MEDLINE Abstracts: Functional Gastrointestinal Disorders: Approach to Management
MEDLINE Abstracts: Functional Gastrointestinal Disorders: Approach to Management
Camilleri M
Aliment Pharmacol Ther 13(Suppl 2):48-53, 1999 May
This review summarizes the clinical evidence to support current therapies in irritable bowel syndrome (IBS). Fibre is indicated at a dose of at least 12 g per day in patients with constipation-predominant IBS. Loperamide (and probably other opioid agonists) are of proven benefit in diarrhoea-predominant IBS; loperamide may also aid continence by enhancing resting anal tone. In general, smooth muscle relaxants are best used sparingly, on an 'as needed' basis, as their overall efficacy is unclear. Psychotropic agents are important in relieving depression and of proven benefit for pain and diarrhoea in patients with depression associated with IBS. Further trials with selective serotonin reuptake inhibitors (SSRIs) are awaited. Psychological treatments including hypnotherapy are less widely available, but may play an important role in relief of pain. In summary, current therapies targeted on the predominant symptoms in IBS are moderately successful. New therapies are needed to more effectively relieve this syndrome, not just symptoms.
Drossman DA
Aliment Pharmacol Ther 13(Suppl 2):3-14, 1999 May
Our understanding of the pathophysiology of irritable bowel syndrome (IBS) has evolved from a disorder of motility to a more integrated understanding of enhanced motility and visceral hypersensitivity associated with brain-gut dysfunction. Psychosocial factors contribute to the predisposition, precipitation and perpetuation of IBS symptoms, and affect the clinical outcome. Newer brain imaging techniques (e.g. PET, fMRI) may help us understand the relationship between altered emotional states with pain enhancement and other gastrointestinal symptoms. Diagnosis using symptom-based (e.g. Rome) criteria and a conservative diagnostic approach is recommended. Treatment is based on an effective physician-patient relationship and a combined pharmacological and behavioural approach. Newer medications acting at the 5-HT receptor may help in reducing pain and bowel dysfunction. For more severe pain, antidepressants may be considered.
Mollen RM, Salvioli B, Camilleri M, Burton D, Kost LJ, Phillips SF, Pemberton JH
Am J Gastroenterol 94(3):751-6, 1999 Mar
Objective: Abnormalities of descending colon motility reported in a subset of patients with rectal evacuation disorders are consistent with a rectocolonic inhibitory reflex. Our aims were to evaluate distal colon motor function and rectal sensation in such patients and assess effects of biofeedback (BF) training on these functions.
Methods: Seven patients (five women, two men; mean age 36 yr) with rectal evacuation disorders were studied before and after 10-days biofeedback training; six healthy volunteers (five women, one man; mean age 30 yr) were studied once. Colonic compliance, motility, sensation thresholds, and perception scores during standardized rectal distentions were measured using two barostat-manometry assemblies inserted into the cleansed colon with the aid of flexible sigmoidoscopy.
Results: Sigmoid compliance, fasting, and postprandial motility index, and perception thresholds were similar in controls and patients before and after biofeedback training. Postprandial sigmoid tone tended (p = 0.09) to be lower in patients than controls; after biofeedback, postprandial tone was comparable to that in controls. Rectal urgency scores at 24 mm Hg distention were greater in patients than in controls (p = 0.02 for both). After biofeedback, there were trends for lower perceptions of urgency to defecate (7.6 +/- 1.1 cm pre- vs 5.3 +/- 1.5 post-; p = 0.04) at 24 mm Hg; conversely, gas sensation at 12 mm Hg was higher (1.2 +/- 0.5 cm pre- vs 3.3 +/- 0.6 post-; p = 0.05).
Conclusions: Normalization of rectal evacuation and postprandial sigmoid tone in patients with evacuation disorders by biofeedback training supports the presence of a rectocolonic inhibitory reflex. Effect of biofeedback on rectal sensation in these patients requires further study.
