually associated with complications. Fecal incontinence may cause psychological problems in affected patients.

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History

The clinical presentation of patients with intestinal motility disorders is protean and may range from simple nausea and indigestion to severe abdominal pain, vomiting, diarrhea, inability to eat, weight loss, and other symptoms. It should be kept in mind that during pregnancy, intestinal motility disorders may worsen as a consequence of uterine compression of intestinal loops.

Obtain a complete patient history, recording information about the following:

• Feelings of abdominal discomfort, cramping, nausea or vomiting, pain, excessive gas, and rectal fullness
• Frequency, amount, and timing of normal defecation and any recent change
• Amount, consistency, and color of last passed feces
• Type of diet, use of laxatives or enemas, and drug use

Chronic intestinal pseudo-obstruction

Patients with chronic intestinal pseudo-obstruction (CIP) generally experience abdominal distention, pain, dizziness, fatigue, nausea, and vomiting for several days or months before their condition is recognized.

One type of pain is directly related to intestinal distention and improves or temporarily disappears if intestinal distention decreases. A second type is probably secondary to smooth muscle spasm or visceral hyperalgesia and is independent of intestinal distention.

Abdominal distention ranges from almost none to the equivalent of a 9-month pregnancy, depending on the nature and extent of the underlying pathology. An audible succussion splash and loud borborygmi may be present. Pain and distention may be almost continuous or may be interrupted by periods of clinical improvement. The vomitus frequently consists of food ingested 12 or more hours previously and may be feculent.

In patients with predominant small intestinal involvement, bacterial overgrowth and stagnant loop syndrome often develop and may lead to steatorrhea and diarrhea. Predominant colonic involvement usually results in constipation, megacolon, or both. Patients with both types of involvement may cycle from diarrhea to constipation, depending on the severity of steatorrhea and the relative involvement of each organ.

Many patients have involvement of the esophagus, which may be asymptomatic or may produce dysphagia, chest pain, regurgitation, reflux, and heartburn. Visceral neuropathies may manifest as symptoms resembling achalasia or diffuse esophageal spasm.

Gastric involvement produces gastroparesis. The abdominal distention and pain produced by any combination of gastric, small intestine, and colonic involvement result in decreased food intake, weight loss, and malnutrition, especially when combined with malabsorption.

Patients with involvement limited to the colon and distal small bowel may have relatively normal weights because their unaffected proximal bowel allows for normal absorption. Patients may have a history of weight loss or previous abdominal operations with no obstructing lesion found, or they may have a family history positive for the condition.

Irritable bowel syndrome

Abdominal pain, nausea, and irregular bowel habits that intensify during stress are the most common symptoms in patients with irritable bowel syndrome (IBS).

Fecal incontinence

Patients may not experience symptoms if the fecal incontinence is related to a comorbid condition (eg, dementia, Parkinson disease, or a demyelinating disease of the spinal cord).

Constipation

Severe constipation can be a life-threatening condition. Patients with constipation report abdominal discomfort, cramping, pain, rectal fullness, or, more rarely, nausea and vomiting.

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Physical Examination

The clinical picture of patients with intestinal motility disorders is protean and may vary greatly, depending on the specific condition present.

Always perform a digital rectal examination in any patient with an intestinal motility disorder to detect the presence of a mass (eg, feces, tumor, or a foreign body) or blood in the rectum.

Chronic intestinal pseudo-obstruction

Decreased or absent bowel sounds and progressive loss of bowel movements are the most common signs in patients with chronic intestinal pseudo-obstruction (CIP).^[17] Patients’ symptoms increase in the 4-7 days before clinical onset and recognition of the disorder.

Physical examination findings may include weight loss, cachexia, and abdominal distention. Patients with small intestinal involvement usually have a succussion splash located in the midabdomen, whereas patients with gastric involvement may have a splash in the left upper quadrant.

Hypertympany to percussion is usually present, and contracting bowel loops are occasionally observed pushing up against the abdominal wall. Bowel sounds are of no value in making a diagnosis of pseudo-obstruction.

Evidence of central and peripheral nervous system disease should be sought, and autonomic nervous system testing should be performed when indicated.

Involvement of the genitourinary system may be indicated by the presence of a palpable urinary bladder. Patients may have positive neurologic findings with signs of systemic disease (eg, progressive sclerosis, amyloidosis, or myxedema).

Irritable bowel syndrome

Patients with irritable bowel syndrome commonly have bloating, heartburn, burping, vomiting, and difficulty swallowing. Symptoms can fluctuate, disappearing during sleep and occurring again during stressing occasions. Heartburn, burping, and difficulty swallowing are usually due to concomitant gastroesophageal reflux disease, a very common condition in such patients.

