Thursday, August 11, 2011
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Monday, November 15, 2010
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Sunday, November 14, 2010
IRRITABLE BOWEL SYNDROME
Introduction
Background
Irritable bowel syndrome (IBS) is a functional GI disorder characterized by abdominal pain and altered bowel habits in the absence of specific and unique organic pathology. Osler coined the term mucous colitis in 1892 when he wrote of a disorder of mucorrhea and abdominal colic with a high incidence in patients with coincident psychopathology. Since that time, the syndrome has been referred to by sundry terms, including spastic colon, irritable colon, and nervous colon.
Traditionally, irritable bowel syndrome is a diagnosis of exclusion. No specific motility or structural correlates have been consistently demonstrated, so irritable bowel syndrome remains a clinically defined illness.
Manning and associates established 6 criteria to distinguish irritable bowel syndrome from organic bowel disease.1 Although historically important, these criteria are insensitive (58%), nonspecific (74%), and less reliable in men. The Manning criteria to distinguish irritable bowel syndrome from organic disease are as follows:
* Onset of pain associated with more frequent bowel movements
* Onset of pain associated with looser bowel movements
* Pain relieved by defecation
* Visible abdominal bloating
* Subjective sensation of incomplete evacuation more than 25% of the time
* Mucorrhea more than 25% of the time
More recently, a consensus panel created and then updated the Rome criteria to provide a standardized diagnosis for research and clinical practice. The Rome III criteria (2006) for the diagnosis of irritable bowel syndrome require that patients must have recurrent abdominal pain or discomfort at least 3 days per month during the previous 3 months that is associated with 2 or more of the following:
* Relieved by defecation
* Onset associated with a change in stool frequency
* Onset associated with a change in stool form or appearance
Supporting symptoms include the following:
* Altered stool frequency
* Altered stool form
* Altered stool passage (straining and/or urgency)
* Mucorrhea
* Abdominal bloating or subjective distention
Four bowel patterns may be seen with irritable bowel syndrome. These patterns include IBS-D (diarrhea predominant), IBS-C (constipation predominant), IBS-M (mixed diarrhea and constipation), and IBS-A (alternating diarrhea and constipation). The usefulness of these subtypes is debatable. Notably, within 1 year, 75% of patients change subtypes, and 29% switch between constipation-predominant IBS and diarrhea-predominant IBS.
Pathophysiology
Traditional theories regarding pathophysiology may be visualized as a 3-part complex of altered GI motility, visceral hyperalgesia, and psychopathology. A unifying mechanism is still unproven.
* Altered GI motility includes distinct aberrations in small and large bowel motility.
o The myoelectric activity of the colon is composed of background slow waves with superimposed spike potentials. Colonic dysmotility in irritable bowel syndrome manifests as variations in slow-wave frequency and a blunted, late-peaking, postprandial response of spike potentials. Patients who are prone to diarrhea demonstrate this disparity to a greater degree than patients who are prone to constipation.
o Small bowel dysmotility manifests in delayed meal transit in patients prone to constipation and in accelerated meal transit in patients prone to diarrhea. In addition, patients exhibit shorter intervals between migratory motor complexes (the predominant interdigestive small bowel motor patterns).
o Current theories integrate these widespread motility aberrations and hypothesize a generalized smooth muscle hyperresponsiveness. They describe increased urinary symptoms, including frequency, urgency, nocturia, and hyperresponsiveness to methacholine challenge.
* Visceral hyperalgesia is the second part of the traditional 3-part complex that characterizes irritable bowel syndrome.
o Enhanced perception of normal motility and visceral pain characterizes irritable bowel syndrome. Rectosigmoid and small bowel balloon inflation produces pain at lower volumes in patients than in controls. Notably, hypersensitivity appears with rapid but not gradual distention.
o Patients who are affected describe widened dermatomal distributions of referred pain.
o Sensitization of the intestinal afferent nociceptive pathways that synapse in the dorsal horn of the spinal cord provides a unifying mechanism.
* Psychopathology is the third aspect.
o Associations between psychiatric disturbances and irritable bowel syndrome pathogenesis are not clearly defined.
o Patients with psychological disturbances relate more frequent and debilitating illness than control populations.
o Patients who seek medical care have a higher incidence of panic disorder, major depression, anxiety disorder, and hypochondriasis than control populations.
o An Axis I disorder coincides with the onset of GI symptoms in as many as 77% of patients.
o A higher prevalence of physical and sexual abuse has been demonstrated in patients with irritable bowel syndrome.
o Whether psychopathology incites development of irritable bowel syndrome or vice versa remains unclear.
* Microscopic inflammation has been documented in some patients. This concept is groundbreaking in that irritable bowel syndrome had previously been considered to have no demonstrable pathologic alterations.
o Both colonic inflammation and small bowel inflammation have been discovered in a subset of patients with irritable bowel syndrome as well as in patients with inception of irritable bowel syndrome after infectious enteritis (postinfectious irritable bowel syndrome). Risk factors for developing postinfectious irritable bowel syndrome include female gender, longer duration of illness, the type of pathogen involved, an absence of vomiting during the infectious illness, and young age.
o Laparoscopic full-thickness jejunal biopsy samples revealed infiltration of lymphocytes into the myenteric plexus and intraepithelial lymphocytes in a subset of patients. Neuronal degeneration of the myenteric plexus was also present in some patients.
o Patients with postinfectious irritable bowel syndrome may have increased numbers of colonic mucosal lymphocytes and enteroendocrine cells.
o Enteroendocrine cells in postinfectious irritable bowel syndrome appear to secrete high levels of serotonin, increasing colonic secretion and possibly leading to diarrhea.
* Small bowel bacterial overgrowth has been heralded as a unifying mechanism for the symptoms of bloating and distention common to patients with irritable bowel syndrome. This has led to proposed treatments with probiotics and antibiotics.
* The fecal microflora also differs among patients with irritable bowel syndrome versus controls. A sophisticated molecular analysis suggested an alteration in the patterns and the contents of gut bacteria.2
Frequency
United States
Population-based studies estimate the prevalence of irritable bowel syndrome at 10-20% and the incidence of irritable bowel syndrome at 1-2% per year. Of people with irritable bowel syndrome, approximately 10-20% seek medical care. An estimated 20-50% of gastroenterology referrals relate to this symptom complex.
International
The incidence is markedly different among countries.
Mortality/Morbidity
* Irritable bowel syndrome is a chronic relapsing condition. Clinicians must be forthcoming with patients because knowledge may help allay undue fears as their disease waxes and wanes. Irritable bowel syndrome does not increase the mortality or the risk of inflammatory bowel disease or cancer.
* The principal associated physical morbidities of irritable bowel syndrome include abdominal pain and lifestyle modifications secondary to altered bowel habits.
* Work absenteeism resulting in lost wages is more frequent in patients with irritable bowel syndrome.
Race
* American and European cultures demonstrate similar frequencies of irritable bowel syndrome across racial and ethnic lines. However, within the United States, survey questionnaires indicate a lower prevalence of irritable bowel syndrome in Hispanics in Texas and Asians in California.
* Populations of Asia and Africa may have a lower prevalence of irritable bowel syndrome.
* The role of different cultural influences and varying health care–seeking behaviors is unclear.
Sex
In Western countries, women are 2-3 times more likely to develop irritable bowel syndrome than men, although males represent 70-80% of patients with irritable bowel syndrome in the Indian subcontinent. Women seek health care more often, but the irritable bowel syndrome-specific influence of this occurrence remains unknown. Other factors, such as a probably greater incidence of abuse in women, may confound interpretation of this statistic.
Age
* Patients often retrospectively note the onset of abdominal pain and altered bowel habits in childhood.
* Approximately 50% of people with irritable bowel syndrome report symptoms beginning before they were aged 35 years.
* The development of symptoms in people older than 40 years does not exclude irritable bowel syndrome but should prompt a closer search for an underlying organic etiology.
Clinical
History
A meticulous history is the key to establish a diagnosis of irritable bowel syndrome. The Rome criteria provide the construct upon which questions are based (see Background).
Symptoms consistent with irritable bowel syndrome include the following:
* Altered bowel habits
o Constipation variably results in complaints of hard stools of narrow caliber, painful or infrequent defecation, and intractability to laxatives.
o Diarrhea usually is described as small volumes of loose stool, with evacuation preceded by urgency or frequent defecation.
o Postprandial urgency is common.
o Alternating habits are common. Characteristically, one feature predominates in a single patient, but significant variability exists among patients.
* Abdominal pain
o Descriptions are protean. Pain frequently is diffuse without radiation. Common sites of pain include the lower abdomen, specifically the left lower quadrant.
o Acute episodes of sharp pain are often superimposed on a more constant dull ache.
o Meals may precipitate pain, and defecation commonly improves pain. Defecation may not fully relieve pain.
o Pain from presumed gas pockets in the splenic flexure may masquerade as anterior chest pain or left upper quadrant abdominal pain. This splenic flexure syndrome is demonstrable by balloon inflation in the splenic flexure and should be considered in the differential of chest or left upper quadrant abdominal pain.
* Abdominal distention
o Patients frequently report increased amounts of bloating and gas. Quantitative measurements fail to support this claim.
o People with irritable bowel syndrome may manifest increasing abdominal circumference throughout the day, as assessed by CT scan. They may also demonstrate intolerance to otherwise normal amounts of abdominal distention.