Camilleri M
Can J Gastroenterol 13(Suppl A):8A-11A, 1999 Mar
The evidence supporting a role of abnormal motor function in irritable bowel syndrome (IBS) is reviewed. Symptoms commonly present in IBS patients, such as vomiting, diarrhea, constipation or incomplete rectal evacuation, indicate that a motor disorder is implicit as either a primary or secondary disturbance. Physiological studies implicate a disturbance of transit through the small bowel and proximal colon, and abnormal motor responses of the rectum to distention in IBS patients. Intestinal contractions (physiological or 'abnormal') are associated with the sensation of pain, suggesting that these contractions are interactions between abnormal motor and sensory functions in IBS. Therapies aimed at correcting abnormal transit or antispasmodics are the main pharmacological approaches to the relief of IBS, and, although the latter are not always effective in the long term response to treatment, they support the role of dysmotility in IBS. Most novel therapies under trial probably modulate both sensory and motor functions, and are discussed briefly. In summary, the weight of clinical, physiological and pharmacological evidence supports a role of abnormal motility in IBS.
Paterson WG, Thompson WG, Vanner SJ, Faloon TR, Rosser WW, Birtwhistle RW, Morse JL, Touzel TA
CMAJ 161(2):154-60, 1999 Jul 27
To help family physicians manage patients with irritable bowel syndrome (IBS), a consensus conference was convened in June 1997 at which 5 internationally recognized experts in IBS presented position papers on selected topics previously circulated to the conference participants. Five working groups comprising family physicians, gastroenterologists and allied health care professionals from across Canada were then charged with developing recommendations for the diagnosis, patient education, psychosocial management, dietary advice and pharmacotherapy, respectively. An evidence-based approach was used where possible; otherwise, recommendations were made by consensus. The participants concluded that family physicians can make a positive diagnosis of IBS using symptom criteria. The pathophysiology is poorly understood, but motility and sensory disturbances appear to play a role. Neither psychological nor specific dietary factors cause IBS, but both can trigger symptoms. Drug therapy is not recommended for the routine treatment of IBS, but short-term trials of drug therapy may be targeted to predominant symptoms in selected patients. A step-wise, patient-centred approach to management is outlined.
Bardou M
Rev Med Interne 20(2):151-7, 1999 Feb
Introduction: Irritable bowel syndrome is a very frequent cause for consulting. The clinical entity is ill-defined and diagnosis is based on clinical features (Rome criteria), as no specific feature helps guide the diagnosis. Since its pathophysiology is currently being better described, this study was aimed at reviewing recent data.
Current Knowledge And Key Points: After involvement of the motor system had been suggested, more recent pathophysiological studies have focused on diffuse abnormalities of visceral perception with decrease in pain thresholds. Involvement of other physiopathological factors, particularly of psychological disturbances, has been suggested.
Future Prospect And Projects: Management of patients suffering from irritable bowel syndrome is still disappointing as pharmacological agent acting on gut motility are only partly efficacious. Better understanding of its physiopathology will open new avenues for the development of therapeutical agents truly efficacious on visceral hypersensitivity.
