Beverly C. Mims and Clarence E. Curry Jr.
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Identify the causes of constipation.
2. Compare the features of functional constipation with those of irritable bowel syndrome (IBS) with constipation (IBS-C).
3. Recommend general and dietary modifications and therapeutic interventions for the treatment of functional constipation.
4. Distinguish between acute and chronic diarrhea.
5. Compare and contrast diarrhea caused by different infectious agents.
6. Explain how medication use can lead to diarrhea.
7. Discuss nonpharmacologic strategies for treating diarrhea.
8. Identify the signs and symptoms of IBS.
9. Contrast IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C).
10. Discuss the goals of IBS treatment.
11. Evaluate the effectiveness of principal pharmaceutical therapies for IBS.
KEY CONCEPTS
Constipation is defined in many ways, and it is important to know what is meant when the term is used.
Functional constipation exists when criteria are fulfilled for at least 3 months with symptom onset at least 6 months before diagnosis.
General and dietary modifications should be employed prior to the use of laxatives in most instances of constipation.
Oral laxatives are the primary pharmacologic intervention for relief of constipation.
When diarrhea is severe and oral intake is limited, dehydration can occur, particularly in the elderly and infants.
The primary treatment of acute diarrhea includes fluid and electrolyte replacement, dietary modifications, and drug therapy.
Irritable bowel syndrome (IBS) is generally described as a functional disorder rather than a distinct disease entity.
IBS symptoms typically cluster around two main types: IBS with diarrhea and IBS with constipation.
Diagnosis of IBS is made by symptom-based criteria and the exclusion of organic disease.
The principal goal of IBS treatment is to reduce or control symptoms.
CONSTIPATION
Constipation is defined in many ways, and it is important to know what is meant when the term is used. Constipation, when not associated with symptoms of irritable bowel syndrome (IBS), can be defined as a heterogeneous disorder characterized by disorganized passage of feces resulting in infrequent stools, difficult passage of stools, or both.1 It may be described as difficulty in passing stool with too much effort, unproductive urges, too small amount of stool, too hard consistency of stool, painful elimination of stool, or a feeling of incomplete evacuation. The existence of some or all of these symptoms suggests the presence of constipation when the frequency of elimination of feces is limited to less than two times weekly or when more than 3 days have passed without elimination of stool.1 Functionalconstipation exists when symptoms last for at least 3 months with onset at least 6 months prior to diagnosis.2
EPIDEMIOLOGY AND ETIOLOGY
Constipation is a common complaint of patients seeking medical attention, and about one-third of patients with constipation seek medical treatment. Constipation occurs in approximately 20% of the population.3 Approximately 2.5 million physician visits and 90,000 hospitalizations per year in the United States are due to constipation.4,5 Many medications and some disease states are associated with constipation. Constipation is associated with high socioeconomic costs and has considerable quality-of-life ramifications.6
Elderly patients, non-Caucasians, women, and those of lower educational and socioeconomic levels are more likely to report being constipated. Constipation in children can occur because of a change in the usual diet or fluid intake, a deviation from usual toileting routines such as during vacations, avoidance of bowel movements because of pain associated with having a stool, or due to the use of medications. Children who are diagnosed with severe constipation at a young age are likely to continue to suffer through puberty.
PATHOPHYSIOLOGY
Constipation can be due to primary and secondary causes (Table 21–1). Primary or idiopathic constipation is typified by normal-transit constipation, slow-transit constipation, and dyssynergic defecation. In the normal-transit type, colonic motility is unchanged and patients tend to experience hard stools despite normal movements. In the slow-transit type, motility is decreased leading to infrequent, harder, drier stools. In dyssynergic defecation (also known as pelvic floor dysfunction), patients have lost the ability to relax the anal sphincter while coordinating muscle contractions of the pelvic floor. Some causes of secondary constipation are listed in Table 21–1.
Table 21–1 Causes of Constipation
|
Primary Causes |
|
Normal-transit constipation (includes idiopathic or functional disorders) |
|
Slow-transit constipation (includes motility disorders) |
|
Defecatory or rectal evacuation disorders (e.g., Hirschsprung’s disease, pelvic floor dyssynergia) |
|
Secondary Causes (Selected) |
|
Endocrine/metabolic conditions (diabetes mellitus, hypothyroidism, hypercalcemia) |
|
Gl conditions (IBS, diverticulitis, hemorrhoids) |
|
Neurogenic conditions (brain trauma, spinal cord injury, cerebrovascular accident, Parkinson’s disease) |
|
Psychogenic (postponing the urge to defecate, psychiatric conditions) |
|
Medications (analgesics, anticholinergerics, calcium channel blockers, clonidine, diuretics, phenothiazines, tricyclic antidepressants [TCAs], iron supplements, calcium- and aluminum-containing antacids) |
|
Miscellaneous (immobility, poor diet, laxative abuse, hormonal disturbances) |
Constipation affects about 50% of pregnant women. Progesterone levels may be responsible in part for slowing digestion. Reabsorption mechanisms may affect colon water during pregnancy leading to harder stools and more difficult bowel movements. Intake of iron supplements may also contribute to constipation during pregnancy.
CLINICAL PRESENTATION AND DIAGNOSIS
Diagnosis
A complete history should be obtained so that the patient’s symptoms can be evaluated and the diagnosis of functional constipation confirmed. The diagnosis of functional constipation is suggested by the presence of two or more of the following criteria: (a) straining, (b) hard or lumpy stools, (c) sensation of incomplete evacuation, (d) sensation of anorectal blockage/obstruction, (e) need for manual maneuvers, or (f) fewer than three defecations per week for at least 25% of defecations. The symptoms must have been present for the last 3 months with onset at least 6 months prior to diagnosis. In addition the criteria for meeting the diagnosis of IBS are not met.2
Clinical Presentation of Constipation
Symptoms
• Functional constipation (constipation occurring in the absence of a demonstrated pathologic condition) involves the presence of at least two of the following symptoms: straining, lumpy or hard stools, sensation of incomplete evacuation, sensation of anorectal obstruction or blockage, need for manual maneuvers to facilitate defecation, and/or infrequent bowel movements (fewer than 3 per week).
• Other complaints may include painful or difficult defecation, bloating, and absence of loose stools.
• Alarm (or red flag) symptoms include worsening of constipation, blood in the stools, weight loss, fever, anorexia, nausea, and vomiting.
• The patient should seek medical attention when symptoms are severe, last longer than 3 weeks, are disabling, when alarm symptoms occur, or whenever a significant change in usual bowel habits occurs.
Laboratory Tests (to Identify Secondary Causes)
• Thyroid function tests; abnormal thyroid hormone levels may suggest hypothyroidism, which may be associated with constipation.
• Serum calcium; either increased or decreased serum calcium levels may be associated with constipation.
• Glucose; increased blood glucose may indicate diabetes mellitus, which may be associated with constipation.
• Serum electrolytes; dehydration may be associated with constipation.
• Urinalysis may also indicate dehydration, if present.
• Complete blood count; anemia may be due to cancer or another systemic disorder accompanied by constipation.
Dietary habits should be evaluated; patients should be encouraged to maintain adequate fiber intake and hydration. Evaluation of psychosocial status is recommended. Constipation may occur in patients who are depressed or in psychosocial distress. A complete family history should be obtained, particularly as it relates to inflammatory bowel disease and colon cancer. A full record of prescription and over-the-counter medications is mandatory to identify drug-related causes of constipation.