Fecal incontinence

In the first stage of the disease, passing gas more than the normal 14-23 times a day characterizes fecal incontinence. In the second stage, liquid incontinence occurs, and patients are unaware that stools are being passed (stage of passive fecal incontinence). In the third stage, which is more severe, involuntary passage of feces through normal sphincter muscles occurs (stage of urge incontinence).

Constipation

The pattern of at least three stools per week and no more than three per day is considered normal defecation. Any reduction in the frequency of defecation may be considered constipation. Abdominal colicky pains are frequent in these patients.

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Approach Considerations

Perform a complete workup to exclude an organic cause for the patient’s symptoms (eg, myxedema, dynamic bowel obstruction, or malignancy, which are eminently treatable conditions). Only after the complete workup has been carried out can the patient be deemed to have a functional problem.

Workup may include laboratory studies, diagnostic imaging, manometry, electromyography (EMG), endoscopy, and diagnostic laparoscopy or laparotomy.^[18]

Please also see recommendations from the International Working Group for Disorders of Gastrointestinal Motility and Function (2018) as well as from the European Society for Neurogastroenterology and Motility (ESNM) (2020) in the Guidelines section.

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Laboratory Studies

Routine laboratory examinations are not very useful for diagnosing primitive intestinal motility disorders, except pseudo-obstructive attacks. However, laboratory studies may be helpful for diagnosing motility disorders of the gut due to intestinal cancers or irritable bowel disease.

The complete blood cell (CBC) count is usually altered in patients with intestinal cancers (in whom it may show anemia) and in patients with irritable bowel disease (in whom leukocytosis is the more frequent result). In such patients, the protein electrophoresis pattern may show alterations of both albumin and globulins (especially alpha-1 and gamma globulins).

Electrolyte imbalance is common in patients with intestinal pseudo-obstruction. Serum levels of triiodothyronine, thyroxine, and glucose are also altered in these patients. Vitamin B-12 levels are reduced in persons with malabsorption. Transaminase levels can be altered in patients with liver metastases. A stool sample should be sent for analysis if the diagnosis of steatorrhea from small bowel bacterial overgrowth is suggested.

Tumor markers may be studied in patients who may have cancer of the digestive system. The most useful tumor markers for these patients are carbohydrate antigen 19-9, cancer antigen 125, and carcinoembryonic antigen (CEA). CEA is nonspecific but is useful in follow-up evaluations. Alpha-fetoprotein evaluation may help detect liver involvement by metastases from intestinal cancers.

Urinalysis is not useful in establishing a diagnosis of an intestinal motility disorder.

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Radiography and Scintigraphy

Achalasia

A typical bird's beak appearance of the esophagus in achalasia can be seen on barium swallow studies.

Intestinal pseudo-obstruction

Plain radiographic films of the abdomen may show bowel blockage (without any actual mechanical bowel obstruction) in patients with intestinal pseudo-obstruction, but findings are usually negative in patients with irritable bowel syndrome (IBS) or constipation (see the image below).

View Image

Intestinal Motility Disorders. This radiograph reveals a dilated cecum (16 cm) and colon in a patient with pseudocolonic obstruction.

A barium meal is a helpful study in the diagnosis of intestinal motility disorders, but it should never be administered to patients with symptoms of pseudo-obstruction, because it may cause irreversible blockage of intestinal transit. It may show a delay in transit time in persons with constipation, or the results may be normal in patients with IBS.

Computed tomography (CT) and nuclear magnetic resonance examinations are expensive and should be reserved for patients with possible intestinal malignancy.

Although defecography offers some information about the kinetics of rectal emptying, scintigraphic study of the small bowel or colonic transit time is currently preferred. Radionuclide gastric emptying tests are also performed when needed. Scintigraphic study of intestinal transit time, accomplished by oral administration of radiolabeled foods, allows study of gastric emptying and intestinal progression of the meal. It is not helpful in the diagnosis of patients with possible intestinal cancer.^[19]

Guidelines for the scintigraphic measurement of solid-phase, liquid-phase, and combined liquid-phase/solid-phase gastric emptying are available from the American College of Radiology (ACR), the Society of Nuclear Medicine (SNM), and the Society for Pediatric Radiology (SPR).^{[20, 21]} The following are among the general indications for gastrointestinal scintigraphy^{[20, 21]} :

• Demonstration of: Salivary gland function and/or tumors; presence and site of acute gastrointestinal bleeding; transit through the small/large intestine; presence/absence of peritoneal loculations before the administration of intraperitoneal chemotherapy or radiopharmaceutical therapy
• Detection of: Ectopic functioning gastric mucosa as seen in Meckel diverticulum; congenital/acquired perforation of the pleuroperitoneal diaphragm
• Confirmation of suspected aspiration
• Evaluation and quantification of transit through and reflux into the esophagus (gastroesophageal and enterogastric reflux)
• Evaluation of patency of peritoneovenous shunts
• Quantification of the rate of emptying of liquid and/or solid meals from the stomach