* Clear or white mucorrhea of a noninflammatory etiology is commonly reported.
* Noncolonic and extraintestinal symptoms
o Epidemiologic associations with dyspepsia, heartburn, nausea, vomiting, sexual dysfunction (including dyspareunia and poor libido), and urinary frequency and urgency have been noted.
o Symptoms may worsen in the perimenstrual period.
o Fibromyalgia is a common comorbidity.
* Stressor-related symptoms
o These symptoms may be revealed with careful questioning.
o Emphasize avoidance of stressors.
* Inconsistent symptoms are an alert to the possibility of an organic pathology. Symptoms not consistent with irritable bowel syndrome include the following:
o Onset in middle age or older
o Acute symptoms: Irritable bowel syndrome is defined by chronicity.
o Progressive symptoms
o Nocturnal symptoms
o Anorexia or weight loss
o Fever
o Rectal bleeding
o Painless diarrhea
o Steatorrhea
o Lactose and/or fructose intolerance
o Gluten intolerance
Physical
* The patient has an overall healthy appearance.
* The patient may be tense or anxious.
* The patient may present with sigmoid tenderness or a palpable sigmoid cord.
Causes
The causes of irritable bowel syndrome remain poorly defined, but they are being avidly researched.
* Postulated etiologies of irritable bowel syndrome
o Abnormal transit profiles and an enhanced perception of normal motility may exist.
o Up to one third of patients with irritable bowel syndrome may have altered colonic transit. Delayed colonic motility may be more common in IBS-C versus healthy controls. Similarly, accelerated colonic transit may be more common in IBS-D versus healthy controls.3
o Local histamine sensitization of the afferent neuron causing earlier depolarization may occur.
* Causes related to enteric infection (see Pathophysiology)
o Colonic muscle hyperreactivity and neural and immunologic alterations of the colon and small bowel may persist after gastroenteritis.
o Psychological comorbidity independently predisposes the patient to the development of postinfectious irritable bowel syndrome.
o Psychological illness may create a proinflammatory cytokine milieu, leading to irritable bowel syndrome through an undefined mechanism after acute infection.
* Central neurohormonal mechanisms
o Abnormal glutamate activation of N- methyl-D- aspartate (NMDA) receptors, activation of nitric oxide synthetase, activation of neurokinin receptors, and induction of calcitonin gene-related peptide have been observed.
o The limbic system mediation of emotion and autonomic response enhances bowel motility and reduces gastric motility to a greater degree in patients who are affected than in controls. Limbic system abnormalities, as demonstrated by positron emission tomography, have been described in patients with irritable bowel syndrome and in those with major depression.
o The hypothalamic-pituitary axis may be intimately involved in the origin. Motility disturbances correspond to an increase in hypothalamic corticotropin-releasing factor (CRF) production in response to stress. CRF antagonists eliminate these changes.
* As discussed in Pathophysiology, Pimentel and colleagues have proposed that small bowel bacterial overgrowth provides a unifying mechanism for the common symptoms of bloating and gaseous distention in patients with irritable bowel syndrome.4
* Bloating and distention may also occur from intolerance to dietary fats. Reflex-mediated small bowel gas clearance is more impaired by lipids (fat) ingestion in patients with irritable bowel syndrome versus patients without irritable bowel syndrome.
* Recent elimination and challenge diets have suggested that poorly absorbed short-chain carbohydrates, in the form of fructose and fructans, may create symptoms among patients with irritable bowel syndrome, as measured by a visual analogue scale.Differential Diagnoses
Abdominal Angina
Hypothyroidism
Anxiety Disorders
Inflammatory Bowel Disease
Bacterial Overgrowth Syndrome
Lactose Intolerance
Biliary Colic
Malignant Neoplasms of the Small Intestine
Biliary Disease
Mesenteric Artery Thrombosis
Celiac Sprue
Mesenteric Venous Thrombosis
Chronic Mesenteric Ischemia
Pancreatic Cancer
Collagenous and Lymphocytic Colitis
Pancreatitis, Chronic
Colon Cancer, Adenocarcinoma
Pheochromocytoma
Endometriosis
Porphyria, Acute Intermittent
Food Allergies
Postcholecystectomy Syndrome
Gastroenteritis, Bacterial
Somatostatinomas
Gastroenteritis, Viral
Toxicity, Lead
Giardiasis
Ulcerative Colitis
Hypercalcemia
Hyperthyroidism
Other Problems to Be Considered
Fructose intolerance
Gastrinoma
Infectious colitis
Medication adverse effects
Secretory diarrhea
VIPoma
Workup
Laboratory Studies
* A comprehensive history, a physical examination, and tailored laboratory and radiographic studies can establish a diagnosis of irritable bowel syndrome in most patients.
* Lab studies may include the following:
o CBC count with differential to screen for anemia, inflammation, and infection
o A comprehensive metabolic panel to evaluate for metabolic disorders and to rule out dehydration/electrolyte abnormalities in patients with diarrhea
* Gastrointestinal bleeding should be ruled out. A hemoccult test may be useful.
* Microbiologic studies to consider include the following stool examinations:
o Ova and parasites: Consider obtaining specimens for Giardia antigen as well.
o Enteric pathogens
o Leukocytes
o Clostridium difficile toxin
* The following selected studies are directed by history:
o Breath testing: Screen for lactose and/or fructose intolerance.
o Thyroid function tests: Screen for hyperthyroidism or hypothyroidism.
o Serum calcium: Screen for hyperparathyroidism.
o Erythrocyte sedimentation rate or C-reactive protein: This is a nonspecific screening test for inflammation.
o Serologies or small bowel biopsy for celiac disease: Consider, especially in diarrhea-predominant IBS.
* H2 breath test to exclude bacterial overgrowth may be considered in patients with diarrhea.
Imaging Studies
* The following selected studies are directed by history:
o Upper GI barium study with small bowel follow-through: Screen for tumor, inflammation, obstruction, and Crohn disease.
o Double-contrast barium enema: Screen for neoplasm and inflammation.
o Gallbladder ultrasonography: Consider this test if the patient has recurrent dyspepsia or characteristic postprandial pain.
o Abdominal CT scan: Screen for tumors, obstruction, and pancreatic disease.
Other Tests
* Direct a lactose-free diet for 1 week in conjunction with lactase supplements. Improvement incriminates lactose intolerance, although the patient's clinical history and response to a trial may be unreliable. Therefore, some gastroenterologists recommend a formal hydrogen breath test. Fructose intolerance must also be considered.
* Direct a 48-hour fast. Persistent diarrhea suggests a secretory etiology.
* Anal manometry may reveal spastic response to rectal distention or other problems.
Procedures
* Endoscopy directed for many patients with irritable bowel syndrome includes flexible sigmoidoscopy to determine inflammation or distal obstruction.
* The following selected studies are directed by history:
o Esophagogastroduodenoscopy with possible biopsy - Indicated for a patient with persistent dyspepsia or if weight loss or symptoms suggest malabsorption or if celiac disease is a concern
o Colonoscopy - Indicated for patients with warning signs, such as bleeding; anemia; chronic diarrhea; older age; history of colon polyps; cancer in the patient or first-degree relatives; or constitutional symptoms, such as weight loss or anorexia. A screening colonoscopy should be performed according to published guidelines.
Histologic Findings
Research suggests that neuronal degeneration and myenteric plexus lymphocytosis may exist in the proximal jejunum. Additionally, colonic lymphocytosis and enteroendocrine cell hyperplasia have been demonstrated in some patients.Treatment
Medical Care
* Successful management relies on a strong patient-provider relationship.
* Reassure the patient that the absence of an organic pathology indicates a normal life expectancy.
* Emphasize the expected chronicity of symptoms with periodic exacerbations.
* Teach the patient to acknowledge stressors and to use avoidance techniques.
Consultations
* Consider psychiatric referral. Previous evidence has supported improvement in GI symptoms with successful treatment of psychiatric comorbidities, but 2 studies indicate caution should be used when interpreting such data.
* Zijdenbos et al conducted a meta-analysis of 25 randomized trials consisting of single psychologic interventions with usual care or mock intervention in patients older than 16 years for the years 1966-2008.{Ref44} The treatment modalities evaluated were psychologic interventions as a group and cognitive behavioral therapy (measuring improvements in abdominal pain and quality of life, relative to usual care and placebo); interpersonal psychotherapy; and relaxation/stress management. Long-term results were also assessed. The investigators noted that differences among studies and quality issues made drawing conclusions difficult; however, they suggested that although cognitive behavioral therapy and interpersonal psychotherapy may be effective immediately post treatment completion, there was no convincing evidence for sustained treatment effects after completion of treatment for any treatment modality. Thus, Zijdenbos et al recommended that future research should focus on current IBS treatment guidelines and their long-term effects.44
* Ford et al reached similar conclusions regarding the use of psychologic interventions in IBS. They also performed a systematic review and meta-analysis of randomized controlled trials (up to May 2008) in adults with IBS; however, their selection criteria included trials comparing antidepressants with placebo as well as those comparing psychologic therapies with control therapy or usual care.45 The investigators noted that the quality of studies were generally good for those involving antidepressants but poor for those involving psychologic therapy. Ford et al concluded that antidepressants are effective for IBS treatment, but despite the fact that the available data suggest psychologic therapies may be of comparable efficacy, there is less high-quality evidence for the routine use of psychologic therapies in patients with IBS.45
Diet
* Fiber supplementation may improve symptoms of constipation and diarrhea. Individualize the treatment because few patients experience exacerbated bloating and distention with high-fiber diets. Polycarbophil compounds (eg, Citrucel, FiberCon) may produce less flatulence than psyllium compounds (eg, Metamucil).