In most cases, there is no underlying cause of constipation, and the physical examination and rectal examination are normal. Endoscopic evaluation is required in patients who have weight loss, rectal bleeding, or anemia with constipation. These examinations can be used to exclude the presence of cancer or strictures, especially in patients over the age of 50 years. Endoscopic evaluation is appropriate in patients without alarm symptoms and those younger than 50 years of age. However, all adults older than 50 years of age who present with new-onset constipation should undergo endoscopic evaluation to rule out malignancy.7
TREATMENT
Desired Outcomes
In patients with constipation, the principal goals are to: (a) identify and treat secondary causes, (b) relieve symptoms, and (c) restore normal bowel function.
Nonpharmacologic Therapy
General and dietary modifications should be employed prior to the use of laxatives in most instances of constipation. Treatment of constipation depends upon the characteristics and severity of symptoms. Intake of dietary fiber increases fecal bulk by promoting movement of water into the feces and bacterial proliferation. Increasing fiber intake to 20 to 35 g/day may help improve symptoms. Foods high in fiber include beans, whole grains, bran cereals, fresh fruits, and vegetables such as asparagus, brussels sprouts, cabbage, and carrots. Persons with constipation should avoid excessively processed low-fiber foods such as luncheon meats, hot dogs, certain cheeses, and ice cream.
Adequate fluid intake is also important; patients should be encouraged to drink when thirsty. The thirst mechanism changes with age; maintenance of a daily intake diary may assist patients who need to be reminded to drink fluids.
Walking and other aerobic exercises help to tone the muscles of the lower abdominal area, which promotes propulsion in the bowel. Constipation is a frequent complaint of sedentary persons.
Each day most persons experience a strong peristaltic wave known as the gastrocolic reflex. A bowel movement usually follows. When the urge to have a bowel movement occurs, it should not be ignored. Some people put off having a stool for various reasons, which may lead to more difficulty in passing stool. Time should be planned daily to attempt having a stool. A busy lifestyle should not be allowed to interfere with normal bowel function.
Pharmacologic Therapy
Oral laxatives are the primary pharmacologic intervention for relief of constipation (Table 21–2). There are several different drug classes, as described below.
Bulk Producers
These agents are either naturally derived (psyllium), semisynthetic (polycarbophil), or synthetic (methylcellulose). They act by swelling in intestinal fluid, forming a gel that aids in fecal elimination and promoting peristalsis. They may cause flatulence (which is less common with methylcellulose) and abdominal cramping. Bulk-forming laxatives must be taken with sufficient water (8 oz or 240 mL/dose) to avoid becoming lodged in the esophagus and producing obstruction or worsening constipation. Hypersensitivity reactions may occur and rarely may be manifested as an anaphylactic reaction.
Hyperosmotics
These products cause water to enter the lumen of the colon. Lactulose, sorbitol, and glycerin are osmolar sugars. Polyethylene glycol 3350 with electrolytes is most useful for acute complete bowel evacuation prior to GI examination. Polyethylene glycol 3350 without electrolytes is useful in patients who are experiencing acute constipation or who have had inadequate response to other agents.8 Lactulose causes acidification of the contents of the colon, increases water content of the gut, and softens the stool. Glycerin causes local irritation and possesses hyperosmotic action. Osmotic agents may cause flatulence, abdominal cramping, and bloating.
Sorbitol and glycerin may be administered rectally for treatment of constipation. Rectal discomfort and irritation may occur when administered rectally. Glucose levels should be monitored in diabetic patients who ingest oral sorbitol.
Lubricants
Lubricant laxatives work by coating the stool, which allows it to be expelled more easily. The oily film covering the stool also keeps the stool from losing its water to intestinal reabsorption processes. Mineral oil (liquid petrolatum) is a nonprescription heavy oil that should be used with caution, if at all, because it can be aspirated into the lungs and cause lipoid pneumonia when ingested orally. This is of particular concern in the young or the elderly. It may also interfere with the absorption of fat-soluble vitamins.
Table 21–2 Dosage Recommendations for Selected Laxatives and Cathartics
Stimulant Laxatives
Diphenylmethane derivatives (e.g., bisacodyl) and anthraquinones (e.g., senna) have a selective action on the nerve plexus of intestinal smooth muscle leading to enhanced motility. Enteric-coated bisacodyl tablets should be swallowed whole to avoid gastric irritation and vomiting. Ingestion should be avoided within 1 to 2 hours of antacids, H2-receptor antagonists, proton pump inhibitors, and milk. The onset of effect is rapid but the effects can be harsh (cramping), depending on the dose taken. Castor oil is another member of this class that is used less frequently. Castor oil is classified as Pregnancy Category X. It is associated with uterine contractions and rupture. The use of castor oil in breast-feeding is considered as “possibly unsafe.”
Emollients
Also known as surfactants and stool softeners, emollients (e.g., salts of docusate) act by increasing the surface-wetting action on the stool leading to a softening effect. They reduce friction and make the stool easier to pass. These agents are not recommended for treating constipation of long duration.
Saline Agents
Salts of sodium, magnesium, and phosphate pull water into the lumen of the intestines resulting in increased enteral pressure. Magnesium and phosphate may accumulate in patients with renal dysfunction. Principal concerns with sodium phosphate derivative use include dehydration, hypernatremia, hyperphosphotemia, acidosis, hypocalcemia, and worsening renal function. Patients with congestive heart failure and renal dysfunction should be advised to avoid these agents. In 2009, nonprescription oral sodium phosphate solutions were voluntarily recalled by the manufacturer because of the risk of acute phosphate nephropathy. Prescription products contain a black-box warning about use in high-risk patients.
Tegaserod Maleate
Tegaserod maleate (Zelnorm) is a partial serotonin (5-HT4) receptor agonist that causes an increase in peristaltic activity and intestinal secretion, and moderation of visceral sensitivity. It increases the frequency of bowel movements and reduces abdominal discomfort, bloating, and straining. The availability of tegaserod maleate is limited to emergency situations in women who are under the age of 55 years and who have a diagnosis of chronic idiopathic constipation who meet specific guidelines. Tegaserod availability was limited because postmarketing safety evaluation found that patients receiving it were at higher risk of suffering cardiac events such as stroke, heart attack, and unstable angina when compared with patients receiving placebo.
Lubiprostone
Lubiprostone (Amitiza), abicyclic acid oral agent, is approved for treatment of chronic idiopathic constipation in adults. It has not been studied in children. Lubiprostone acts locally on intestinal chloride channels and increases intestinal fluid secretion, resulting in increased intestinal motility and thereby increasing the passage of stool.9
Lubiprostone is contraindicated in patients with a history of mechanical GI obstruction and should not be used in patients suspected of having GI obstruction. Safety has not been established in pregnant women; animal studies indicated the potential to cause fetal loss. Women who could become pregnant should have a negative pregnancy test result prior to beginning therapy with lubiprostone.
GI adverse events reported with lubiprostone include nausea, diarrhea, abdominal distention, abdominal pain, flatulence, vomiting, loose stools, and dyspepsia. Nausea is a prominent adverse effect and may be minimized when lubiprostone is taken with food.
The recommended dose of lubiprostone is 24 mcg orally twice daily with food and water. Studies evaluated lubiprostone use for no longer than 4 weeks. Patients should be assessed periodically for the need to continue therapy.
Methylnaltrexone Bromide
Methylnaltrexone bromide (Relistor) is indicated for opioid-induced constipation in patients with advanced illness, receiving palliative care, and who have experienced insufficient response to laxative therapy. It is a selective antagonist of opioid binding at the μ-receptor. It has limited ability to cross to the blood-brain barrier and causes laxation in patients with opioid-induced constipation without reducing the analgesic effects of opioids or inducing opioid withdrawal. Methynaltrexone bromide is administered subcutaneously no more than once daily or every other day at individualized dosages based on patient weight. In patients with renal impairment (creatinine clearance less than 30 mL/min) the dose should be reduced by 50%. The most common side effects are abdominal pain, flatulence, nausea, dizziness, and diarrhea. It is contraindicated in known or suspected GI obstruction.