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Manometry and Electromyography

Rectal manometry, a procedure for measuring the intestinal pressure exerted by the muscles of the pelvic floor, may provide some important information in patients with intestinal motility disorders, especially in those with fecal incontinence. Esophageal or gastroduodenal manometry or cystometrography may be performed as indicated. High-resolution manometry in conjunction with pressure-flow measurements appears to allow discrimination of the cause of dysphagia in children, such as differentiating weak peristalsis (poor bolus clearance) from abnormal bolus flow resistance (esophageal outflow obstruction), which may aid in treatment planning and decision making.^[22]

EMG of the pelvic floor yields information about nervous conduction and muscle function, though it is not very accurate. Such information makes it possible to distinguish between functional and organic disorders of defecation.

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Endoscopy

Endoscopy usually provides information about morphologic and functional patterns of the digestive tract. Perform endoscopic studies of the upper and lower digestive tracts in any patient with an intestinal motility disorder because, in most of these patients, dysmotility has been described in the whole digestive tract.

A rectal mucosal or full-thickness biopsy may be useful in helping to diagnose amyloidosis or pathologic abnormalities of the muscularis propria or the nerve plexus (myopathies and neuropathies). Echoendoscopy may provide additional information about the muscular layer of the gastrointestinal (GI) tract.

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Diagnostic Laparoscopy or Laparotomy

Diagnostic laparoscopy or laparotomy, with full-thickness biopsy or resection, and immunohistochemistry can be performed to assess for c-kit –positive cells. A full-thickness biopsy sample of the small intestine can be obtained via laparoscopy, with or without a feeding jejunostomy tube. Full-thickness biopsy specimens should be examined for muscle disease, inflammatory infiltrates of the myenteric plexus, neuronal intranuclear and intracytoplasmic inclusions, neuronal destruction, and absent or deficient c-kit immunoreactivity.

If laparotomy is performed, specimens should be taken from two sites, with tissue obtained from dilated and nondilated segments of intestine and processed for conventional light microscopy and immunohistochemistry.

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Histologic Findings

Because of their functional origin, no specific histologic pattern has been associated with primary intestinal motility disorders. Some sort of molecular damage in muscle fibers of the digestive tract is thought to occur, or intrinsic innervation (enteric nervous system) may cause motor incoordination as a result of alterations of migrating myoelectric complexes.

Testing of c-kit immunoreactivity is used to assess the volume of the interstitial cells of Cajal. Literature suggests that a decrease in the volume of these cells is associated with slow transit of the bowel.^{[23, 24, 25, 26]}

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Approach Considerations

Several different drugs can cause intestinal motility disorders, therefore, avoiding them, if possible, may resolve the condition. In selected patients, pharmacotherapy may be helpful. Gastric preprandial dysrhythmia may lead to impaired gastric emptying, thus contributing to irregular absorption of drugs from the small intestine and conducing to disabling response fluctuations of the therapy.

Cognitive interventions (eg, cognitive behavorial therapy, hypnotherapy) have been successful in managing abdominal pain in patients with irritable bowel syndrome; however, they have limited utility for routine use in daily practice owing to their labor intensiveness and tight availability.^[27]

Surgery is not usually performed to treat patients with primary intestinal motility disorders, except in the treatment of idiopathic constipation that does not respond to medical therapies and in the treatment of intestinal pseudo-obstruction. Surgery for these patients is always palliative. Only patients who are incapacitated by their symptoms or those whose nutritional status is adversely affected undergo surgery.

Neural stem cell transplantation may be beneficial for patients with intestinal motility disorders associated with enteric neuropathy.^[28] A murine study demonstrated that transplanted enteric neural progenitor cells could generate functional enteric neurons in the postnatal bowel.^[28]

Patients with intestinal motility disorders must be educated in ways of coping with their condition and instructed to avoid any situation or substance that may cause the symptoms to worsen. Psychological counseling may be helpful.

Please also see recommendations from the International Working Group for Disorders of Gastrointestinal Motility and Function (2018) as well as from the European Society for Neurogastroenterology and Motility (ESNM) (2020) in the Guidelines section.

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Pharmacologic Therapy

Avoidance of drugs that can cause intestinal motility disorders is recommended if doing so is feasible. In patients with primitive (idiopathic) intestinal motility disorders, the administration of some drugs may be useful to control symptoms.