* The data regarding the effectiveness of fiber are controversial because 40-70% of patients improve with placebo.
* Judicious water intake in patients who predominantly experience constipation is recommended.
* Caffeine avoidance may limit anxiety and symptom exacerbation.
* Legume avoidance may decrease abdominal bloating.
* Lactose and/or fructose should be limited or avoided in patients with these contributing disorders. Take care to supplement calcium in patients limiting lactose intake.
Activity
No limitation is recommended.
Medication
The selection of pharmacologic treatment remains symptom directed.
The nonabsorbed antibiotic rifaximin (<0.4%) is a broad-spectrum antibiotic specific for enteric pathogens (ie, gram-positive, gram-negative, aerobic and anaerobic) of the GI tract. Rifaximin is a structural analog. It binds to a beta-subunit of bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis. It is indicated for Escherichia coli (enterotoxigenic and enteroaggregative strains) associated with travelers' diarrhea. Rifaximin has been studied in patients with irritable bowel syndrome and is believed to improve the symptoms of bloating, diarrhea, abdominal pain, and constipation. Anticholinergics Are antispasmodics that inhibit intestinal smooth-muscle depolarization at the muscarinic receptor. Dicyclomine hydrochloride (Bentyl) This drug decreases fecal urgency and pain. It is useful with diarrhea-predominant symptoms. Blocks the action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and CNS. Adverse effects are dose dependent. * Dosing * Interactions * Contraindications * Precautions Adult 10-40 mg PO qid ac or at onset of pain Pediatric Not established * Dosing * Interactions * Contraindications * Precautions May increase anticholinergic effects with concurrent administration of amantadine, class I antiarrhythmics, antihistamines, antipsychotics, benzodiazepines, MAOIs, narcotics, nitrates, sympathomimetics, and tricyclic antidepressants; dicyclomine may increase serum digoxin concentration; antacids may interfere with absorption of dicyclomine * Dosing * Interactions * Contraindications * Precautions Documented hypersensitivity; obstructive uropathy; myasthenia gravis; glaucoma; GI tract obstruction; paralytic ileus; toxic megacolon * Dosing * Interactions * Contraindications * Precautions Pregnancy B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals Precautions Caution when administering to patients with hepatic or renal insufficiency, cardiovascular disease, urinary tract obstruction, ulcerative colitis, GI obstruction, hyperthyroidism, or hypertension; may cause sedation, constipation, urinary retention, tachycardia, blurred vision, xerostomia, or dizziness Hyoscyamine sulfate (Levsin) Blocks action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS, which, in turn, has antispasmodic effects. Decreases fecal urgency and pain. Useful with diarrhea-predominant symptoms. * Dosing * Interactions * Contraindications * Precautions Adult 0.125-0.25 mg PO q4h or prn; not to exceed 1.5 mg/d (12 tab/d) Pediatric <2 years: Not recommended 2-12 years: 0.0625-0.125 mg (1/2-1 tab) PO q4h or prn; not to exceed 0.75 mg/d (6 tab/d) >2 years: Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
May increase anticholinergic effects with amantadine, class I antiarrhythmics, antihistamines, antipsychotics, benzodiazepines, MAOIs, narcotics, nitrates, sympathomimetics, and tricyclic antidepressants; may increase serum digoxin concentration; antacids may interfere with absorption
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; obstructive uropathy; myasthenia gravis; glaucoma; GI tract obstruction; paralytic ileus; toxic megacolon
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in elderly patients; some products contain sodium metabisulfite, which can cause allergic-type reactions; may cause sedation, constipation, urinary retention, tachycardia, blurred vision, xerostomia, or dizziness
Antidiarrheals
Are nonabsorbable synthetic opioids. They prolong GI transit time and decrease secretion via peripheral ยต-opioid receptors. They reduce visceral nociception via afferent pathway inhibition.
Diphenoxylate hydrochloride 2.5 mg with atropine sulfate 0.025 mg (Lomotil)
Drug combination that consists of diphenoxylate, which is a constipating meperidine congener, and atropine to discourage abuse. Inhibits excessive GI propulsion and motility. It may exacerbate constipation.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
1-2 tab PO qid ac
Pediatric
<2 years: Not recommended 2-5 years: 2 mg PO tid 5-8 years: 2 mg PO qid 8-12 years: 2 mg PO 5 times/d >12 years: Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
May delay metabolism of drugs in liver; CNS depressants, MAOIs, and antimuscarinic agents may increase toxicity of this drug combination; diphenoxylate HCl may potentiate the action of barbiturates, tranquilizers, and alcohol; atropine sulfate interacts with MAOIs
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; narrow-angle glaucoma; hepatic insufficiency; advanced hepatorenal disease; pseudomembranous colitis; enterotoxigenic infections
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
In young children, dehydration may influence variability of response and predispose patient to delayed diphenoxylate intoxication; caution in patients with ulcerative colitis; a decrease in intestinal motility may be detrimental to patients with diarrhea resulting from Shigella, Salmonella, and toxigenic strains of E coli; may cause sedation, constipation, urinary retention, tachycardia, blurred vision, xerostomia, dizziness, or respiratory depression
Loperamide (Imodium)
Acts on intestinal muscles to inhibit peristalsis and to slow intestinal motility. Prolongs movement of electrolytes and fluid through bowel and increases viscosity and loss of fluids and electrolytes. Available over the counter. Improves stool frequency and consistency, reduces abdominal pain and fecal urgency, and may exacerbate constipation.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
4 mg PO after first loose stool initially; then 2 mg after each subsequent stool; not to exceed 16 mg/d
Pediatric
Maintenance: 0.1 mg/kg PO after each loose stool, not to exceed initial dose
Chronic diarrhea: 0.08-0.24 mg/kg/d divided bid/tid; not to exceed 2 mg/dose
* Dosing
* Interactions
* Contraindications
* Precautions
Phenothiazines, tricyclic antidepressants, and CNS depressants may increase loperamide toxicity
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; diarrhea resulting from infections; pseudomembranous colitis
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue use if no clinical improvement in 48 h; because loperamide primarily metabolized in liver, monitor for CNS toxicity in patients with hepatic insufficiency; do not use medication if high fever or blood in stool coincides with diarrhea
Tricyclic Antidepressants
Provide antidepressive and analgesic properties. Various agents have efficacy; much research has concentrated on imipramine and amitriptyline (off-label use).
Imipramine (Tofranil)
This drug provides a visceral analgesic effect by increasing pain threshold in the gut. It prolongs oral-cecal transit time, reduces abdominal pain, mucorrhea, and stool frequency, and increases global well being variably in studies. The effect at doses subtherapeutic for antidepressive actions suggests an independent mechanism.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
10-100 mg/d PO; start low and titrate as necessary
Pediatric
Not recommended
* Dosing
* Interactions
* Contraindications
* Precautions
Increases toxicity of sympathomimetic agents, such as isoproterenol and epinephrine, by potentiating effects and inhibiting antihypertensive effects of clonidine
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; narrow-angle glaucoma; in acute recovery phase following myocardial infarction; avoid in patients taking MAOIs or fluoxetine or in patients who took them in the previous 2 weeks
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May impair mental or physical abilities required for performance of potentially hazardous tasks; caution in cardiovascular disease, seizure disorders, urinary retention, hyperthyroidism, or receiving thyroid replacement; may cause sedation, confusion, constipation, tachycardia, AV conduction delay, orthostasis, blurred vision, xerostomia
Amitriptyline (Elavil)
This drug provides a visceral analgesic effect by increasing pain threshold in the gut. Prolongs oral-cecal transit time, reduces abdominal pain, mucorrhea, and stool frequency, and increases global well-being variably in studies. The effect at doses subtherapeutic for antidepressive actions suggests an independent mechanism.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
10-100 mg/d PO; start low and titrate as necessary
Pediatric
Not recommended
* Dosing
* Interactions
* Contraindications
* Precautions
Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase amitriptyline levels; amitriptyline inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; patient has taken MAOIs in past 14 d; history of seizures, cardiac arrhythmias, glaucoma, or urinary retention
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in cardiac conduction disturbances, history of hyperthyroidism, and renal or hepatic impairment; avoid using in elderly persons; may cause sedation, confusion, constipation, urinary retention, tachycardia, AV conduction delay, orthostasis, blurred vision, xerostomia, or dizziness; may provoke psychosis in schizophrenics
Prokinetics
Are promotility agents, proposed for use with constipation-predominant symptoms. Unfortunately, cisapride availability is restricted in the United States, and other motility agents, such as metoclopramide, domperidone, and erythromycin, have not yielded consistent benefits in patients with irritable bowel syndrome.
Tegaserod marketing 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. The treatment IND protocol will allow 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.