Treatment Recommendations
Slow-transit constipation can be treated with chronic administration of hyperosmotic laxatives. Senna, bisacodyl, and other stimulants should be used only when the others fail to deliver the desired effect.
Laxatives may provide appropriate relief when constipation occurs during the postpartum period, when not breastfeeding, and in immobile patients. Patients who are not constipated but who need to avoid straining (e.g., patients with hemorrhoids, hernia, or myocardial infarction) may benefit from stool softeners or mild laxatives such as polyethylene glycol 3350.
Laxatives should not be given to children younger than 6 years of age unless prescribed by a physician. Because children may not be able to describe their symptoms well, they should be evaluated by a physician before being given a laxative. Treating secondary causes may resolve the constipation without the use of laxatives. As in adults, children benefit from a healthy balanced diet, adequate fluid, and regular exercise.
Because many elderly persons experience constipation, laxative use is sometimes viewed as a normal part of daily life. However, oral ingestion of mineral oil can be a special hazard in bedridden elderly persons because it can lead to pneumonia through inhalation of oil droplets into the lungs. Lactulose maybe a better choice in this situation. Regular use of any laxative that affects fluid and electrolytes may result in significant unwanted adverse effects.
Patient Encounter 1
DB is a 72-year-old woman who complains of small, hard stools for the last 3 weeks. She noted that lately she has to strain to have bowel movements. She states that this difficulty with having bowel movements has occurred off and on for several months. She denies abdominal pain. She has a history of hypertension, osteoarthritis, and Type 2 diabetes mellitus.
What general approach to this patient should be employed?
What are the possible contributing causes of her constipation?
What nonpharmacologic and pharmacologic therapies would be appropriate for her condition?
Bulk producers are commonly used during pregnancy. Stool softeners (Pregnancy Category C) are probably safe to use at any time during a pregnancy because they are poorly absorbed. Lactulose and magnesium products are classified as Pregnancy Category B. Specifically, no human studies are available concerning use of lactulose in pregnant women. Magnesium-based antacids are not classified according to pregnancy categories and are associated with low-risk and minimal absorption in pregnant women. Long-term use of magnesium citrate should be avoided (Pregnancy Category B).
To avoid constipation, pregnant women should be advised to eat regular meals that are balanced among fruits, vegetables, and whole grains; maintain adequate water intake; and get appropriate exercise.
Patients with the following conditions should use laxatives only under the supervision of a health care provider: (a) colostomy, (b) diabetes mellitus (some laxatives contain large amounts of sugars such as dextrose, galactose, and/or sucrose), (c) heart disease (some products contain sodium), (d) kidney disease, and (e) swallowing difficulty (bulk-formers may produce esophageal obstruction).
OUTCOME EVALUATION
• Ask the patient about the absence or improvement in symptoms to determine whether laxative therapy is effective. Patients should have an increase in stool frequency to three or more well-formed stools per week. Patients should report the absence of prolonged defecation time or the absence of the need for excessive straining.
Patient Care and Monitoring for Constipation
1. Assess the patient’s symptoms to determine if patient-directed therapy is appropriate or whether the patient should be evaluated by a physician. Determine type and frequency of symptoms.
2. Review available information to determine the most likely cause or type of constipation.
3. Obtain a thorough history of prescription, nonpre-scription, and dietary supplement use. Determine what treatments have been helpful in the past. Is the patient taking any medications that may contribute to constipation?
4. Remember that no single therapy has proven effective for all patients who present with constipation.
5. Develop a plan to assess the effectiveness of laxative use in cases of functional constipation.
6. Evaluate the patient for the presence of adverse drug reactions, drug allergies, and drug interactions.
7. Provide patient education about constipation, general and dietary modifications, and drug therapy.
• When acute overuse or chronic misuse of saline or stimulant laxatives is suspected, it may be necessary to check for electrolyte disturbances (e.g., hypokalemia, hypernatremia, hyperphosphatemia, or hypocalcemia).
• Some laxatives (e.g., bulk producers) contain significant amounts of sodium or sugar and may be unsuitable for salt-restricted or diabetic patients. Monitoring of fluid retention (edema) and blood pressure changes are indicated in patients on sodium-restricted diets. Glucose monitoring maybe required in diabetic patients as needed with chronic use. Use of low-sodium or sugar-free products maybe indicated.
• Saline laxatives containing magnesium, potassium, or phosphates should be used cautiously in persons with reduced kidney function. Monitor appropriate serum electrolyte concentrations in patients with unstable renal function evidenced by changing serum creatinine or creatinine clearance.
• All laxatives are contraindicated in patients with abdominal pain, nausea, vomiting, symptoms of appendicitis, or undiagnosed abdominal pain. Patients should consult their physicians if sudden changes in bowel habits persist for more than 14 days or if use of a laxative for 7 days results in no effect.
DIARRHEA
Diarrhea is a symptom of an underlying problem, not a disease. It is characterized by increased stool frequency (usually more than three times daily), stool weight, liquidity, and decreased consistency of stools compared to a patient’s usual pattern. Acute diarrhea is defined as diarrhea lasting for 14 days or less. Diarrhea lasting more than 30 days is called chronic diarrhea. Illness of 15 to 30 days is referred to as persistent diarrhea.10
EPIDEMIOLOGY AND ETIOLOGY
Most cases of diarrhea in adults are mild and resolve quickly. Infants and children (especially under 3 years of age) are highly susceptible to the dehydrating effect of diarrhea, and its occurrence in this age group should be taken seriously.
Acute Diarrhea
Acute diarrhea has many possible causes, but infection is the most common. Infectious diarrhea occurs because of food and water contamination via the fecal-oral route. Viruses are the cause in a large proportion of cases. Likely viral suspects include Rotavirus, Norwalk, and adenovirus. Patients usually exhibit sudden low-grade fever, vomiting, and watery stools.
Bacterial precipitants in many other cases include Escherichia coli, Salmonella species, Shigella species, Vibrio cholerae, and Clostridium difficile. The term dysentery describes some of these bacterial infections when associated with serious occurrences of bloody diarrhea. Additionally, acute diarrheal conditions can be prompted by parasites-protozoa such as Entamoeba histolytica, Microsporidium, Giardia lamblia, and Cryptosporidium parvum. Most of these infectious agents can cause traveler’s diarrhea, a common malady afflicting travelers worldwide. It usually occurs during or just after travel following the ingestion of fecally contaminated food or water. It has an abrupt onset but usually subsides within 2 to 3 days.
Noninfectious causes of acute diarrhea include drugs and toxins (Table 21–3), laxative abuse, food intolerance, IBS, inflammatory bowel disease, ischemic bowel disease, lactase deficiency, Whipple’s disease, pernicious anemia, diabetes mellitus, malabsorption, fecal impaction, diverticulosis, and celiac sprue.
Table 21–3 Selected Drugs and Substances That May Cause Acute Diarrhea
Lactose intolerance is responsible for many cases of acute diarrhea, especially in patients of African descent, Asians, and Native Americans. Possible food-related causes include fat substitutes, dairy products, and products containing nonabsorbable carbohydrates.
The diarrhea of IBS is sudden and perhaps watery but likely loose, usually accompanied by urgency, bloating, and abdominal pain occurring upon arising in the morning or immediately following a meal. Inflammatory bowel disease is typically associated with the sudden onset of bloody diarrhea accompanied by urgency, crampy abdominal pain, and fever. Patients who experience bowel ischemia may develop bloody diarrhea, particularly if they progress to shock.
Chronic Diarrhea
Chronic diarrhea lasts 4 weeks or more. Most cases result from functional or inflammatory bowel disorders, endocrine disorders, malabsorption syndromes, and drugs (including laxative abuse). In chronic diarrhea, daily watery stools may not occur. Diarrhea maybe either intermittent or persistent.