Drugs used in the management of intestinal motility disorders include parasympathomimetics, prokinetic agents, opioid antagonists, antidiarrheals, and antibiotics. The agents that are most useful in the treatment of these disorders are neostigmine, bethanechol, metoclopramide, cisapride, and loperamide.^{[29, 30, 31, 32]} Prucalopride appears promising for the treatment of chronic constipation^{[33, 34]} ; its low side-effect and drug-interaction profile appear to allow it to be a safe option in elderly patients with chronic constipation.^[35]

Neostigmine is an acetylcholinesterase inhibitor. It is especially important in the treatment of intestinal pseudo-obstruction, particularly in patients in whom conservative treatment has failed and who have a cecal dilation measuring larger than 12 cm.^[36]  Intravenous neostigmine 2 mg is given slowly over 5 minutes. Continuously monitor the patient's vital signs and electrocardiogram for 30 minutes. The patient should be sitting on a bedpan during the infusion, and atropine should be available at the bedside for potential bradycardia associated with the administration of the drug.

Lubiprostone and linaclotide are secretagogues that work by increasing intestinal secretion of chloride, which is followed by secretion of water into the intestinal lumen. Both medications are approved in the treatment of treating chronic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone is also approved for the treatment of opioid-induced constipation.

Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) provide symptomatic relief, but this has been demonstrated only for TCAs in meta-analyses.^[27]

The use of injectable bulking treatment appears to be effective and safe in the long-term management of fecal incontinence.^[37] In one study, symptomatic reduction with non-animal stabilized hyaluronic acid/dextranomer (NASHA Dx) occurred in 52% of 136 patients at 6 months, with sustained results at 12 months (57%) and at 36 months (52%). Mean change from baseline Cleveland Clinic Florida Fecal Incontinence Score (CCFIS) and Fecal Incontinence Quality of Life Scale (FIQL) scores improved between baseline and at 36-month follow-up.^[37]

Broad-spectrum antibiotics (not discussed in detail in this topic) may be needed to treat stagnant loop syndrome with bacterial colonization. A 7-day course of antibiotics (eg, tetracycline, doxycycline, ampicillin, quinolones, metronidazole) may lead to remission of the diarrhea.^[38]

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Endoscopy, Ostomy, and Bowel Resection

Before the decision is made to perform a particular operation, it is extremely important to determine which symptoms are being palliated and from which area of the intestine these symptoms emanate. Surgery is always indicated if the patient has complications such as perforation of the bowel or peritonitis.

In patients with acute intestinal pseudo-obstruction, endoscopic decompression is suitable and may resolve the problem. When indicated, endoscopic decompression should always be attempted before any open surgical intervention. Some patients may benefit from laparoscopy and lysis of adhesions. Surgical procedures such as feeding jejunostomies, decompressive gastrostomy, or ileostomy also may be necessary.

Transplantation of the small intestine is still in the experimental stages, but steady progress has been made, and improved survival is being reported.^{[39, 40]}

Patients with chronic intestinal motility disorders may experience symptom relief after total colectomy in conjunction with near-total proctectomy. This surgical procedure is successful in nearly 90% of patients. Some surgeons prefer to perform a total proctocolectomy with ileoanal anastomosis on a J-pouch.

This procedure may be necessary in patients who have a megacolon and severe abdominal distention. However, even with such treatment, some patients continue to have severe symptoms from coexisting disease of the small intestine. In addition, colectomy may exacerbate diarrhea. Accordingly, palliative surgery should be undertaken only after careful consideration; unnecessary surgery must be avoided at all costs.

After any abdominal procedure, exclusion of mechanical obstruction caused by adhesions may be difficult if the patient returns with symptoms of intestinal obstruction. On the other hand, surgery may be necessary for acute problems, such as intestinal volvulus, perforation, or herniation, all of which can occur in patients with pseudo-obstruction.

Extensive, sometimes radical, small-bowel resection may be necessary in rare cases of unrelenting intestinal obstruction and massive intestinal fluid secretion that make it impossible to keep up with fluid losses or control severe obstructive symptoms. Some patients continue to have abdominal pain or such copious intestinal secretion that vomiting and fluid and electrolyte losses remain substantial. They may require a decompressive enterostomy or an extended small-bowel resection; in such cases, they are invariably on home parenteral nutrition.

If the patient is unable to maintain adequate nutritional intake or continues to have severe symptoms despite palliative treatment, long-term home parenteral nutrition may be necessary. Many patients who are on home parenteral nutrition seem to do well, though some develop sepsis and thrombotic complications of the central intravenous catheter, depression, prolonged suffering, and analgesic dependence.

Support groups, such as the American Association of Gastrointestinal Motility Disorders and the American Pseudo-Obstruction and Hirschsprung Society, provide advice, information, educational meetings, and psychological support to patients and their families.

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Diet and Activity

Changes in dietary habits alone can help cure motility disorders. Correct fiber intake is useful in patients with either constipation or stool leakage. Fiber and water must be abundant in the diet of patients with constipation; fermentable foods should be avoided. Patients should take small frequent meals (6-8 times a day), avoid foods high in fat or lactose, and avoid residue- and gas-producing foods.^[27] Pureed foods (via a blender or other means) may be tolerated by some individuals.