Scarpignato C, Pelosini I
Can J Gastroenterol 13(Suppl A):50A-65A, 1999 Mar
Although it is unclear to what extent irritable bowel syndrome (IBS) symptoms represent a normal perception of abnormal function or an abnormal perception of normal function, many believe that IBS constitutes the clinical expression of an underlying motility disorder, affecting primarily the mid- and lower gut. Indeed, transit and contractile abnormalities have been demonstrated with sophisticated techniques in a subset of patients with IBS. As a consequence, drugs affecting gastrointestinal (GI) motility have been widely employed with the aim of correcting the major IBS manifestations, ie, pain and altered bowel function. Unfortunately, no single drug has proven to be effective in treating IBS symptom complex. In addition, the use of some medications has often been associated with unpleasant side effects. Therefore, the search for a truly effective and safe drug to control motility disturbances in IBS continues. Several classes of drugs look promising and are under evaluation. Among the motor-inhibiting drugs, gut selective muscarinic antagonists (such as zamifenacin and darifenacin), neurokinin2 antagonists (such as MEN-10627 and MEN-11420), beta3-adrenoreceptor agonists (eg, SR-58611A) and GI-selective calcium channel blockers (eg, pinaverium bromide and octylonium) are able to decrease painful contractile activity in the gut (antispasmodic effect), without significantly affecting other body functions. Novel mechanisms to stimulate GI motility and transit include blockade of cholecystokinin (CCK)A receptors and stimulation of motilin receptors. Loxiglumide (and its dextroisomer, dexloxiglumide) is the only CCKA receptor antagonist that is being evaluated clinically. This drug accelerates gastric emptying and colonic transit, thereby increasing the number of bowel movements in patients with chronic constipation. It is also able to reduce visceral perception. Erythromycin and related 14-member macrolide compounds inhibit the binding of motilin to its receptors on GI smooth muscle and, therefore, act as motilin agonists. This antibiotic accelerates gastric emptying and shortens orocecal transit time. In the large bowel a significant decrease in transit is observed only in the right colon, which suggests a shift in fecal distribution. Several 'motilinomimetics' have been synthesized. Their development depends on the lack of antimicrobial activity and the absence of fading of the prokinetic effect during prolonged administration. 5-hydroxytryptamine (5-HT)4 agonists with significant pharmacological effects on the mid- and distal gut (such as prucalopride and tegaserod) are available for human use. These 'enterokinetic' compounds are useful for treating constipation-predominant IBS patients. 5-HT3 receptor antagonists also possess a number of interesting pharmacological properties that may make them suitable for treatment of IBS. Besides decreasing colonic sensitivity to distension, these drugs prolong intestinal transit and may be particularly useful in diarrhea-predominant IBS. Finally, when administered in small pulsed doses, octreotide, besides reducing the perception of rectal distension, accelerates intestinal transit, although other evidence disputes such an effect.
Camilleri M
Aliment Pharmacol Ther 13(Suppl 2):48-53, 1999 May
This review summarizes the clinical evidence to support current therapies in irritable bowel syndrome (IBS). Fibre is indicated at a dose of at least 12 g per day in patients with constipation-predominant IBS. Loperamide (and probably other opioid agonists) are of proven benefit in diarrhoea-predominant IBS; loperamide may also aid continence by enhancing resting anal tone. In general, smooth muscle relaxants are best used sparingly, on an 'as needed' basis, as their overall efficacy is unclear. Psychotropic agents are important in relieving depression and of proven benefit for pain and diarrhoea in patients with depression associated with IBS. Further trials with selective serotonin reuptake inhibitors (SSRIs) are awaited. Psychological treatments including hypnotherapy are less widely available, but may play an important role in relief of pain. In summary, current therapies targeted on the predominant symptoms in IBS are moderately successful. New therapies are needed to more effectively relieve this syndrome, not just symptoms.
Drossman DA
Aliment Pharmacol Ther 13(Suppl 2):3-14, 1999 May
Our understanding of the pathophysiology of irritable bowel syndrome (IBS) has evolved from a disorder of motility to a more integrated understanding of enhanced motility and visceral hypersensitivity associated with brain-gut dysfunction. Psychosocial factors contribute to the predisposition, precipitation and perpetuation of IBS symptoms, and affect the clinical outcome. Newer brain imaging techniques (e.g. PET, fMRI) may help us understand the relationship between altered emotional states with pain enhancement and other gastrointestinal symptoms. Diagnosis using symptom-based (e.g. Rome) criteria and a conservative diagnostic approach is recommended. Treatment is based on an effective physician-patient relationship and a combined pharmacological and behavioural approach. Newer medications acting at the 5-HT receptor may help in reducing pain and bowel dysfunction. For more severe pain, antidepressants may be considered.