PATHOPHYSIOLOGY
During normal processes, approximately 9 L (about 2.4 gallons) of fluid traverse the GI tract daily. Of this amount, 2 L represent gastric juice, 1 L is saliva, 1 L is bile, 2 L are pancreatic juice, 1 L is intestinal secretions, and 2 L are ingested. Of these 9 L of fluid presented to the intestine, only about 150 to 200 mL remain in the stool after reabsorptive processes occur.
Any event that leads to a significant increase in the amount of fluid retained in the stool may result in diarrhea. Large-stool diarrhea often signifies small intestinal involvement, whereas small-stool diarrhea usually originates in the colon. Diarrhea may be classified according to pathophysiologic mechanisms, which include osmotic, secretory, inflammatory, and altered motility.
Osmotic diarrhea results from the intake of unabsorbable but water-soluble solutes in the intestinal lumen leading to water retention. Common causes include lactose intolerance and ingestion of magnesium-containing antacids.
Secretory diarrhea results in an increase in the net movement (secretion) ofions into the intestinal lumen leading to an increase in intraluminal fluid. Medications, hormones, and toxins may be responsible for secretory activity.
Inflammatory (or exudative) diarrhea results from changes to the intestinal mucosa that damage absorption processes and lead to an increase in proteins and other products in the intestinal lumen with fluid retention. The presence of blood or fecal leukocytes in the stool is indicative of an inflammatory process. The diarrhea of inflammatory bowel disease (e.g., ulcerative colitis) is inflammatory in nature.
Increased motility results in decreased contact between ingested food and drink and the intestinal mucosa, leading to reduced reabsorption and increased fluid in the stool. Diarrhea resulting from altered motility is often established after other mechanisms have been excluded. IBS-related diarrhea is due to altered motility.
Although diarrhea can often be attributed to a specific mechanism, some patients develop diarrhea due to overlapping mechanisms. For example, malabsorption syndromes and traveler’s diarrhea are associated with both secretory and osmotic diarrhea.
Drug-induced diarrhea can occur by several mechanisms. First, water can be drawn into the intestinal lumen osmotically. Second, the intestinal bacterial ecosystem can be upset leading to the emergence of invasive pathologic organisms triggering secretory and inflammatory processes. Saline laxatives are an example of the first mechanism, and many antibiotics act by the second. A third way is through altered motility as may occur with tegaserod maleate. Other drugs such as procainamide or colchicine produce diarrhea through undetermined mechanisms. Discontinuation of the offending drug may be the only measure needed to ameliorate the diarrhea.
CLINICAL PRESENTATION AND DIAGNOSIS
Diagnosis
Patients with diarrhea should be questioned about the onset of symptoms, recent travel, diet, source of water, and medication use. Other important considerations include duration and severity of the diarrhea along with an accounting of the presence of associated abdominal pain or vomiting, blood in the stool, stool consistency, stool appearance, stool frequency, and weight loss. Although most cases of diarrhea are self-limited, infants, children, elderly persons, and immunocompromised patients are at risk for increased morbidity.
Findings on physical examination can assist in determining hydration status and disease severity. The presence of blood in the stool suggests an invasive organism, an inflammatory process, or perhaps a neoplasm. Large-volume stools suggest a small-intestinal disorder, whereas small-volume stools suggest a colon or rectal disorder. Patients with prolonged or severe symptoms may require colonoscopic evaluation to identify the underlying cause.
TREATMENT
Most healthy adults with diarrhea do not develop significant dehydration or other complications and can be treated symptomatically by self-medication. When diarrhea is severe and oral intake is limited, dehydration can occur, particularly in the elderly and infants. Other complications of diarrhea resulting from fluid loss include electrolyte disturbances, metabolic acidosis, and cardiovascular collapse.
Children are more susceptible to dehydration (particularly when vomiting occurs) and may require medical attention early in their course, especially if younger than 3 years of age. Physician intervention is also necessary for elderly patients who are sensitive to fluid loss and electrolyte changes due to concurrent chronic illness.
Clinical Presentation of Diarrhea
Signs and Symptoms of Acute Diarrhea
• Patients with acute diarrhea have the abrupt onset of loose, watery, or semi-formed stools.
• Abdominal cramps and tenderness, rectal urgency, nausea, bloating, and fever may be present.
• The disorder is generally self-limited, lasting 3 to 4 days even without treatment.
• Patients with acute infectious diarrhea from invasive organisms also have bloody stools and severe abdominal pain.
Laboratory Tests in Acute Diarrhea
• Stool cultures can help identify infectious causes. Cultures are subject to time delay. New methodology using real-time polymerase chain reaction (PCR) shortens the reporting time.
• Stool may also be analyzed for mucus, fat, osmolality, fecal leukocytes, and pH. The presence of mucus suggests colonic involvement. Fat in the stool may be due to a malabsorption disorder. Fecal leukocytes can be found in inflammatory diarrheas including infections and caused by invasive bacteria (e.g., E. coli, and Shigella and Campylobacter species). Stool pH (normally greater than 6) is decreased by bacterial fermentation processes.
• Stool volume and electrolytes can be assessed in large-volume watery stools to determine whether the diarrhea is osmotic or secretory.
• CBC and blood chemistries may be helpful in patients whose symptoms persist. The presence of anemia, leukocytosis, or neutropenia may provide further clues to the underlying cause.
Signs and Symptoms of Chronic Diarrhea
• In patients with chronic diarrhea, symptoms may be severe or mild. Weight loss can be demonstrated, and weakness may be present.
• Dehydration may be manifested by decreased urination, dark-colored urine, dry mucous membranes, increased thirst, and tachycardia.
Laboratory Tests in Chronic Diarrhea
• All of the tests described for acute diarrhea would be used to establish a diagnosis of chronic diarrhea because the differential diagnosis is more complicated. The data obtained can help categorize the diarrhea as watery, inflammatory, or fatty, narrowing the focus on a primary disorder.
• Colonoscopy allows visualization and biopsy of the colon and is preferred if blood has been found in the stool or if the patient has AIDS.
Patients should undergo medical evaluation in the following circumstances: (a) moderate to severe abdominal tenderness, distention, or cramping; (b) bloody stools; (c) evidence of dehydration (e.g., thirst, dry mouth, fatigue, dark-colored urine, infrequent urination, reduced urine, dry skin, lack of skin elasticity, rapid pulse, rapid breathing, muscle cramps, muscle weakness, sunken eyes, or lightheadedness); (d) high fever (greater than or equal to 38°C or 101°F); (e) evidence of weight loss greater than 5% of total body weight; and (f) diarrhea that lasts longer than 48 hours.
Desired Outcomes
The goals of treatment for diarrhea are to relieve symptoms, maintain hydration, treat the underlying cause(s), and maintain nutrition. The primary treatment of acute diarrhea includes fluid and electrolyte replacement, dietary modifications, and drug therapy.
Nonpharmacologic Therapy
Fluid and Electrolytes
Fluid replacement is not a treatment to relieve diarrhea but rather an attempt to restore fluid balance. In many parts of the world where diarrheal states are frequent and severe, fluid replacement is accomplished using oral rehydration solution (ORS), a measured mixture of water, salts, and glucose. The WHO-recognized solution consists of 75 mEq/L sodium, 75 mmol/L glucose, 65 mEq/L chloride, 20 mEq/L potassium, and 10 mEq/L citrate, having a total osmolarity of 245 mOsm/L. A simple solution can be prepared from 1 L water mixed with eight teaspoonfuls of sugar and one teaspoonful of table salt. Some commercial products include Pedialyte, Rehydralyte, and Ceralyte.