Patients can receive supplementation with liquid formulations, vitamins, and minerals (eg, vitamin B-12, iron, calcium, folic acid, water-soluble vitamins, vitamin A, vitamin D, vitamin E, vitamin K, trace elements) as needed to meet the requirements. Consultation with a dietitian helps provide the patient with a number of options.

Mild physical exercise is not contraindicated and may be very useful for symptom relief in patients with irritable bowel syndrome or constipation.

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Prevention

A healthy lifestyle is the best prevention for intestinal motility disorders. A diet rich in fiber, especially insoluble fibers, cannot prevent colon cancer, but it may prevent constipation and impaction, its more severe complication. In addition, because insoluble fibers create a mass effect in the stomach, they may be helpful in weight control, preventing diseases related to obesity (eg, cardiovascular accidents and endocrine disturbances).

Prescriptions of laxatives, diuretics, benzodiazepines, and anticholinergic drugs should be limited. Such agents may interfere with gastrointestinal motility; they should be administered only if they are clearly useful for patients, and only for a limited time.

Any patients older than 50 years should be scheduled for colonoscopy, even if they are not symptomatic.

Patients with a history of abdominal surgery who have recurrent bowel habit disorders should be carefully evaluated with an eye to detecting eventual adhesions. The same consideration is valid for patients with a history of radiotherapy of the abdomen or pelvis.

• References

European Society for Neurogastroenterology and Motility (ESNM)

In 2020, the European Society for Neurogastroenterology and Motility (ESNM) released their recommendations for conducting gastrointestinal motility and function testing in the early recovery phase of the 2019 coronavirus (COVID-19) pandemic.^[41]  These guidelines suggest healthcare personnel evaluate the following:

• Urgency of the procedure
• Risk of infection relative to patient(s) and healthcare professional(s)
• Provision of the test planning
• Staff education and training
• Personnel protection equipment (PPE) use

Urgency of the procedure

Urgent procedures include the following:

• High-resolution manometry (HRM) for functional severe dysphagia with weight loss and/or aspiration risk
• HRM before treatment for achalasia with major impact, to assess the manometric disease pattern
• HRM and 24-hour pH-MII (pH-multichannel intraluminal impedance) for noncardiac chest pain with high impact in quality of life (QoL) (eg, repeated access to the emergency department [ED]), as well as for refractory esophageal symptoms with weight loss, persistent regurgitation, aspiration risk, and/or high impact in QoL
• Anorectal manometry plus balloon expulsion test in the pre- and postoperative assessment before colorectal surgery for cancer, and to exclude Hirschsprung disease

Elective procedures include HRM and 24-hour pH-MI for the following:

• Gastrointestinal (GI) symptoms of nonorganic origin, with incomplete response to medical therapy (Based on the symptomatic pattern, other tests may be considered.)
• Atypical symptoms of gastroesophageal reflux disease (GERD)
• Preoperative GERD assessment, when surgery is considered

In addition, anorectal manometry plus balloon expulsion test is also an elective procedure in the pre- and postoperative assessment of benign anorectal diseases.

Risk of COVID-19 infection relative to patient(s) and healthcare professional(s)

Stratify patients according to their risk of COVID‐19.

Confirmed COVID-19 cases are those individuals who have tested positive for COVID-19 on polymerase chain reaction (PCR) and those who have a COVID-19-positive high-resolution computed tomography (HR-CT) scan.

Individuals with suspected COVID-19 cases may have the following symptoms/signs:

• Common cold symptoms such as runny nose, sneezing, fatigue, and/or cough
• A body temperature of 37.5ºC or higher
• Severe fatigue, migrating body pain, and stuffiness
• Dysgeusia and anosmia without an apparent cause
• Digestive symptoms, such as diarrhea lasting 4-5 days without apparent cause

A high-risk state of COVID-19 includes a history of close contact with COVID-19 patients within a 2-week period and/or a history of travel to an area of COVID-19 outbreak within 2 weeks.

Screening options that confirm the low-risk status of the patient for COVID-19 include the following:

• Absence of symptoms and temperature below 37.2ºC
• A confirmed negative COVID-19 test by reverse transcriptase (RT)-PCR test 48 hours before the study
• Antibody test for immunoglobulin (Ig)-G-positive and IgM-negative
• Negative thoracic HR-CT scan

Risk stratification for a study/investigation in a patient is scored as follows:

• Healthcare professional: 0, if immunized; 1, if unknown
• Patient: 0, if immunized; 1, if unknown; 4, if suspected or at high infectious risk; 5, if confirmed infection
• Procedure: 1, if nonaerosol generation; 2, if aerosal generation

If the sum of the score is 0-2, the procedure is considered low risk. If the sum of the score is 3-4, the procedure is considered moderate risk. A high-risk procedure is one with a sum score above 4.

Provision of the test planning

Avoid crowding by planning the timing of the test and access to the unit.

