Medical Management for Irritable Bowel Syndrome
What Is Irritable Bowel Syndrome?
Irritable bowel syndrome (IBS) is a common disorder characterized by abdominal pain or discomfort associated with altered bowel dysfunction, where structural and biochemical abnormalities are absent. IBS is a prevalent and expensive condition associated with a significant low-health-related quality of life (Brandt, 2009). About 10-20% of adults and adolescents all over the world have symptoms that are consistent with IBS. Studies show that IBS is two to three times more common among women (Longo, 2012). It is more common in lower socioeconomic groups, and it is more commonly diagnosed in patients younger than 50 years old (Brandt, 2009).
IBS can be categorized into three subtypes according to the predominating bowel habit:
- IBS-constipation (IBS-C)
- IBS-diarrhea (IBS-D)
- Mixed IBS (IBS-M)
In IBS-C, stools are commonly hard or lumpy. The bowel movement frequency is less than three per week. Straining during bowel movement is also a usual finding. IBS-D is characterized by loose, mushy, or watery stools wherein bowel movements happen more than three times in a day. Urgency to defecate is also common. IBS-M refers to patients having both constipation and diarrhea, for at least 25% of bowel movements. The change usually occurs rapidly within hours, or at times happens after a week. (Hillilia, 2010).
A Case in Point
This article will discuss a diagnosed case of IBS in a 47-year-old woman presenting with a history of more than 6 months of frequent and severe abdominal discomfort, frequent bowel urgency with watery stool and restrictions of normal daily activities. The patient was noted to have tried diet and lifestyle modifications to no avail. Also, no anatomic or biochemical disorder or infectious etiology was found in work-ups performed by her previous physician.
The prevalence of IBS in Europe and North America is estimated to be 10–15%. In Sweden, the most commonly cited figure is 13.5%. The prevalence of IBS is increasing in countries in the Asia-Pacific region, particularly in those with developing economies. Estimates of the prevalence of IBS (using the Rome II diagnostic criteria) vary widely in the Asia-Pacific region.— World Gastroenterology Organisation Global Guidelines, 2015
Approach to Diagnosis
Diagnosis of IBS is based on exclusion. Currently, the ROME II criteria for diagnosis of IBS is employed. Symptom onset must be at least be 6 months before diagnosis and criteria must be met and occur for the last 3 months. Abdominal discomfort or pain the major symptom for the diagnosis of IBS. It is a prerequisite feature that must be met in order to proceed with the other minor conditions in the ROME II. This must be accompanied by defecation that improves the discomfort and/or onset of symptoms accompanied by alterations in the consistency of stool and rate of defecation. Additional symptoms such as straining during defecation, feeling of incomplete bowel elimination, urgency, bloating and passage of mucus are conditions that serve to support the diagnosis of IBS. This disorder has no predilection in terms of age and is said to affect all ages of the population. Women are affected more than men and presentation of symptoms usually appear before 45 years of age. The main clinical features associated with Irritable Bowel Disease are enumerated as follows: Abdominal pain, altered bowel habits, gas and flatulence and upper gastrointestinal symptoms such as nausea, dyspepsia, heartburn and vomiting.
The enteric nervous system is an axis which is controlled by a diffuse network running from the esophagus down to the rectum. This is managed independently by migrating motor complexes forming organized and sequential peristalsis pattern. The organization throughout the length of the GIT is mainly coordinated by neurotransmitters and peptides mainly by the brain-gut axis forming the normal gastrointestinal function (Grundfast & Komar, 2001).
IBS is a disease defined as a functional disorder of the gastrointestinal tract. This is usually considered when there is a failure for laboratory studies to show any morphologic, microbiologic, histologic, or biochemical abnormalities in patients which characterizes IBS as a primary disorder of GI motility (Grundfast & Komar, 2001). The exact pathophysiology of IBS is currently unknown, but it is associated a complex interplay between sensory and motor dysfunction of the gastrointestinal tract secondary to various stimuli (Mertz, 2003). The mechanism involved affecting patients with irritable bowel syndrome can generally be grouped into three: alteration in (1) psychosocial function, (2) motility, and (3) hypersensitivity. The emotional response can affect visceral stimulation and influence the timing and severity of the disease (Camilleri, 2005).
The innervation of the GIT is dependent on signals of the vagal afferent pathways from the nodose ganglia and projecting centrally to the NTS. The vagus nerve sends non-noxious physiologic stimuli specifically originating from the GIT proximal portion, while the pelvic nerves predominate in the distal portion (Keszthelyi, Troost, & Masclee, 2012).
Motor dysfunction causes the prominent symptoms which usually lie in the spectrum between diarrhea or constipation dominant types. This is also correlated with the effect of visceral stimulation and hyperalgesia which is affected by the limbic and emotional motor systems (Camilleri, 2005). Visceral hypralgesia is defined as long-term changes in the threshold and gain in visceral afferent pathways. This means that even small quantities of bowel content may cause initiation of bowel movement. Normally, there are 6-8 high amplitude peristaltic contractions grouped whenever a health individual consumes food. This is markedly decreased in patients with constipation-predominant symptoms (Grundfast & Komar, 2001)
The role of infection with the development of IBS has varying evidences in literature but the persistence of inflammatory response is correlated on several studies. Basing on the persistence of immune cells in the gut flora, it was postulated that inflammatory reactions may cause the response in the intestinal tract leading to the signs and symptoms. Furthermore, one study has shown that there is decrease in incidence of IBS in patients having a prednisone regimen as compared to controls (Camilleri, 2005) and another has noted that post infectious IBS was seen in 25% of patients within 6 months after an initial protozoal or nematodal infection, with 10% developing persistent symptoms (El-Salhy, 2012).