Consistent intake of water (perhaps by slowly sipping) along with eating as tolerated, should restore lost fluids and salt for typical diarrhea sufferers. Patients may also replace lost fluid by drinking flat soft drinks such as ginger ale, tea, fruit juice, broth, or soup. Caution is advised in using sports drinks for dehydration, as they may not provide an appropriate amount of electrolytes. Severe diarrhea may require the use of parenteral solutions such as lactated Ringer’s or normal saline solution to replace large and life-threatening fluid losses.10
Dietary Modifications
Once an acute diarrheal situation ensues, patients typically eat less as they become focused on the diarrhea. Both children and adults should attempt to maintain nutrition. Food provides nutrients and fluid volume that help replace what is lost. However, food-related fluid may not be enough to compensate for diarrheal losses. Some foods may be inappropriate if they irritate the GI tract or if they are implicated as the cause of the diarrhea. Patients with chronic diarrhea may find that increasing bulk in the diet may help (e.g., rice, bananas, whole wheat, and bran).
Pharmacologic Therapy
The goal of drug therapy is to control symptoms, enabling the patient to continue with as normal a routine as possible while avoiding complications (Table 21–4). Most infectious diarrheas are self-limited or curable with anti-infective agents.
Adsorbents and Bulk Agents
Attapulgite adsorbs excess fluid in the stool with few adverse effects. Calcium polycarbophil is a hydrophilic polyacrylic resin that also works as an adsorbent, binding about 60 times its weight in water and leading to the formation of a gel that enhances stool formation. Neither attapulgite nor polycarbophil is systemically absorbed. Not only are both products effective in reducing fluid in the stool but they can also adsorb nutrients and other medications. Their administration should be separated from other oral medications by 2 to 3 hours. Psyllium and methylcellulose products may also be used to reduce fluid in the stool and relieve chronic diarrhea.
Table 21–4 Pharmacotherapy for Diarrhea
Antiperistaltic (Antimotility) Agents
Antiperistaltic drugs prolong intestinal transit time, thereby reducing the amount of fluid lost in the stool. The two drugs in this category are loperamide HCI (available over-the-counter as Imodium A-D and generically) and diphenoxylate HCI with atropine sulfate (available by prescription as Lomotil and generically). The atropine is included only as an abuse deterrent; when taken in large doses, the unpleasant anticholinergic effects of atropine negate the euphoric effect of diphenoxylate. Both loperamide and diphenoxylate are effective in relieving symptoms of acute noninfectious diarrhea and are safe for most patients experiencing chronic diarrhea. These products should be discontinued in patients whose diarrhea worsens despite therapy.
Antisecretory Agents
Bismuth subsalicylate (BSS) is thought to have antisecretory and antimicrobial effects and is used to treat acute diarrhea. Although it passes largely unchanged through the GI tract, the salicylate portion is absorbed in the stomach and small intestine. For this reason, BSS should not be given to people who are allergic to salicylates, including aspirin. Caution should be exercised with regard to the total dose given to patients taking salicylates for other reasons to avoid salicylism. Patients taking BSS should be informed that their stool will turn black.
Octreotide is an antisecretory agent that has been used for severe secretory diarrhea associated with cancer chemotherapy, HIV, diabetes, gastric resection, and GI tumors. It is administered as a subcutaneous or IV bolus injection in an initial dose of 500 mcg three times daily to assess the patient’s tolerance to GI adverse effects. Biweekly serum levels of insulin-like growth factor-1 (IGF-1 or somatomedin C) can be used as a guide to dose titration. Possible adverse effects include nausea, bloating, pain at the injection site, and gallstones (with prolonged therapy).
Probiotics
Probiotics are dietary supplements containing bacteria that may promote health by enhancing the normal microflora of the GI tract while resisting colonization by potential pathogens. Probiotics can stimulate the immune response and suppress the inflammatory response. Yogurt can provide relief from diarrhea due to lactose intolerance. It supports digestion of lactose because the bacteria used to make yogurt produce lactase and digest the lactose before it reaches the colon. The Lactobacillus acidophilus in yogurt, cottage cheese, and acidophilus milk improve digestion of lactose and may prevent or relieve diarrhea related to lactose deficiency and milk intake. Although lactase is not a probiotic, lactase tablets may also be used to prevent diarrhea in susceptible patients.
Patient Encounter 2
KW, a 31 -year-old day care teacher, complains of nausea, vomiting, abdominal cramps, and frequent watery stools for the past 2 days. She also indicates that her heart has been “beating faster” and her mouth has been dry. Although she looks ill, she does not have a fever. She does not have any current medical problems or drug therapy.
What is the likelihood that her diarrhea is due to an invasive microorganism?
Which of her symptoms suggest the presence of dehydration?
Discuss potential treatment measures for this woman.
Anti-infectives
Empiric antibiotic therapy is an appropriate approach to traveler’s diarrhea. Eradication of the causal microbe depends on the etiologic agent and its antibiotic sensitivity. Most cases of traveler’s diarrhea and other community-acquired infections result from enterotoxigenic (ETEC) or enteropathogenic Escherichia coli (EPEC). Routine stool cultures do not identify these strains; primary empiric antibiotic choices include fluoroquinolones such as ciprofloxacin or levofloxacin. Azithromycin may be a feasible option when fluoroquinolone resistance is encountered.
Although most cases of infectious diarrhea resolve with therapy, routine antibiotic use may contribute to antimicrobial resistance. Empiric treatment should be considered for other acute infectious diarrhea including those caused by nonhospital-acquired invasive organisms such as Shiga toxin-producing Escherichia coli (STEC) O157, Campylo-bacter, Salmonella, and Shigella organisms producing moderate to severe fever, tenesmus, and bloody stools.11
OUTCOME EVALUATION
• Monitor the patient with diarrhea from the point of first contact until symptoms resolve, keeping in mind that most episodes are self-limiting.
• Question the patient to determine whether symptom resolution occurs within 48 to 72 hours in acute diarrhea.
• Monitor for the maintenance of hydration, particularly when symptoms continue for more than 48 hours. Look for increasing thirst, decreased urination, dark-colored urine, dry mucous membranes, and rapid heartbeat as suggestive of dehydration, especially when nausea and vomiting have been present.
• Monitor for symptom control in patients with chronic diarrhea.
• When antibiotics are used, monitor for completion of the course of therapy.
Patient Care and Monitoring for Diarrhea
1. Assess the patient’s symptoms to determine if patient-directed therapy is appropriate or whether the patient should be evaluated by a physician. Determine the type of symptoms, severity, frequency, and exacerbating factors. Remember to inquire about recent foreign travel.
2. Determine if the patient is dehydrated.
3. Determine whether the patient has a history of disease that might be associated with diarrhea.
4. Obtain a thorough current history of prescription, nonprescription, and dietary supplement use. Remember to review the current therapy as a potential cause of diarrhea.
5. Determine if any diarrhea treatments have been attempted, including home remedies.
6. Medical referral is advised if the patient is pregnant, breast-feeding, younger than 3 or older than 70 years of age, or suffers from multiple medical conditions.
7. If home care is recommended, provide clear instructions about how to proceed if symptoms do not improve or new symptoms emerge.
8. Discuss the importance of maintaining nutrition by modifying the diet to include low-residue meals (low-fiber meals).
9. Educate the patient about: (a) the causes of acute and chronic diarrhea, (b) the possible complications of diarrhea, (c) the goals of treatment for diarrhea, (d) the antidiarrheal medication used to manage acute or chronic diarrhea, and (e) if appropriate, the circumstances when antibiotics are used to treat diarrhea.