Staff education and training

Educate and train staff for dealing with the risk of COVID‐19 infection, as well as appropriate cleaning and disinfection of the unit and decontamination of the equipment and any accessories.

For patients classified as low risk, staff PPEs include gloves, optional surgical cap, protective eyewear such as goggles or a face face shield, gowns, and surgical masks.

For patients of uncertain status, staff PPEs include waterproof gowns, shoe covers, surgical caps, protective eyewear, and level 2 PPE with FFP2/FFP3/N95 mask, and two pairs of gloves.

PPE use

Patients and staff should use appropriate PPE, and follow proper donning and doffing procedures.

The ESNM guidelines also provide protective measures for specific procedures, including the following:

• Esophageal manometry
• pH, pH‐MII, and wireless pH‐capsule monitoring
• Anorectal manometry
• Breath tests (¹³C, ¹⁴C, and H₂‐based breath tests)

• References

International Working Group for Disorders of Gastrointestinal Motility and Function

In 2018, the International Working Group for Disorders of Gastrointestinal Motility and Function released their expert consensus document regarding advances in the diagnosis of gastric and intestinal motility diorders, such as the following key advances^[42] :

• There is poor concordance between symptoms with gastrointestinal (GI) dysfunction on clinical investigations of GI motility and function, which underscores the need for testing to guide treatment.
• Scintigraphy is the reference standard for measurement of gastric emptying; alternatively, ¹³C-gastric emptying breath tests can be used.
• For all GI function tests, it is essential to adhere to adequately validated, standardized study protocols.
• In patients with treatment-refractory constipation who are being considered for colectomy, those who have major disorders of upper GI motility and evacuation disorders should be excluded owing to the negative influence of these disorders on therapeutic outcome.
• The presence of abnormal GI function on clinical investigation can direct management and predict responsiveness to medical therapy in several conditions.
• Valid reference values are available for many investigations of GI motility (particularly, gastric, colonic and anorectal function) based on results from healthy individuals and patient data, thus defining definitively pathologic results.

General considerations

Adherence to standardized and adequately validated study protocols is necessary.

Patient preparation for GI motor function testing usually requires overnight or prolonged fast and avoidance of medications that affect GI motility.

For gastric emptying testing, fasting blood glucose should be reasonably well controlled.

Detail in the clinical history and consider when interpreting test results other factors such as use of medications known to influence GI motility (eg, prokinetics, opioids, tricyclic antidepressants, laxatives, and others), prior surgery (eg, fundoplication, some forms of bariatric surgery or intestinal resections), and drug abuse (eg, of opioids or cannabinoids).

Consider behavioral conditions (eg, rumination syndrome, eating disorders) as a cause of symptoms.

There is a marked and unclear overlap in symptoms between patients with GI dysmotility and patients with functional GI disorders, in whom altered motility is thought to be one among several pathophysiologic mechanisms.

Clinical application of motility testing

Before investigation of GI motor function, rule out mucosal or structural diseases such as inflammatory or malignant disease.

Investigation of gastric motor function

Indications and clinical importance

Tests of gastric motor function comprise gastric emptying tests and intraluminal measurements of contractility.

• Clinical investigation of gastric motor function is indicated in patients in whom upper GI endoscopy is normal or does not provide a definitive diagnosis and in patients in whom there is suspicion of gastroparesis, unexplained nausea and vomiting or dumping syndrome.
• Abdominal symptoms of accelerated and delayed gastric emptying are similar; thus, gastric emptying tests can be necessary for delineation of motor dysfunction.
• The diagnosis of gastroparesis requires objective evidence of clearly delayed gastric emptying in symptomatic patients.
• In patients with upper GI surgery, diagnosis of dumping syndrome can be made on the basis of typical symptoms and findings such as postprandial hypoglycaemia or hypotension. In unclear cases, provocation tests that prove dumping syndrome are the basis of diagnosis, which is supported by evidence of accelerated gastric emptying, preferably of liquids.
• Investigation of gastric emptying can be useful in the following situations: poorly controlled diabetes mellitus; severe gastroesophageal reflux disease (GERD) unresponsive to acid suppressants (particularly before fundoplication); systemic sclerosis; after lung transplantation; Parkinson disease; generalized GI motility disorders; and patients under consideration for intestinal or colonic surgery or transplantation because of motility disorders.
• Consider investigation of antral or antropyloroduodenal contraction patterns in those with severely impaired function and marked symptoms in whom patient management requires knowledge of the pathophysiology and/or severity of a gastric or GI motility disorder.

Recommended diagnostic approaches

Scintigraphy is the reference standard for measurement of gastric emptying. ¹³C-gastric emptying breath tests (13C-GEBTs) can be used as an alternative to scintigraphy.

Markedly prolonged retention of the wireless motility capsule (WMC) might be a marker of delayed gastric emptying.