In early 2007, tegaserod marketing was suspended because of a meta-analysis of safety data pooled from 29 clinical trials that involved more than 18,000 patients. The results showed an excess number of serious cardiovascular adverse events, including angina, myocardial infarction, and stroke, in those taking tegaserod compared with placebo. In each study, patients were assigned at random to either tegaserod or placebo. Tegaserod was taken by 11,614 patients, and placebo was taken by 7,031 patients. The average age of patients in these studies was 43 years, and most patients (ie, 88%) were women. Serious and life-threatening cardiovascular adverse effects occurred in 13 patients (0.1%) treated with tegaserod; among these, 4 patients had a heart attack (1 died), 6 had unstable angina, and 3 had a stroke. Among the patients taking placebo, only 1 (0.01%) had symptoms suggesting the beginning of a stroke that went away without complication.
For more information, see the FDA MedWatch Product Safety Alert.
Cisapride monohydrate (Propulsid)
Available only through an investigational limited access program by Janssen Pharmaceutical. Perform 12-lead ECG prior to administration, and do not initiate treatment if QTc value exceeds 450 milliseconds. This information is maintained for those who can acquire cisapride through this program. This is a serotonin receptor agonist (5-HT4) and antagonist (5-HT3) that promotes acetylcholine release at the myenteric plexus. Accelerates GI transit, thus increasing stool frequency and improving consistency.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
5-20 mg PO qac and hs 15-30 min ac
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Fatal ventricular arrhythmia in conjunction with other medications that inhibit cytochrome P-450 3A4 (certain macrolide antibiotics, antifungals, antidepressant, protease inhibitors, antipsychotics, class IA and III antiarrhythmics)
* Dosing
* Interactions
* Contraindications
* Precautions
Concomitant administration of medications is metabolized by cytochrome P-450; do not use in GI hemorrhage, mechanical bowel obstruction, or perforation in which enhanced GI motility may be harmful; do not use if QT interval exceeds 450 milliseconds; avoid in hypokalemia, hypocalcemia, and hypomagnesemia
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Potentiates the sedative effects of benzodiazepines and alcohol
Tegaserod (Zelnorm)
Available in US by restricted treatment IND for irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. Used for the treatment of women with irritable bowel syndrome when constipation is the predominant symptom. A selective partial agonist of the serotonin-4 (5HT4) receptor and possesses GI prokinetic activity. Tegaserod has been shown to promote clearance of gas in the small bowel.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Women: 6 mg PO bid 30 min ac for 4-6 wk; in patients who respond to treatment, an additional 4-6 wk of therapy may be considered
Men: Not established
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
None reported
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; moderate or severe renal impairment; history of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
In April 2004, in response to postmarketing reports, the FDA issued an advisory regarding serious side effects of tegaserod use; the advisory indicates that severe diarrhea with dehydration requiring hospitalization, syncope and hypotension, and intestinal ischemia, have been reported with tegaserod use; tegaserod should not be used in patients with diarrhea and should be discontinued if any signs or symptoms of these complications arise
Serotonin (5-HT3) Receptor Antagonists
Inhibit activation of nonselective cation channels, which modulate the enteric nervous system.
Alosetron (Lotronex)
A potent and selective antagonist of the serotonin 5-HT3 receptor type. 5-HT3 receptors are extensively located on enteric neurons of the GI tract, and stimulation causes hypersensitivity and hyperactivity of the intestine. Alosetron blocks these receptors and thus is effective in controlling irritable bowel syndrome symptoms. It is approved only for treatment of women with severe chronic diarrhea-predominant IBS who have not responded to conventional irritable bowel syndrome therapy. Fewer than 5% of irritable bowel syndrome cases are considered severe, and only a fraction of severe cases are diarrhea-predominant IBS. Limiting its use to this severely affected population is intended to maximize the benefit-to-risk ratio. The drug was previously removed from the US market but was reintroduced with new restrictions approved by the FDA on June 7, 2002. Restrictions are because of serious and unpredictable GI adverse events (including some that resulted in death) reported in association with its use following its original approval in February 2000.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Women: 1 mg PO qd for 4 wk initially, may increase to 1 mg PO bid if qd dose does not control symptoms; discontinue if inadequate response to 1 mg bid after 4 wk
Men: Not established
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Substrate of CYP-450 isoenzymes 2C9, 3A4 (minor), and 1A2 (minor); coadministration with isoenzyme inhibitors (eg, cimetidine, fluvoxamine, fluoxetine, sertraline, metronidazole, omeprazole, co-trimoxazole) may decrease elimination and increase risk of toxicity; coadministration with isoenzyme inducers (eg, phenobarbital, fluconazole, carbamazepine, phenytoin) may increase clearance
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; history of constipation, intestinal obstruction, stricture, toxic megacolon, GI perforation, adhesions, ischemic colitis, impaired intestinal circulation, thrombophlebitis, hypercoagulable state, Crohn disease, ulcerative colitis, or diverticulitis
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue immediately if serious GI adverse events occur (eg, ischemic colitis, serious complications of constipation), these adverse effects have resulted in hospitalization, blood transfusion, surgery, and death; constipation is a dose-related adverse effect; elderly patients are more prone to the GI risks; caution in hepatic insufficiency (decrease dose); pharmacists may only dispense prescriptions that display a prescribing program sticker affixed by an enrolled clinician, and must distribute a copy of the FDA-approved medication guide with each prescription; to enroll in the prescribing program call GlaxoSmithKline at 1-888-825-5249 or visit www.Lotronex.com
Chloride-Channel Activator
These agents enhance chloride-rich intestinal fluid secretions without altering sodium and potassium concentrations in the serum.
Lubiprostone (Amitiza)
Activates chloride channels on the apical part of the small bowel epithelium. As a result, chloride ions are secreted. Sodium and water passively diffuse into the lumen to maintain isotonicity.
This medication is FDA approved for use in idiopathic constipation.
Studies have shown effectiveness over 12 weeks in patients with constipation-predominant IBS as well.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
24 mcg PO bid with food
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Data limited, none reported
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; history of mechanical GI obstruction; severe diarrhea
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include headache, nausea, diarrhea, abdominal pain, and abdominal distension; discontinue if diarrhea persists
Bulk-Forming Laxatives
May use these agents as fiber supplementation to improve symptoms of constipation and diarrhea. Use is controversial. These products are made of natural and semisynthetic hydrophilic polysaccharides and cellulose derivatives that dissolve or swell in the intestinal fluid, forming emollient gels that facilitate passage of intestinal contents and stimulate peristalsis.
Methylcellulose (Citrucel)
Promotes bowel evacuation by forming a viscous liquid and promoting peristalsis.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
1-2 wafers, 1-2 packets, or 1-2 rounded teaspoonfuls PO qd/tid dissolved in 240 mL of liquid
Pediatric
<6 years: Not recommended 6-12 years: 1/2-1 rounded teaspoonful PO qd/tid dissolved in 120 mL of liquid >12 years: Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
Psyllium may decrease absorption and thus effects of salicylates, nitrofurantoin, tetracyclines, and diuretics
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; fecal impaction, intestinal obstruction, undiagnosed abdominal pain
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Caution in patients diagnosed with intestinal adhesions, ulcers, or stenosis
Psyllium (Metamucil, Fiberall, Reguloid, Konsyl)
Promotes bowel evacuation by forming viscous liquid and inducing peristalsis.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
1-2 wafers, 1-2 packets, or 1-2 rounded teaspoonfuls PO qd/tid dissolved in 240 mL of liquid
Pediatric
<6 years: Not recommended 6-12 years: 1/2-1 rounded teaspoonful PO qd/tid dissolved in 120 mL of liquid >12 years: Administer as in adultsFollow-up
Further Outpatient Care
* Frequent visits with the clinician enhance the patient-provider relationship, especially in patients who were recently diagnosed with irritable bowel syndrome. Visits become less frequent as patients are educated and reassured.
Inpatient & Outpatient Medications
* Pharmacologic management of irritable bowel syndrome is an adjunct to psychological support and dietary modifications and should be directed at symptoms.
Deterrence/Prevention
* Deterrence of irritable bowel syndrome depends on patient avoidance of stressors and on development of coping mechanisms.
* No specific modalities completely prevent irritable bowel syndrome.
Complications
* No increased risk of developing an organic pathology exists in patients with irritable bowel syndrome.
Prognosis
* Irritable bowel syndrome is a chronic relapsing disorder characterized by recurrent symptoms of variable severity; however, life expectancy remains similar to that of the general population.
Patient Education
* Patient education remains the cornerstone of successful treatment of irritable bowel syndrome.
* Teach the patient to acknowledge stressors and to develop avoidance techniques.
* For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center and Muscle Disorders Center. Also, see eMedicine's patient education articles Irritable Bowel Syndrome, Inflammatory Bowel Disease, and Chronic Pain.
Miscellaneous
Medicolegal Pitfalls
* Failure to consider the possibility of coexistent organic pathology, especially in patients with atypical symptoms, is a potential pitfall.
* Failure to recognize suicidal ideation and/or depression would be detrimental. A study has suggested that patients with irritable bowel syndrome may have suicidal ideation and/or suicide attempts strictly as a result of their bowel symptoms.6 Clinical alertness to depression and hopelessness is mandatory. This is underscored by another study that revealed that patient complaints that relate to functional bowel disorders may be trivialized.