IRRITABLE BOWEL SYNDROME
IBS is a disorder of the GI tract that interferes with the normal functions of the colon. At various points in the past, IBS has been referred to as mucous colitis, spastic colon, irritable colon, or nervous stomach. IBS is generally described as a functional disorder rather than a disease per se. A functional disorder involves symptoms that cannot be attributed to a specific injury, infection, or other physical problem.A functional disorder occurs because of altered physiologic processes rather than structural or biochemical defects and may be subject to nervous system influence.
IBS is associated with frequent fluctuation in symptoms, loss of productivity, and decreased quality of life. Although IBS has been referred to as functional bowel disease, true functional bowel disease may be more indicative of widespread GI involvement including (but not limited to) the colon.
EPIDEMIOLOGY AND ETIOLOGY
IBS is one of the most common disorders seen in primary care and the most common reason for referral to gastroenterol-ogists. Although between 15% and 20% of Americans suffer from IBS, only about one-quarter of those affected seek medical attention. The associated costs to society are significant, and the recurrent nature of IBS contributes to these costs through missed workdays, inattention on the job, and high consumption of health services.12
In the United States, IBS affects women about twice as often as men. However, this may reflect a woman’s tendency to seek medical care more often than a man’s. IBS can occur at any age but is most common between 20 and 50 years; onset beyond age 60 is rare. However, prevalence for older adults is the same as for young persons. Prevalence is similar in Caucasians and African Americans but may be lower in people of Hispanic origin. A genetic link is unproven, but IBS seems more common in certain families.
There is a strong association between emotional distress and IBS. Psychosocial trauma (e.g., a history of abuse, recent death of a close relative or friend, or divorce) is more likely to be found in patients presenting with IBS than in the general population. An increased prevalence of psychiatric disorders such as anxiety, depression, personality disorders, and somatization (psychological distress expressed as physical symptoms) occurs among adult patients with IBS. Alcohol consumption and smoking have not been shown to be risk factors for developing IBS.13
Some people show first evidence of IBS after contracting gastroenteritis, which has led to speculation about whether infection heightens GI tract susceptibility. Women with IBS may have symptoms triggered by menstrual periods.
PATHOPHYSIOLOGY
Enteric nerves control intestinal smooth muscle action and are connected to the brain by the autonomic nervous system. IBS is thought to result from dysregulation of this “brain-gut axis.” The enteric nervous system is composed of two ganglionated plexuses that control gut innervation: the submucous plexus (Meissner’s plexus) and the myenteric plexus (Auerbach’s plexus). The enteric nervous system and the CNS are interconnected and interdependent. A number of neurochemicals mediate their function, including serotonin (5-hydroxytryptamine or 5-HT), acetylcholine, substance P, and nitric oxide, among others.
Two 5-HT receptor subtypes, 5-HT3 and 5-HT4, are involved in gut motility, visceral sensitivity, and gut secretion. The 5-HT3 receptors slow colonic transit and increase fluid absorption, whereas 5-HT4receptor stimulation results in accelerated colonic transit.
Although no single pathologic defect has been found to account for the pattern of exacerbations and remissions seen in IBS, CNS abnormalities, dysmotility, visceral hypersensitivity, and a number of other factors have been implicated.14
The passage of fluids into and out of the colon is regulated by epithelial cells. In IBS, the colonic lining (epithelium) appears to work properly. However, increased movement of the contents in the colon can overwhelm its absorptive capacity. Disturbed intestinal motility appears to be a central feature of IBS, which leads to altered stool consistency. Studies suggest that the colon of IBS sufferers is abnormally sensitive to normal stimuli.15 This enhanced visceral sensitivity manifests as pain, especially related to gut distention.
IBS activity may be affected by the immune system. Some IBS patients have been found to have antibodies that may indicate food hypersensitivity that might be involved in symptom production.16Specifically, sensitivity has been demonstrated to common foods such as wheat, beef, pork, soy, and eggs.
CLINICAL PRESENTATION AND DIAGNOSIS
Diagnosis
The diagnosis of IBS is made by symptom-based criteria and the exclusion of organic disease. IBS is diagnosed by obtaining a careful and thorough history to identify symptoms characteristic of the disorder. It is equally important to distinguish among IBS and conditions having similar symptoms. Patients should be questioned about the character of their stools. This should include questions about frequency, consistency, color, and size. Moreover, because of the functional nature of IBS, a patient may present with symptoms of upper GI problems such as gastroesophageal reflux disease or with excessive flatulence. Patients should also be questioned about diet to determine whether symptoms seem to occur in relationship to meals or specifically after consumption of certain dietary products.
Barium enema, sigmoidoscopy, or colonoscopy may be indicated in the presence of red flag symptoms (fever, weight loss, bleeding, and anemia, which may be accompanied by persistent severe pain), which often point to a potentially serious non-IBS problem. A barium enema may identify polyps, diverticulosis, tumors, or other abnormalities that might be responsible for the symptoms. In addition, exaggerated haustral contractions may be noted with barium enema. Such contractions impede stool movement and contribute to constipation. Flexible sigmoidoscopy can be performed to identify obstruction in the rectum and lower colon, whereas colonoscopy can evaluate the entire colon for organic disease.
Clinical Presentation of IBS
Symptoms
• Patients report a history of abdominal pain or discomfort that is relieved with defecation. Symptom onset is associated with change in frequency or appearance of stool. Some persons experience hard, dry stools whereas others experience loose or watery stools. Some stools may be small and pellet-like in appearance while others may be narrow and pencil-like.
• Symptoms can typically be categorized as either IBS with diarrhea (IBS-D) or IBS with constipation (IBS-C). Patients with IBS-D usually report more than three loose or watery stools daily. Those with IBS-C usually have fewer than three bowel movements per week; stools are typically hard and lumpy and accompanied by straining. However, stool frequency may be normal in many cases. The Rome III diagnostic criteria (see Diagnosis) place more emphasis on stool form unlike Rome II, which emphasized frequency.
• While many patients fit into one of these subtypes, some patients report alternating episodes of diarrhea and constipation (irritable bowel syndrome with constipation and diarrhea [IBS-M], where M represents mixed).
• Other common symptoms include: (a) feelings of incomplete evacuation, (b) abdominal fullness, (c) bloating, (d) flatulence, (e) passage of clear or white mucus with a stool, and (f) occasional fecal incontinence.
• Periods of normal stools and bowel function are punctuated by episodes of sudden symptoms.
• Symptoms are often exacerbated by stress.
• Left lower quadrant abdominal pain is often brought on or made worse by eating. Passage of stool or flatus may provide some relief.
• IBS-C can often be distinguished from functional constipation primarily by the presence of abdominal pain and discomfort. Although pain and discomfort may be present in some patients with functional constipation, it is an expected feature of IBS.
• Patients with IBS may experience comorbidities outside the Gl tract such as fibromyalgia, sleep disturbances, headaches, dyspareunia, and temporomandibular joint syndrome.
Signs
• The physical examination is often normal in IBS.
• The patient may appear to be anxious.
• Palpation of the abdomen may reveal left lower quadrant tenderness, which may indicate a tender sigmoid colon.
• Abdominal distention may be present in some cases.
• The following “red flag” or alarm features are not associated with IBS and may indicate inflammatory bowel disease, cancer, or other disorders: fever, weight loss, bleeding, and anemia, which may be accompanied by persistent severe pain.
Laboratory Tests
• In most cases, laboratory testing reveals no abnormalities in IBS, but certain tests can be used to identify other causes for the patient’s symptoms.
• CBC may identify anemia, which may suggest blood loss and an organic source for Gl symptoms.
• Serum electrolytes and chemistries may indicate metabolic causes of symptoms.
• Thyroid-stimulating hormone (TSH) should be ordered when thyroid dysfunction is suspected. Hypothyroidism may be responsible for constipation and related symptoms.
• Stool testing for ova and parasites may identify C. difficile and amoebae as possible causes of diarrhea rather than IBS.