Mollen RM, Salvioli B, Camilleri M, Burton D, Kost LJ, Phillips SF, Pemberton JH
Am J Gastroenterol 94(3):751-6, 1999 Mar
Objective: Abnormalities of descending colon motility reported in a subset of patients with rectal evacuation disorders are consistent with a rectocolonic inhibitory reflex. Our aims were to evaluate distal colon motor function and rectal sensation in such patients and assess effects of biofeedback (BF) training on these functions.
Methods: Seven patients (five women, two men; mean age 36 yr) with rectal evacuation disorders were studied before and after 10-days biofeedback training; six healthy volunteers (five women, one man; mean age 30 yr) were studied once. Colonic compliance, motility, sensation thresholds, and perception scores during standardized rectal distentions were measured using two barostat-manometry assemblies inserted into the cleansed colon with the aid of flexible sigmoidoscopy.
Results: Sigmoid compliance, fasting, and postprandial motility index, and perception thresholds were similar in controls and patients before and after biofeedback training. Postprandial sigmoid tone tended (p = 0.09) to be lower in patients than controls; after biofeedback, postprandial tone was comparable to that in controls. Rectal urgency scores at 24 mm Hg distention were greater in patients than in controls (p = 0.02 for both). After biofeedback, there were trends for lower perceptions of urgency to defecate (7.6 +/- 1.1 cm pre- vs 5.3 +/- 1.5 post-; p = 0.04) at 24 mm Hg; conversely, gas sensation at 12 mm Hg was higher (1.2 +/- 0.5 cm pre- vs 3.3 +/- 0.6 post-; p = 0.05).
Conclusions: Normalization of rectal evacuation and postprandial sigmoid tone in patients with evacuation disorders by biofeedback training supports the presence of a rectocolonic inhibitory reflex. Effect of biofeedback on rectal sensation in these patients requires further study.
Camilleri M
Can J Gastroenterol 13(Suppl A):8A-11A, 1999 Mar
The evidence supporting a role of abnormal motor function in irritable bowel syndrome (IBS) is reviewed. Symptoms commonly present in IBS patients, such as vomiting, diarrhea, constipation or incomplete rectal evacuation, indicate that a motor disorder is implicit as either a primary or secondary disturbance. Physiological studies implicate a disturbance of transit through the small bowel and proximal colon, and abnormal motor responses of the rectum to distention in IBS patients. Intestinal contractions (physiological or 'abnormal') are associated with the sensation of pain, suggesting that these contractions are interactions between abnormal motor and sensory functions in IBS. Therapies aimed at correcting abnormal transit or antispasmodics are the main pharmacological approaches to the relief of IBS, and, although the latter are not always effective in the long term response to treatment, they support the role of dysmotility in IBS. Most novel therapies under trial probably modulate both sensory and motor functions, and are discussed briefly. In summary, the weight of clinical, physiological and pharmacological evidence supports a role of abnormal motility in IBS.
Paterson WG, Thompson WG, Vanner SJ, Faloon TR, Rosser WW, Birtwhistle RW, Morse JL, Touzel TA
CMAJ 161(2):154-60, 1999 Jul 27
To help family physicians manage patients with irritable bowel syndrome (IBS), a consensus conference was convened in June 1997 at which 5 internationally recognized experts in IBS presented position papers on selected topics previously circulated to the conference participants. Five working groups comprising family physicians, gastroenterologists and allied health care professionals from across Canada were then charged with developing recommendations for the diagnosis, patient education, psychosocial management, dietary advice and pharmacotherapy, respectively. An evidence-based approach was used where possible; otherwise, recommendations were made by consensus. The participants concluded that family physicians can make a positive diagnosis of IBS using symptom criteria. The pathophysiology is poorly understood, but motility and sensory disturbances appear to play a role. Neither psychological nor specific dietary factors cause IBS, but both can trigger symptoms. Drug therapy is not recommended for the routine treatment of IBS, but short-term trials of drug therapy may be targeted to predominant symptoms in selected patients. A step-wise, patient-centred approach to management is outlined.