Background
Irritable bowel syndrome (IBS) is a functional GI disorder characterized by abdominal pain and altered bowel habits in the absence of specific and unique organic pathology. Osler coined the term mucous colitis in 1892 when he wrote of a disorder of mucorrhea and abdominal colic with a high incidence in patients with coincident psychopathology. Since that time, the syndrome has been referred to by sundry terms, including spastic colon, irritable colon, and nervous colon.
Traditionally, irritable bowel syndrome is a diagnosis of exclusion. No specific motility or structural correlates have been consistently demonstrated, so irritable bowel syndrome remains a clinically defined illness.
Manning and associates established 6 criteria to distinguish irritable bowel syndrome from organic bowel disease.1 Although historically important, these criteria are insensitive (58%), nonspecific (74%), and less reliable in men. The Manning criteria to distinguish irritable bowel syndrome from organic disease are as follows:
* Onset of pain associated with more frequent bowel movements
* Onset of pain associated with looser bowel movements
* Pain relieved by defecation
* Visible abdominal bloating
* Subjective sensation of incomplete evacuation more than 25% of the time
* Mucorrhea more than 25% of the time
More recently, a consensus panel created and then updated the Rome criteria to provide a standardized diagnosis for research and clinical practice. The Rome III criteria (2006) for the diagnosis of irritable bowel syndrome require that patients must have recurrent abdominal pain or discomfort at least 3 days per month during the previous 3 months that is associated with 2 or more of the following:
* Relieved by defecation
* Onset associated with a change in stool frequency
* Onset associated with a change in stool form or appearance
Supporting symptoms include the following:
* Altered stool frequency
* Altered stool form
* Altered stool passage (straining and/or urgency)
* Mucorrhea
* Abdominal bloating or subjective distention
Four bowel patterns may be seen with irritable bowel syndrome. These patterns include IBS-D (diarrhea predominant), IBS-C (constipation predominant), IBS-M (mixed diarrhea and constipation), and IBS-A (alternating diarrhea and constipation). The usefulness of these subtypes is debatable. Notably, within 1 year, 75% of patients change subtypes, and 29% switch between constipation-predominant IBS and diarrhea-predominant IBS.
Pathophysiology
Traditional theories regarding pathophysiology may be visualized as a 3-part complex of altered GI motility, visceral hyperalgesia, and psychopathology. A unifying mechanism is still unproven.
* Altered GI motility includes distinct aberrations in small and large bowel motility.
o The myoelectric activity of the colon is composed of background slow waves with superimposed spike potentials. Colonic dysmotility in irritable bowel syndrome manifests as variations in slow-wave frequency and a blunted, late-peaking, postprandial response of spike potentials. Patients who are prone to diarrhea demonstrate this disparity to a greater degree than patients who are prone to constipation.
o Small bowel dysmotility manifests in delayed meal transit in patients prone to constipation and in accelerated meal transit in patients prone to diarrhea. In addition, patients exhibit shorter intervals between migratory motor complexes (the predominant interdigestive small bowel motor patterns).
o Current theories integrate these widespread motility aberrations and hypothesize a generalized smooth muscle hyperresponsiveness. They describe increased urinary symptoms, including frequency, urgency, nocturia, and hyperresponsiveness to methacholine challenge.
* Visceral hyperalgesia is the second part of the traditional 3-part complex that characterizes irritable bowel syndrome.
o Enhanced perception of normal motility and visceral pain characterizes irritable bowel syndrome. Rectosigmoid and small bowel balloon inflation produces pain at lower volumes in patients than in controls. Notably, hypersensitivity appears with rapid but not gradual distention.
o Patients who are affected describe widened dermatomal distributions of referred pain.
o Sensitization of the intestinal afferent nociceptive pathways that synapse in the dorsal horn of the spinal cord provides a unifying mechanism.
* Psychopathology is the third aspect.
o Associations between psychiatric disturbances and irritable bowel syndrome pathogenesis are not clearly defined.
o Patients with psychological disturbances relate more frequent and debilitating illness than control populations.
o Patients who seek medical care have a higher incidence of panic disorder, major depression, anxiety disorder, and hypochondriasis than control populations.
o An Axis I disorder coincides with the onset of GI symptoms in as many as 77% of patients.
o A higher prevalence of physical and sexual abuse has been demonstrated in patients with irritable bowel syndrome.
o Whether psychopathology incites development of irritable bowel syndrome or vice versa remains unclear.
* Microscopic inflammation has been documented in some patients. This concept is groundbreaking in that irritable bowel syndrome had previously been considered to have no demonstrable pathologic alterations.
o Both colonic inflammation and small bowel inflammation have been discovered in a subset of patients with irritable bowel syndrome as well as in patients with inception of irritable bowel syndrome after infectious enteritis (postinfectious irritable bowel syndrome). Risk factors for developing postinfectious irritable bowel syndrome include female gender, longer duration of illness, the type of pathogen involved, an absence of vomiting during the infectious illness, and young age.
o Laparoscopic full-thickness jejunal biopsy samples revealed infiltration of lymphocytes into the myenteric plexus and intraepithelial lymphocytes in a subset of patients. Neuronal degeneration of the myenteric plexus was also present in some patients.
o Patients with postinfectious irritable bowel syndrome may have increased numbers of colonic mucosal lymphocytes and enteroendocrine cells.
o Enteroendocrine cells in postinfectious irritable bowel syndrome appear to secrete high levels of serotonin, increasing colonic secretion and possibly leading to diarrhea.
* Small bowel bacterial overgrowth has been heralded as a unifying mechanism for the symptoms of bloating and distention common to patients with irritable bowel syndrome. This has led to proposed treatments with probiotics and antibiotics.
* The fecal microflora also differs among patients with irritable bowel syndrome versus controls. A sophisticated molecular analysis suggested an alteration in the patterns and the contents of gut bacteria.2
Frequency
United States
Population-based studies estimate the prevalence of irritable bowel syndrome at 10-20% and the incidence of irritable bowel syndrome at 1-2% per year. Of people with irritable bowel syndrome, approximately 10-20% seek medical care. An estimated 20-50% of gastroenterology referrals relate to this symptom complex.
International
The incidence is markedly different among countries.
Mortality/Morbidity
* Irritable bowel syndrome is a chronic relapsing condition. Clinicians must be forthcoming with patients because knowledge may help allay undue fears as their disease waxes and wanes. Irritable bowel syndrome does not increase the mortality or the risk of inflammatory bowel disease or cancer.
* The principal associated physical morbidities of irritable bowel syndrome include abdominal pain and lifestyle modifications secondary to altered bowel habits.
* Work absenteeism resulting in lost wages is more frequent in patients with irritable bowel syndrome.
Race
* American and European cultures demonstrate similar frequencies of irritable bowel syndrome across racial and ethnic lines. However, within the United States, survey questionnaires indicate a lower prevalence of irritable bowel syndrome in Hispanics in Texas and Asians in California.
* Populations of Asia and Africa may have a lower prevalence of irritable bowel syndrome.
* The role of different cultural influences and varying health care–seeking behaviors is unclear.
Sex
In Western countries, women are 2-3 times more likely to develop irritable bowel syndrome than men, although males represent 70-80% of patients with irritable bowel syndrome in the Indian subcontinent. Women seek health care more often, but the irritable bowel syndrome-specific influence of this occurrence remains unknown. Other factors, such as a probably greater incidence of abuse in women, may confound interpretation of this statistic.
Age
* Patients often retrospectively note the onset of abdominal pain and altered bowel habits in childhood.
* Approximately 50% of people with irritable bowel syndrome report symptoms beginning before they were aged 35 years.
* The development of symptoms in people older than 40 years does not exclude irritable bowel syndrome but should prompt a closer search for an underlying organic etiology.
Clinical
History
A meticulous history is the key to establish a diagnosis of irritable bowel syndrome. The Rome criteria provide the construct upon which questions are based (see Background).
Symptoms consistent with irritable bowel syndrome include the following:
* Altered bowel habits
o Constipation variably results in complaints of hard stools of narrow caliber, painful or infrequent defecation, and intractability to laxatives.
o Diarrhea usually is described as small volumes of loose stool, with evacuation preceded by urgency or frequent defecation.
o Postprandial urgency is common.
o Alternating habits are common. Characteristically, one feature predominates in a single patient, but significant variability exists among patients.
* Abdominal pain
o Descriptions are protean. Pain frequently is diffuse without radiation. Common sites of pain include the lower abdomen, specifically the left lower quadrant.
o Acute episodes of sharp pain are often superimposed on a more constant dull ache.
o Meals may precipitate pain, and defecation commonly improves pain. Defecation may not fully relieve pain.
o Pain from presumed gas pockets in the splenic flexure may masquerade as anterior chest pain or left upper quadrant abdominal pain. This splenic flexure syndrome is demonstrable by balloon inflation in the splenic flexure and should be considered in the differential of chest or left upper quadrant abdominal pain.
* Abdominal distention
o Patients frequently report increased amounts of bloating and gas. Quantitative measurements fail to support this claim.
o People with irritable bowel syndrome may manifest increasing abdominal circumference throughout the day, as assessed by CT scan. They may also demonstrate intolerance to otherwise normal amounts of abdominal distention.