Antral or antropyloroduodenal manometry is the reference method for evaluation of gastric contraction patterns.

Investigation of small bowel motor function

Indications and clinical importance

• Tests of small intestinal motility are indicated in patients with suspected severe chronic small bowel dysmotility.
• Only those results of intestinal transit tests that deviate substantially from normal values are considered diagnostic of abnormality and indicative of either accelerated or delayed small bowel transit.
• Limit manometric evaluation of small bowel contraction patterns to patients with chronic severe and otherwise insufficiently explained symptoms, or such assessment should be used when knowledge of small bowel motility disturbances is required for management.
• Antroduodenojejunal manometry can serve to exclude major motility disturbances in patients with otherwise equivocal findings.
• Altered small bowel motility on manometry could suggest underlying myopathy or neuropathy. Severe motor pattern alterations in combination with documented episodes mimicking mechanical obstruction enable the diagnosis of chronic intestinal pseudo-obstruction (CIPO).

Recommended diagnostic approaches

Scintigraphy is the reference method for evaluation of small bowel transit time. The WMC can be used to measure small bowel transit.

The lactulose H₂ breath test (LHBT) is an inexpensive and noninvasive but less precise alternative marker of small bowel transit.

Small bowel manometry is the reference method for evaluation of intestinal contractile patterns.

Investigation of colonic motor function

Indications and clinical importance

• The main indication for colonic motor function testing is severe constipation refractory to conventional treatment and not explained by common imaging techniques. Certain measurements of colonic motility might provide useful information in a subset of patients with diarrhea.
• Exclude evacuation disorders as a potential cause of constipation symptoms before considering intraluminal tests of colonic motility .
• Colonic transit tests are required to distinguish normal from slow-transit constipation.
• Colonic scintigraphy and radio-opaque markers (ROM) can provide initial information to differentiate between diffuse and localized colonic dysmotility and/or evacuation disorders. However, transit measurements alone are not diagnostic of evacuation disorders and require confirmation by specialized tests of evacuation.
• Invasive therapeutic measures for severe constipation (ie, subtotal colectomy) require proof of colonic dysmotility. In such patients, colonic transit tests are mandatory. Tests of colonic contractility are desirable, including measurement of colonic tone or compliance in some cases.
• Measurement of compliance and tone by barostat confirms radiologically-identified overt megacolon and can identify less-severe cases of chronic megacolon.

Recommended diagnostic approaches

ROM studies and colonic scintigraphy are best suited for measurement of colonic transit time. The WMC can be used as an alternative to assess overall (although not regional) colonic transit.

Colonic manometry (high resolution preferred) is the reference method for evaluation of colonic contractile patterns.

A barostat enables the assessment of colonic compliance, tone, and phasic contractility.

Additional tests

Tests of neuromuscular function and structures

The clinical utility of the following tests is limited or subject to ongoing studies:

• Magnetic resonance imaging (MRI)
• Gastric barostat
• Abdominal ultrasonography
• Proximal gastric high-resolution manometry (HRM)
• Impedance planimetry for functional lumen imaging
• Cutaneous electrogastrography
• Single-photon emission computed tomography (SPECT) scanning
• Endoluminal image analysis
• Magnetic pill

A WMC can be used to obtain limited data on the amplitude of GI contractions.

In selected cases with severe disease, full-thickness biopsy could be useful for therapeutic decisions.

Other emerging technologies

Some emerging technologies include the following:

• High-resolution electrical mapping
• Biomarkers
• Autoimmune mechanisms
• Autonomic dysfunction

• References

Medication Summary

Drugs used in the management of intestinal motility disorders include cholinergic agonists, prokinetic agents, opioid antagonists, antidiarrheals, and antibiotics. The agents that are most useful in the treatment of these disorders are neostigmine,^[43] bethanechol, metoclopramide, cisapride, and loperamide. Neostigmine appears to increase antral and intestinal motor activity in patients with hypomotility, including intestinal dysmotility.^[43]

• References

Bethanechol (Urecholine)

• Dosing, Interactions, etc.

Clinical Context:  Bethanechol is a synthetic muscarinic stimulant. It should never be administered intravenously (IV) or intramuscularly (IM).

• References

Class Summary

Excessive parasympathetic suppression appears to be involved in the genesis of intestinal pseudo-obstruction. Cholinergic agents may allow early resolution of pseudo-obstruction and obviate surgery.

• References

Tegaserod (Zelnorm)

Clinical Context:  Tegaserod was temporarily withdrawn from the US market in March 2007; however, as of July 27, 2007, restricted use of tegaserod is now permitted via a treatment investigational new drug (IND) protocol. This protocol allows tegaserod treatment of irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. Its use is further restricted to those in critical need who have no known or preexisting heart disease. (See the FDA MedWatch Product Safety Alert.)