Bardou M
Rev Med Interne 20(2):151-7, 1999 Feb
Introduction: Irritable bowel syndrome is a very frequent cause for consulting. The clinical entity is ill-defined and diagnosis is based on clinical features (Rome criteria), as no specific feature helps guide the diagnosis. Since its pathophysiology is currently being better described, this study was aimed at reviewing recent data.
Current Knowledge And Key Points: After involvement of the motor system had been suggested, more recent pathophysiological studies have focused on diffuse abnormalities of visceral perception with decrease in pain thresholds. Involvement of other physiopathological factors, particularly of psychological disturbances, has been suggested.
Future Prospect And Projects: Management of patients suffering from irritable bowel syndrome is still disappointing as pharmacological agent acting on gut motility are only partly efficacious. Better understanding of its physiopathology will open new avenues for the development of therapeutical agents truly efficacious on visceral hypersensitivity.
Scarpignato C, Pelosini I
Can J Gastroenterol 13(Suppl A):50A-65A, 1999 Mar
Although it is unclear to what extent irritable bowel syndrome (IBS) symptoms represent a normal perception of abnormal function or an abnormal perception of normal function, many believe that IBS constitutes the clinical expression of an underlying motility disorder, affecting primarily the mid- and lower gut. Indeed, transit and contractile abnormalities have been demonstrated with sophisticated techniques in a subset of patients with IBS. As a consequence, drugs affecting gastrointestinal (GI) motility have been widely employed with the aim of correcting the major IBS manifestations, ie, pain and altered bowel function. Unfortunately, no single drug has proven to be effective in treating IBS symptom complex. In addition, the use of some medications has often been associated with unpleasant side effects. Therefore, the search for a truly effective and safe drug to control motility disturbances in IBS continues. Several classes of drugs look promising and are under evaluation. Among the motor-inhibiting drugs, gut selective muscarinic antagonists (such as zamifenacin and darifenacin), neurokinin2 antagonists (such as MEN-10627 and MEN-11420), beta3-adrenoreceptor agonists (eg, SR-58611A) and GI-selective calcium channel blockers (eg, pinaverium bromide and octylonium) are able to decrease painful contractile activity in the gut (antispasmodic effect), without significantly affecting other body functions. Novel mechanisms to stimulate GI motility and transit include blockade of cholecystokinin (CCK)A receptors and stimulation of motilin receptors. Loxiglumide (and its dextroisomer, dexloxiglumide) is the only CCKA receptor antagonist that is being evaluated clinically. This drug accelerates gastric emptying and colonic transit, thereby increasing the number of bowel movements in patients with chronic constipation. It is also able to reduce visceral perception. Erythromycin and related 14-member macrolide compounds inhibit the binding of motilin to its receptors on GI smooth muscle and, therefore, act as motilin agonists. This antibiotic accelerates gastric emptying and shortens orocecal transit time. In the large bowel a significant decrease in transit is observed only in the right colon, which suggests a shift in fecal distribution. Several 'motilinomimetics' have been synthesized. Their development depends on the lack of antimicrobial activity and the absence of fading of the prokinetic effect during prolonged administration. 5-hydroxytryptamine (5-HT)4 agonists with significant pharmacological effects on the mid- and distal gut (such as prucalopride and tegaserod) are available for human use. These 'enterokinetic' compounds are useful for treating constipation-predominant IBS patients. 5-HT3 receptor antagonists also possess a number of interesting pharmacological properties that may make them suitable for treatment of IBS. Besides decreasing colonic sensitivity to distension, these drugs prolong intestinal transit and may be particularly useful in diarrhea-predominant IBS. Finally, when administered in small pulsed doses, octreotide, besides reducing the perception of rectal distension, accelerates intestinal transit, although other evidence disputes such an effect.