* Clear or white mucorrhea of a noninflammatory etiology is commonly reported.
* Noncolonic and extraintestinal symptoms
o Epidemiologic associations with dyspepsia, heartburn, nausea, vomiting, sexual dysfunction (including dyspareunia and poor libido), and urinary frequency and urgency have been noted.
o Symptoms may worsen in the perimenstrual period.
o Fibromyalgia is a common comorbidity.
* Stressor-related symptoms
o These symptoms may be revealed with careful questioning.
o Emphasize avoidance of stressors.
* Inconsistent symptoms are an alert to the possibility of an organic pathology. Symptoms not consistent with irritable bowel syndrome include the following:
o Onset in middle age or older
o Acute symptoms: Irritable bowel syndrome is defined by chronicity.
o Progressive symptoms
o Nocturnal symptoms
o Anorexia or weight loss
o Fever
o Rectal bleeding
o Painless diarrhea
o Steatorrhea
o Lactose and/or fructose intolerance
o Gluten intolerance
Physical
* The patient has an overall healthy appearance.
* The patient may be tense or anxious.
* The patient may present with sigmoid tenderness or a palpable sigmoid cord.
Causes
The causes of irritable bowel syndrome remain poorly defined, but they are being avidly researched.
* Postulated etiologies of irritable bowel syndrome
o Abnormal transit profiles and an enhanced perception of normal motility may exist.
o Up to one third of patients with irritable bowel syndrome may have altered colonic transit. Delayed colonic motility may be more common in IBS-C versus healthy controls. Similarly, accelerated colonic transit may be more common in IBS-D versus healthy controls.3
o Local histamine sensitization of the afferent neuron causing earlier depolarization may occur.
* Causes related to enteric infection (see Pathophysiology)
o Colonic muscle hyperreactivity and neural and immunologic alterations of the colon and small bowel may persist after gastroenteritis.
o Psychological comorbidity independently predisposes the patient to the development of postinfectious irritable bowel syndrome.
o Psychological illness may create a proinflammatory cytokine milieu, leading to irritable bowel syndrome through an undefined mechanism after acute infection.
* Central neurohormonal mechanisms
o Abnormal glutamate activation of N- methyl-D- aspartate (NMDA) receptors, activation of nitric oxide synthetase, activation of neurokinin receptors, and induction of calcitonin gene-related peptide have been observed.
o The limbic system mediation of emotion and autonomic response enhances bowel motility and reduces gastric motility to a greater degree in patients who are affected than in controls. Limbic system abnormalities, as demonstrated by positron emission tomography, have been described in patients with irritable bowel syndrome and in those with major depression.
o The hypothalamic-pituitary axis may be intimately involved in the origin. Motility disturbances correspond to an increase in hypothalamic corticotropin-releasing factor (CRF) production in response to stress. CRF antagonists eliminate these changes.
* As discussed in Pathophysiology, Pimentel and colleagues have proposed that small bowel bacterial overgrowth provides a unifying mechanism for the common symptoms of bloating and gaseous distention in patients with irritable bowel syndrome.4
* Bloating and distention may also occur from intolerance to dietary fats. Reflex-mediated small bowel gas clearance is more impaired by lipids (fat) ingestion in patients with irritable bowel syndrome versus patients without irritable bowel syndrome.
* Recent elimination and challenge diets have suggested that poorly absorbed short-chain carbohydrates, in the form of fructose and fructans, may create symptoms among patients with irritable bowel syndrome, as measured by a visual analogue scale.Differential Diagnoses
Abdominal Angina
Hypothyroidism
Anxiety Disorders
Inflammatory Bowel Disease
Bacterial Overgrowth Syndrome
Lactose Intolerance
Biliary Colic
Malignant Neoplasms of the Small Intestine
Biliary Disease
Mesenteric Artery Thrombosis
Celiac Sprue
Mesenteric Venous Thrombosis
Chronic Mesenteric Ischemia
Pancreatic Cancer
Collagenous and Lymphocytic Colitis
Pancreatitis, Chronic
Colon Cancer, Adenocarcinoma
Pheochromocytoma
Endometriosis
Porphyria, Acute Intermittent
Food Allergies
Postcholecystectomy Syndrome
Gastroenteritis, Bacterial
Somatostatinomas
Gastroenteritis, Viral
Toxicity, Lead
Giardiasis
Ulcerative Colitis
Hypercalcemia
Hyperthyroidism
Other Problems to Be Considered
Fructose intolerance
Gastrinoma
Infectious colitis
Medication adverse effects
Secretory diarrhea
VIPoma
Workup
Laboratory Studies
* A comprehensive history, a physical examination, and tailored laboratory and radiographic studies can establish a diagnosis of irritable bowel syndrome in most patients.
* Lab studies may include the following:
o CBC count with differential to screen for anemia, inflammation, and infection
o A comprehensive metabolic panel to evaluate for metabolic disorders and to rule out dehydration/electrolyte abnormalities in patients with diarrhea
* Gastrointestinal bleeding should be ruled out. A hemoccult test may be useful.
* Microbiologic studies to consider include the following stool examinations:
o Ova and parasites: Consider obtaining specimens for Giardia antigen as well.
o Enteric pathogens
o Leukocytes
o Clostridium difficile toxin
* The following selected studies are directed by history:
o Breath testing: Screen for lactose and/or fructose intolerance.
o Thyroid function tests: Screen for hyperthyroidism or hypothyroidism.
o Serum calcium: Screen for hyperparathyroidism.
o Erythrocyte sedimentation rate or C-reactive protein: This is a nonspecific screening test for inflammation.
o Serologies or small bowel biopsy for celiac disease: Consider, especially in diarrhea-predominant IBS.
* H2 breath test to exclude bacterial overgrowth may be considered in patients with diarrhea.
Imaging Studies
* The following selected studies are directed by history:
o Upper GI barium study with small bowel follow-through: Screen for tumor, inflammation, obstruction, and Crohn disease.
o Double-contrast barium enema: Screen for neoplasm and inflammation.
o Gallbladder ultrasonography: Consider this test if the patient has recurrent dyspepsia or characteristic postprandial pain.
o Abdominal CT scan: Screen for tumors, obstruction, and pancreatic disease.
Other Tests
* Direct a lactose-free diet for 1 week in conjunction with lactase supplements. Improvement incriminates lactose intolerance, although the patient's clinical history and response to a trial may be unreliable. Therefore, some gastroenterologists recommend a formal hydrogen breath test. Fructose intolerance must also be considered.
* Direct a 48-hour fast. Persistent diarrhea suggests a secretory etiology.
* Anal manometry may reveal spastic response to rectal distention or other problems.
Procedures
* Endoscopy directed for many patients with irritable bowel syndrome includes flexible sigmoidoscopy to determine inflammation or distal obstruction.
* The following selected studies are directed by history:
o Esophagogastroduodenoscopy with possible biopsy - Indicated for a patient with persistent dyspepsia or if weight loss or symptoms suggest malabsorption or if celiac disease is a concern
o Colonoscopy - Indicated for patients with warning signs, such as bleeding; anemia; chronic diarrhea; older age; history of colon polyps; cancer in the patient or first-degree relatives; or constitutional symptoms, such as weight loss or anorexia. A screening colonoscopy should be performed according to published guidelines.
Histologic Findings
Research suggests that neuronal degeneration and myenteric plexus lymphocytosis may exist in the proximal jejunum. Additionally, colonic lymphocytosis and enteroendocrine cell hyperplasia have been demonstrated in some patients.Treatment
Medical Care
* Successful management relies on a strong patient-provider relationship.
* Reassure the patient that the absence of an organic pathology indicates a normal life expectancy.
* Emphasize the expected chronicity of symptoms with periodic exacerbations.
* Teach the patient to acknowledge stressors and to use avoidance techniques.
Consultations
* Consider psychiatric referral. Previous evidence has supported improvement in GI symptoms with successful treatment of psychiatric comorbidities, but 2 studies indicate caution should be used when interpreting such data.
* Zijdenbos et al conducted a meta-analysis of 25 randomized trials consisting of single psychologic interventions with usual care or mock intervention in patients older than 16 years for the years 1966-2008.{Ref44} The treatment modalities evaluated were psychologic interventions as a group and cognitive behavioral therapy (measuring improvements in abdominal pain and quality of life, relative to usual care and placebo); interpersonal psychotherapy; and relaxation/stress management. Long-term results were also assessed. The investigators noted that differences among studies and quality issues made drawing conclusions difficult; however, they suggested that although cognitive behavioral therapy and interpersonal psychotherapy may be effective immediately post treatment completion, there was no convincing evidence for sustained treatment effects after completion of treatment for any treatment modality. Thus, Zijdenbos et al recommended that future research should focus on current IBS treatment guidelines and their long-term effects.44
* Ford et al reached similar conclusions regarding the use of psychologic interventions in IBS. They also performed a systematic review and meta-analysis of randomized controlled trials (up to May 2008) in adults with IBS; however, their selection criteria included trials comparing antidepressants with placebo as well as those comparing psychologic therapies with control therapy or usual care.45 The investigators noted that the quality of studies were generally good for those involving antidepressants but poor for those involving psychologic therapy. Ford et al concluded that antidepressants are effective for IBS treatment, but despite the fact that the available data suggest psychologic therapies may be of comparable efficacy, there is less high-quality evidence for the routine use of psychologic therapies in patients with IBS.45
Diet
* Fiber supplementation may improve symptoms of constipation and diarrhea. Individualize the treatment because few patients experience exacerbated bloating and distention with high-fiber diets. Polycarbophil compounds (eg, Citrucel, FiberCon) may produce less flatulence than psyllium compounds (eg, Metamucil).