• Fecal leukocytes can be found in inflammatory diarrhea, especially when due to invasive microorganisms.
• A positive stool guaiac test indicating blood in the Gl tract does not support a diagnosis of IBS.
• An elevated erythrocyte sedimentation rate is consistent with a systemic inflammatory process such as inflammatory bowel disease rather than IBS.
• Testing for lactase deficiency can confirm the presence of lactose intolerance, which may explain the symptoms.
IBS diagnosis has long been symptom based. Manning defined the first widely used practical criteria: (a) abdominal pain relieved by defecation with either (i) looser stools with pain onset, or (ii) frequent stools with pain onset; (b) abdominal distention; (c) mucus in the stool; and (d) sensation of incomplete evacuation.17,18
The Rome III criteria are the most current diagnostic criteria and can also be applied clinically.19 They presume the absence of a structural or biochemical explanation for the symptoms. The Rome III criteria define IBS as occurring when symptoms of recurrent abdominal pain or discomfort exist for at least 3 days/month in the last 3 months associated with two or more of the following: (a) improvement with defecation, (b) onset associated with a change in the frequency of stool, and/or (c) onset associated with a change in the form (appearance) of stool. These criteria should be fulfilled for the previous 3 months with symptom onset at least 6 months prior to diagnosis. IBS is unlikely if symptom onset occurs in old age, the disorder has a steady but aggressive course, or the patient experiences frequent awakening because of symptoms.
Patient Encounter 3, Part 1
A 38-year-old woman presents complaining of headache, abdominal pain, bloating, occasional nausea, and excessive belching. These symptoms have occurred with increasing frequency over the past 2 to 3 weeks. She has missed 2 days of work recently. The abdominal pain is crampy in character and located in the left lower abdominal area. She has also had alternating episodes of loose stools and hard dry stools and the presence of white thread-like material in her stool during some of the past 3 weeks. She reports no family history of Gl problems.
Which of the patient’s symptoms are characteristics of IBS?
How well does this woman fit the typical epidemiologic profile of patients with IBS?
TREATMENT
General Approach to Treatment
The principal goal of IBS treatment is to reduce or control1 symptoms. The treatment strategy is based on: (a) the prevailing symptoms and their severity, (b) the degree of functional impairment, and (c) the presence of psychological components. A standard treatment regimen is not possible because of the heterogeneous nature of the IBS patient population. Patients suffering from IBS can benefit from clinician support and reassurance, because specific pathology is unlikely to be found.
Nonpharmacologic Therapy
Diet and Other General Modifications
Dietary modification is a standard therapeutic modality. Food hypersensitivities and adverse effects are thought to occur widely in IBS patients, especially those with IBS with diarrhea subtype. Elimination diets are the most commonly used strategy, usually focusing on milk and dairy products, fructose and sorbitol, wheat, and beef. Flatulence may be controlled by reducing gas-causing foods such as beans, celery, onions, prunes, bananas, carrots, and raisins. Response to elimination diets varies widely, but they may be useful in individual patients. Care must be taken to avoid creating nutritional deficits while attempting to eliminate an offending food.
Probiotics may also be an option for some patients with IBS. Bifidobacterium infantis is one product used for its effect in constipation, diarrhea, gaseousness, bloating, and abdominal discomfort. Reportedly, it is not associated with significant untoward effects.2 The usual dose is one 4-mg capsule daily.
Psychological Treatments
Psychotherapy focused on reducing the influence of the CNS on the gut has been studied. Cognitive behavioral therapy (CBT), dynamic psychotherapy, relaxation therapy, and hypnotherapy have been reported to be effective in some patients. However, CBT and relaxation therapy do not appear to be better than standard approaches.20 Biofeedback may provide relief in cases of severe constipation, but definitive evidence is lacking.21,22 Psychotherapy interventions provide relief from pain and diarrhea but not from constipation.23
Pharmacologic Therapy
Botanicals
Peppermint oil is widely advocated; it acts as an antispasmodic agent due to its ability to relax GI smooth muscle. However, it also relaxes the lower esophageal sphincter, which could allow reflux of gastric contents into the esophagus. The usual dose is 1 to 2 enteric-coated capsules containing 0.2 mL of peppermint oil two to three times daily.
Matricaria recutita, known as German chamomile, is also purported to have antispasmodic properties. It is taken most often as a tea up to four times a day. Benzodiazepine, alcohol, and warfarin users should be cautioned against taking this product because it can cause drowsiness, and it contains coumarin derivatives.24
Antispasmodics
Antispasmodic agents such as dicyclomine or hyoscyamine have been among the most frequently used medications for treating abdominal pain in patients with IBS (Table 21–5). Side effects include blurred vision, constipation, urinary retention, and (rarely) psychosis. Although their effectiveness remains unconfirmed, these drugs may deserve a trial in patients with intermittent postprandial pain.18
Antidepressants
Tricyclic antidepressants (TCAs) such as amitriptyline and doxepin have been used with some success in the treatment of IBS-related pain (Table 21–5). They modulate pain principally through their effect on neurotransmitter reuptake, especially norepinephrine and serotonin. Their helpfulness in functional GI disorders seems independent of mood-altering effects normally associated with these agents. Low-dose TCAs (e.g., amitriptyline, desipramine, or doxepin 10–25 mg daily) may help patients with IBS who predominantly experience diarrhea or pain.
The selective serotonin-reuptake inhibitors (SSRIs) paroxetine, fluoxetine, and sertraline are potentially useful due to the significant effect of serotonin in the gut. SSRIs principally act on 5-HT1 or 5-HT2receptors, but they can also have some effect on gut-predominant 5-HT3 and 5-HT4 receptors, perhaps reducing visceral hypersensitivity. They maybe beneficial for patients with IBS-C or when the patient presents with IBS complicated by a mood disorder.24 SSRIs should be reserved for use when TCAs are not effective because evidence supporting their use solely in IBS is lacking.
Table 21–5 Common Pharmacologic Treatments for IBS
Bulk Producers
Bulk producers may improve stool passage in IBS-C but are unlikely to have a favorable effect on pain or global IBS symptoms.25 Psyllium may increase flatulence, which may worsen discomfort in some patients. Methylcellulose products are less likely to increase gas production. Although fiber-based supplements are more likely to be useful in IBS-C, these products may be dose-adjusted in diarrhea to increase stool consistency. Other laxative products might be used in IBS-C, but most are less desirable than bulking agents due to the potential for unwanted effects.
Antimotility Agents
Loperamide stimulates enteric nervous system receptors, inhibiting peristalsis and fluid secretion. It improves stool consistency and reduces the number of stools.25 Consequently, it is most useful in patients who have diarrhea as a prominent symptom. However, it can occasionally aggravate abdominal pain.
Alosetron
Stimulation of 5-HT3 receptors triggers hypersensitivity and hyperactivity of the large intestine. Alosetron (Lotronex) is a selective 5-HT3 antagonist that blocks these receptors and is used to treat women with severe IBS-D. Eligible patients should have frequent and severe abdominal pain, frequent bowel urgency or incontinence, and restricted daily activities. Alosetron has been shown to improve overall symptoms and quality of life. Alosetron can cause constipation in some patients.
Because alosetron has been associated with ischemic colitis, it may be prescribed only under strict guidelines, including signing of a consent form by both patient and physician. Patients selected for therapy should exhibit severe chronic IBS symptoms and should have failed to respond to conventional therapy.
Tegaserod Maleate
Tegaserod maleate (Zelnorm) stimulates 5-HT4 receptors in the GI tract, thereby increasing intestinal secretion, peristalsis, and small bowel transit. It also reduces sensitivity related to abdominal distention. It has been shown to be more effective than placebo in improving global IBS symptoms and altered bowel habits in IBS-C.25 However, because a higher risk of heart attack, stroke, and unstable angina (heart/chest pain) in patients treated with tegaserod maleate is suspected, the drug has been withdrawn from general use. The FDA can authorize use of tegaserod maleate for emergency situations only. The FDA must also authorize the drug to be shipped.