Tegaserod is used for short-term treatment of women with IBS in which constipation is the predominant symptom. It is also indicated to treat CIC. Tegaserod is a serotonin type 4 receptor partial agonist with no affinity for 5-HT3 receptors. It may trigger peristaltic reflex via 5-HT4 activation, which enhances basal motor activity and normalizes impaired gastrointestinal (GI) motility. Research studies have shown inhibitory activity of the drug on visceral activity in the GI tract.

• References

Metoclopramide (Reglan, Metozolv)

• Dosing, Interactions, etc.

Clinical Context:  Metoclopramide is characterized by remarkable coordination of gastric and duodenal motility.

• References

Cisapride (Propulsid)

• Dosing, Interactions, etc.

Clinical Context:  Cisapride indirectly improves GI motility by promoting acetylcholine release from postganglionic nerve endings in the myenteric plexus. It was withdrawn from the US market on July 14, 2000, but the manufacturer will make it available to certain patients meeting clinical eligibility criteria for a limited-access protocol only.

• References

Class Summary

Prokinetics are promotility agents, proposed for use with severe constipation-predominant symptoms.

• References

Methylnaltrexone (Relistor)

• Dosing, Interactions, etc.

Clinical Context:  Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist. It selectively displaces opioids from mu-opioid receptors outside the central nervous system (CNS), including those located in the GI tract, thereby decreasing constipating effects. Methylnaltrexone is indicated for opioid-induced constipation in patients with advanced illness who are receiving palliative care and whose response to laxatives has not been sufficient. It is available as a 12-mg/0.6-mL injectable solution for subcutaneous use.

• References

Naloxegol (Movantik)

• Dosing, Interactions, etc.

Clinical Context:  Naloxegol selectively antagonizes peripheral mu-opioid receptors, inhibiting opioid-induced GI hypomotility. In chronic constipation, dosing is 25 mg PO once daily 1 hour prior to eating or 2 hours post-prandial. If creatinine clearance is < 60 mL/min, then start at 12.5 mg PO once daily.

• References

Class Summary

Consider using a peripherally selective opioid antagonist to treat constipation in patients who have advanced illness requiring chronic opioid analgesia and are unresponsive to laxatives.

• References

Loperamide (Imodium)

• Dosing, Interactions, etc.

Clinical Context:  Loperamide inhibits peristalsis by acting directly on the muscles of the intestinal wall, thereby slowing intestinal motility. It prolongs movement of electrolytes and fluid through the bowel and increases viscosity and loss of fluids and electrolytes.

• References

Diphenoxylate and atropine (Lomotil)

• Dosing, Interactions, etc.

Clinical Context:  Diphenoxylate and atropine is an antidiarrheal drug combination wherein diphenoxylate is chemically related to the narcotic analgesic meperidine. It acts on intestinal muscles to inhibit peristalsis and slow intestinal motility. It prolongs the movement of electrolytes and fluid through the bowel and increases viscosity and loss of fluids and electrolytes. A subtherapeutic dose of anticholinergic atropine sulfate is added to discourage overdosage, in which case diphenoxylate may clinically mimic the effects of codeine.

• References

Difenoxin and atropine (Motofen)

• Dosing, Interactions, etc.

Clinical Context:  Difenoxin and atropine is an antidiarrheal drug combination wherein diphenoxylate is chemically related to the narcotic analgesic meperidine. Difenoxin is the active metabolite of diphenoxylate, and it is active at one fifth the dose of diphenoxylate.

• References

Class Summary

Antidiarrheal agents inhibit peristalsis and slow intestinal motility.

• References

Erythromycin (E.E.S., Erythrocin, Ery-Tab)

• Dosing, Interactions, etc.

Clinical Context:  Erythromycin is a macrolide antibiotic that duplicates the action of motilin and is responsible for migrating motor complex activity by binding to and activating motilin receptors. IV administration enhances the emptying rate of liquids and solids. The effect can be seen with oral erythromycin. The enteric-coated form may be better tolerated.

• References

Class Summary

Erythromycin is a prokinetic agent for the stomach. It is indicated in patients with gastroparesis.

• References

Neostigmine (Prostigmin)

• Dosing, Interactions, etc.

Clinical Context:  Neostigmine reversibly binds to and inactivates acetylcholinesterase.

• References

Lubiprostone (Amitiza)

• Dosing, Interactions, etc.

Clinical Context:  Lubiprostone activates chloride channel-2 (ClC-2) chloride channels, increasing intestinal fluid secretion and motility, reducing intestinal permeabiliaty, and stimulating recovery of mucosal barrier function.

• References

Linaclotide (Linzess)

• Dosing, Interactions, etc.

Clinical Context:  Linaclotide activates guanylate cyclase-C, stimulating cGMP production and increasing intestinal fluid secretion and motility.

• References