* The data regarding the effectiveness of fiber are controversial because 40-70% of patients improve with placebo.
* Judicious water intake in patients who predominantly experience constipation is recommended.
* Caffeine avoidance may limit anxiety and symptom exacerbation.
* Legume avoidance may decrease abdominal bloating.
* Lactose and/or fructose should be limited or avoided in patients with these contributing disorders. Take care to supplement calcium in patients limiting lactose intake.
Activity
No limitation is recommended.
Medication
The selection of pharmacologic treatment remains symptom directed.
The nonabsorbed antibiotic rifaximin (<0.4%) is a broad-spectrum antibiotic specific for enteric pathogens (ie, gram-positive, gram-negative, aerobic and anaerobic) of the GI tract. Rifaximin is a structural analog. It binds to a beta-subunit of bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis. It is indicated for Escherichia coli (enterotoxigenic and enteroaggregative strains) associated with travelers' diarrhea. Rifaximin has been studied in patients with irritable bowel syndrome and is believed to improve the symptoms of bloating, diarrhea, abdominal pain, and constipation. Anticholinergics Are antispasmodics that inhibit intestinal smooth-muscle depolarization at the muscarinic receptor. Dicyclomine hydrochloride (Bentyl) This drug decreases fecal urgency and pain. It is useful with diarrhea-predominant symptoms. Blocks the action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and CNS. Adverse effects are dose dependent. * Dosing * Interactions * Contraindications * Precautions Adult 10-40 mg PO qid ac or at onset of pain Pediatric Not established * Dosing * Interactions * Contraindications * Precautions May increase anticholinergic effects with concurrent administration of amantadine, class I antiarrhythmics, antihistamines, antipsychotics, benzodiazepines, MAOIs, narcotics, nitrates, sympathomimetics, and tricyclic antidepressants; dicyclomine may increase serum digoxin concentration; antacids may interfere with absorption of dicyclomine * Dosing * Interactions * Contraindications * Precautions Documented hypersensitivity; obstructive uropathy; myasthenia gravis; glaucoma; GI tract obstruction; paralytic ileus; toxic megacolon * Dosing * Interactions * Contraindications * Precautions Pregnancy B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals Precautions Caution when administering to patients with hepatic or renal insufficiency, cardiovascular disease, urinary tract obstruction, ulcerative colitis, GI obstruction, hyperthyroidism, or hypertension; may cause sedation, constipation, urinary retention, tachycardia, blurred vision, xerostomia, or dizziness Hyoscyamine sulfate (Levsin) Blocks action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS, which, in turn, has antispasmodic effects. Decreases fecal urgency and pain. Useful with diarrhea-predominant symptoms. * Dosing * Interactions * Contraindications * Precautions Adult 0.125-0.25 mg PO q4h or prn; not to exceed 1.5 mg/d (12 tab/d) Pediatric <2 years: Not recommended 2-12 years: 0.0625-0.125 mg (1/2-1 tab) PO q4h or prn; not to exceed 0.75 mg/d (6 tab/d) >2 years: Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
May increase anticholinergic effects with amantadine, class I antiarrhythmics, antihistamines, antipsychotics, benzodiazepines, MAOIs, narcotics, nitrates, sympathomimetics, and tricyclic antidepressants; may increase serum digoxin concentration; antacids may interfere with absorption
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; obstructive uropathy; myasthenia gravis; glaucoma; GI tract obstruction; paralytic ileus; toxic megacolon
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in elderly patients; some products contain sodium metabisulfite, which can cause allergic-type reactions; may cause sedation, constipation, urinary retention, tachycardia, blurred vision, xerostomia, or dizziness
Antidiarrheals
Are nonabsorbable synthetic opioids. They prolong GI transit time and decrease secretion via peripheral ยต-opioid receptors. They reduce visceral nociception via afferent pathway inhibition.
Diphenoxylate hydrochloride 2.5 mg with atropine sulfate 0.025 mg (Lomotil)
Drug combination that consists of diphenoxylate, which is a constipating meperidine congener, and atropine to discourage abuse. Inhibits excessive GI propulsion and motility. It may exacerbate constipation.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
1-2 tab PO qid ac
Pediatric
<2 years: Not recommended 2-5 years: 2 mg PO tid 5-8 years: 2 mg PO qid 8-12 years: 2 mg PO 5 times/d >12 years: Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
May delay metabolism of drugs in liver; CNS depressants, MAOIs, and antimuscarinic agents may increase toxicity of this drug combination; diphenoxylate HCl may potentiate the action of barbiturates, tranquilizers, and alcohol; atropine sulfate interacts with MAOIs
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; narrow-angle glaucoma; hepatic insufficiency; advanced hepatorenal disease; pseudomembranous colitis; enterotoxigenic infections
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
In young children, dehydration may influence variability of response and predispose patient to delayed diphenoxylate intoxication; caution in patients with ulcerative colitis; a decrease in intestinal motility may be detrimental to patients with diarrhea resulting from Shigella, Salmonella, and toxigenic strains of E coli; may cause sedation, constipation, urinary retention, tachycardia, blurred vision, xerostomia, dizziness, or respiratory depression
Loperamide (Imodium)
Acts on intestinal muscles to inhibit peristalsis and to slow intestinal motility. Prolongs movement of electrolytes and fluid through bowel and increases viscosity and loss of fluids and electrolytes. Available over the counter. Improves stool frequency and consistency, reduces abdominal pain and fecal urgency, and may exacerbate constipation.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
4 mg PO after first loose stool initially; then 2 mg after each subsequent stool; not to exceed 16 mg/d
Pediatric
Maintenance: 0.1 mg/kg PO after each loose stool, not to exceed initial dose
Chronic diarrhea: 0.08-0.24 mg/kg/d divided bid/tid; not to exceed 2 mg/dose
* Dosing
* Interactions
* Contraindications
* Precautions
Phenothiazines, tricyclic antidepressants, and CNS depressants may increase loperamide toxicity
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; diarrhea resulting from infections; pseudomembranous colitis
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue use if no clinical improvement in 48 h; because loperamide primarily metabolized in liver, monitor for CNS toxicity in patients with hepatic insufficiency; do not use medication if high fever or blood in stool coincides with diarrhea
Tricyclic Antidepressants
Provide antidepressive and analgesic properties. Various agents have efficacy; much research has concentrated on imipramine and amitriptyline (off-label use).
Imipramine (Tofranil)
This drug provides a visceral analgesic effect by increasing pain threshold in the gut. It prolongs oral-cecal transit time, reduces abdominal pain, mucorrhea, and stool frequency, and increases global well being variably in studies. The effect at doses subtherapeutic for antidepressive actions suggests an independent mechanism.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
10-100 mg/d PO; start low and titrate as necessary
Pediatric
Not recommended
* Dosing
* Interactions
* Contraindications
* Precautions
Increases toxicity of sympathomimetic agents, such as isoproterenol and epinephrine, by potentiating effects and inhibiting antihypertensive effects of clonidine
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; narrow-angle glaucoma; in acute recovery phase following myocardial infarction; avoid in patients taking MAOIs or fluoxetine or in patients who took them in the previous 2 weeks
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May impair mental or physical abilities required for performance of potentially hazardous tasks; caution in cardiovascular disease, seizure disorders, urinary retention, hyperthyroidism, or receiving thyroid replacement; may cause sedation, confusion, constipation, tachycardia, AV conduction delay, orthostasis, blurred vision, xerostomia
Amitriptyline (Elavil)
This drug provides a visceral analgesic effect by increasing pain threshold in the gut. Prolongs oral-cecal transit time, reduces abdominal pain, mucorrhea, and stool frequency, and increases global well-being variably in studies. The effect at doses subtherapeutic for antidepressive actions suggests an independent mechanism.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
10-100 mg/d PO; start low and titrate as necessary
Pediatric
Not recommended
* Dosing
* Interactions
* Contraindications
* Precautions
Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase amitriptyline levels; amitriptyline inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; patient has taken MAOIs in past 14 d; history of seizures, cardiac arrhythmias, glaucoma, or urinary retention
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in cardiac conduction disturbances, history of hyperthyroidism, and renal or hepatic impairment; avoid using in elderly persons; may cause sedation, confusion, constipation, urinary retention, tachycardia, AV conduction delay, orthostasis, blurred vision, xerostomia, or dizziness; may provoke psychosis in schizophrenics
Prokinetics
Are promotility agents, proposed for use with constipation-predominant symptoms. Unfortunately, cisapride availability is restricted in the United States, and other motility agents, such as metoclopramide, domperidone, and erythromycin, have not yielded consistent benefits in patients with irritable bowel syndrome.
Tegaserod marketing 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. The treatment IND protocol will allow 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.