OUTCOME EVALUATION
• Because symptoms vary in intensity and among patients, a specific drug therapy may not lead to equivalent symptom abatement in different patients.
• Monitor for adequate relief of symptoms. Patients whose pain does not respond to drug therapy may have a psychological comorbid condition and may require psychiatric intervention.
• Specifically, monitor for relief of pain if present initially. Monitor patients with symptoms of constipation or diarrhea for frequency, appearance, and size of stools
in relationship to their normal characteristics. As stools normalize, associated symptoms such as bloating and abdominal distention should resolve.
• For IBS-C patients taking bulk producers, monitor for relief of constipation. Hard stools should become softer within 72 hours. IBS-M patients may gain relief with these agents as well.
Patient Encounter 3, Part 2
Upon further questioning, the patient states that she had similar symptoms (often following menses) near the end of graduate school 6 years ago. The symptoms gradually subsided after graduation, so she did not seek medical attention. She is an accountant and recently received a promotion at work. As a result, she has taken on considerably more responsibility.
PMH: Anxiety; muscle contractions; headaches
FH: Mother has migraine headaches
SH: Nonsmoker; drinks a glass of wine occasionally
Meds: Naproxen 220 mg every 12 hours as needed for headaches and menstrual pain; loperamide 2 mg as needed for diarrhea
Allergies: No known drug allergies
PE:
Gen: Alert and oriented; well-developed and well-nourished, anxious black woman
VS: BP 137/88 mm Hg, P 80 bpm, RR 21 per minute, T 37.1 °C (98.7°F), Ht 57” (170 cm), Wt 74 kg (173 lb)
Integ: Hair and nails unremarkable; scalp dry and flaky; skin otherwise unremarkable
HEENT: PERRLA, EOMI
Chest: Clear to A & P bilaterally
CV: RRR, normal S1, and S2; no S3 or S4
Abd: (+) BS, mildly tender LLQ
Rectal: No palpable masses; no hemorrhoids; stool negative for occult blood
What information is consistent with a diagnosis of IBS?
Outline an appropriate therapeutic plan for this patient.
• Monitor antidepressant therapy for relief of lower abdominal pain.
• Antispasmodics may provide limited relief of crampy abdominal pain.
• Assess 5-HT4 receptor agonists (tegaserod) for relief of crampy abdominal pain and bloating.
• Evaluate 5-HT3 receptor antagonists (alosetron) for relief of abdominal pain and fecal incontinence.
• Antimotility agents should be expected to reduce stool frequency and control diarrhea.
• Monitor complete blood cell count, serum electrolytes and chemistries, stool guaiac, and erythrocyte sedimentation rate yearly for changes that might signal an overlapping organic problem.
• Refer any patient presenting with red flag signs for medical evaluation.
Patient Care and Monitoring for IBS
1. Assess symptoms to determine if patient-directed therapy is appropriate or whether physician evaluation is needed.
2. Determine the type, severity, and frequency of symptoms and possible exacerbating factors.
3. Listen attentively to the patient’s complaints and reassure the patient to allay fears about invasive disease.
4. Obtain a thorough current history of prescription, nonprescription, and dietary supplement use.
5. Determine if any IBS treatments have been attempted and how effective they have been.
6. Determine whether the patient has received educational intervention about IBS, health promotion, and symptom prevention measures.
7. Provide patient education about IBS symptoms, lifestyle modifications, and drug therapy for IBS:
• Explain how to use medications relative to symptom intensity.
• If taking alosetron, determine nonadherence with special use requirements.
• Describe potential adverse effects.
• List drugs that may interact with the therapy.
• Discuss what to do if red flag symptoms occur.
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
REFERENCES
1. Brandt L, Schoenfeld P, Prather C, et al. American College of Gastroenterology Functional Gastrointestinal Disorders Task Force. An evidence based approach to the management of chronic constipation in North America. Am J Gastroenterol 2005;100:S1-S21.
2. Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology 2006;130:1377-1390.
3. Locke GR, Pemberton JH, Phillips SF. American Gastroenterological Association medical position statement on constipation. Gastroenterology 2000;119:1766-1778.
4. Irvine EJ, Ferrazzi S, Pare P. Health-related quality of life in functional GI disorders: Focus on constipation and resource utilization. Am J Gastroenterol 1998;97:1986-1993.
5. Sonnenberg A, Koch TR. Physician visits in the United States for constipation: 1958 to 1986. Dig Dis Sci 1989;34:606-611.
6. Drossman DA, Li Z, Andruzzi E, et al. US householder survey of functional gastrointestinal disorders: Prevalence, sociodemography, and health impact. Dig Dis Sci 1993;38:1569-1580.
7. Longstreth GF, Thompson WG, Chey WD. Functional bowel disorders. Gastroenterology 2006;130:1480-1491.
8. Lembo A, Camilleri M. Chronic constipation. N Engl J Med 2003;349:1360-1368.
9. Amitiza package insert. Bethesda, MD: Sucampo Pharmaceuticals, 2006.
10. Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001;32:331-351.
11. King CK, Glass R, Bresee JS, et al. Managing acute gastroenteritis among children: Oral rehydration, maintenance, and nutritional therapy. Morbid Mortal Wkly Rep 2003;52(RR16):1-16.
12. Gore JI, Surawicz C. Severe acute diarrhea. Gastroenterol Clin North Am 2003;32:1249-1267.
13. Cash B, Sullivan S, Barghout V. Total costs of IBS: Employer and managed care perspective. Am J Manag Care 2005;11(Suppl):S7-S16.
14. Cremonini F, Talley NJ. Irritable bowel syndrome: Epidemiology, natural history, health care seeking, and emerging risk factors. Gastroenterol Clin North Am 2005;34:189-204.
15. Morgan T, Robson KM. Irritable bowel syndrome: Diagnosis is based on clinical criteria. Postgrad Med 2002;112(5):30-40.
16. Schwetz I, Bradesi S, Mayer EA. The pathophysiology of irritable bowel syndrome. Minerva Med 2004;95:418-426.
17. Atkinson W, Sheldon TA, Shaath N, et al. Food elimination based on IgG antibodies in irritable bowel syndrome: A randomised controlled trial. Gut 2004;53:1459-1464.
18. Fass R, Longstreth GF, Pimentel M, et al. Evidence- and consensus-based practice guidelines for the diagnosis of irritable bowel syndrome. Arch Intern Med 2001;161:2081-2088.
19. Talley NJ, Spiller R. Irritable bowel syndrome: A little understood organic bowel disease? Lancet 2002;359:555-564.
20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and Bifido-bacterium in irritable bowel syndrome: Symptom responses and relationship to cytokine profiles. Gastroenterology 2005;128:541-551.
21. Boyce PM, Talley NJ, Balaam B, et al. A randomized controlled trial of cognitive behavior therapy, relaxation training, and routine clinical care for the irritable bowel syndrome. Am J Gastroenterol 2003;98:2209-2218.
22. Mertz HR. Drug therapy: Irritable bowel syndrome. N Engl J Med 2003;349:2136-2146.
23. Miller LG. Herbal medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-2211.
24. Schoenfeld P. Efficacy of current drug therapies in irritable bowel syndrome: What works and does not work. Gastroenterol Clin North Am 2005;34:319-335.
25. Jones MP, Dilley JB, Drossman D, Crowell MD. Brain-gut connections in functional GI disorders: Anatomic and physiologic relationships. Neurogastroent Motil 2006;18:91-103.