In early 2007, tegaserod marketing was suspended because of a meta-analysis of safety data pooled from 29 clinical trials that involved more than 18,000 patients. The results showed an excess number of serious cardiovascular adverse events, including angina, myocardial infarction, and stroke, in those taking tegaserod compared with placebo. In each study, patients were assigned at random to either tegaserod or placebo. Tegaserod was taken by 11,614 patients, and placebo was taken by 7,031 patients. The average age of patients in these studies was 43 years, and most patients (ie, 88%) were women. Serious and life-threatening cardiovascular adverse effects occurred in 13 patients (0.1%) treated with tegaserod; among these, 4 patients had a heart attack (1 died), 6 had unstable angina, and 3 had a stroke. Among the patients taking placebo, only 1 (0.01%) had symptoms suggesting the beginning of a stroke that went away without complication.
For more information, see the FDA MedWatch Product Safety Alert.
Cisapride monohydrate (Propulsid)
Available only through an investigational limited access program by Janssen Pharmaceutical. Perform 12-lead ECG prior to administration, and do not initiate treatment if QTc value exceeds 450 milliseconds. This information is maintained for those who can acquire cisapride through this program. This is a serotonin receptor agonist (5-HT4) and antagonist (5-HT3) that promotes acetylcholine release at the myenteric plexus. Accelerates GI transit, thus increasing stool frequency and improving consistency.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
5-20 mg PO qac and hs 15-30 min ac
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Fatal ventricular arrhythmia in conjunction with other medications that inhibit cytochrome P-450 3A4 (certain macrolide antibiotics, antifungals, antidepressant, protease inhibitors, antipsychotics, class IA and III antiarrhythmics)
* Dosing
* Interactions
* Contraindications
* Precautions
Concomitant administration of medications is metabolized by cytochrome P-450; do not use in GI hemorrhage, mechanical bowel obstruction, or perforation in which enhanced GI motility may be harmful; do not use if QT interval exceeds 450 milliseconds; avoid in hypokalemia, hypocalcemia, and hypomagnesemia
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Potentiates the sedative effects of benzodiazepines and alcohol
Tegaserod (Zelnorm)
Available in US by restricted treatment IND for irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. Used for the treatment of women with irritable bowel syndrome when constipation is the predominant symptom. A selective partial agonist of the serotonin-4 (5HT4) receptor and possesses GI prokinetic activity. Tegaserod has been shown to promote clearance of gas in the small bowel.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Women: 6 mg PO bid 30 min ac for 4-6 wk; in patients who respond to treatment, an additional 4-6 wk of therapy may be considered
Men: Not established
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
None reported
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; moderate or severe renal impairment; history of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
In April 2004, in response to postmarketing reports, the FDA issued an advisory regarding serious side effects of tegaserod use; the advisory indicates that severe diarrhea with dehydration requiring hospitalization, syncope and hypotension, and intestinal ischemia, have been reported with tegaserod use; tegaserod should not be used in patients with diarrhea and should be discontinued if any signs or symptoms of these complications arise
Serotonin (5-HT3) Receptor Antagonists
Inhibit activation of nonselective cation channels, which modulate the enteric nervous system.
Alosetron (Lotronex)
A potent and selective antagonist of the serotonin 5-HT3 receptor type. 5-HT3 receptors are extensively located on enteric neurons of the GI tract, and stimulation causes hypersensitivity and hyperactivity of the intestine. Alosetron blocks these receptors and thus is effective in controlling irritable bowel syndrome symptoms. It is approved only for treatment of women with severe chronic diarrhea-predominant IBS who have not responded to conventional irritable bowel syndrome therapy. Fewer than 5% of irritable bowel syndrome cases are considered severe, and only a fraction of severe cases are diarrhea-predominant IBS. Limiting its use to this severely affected population is intended to maximize the benefit-to-risk ratio. The drug was previously removed from the US market but was reintroduced with new restrictions approved by the FDA on June 7, 2002. Restrictions are because of serious and unpredictable GI adverse events (including some that resulted in death) reported in association with its use following its original approval in February 2000.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Women: 1 mg PO qd for 4 wk initially, may increase to 1 mg PO bid if qd dose does not control symptoms; discontinue if inadequate response to 1 mg bid after 4 wk
Men: Not established
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Substrate of CYP-450 isoenzymes 2C9, 3A4 (minor), and 1A2 (minor); coadministration with isoenzyme inhibitors (eg, cimetidine, fluvoxamine, fluoxetine, sertraline, metronidazole, omeprazole, co-trimoxazole) may decrease elimination and increase risk of toxicity; coadministration with isoenzyme inducers (eg, phenobarbital, fluconazole, carbamazepine, phenytoin) may increase clearance
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; history of constipation, intestinal obstruction, stricture, toxic megacolon, GI perforation, adhesions, ischemic colitis, impaired intestinal circulation, thrombophlebitis, hypercoagulable state, Crohn disease, ulcerative colitis, or diverticulitis
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue immediately if serious GI adverse events occur (eg, ischemic colitis, serious complications of constipation), these adverse effects have resulted in hospitalization, blood transfusion, surgery, and death; constipation is a dose-related adverse effect; elderly patients are more prone to the GI risks; caution in hepatic insufficiency (decrease dose); pharmacists may only dispense prescriptions that display a prescribing program sticker affixed by an enrolled clinician, and must distribute a copy of the FDA-approved medication guide with each prescription; to enroll in the prescribing program call GlaxoSmithKline at 1-888-825-5249 or visit www.Lotronex.com
Chloride-Channel Activator
These agents enhance chloride-rich intestinal fluid secretions without altering sodium and potassium concentrations in the serum.
Lubiprostone (Amitiza)
Activates chloride channels on the apical part of the small bowel epithelium. As a result, chloride ions are secreted. Sodium and water passively diffuse into the lumen to maintain isotonicity.
This medication is FDA approved for use in idiopathic constipation.
Studies have shown effectiveness over 12 weeks in patients with constipation-predominant IBS as well.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
24 mcg PO bid with food
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Data limited, none reported
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; history of mechanical GI obstruction; severe diarrhea
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include headache, nausea, diarrhea, abdominal pain, and abdominal distension; discontinue if diarrhea persists
Bulk-Forming Laxatives
May use these agents as fiber supplementation to improve symptoms of constipation and diarrhea. Use is controversial. These products are made of natural and semisynthetic hydrophilic polysaccharides and cellulose derivatives that dissolve or swell in the intestinal fluid, forming emollient gels that facilitate passage of intestinal contents and stimulate peristalsis.
Methylcellulose (Citrucel)
Promotes bowel evacuation by forming a viscous liquid and promoting peristalsis.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
1-2 wafers, 1-2 packets, or 1-2 rounded teaspoonfuls PO qd/tid dissolved in 240 mL of liquid
Pediatric
<6 years: Not recommended 6-12 years: 1/2-1 rounded teaspoonful PO qd/tid dissolved in 120 mL of liquid >12 years: Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
Psyllium may decrease absorption and thus effects of salicylates, nitrofurantoin, tetracyclines, and diuretics
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; fecal impaction, intestinal obstruction, undiagnosed abdominal pain
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Caution in patients diagnosed with intestinal adhesions, ulcers, or stenosis
Psyllium (Metamucil, Fiberall, Reguloid, Konsyl)
Promotes bowel evacuation by forming viscous liquid and inducing peristalsis.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
1-2 wafers, 1-2 packets, or 1-2 rounded teaspoonfuls PO qd/tid dissolved in 240 mL of liquid
Pediatric
<6 years: Not recommended 6-12 years: 1/2-1 rounded teaspoonful PO qd/tid dissolved in 120 mL of liquid >12 years: Administer as in adultsFollow-up
Further Outpatient Care
* Frequent visits with the clinician enhance the patient-provider relationship, especially in patients who were recently diagnosed with irritable bowel syndrome. Visits become less frequent as patients are educated and reassured.
Inpatient & Outpatient Medications
* Pharmacologic management of irritable bowel syndrome is an adjunct to psychological support and dietary modifications and should be directed at symptoms.
Deterrence/Prevention
* Deterrence of irritable bowel syndrome depends on patient avoidance of stressors and on development of coping mechanisms.
* No specific modalities completely prevent irritable bowel syndrome.
Complications
* No increased risk of developing an organic pathology exists in patients with irritable bowel syndrome.
Prognosis
* Irritable bowel syndrome is a chronic relapsing disorder characterized by recurrent symptoms of variable severity; however, life expectancy remains similar to that of the general population.
Patient Education
* Patient education remains the cornerstone of successful treatment of irritable bowel syndrome.
* Teach the patient to acknowledge stressors and to develop avoidance techniques.
* For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center and Muscle Disorders Center. Also, see eMedicine's patient education articles Irritable Bowel Syndrome, Inflammatory Bowel Disease, and Chronic Pain.
Miscellaneous
Medicolegal Pitfalls
* Failure to consider the possibility of coexistent organic pathology, especially in patients with atypical symptoms, is a potential pitfall.
* Failure to recognize suicidal ideation and/or depression would be detrimental. A study has suggested that patients with irritable bowel syndrome may have suicidal ideation and/or suicide attempts strictly as a result of their bowel symptoms.6 Clinical alertness to depression and hopelessness is mandatory. This is underscored by another study that revealed that patient complaints that relate to functional bowel disorders may be trivialized.
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