- To be able to relieve symptoms of abdominal pain and diarrhea secondary to irritable bowel syndrome
- To prevent recurrence of associated symptoms
The management of IBS is patient-centered and dependent on the signs and symptoms presenting in the case. During primary care visit it is often advised to initiate both pharmacologic and non-pharmacologic treatment coupled with assessment of psychosocial factors that may be contributory to the disease process. Patients must also be informed on the nature of the condition, treatment options, impact of anxiety, and stress in the development of symptoms (Gunn, Cavin, & Mansfield, 2003).
The first-line management will to address possible diet problems that the patient is having. The role of food allergy and intolerance, usually to carbohydrates, should be assessed and intervened on as needed. Alteration in fiber intake is suggested as the initial approach, but evidences suggested varying effects on patients. The most usual advice is to take cereals and bran containing fibers. There are reports that some secondary care patients develop worsening of symptoms at around 55% of cases, with only 11% reporting benefit.
In the case presented, the diarrhea component predominates. The pathophysiology is mainly addressed by symptomatic relief by decreasing acceleration of the intestinal transit in the small bowel and the proximal colon. Opioids are usually the ones being used, but this drug has a tendency to cause constipation, hence it must be titrated accordingly (Gunn et al., 2003). Several other drug groups are used predominantly for patients with diarrhea-predominant symptoms, this include 5HT receptor antagonists, and some antidepressants as treatment for those that may have partly psychological component.
Antispasmodics are used frequently since they act on the smooth muscles leading to their capacity to coordinate contractions during stress or meals (Chey, 2004). In the case of the patient, it was reported that she experiences abdominal discomfort so these agents can be used to help relieve her symptoms.
Approach to Management
Drug Types Used in Treating IBS
The goal for treatment of patients with IBS is symptom-based. The patient is classified under IBS-D, meaning there is predominance in the presentation of diarrhea as per clinical manifestation. The goal, therefore, is to address the diarrhea and to prevent its recurrence.
Antidiarrheal Drugs: Opoid Agonists
Opioids are derived from poppy which puts it in close relation to opium. The endogenous opioid system has a wide array of functions that includes inhibition of painful sensory stimulus, regulation of the gastrointestinal function, autonomic, endocrine, emotional and addictive responses. Opioid agonists have 4 major receptor subtypes, the most relevant of which with regards to the gastrointestinal system in the mu receptor which is distributed all on along the alimentary tract (Brunton, Parker, Blumenthal, & Buxton, 2008).
- The μ (mu) receptor present in abundance in the gastrointestinal tract allows opioid agonists to exert constipating effects. Action of opioids is mediated through the central and enteric nervous system. In the stomach, presence of rhythmic relaxation and contraction which affects motility possibly lessens but persistent contraction in the central portion is notably increased (Katzung & Masters, 2010).
- This is in support of the decrease in the nonpropulsive contractions and increase in the resting tone of the small intestine.
- To further elaborate the constipating effect of the opioids, propulsive peristaltic waves in the large colon are minimal and tone is again increased. This effect allows greater time for absorption of water to occur and delay the transit of the fecal material. It is important to note that no tolerance on diarrheal effect is observed on use of this class of drugs.
- Acts by modulating gastrointestinal tract function which includes the following (Parrish, 2008): 1). Changes in the tonic/segmental contractions 2.) Decreased motility and transit time.
- Piperidine and Phenylpiperidine group under opioid agonist includes drugs such as Loperimide and Diphenoxylate which are the only drugs under opioids to be approved by FDA for diarrhea (Parrish, 2008).
- Therapeutic effect is achieved in low doses with proven high safety profile for loperamide under the piperidine and phenylpiperidine group.
- True opioid sensitivity is rare although opioid-induced histamine released may produce effects such as itching and mild erythema without secondary lesions (Parrish, 2008).
- Common side effects of opioid use are nausea and vomiting.
- Constipation and ileus are considered as untoward effects however this is proven to be beneficial for IBS patients with predominant presentation of diarrhea.
- Usage of drugs under this class is observed to be safe as long as it is taken as advised such that the route, dose and frequency do not deviate from what is directed (Ibhanesebhor, 2010).
Antidiarrheal Drugs: Serotonin 5-HT3 antagonists
The only known monoamine neurotransmitter receptor that is a a ligand-operated ion channel is the 5-HT3 receptor. They can be found in parasympathetic terminals in the GI tract, including vagal and splanchnic afferents. Blockade of which is provided by the Serotonin 5-HT3 antagonists (Brunton, Parker, Blumenthal, & Buxton, 2008).
- The 5-HT3 receptors are found in locations such as sensory neurons of the gut which mediates gastrointestinal motility and bowel function (Gershon, 1999).
- This drug blocks the enteric cholinergic neuron terminal which produces decreased colonic motility primarily in the left colon to produce and increased duration of total colonic passage of feces (Katzung & Masters, 2010).
- It promotes slow passage of feces in the colon which leads to an increase in the consistency and decrease in water content of the stool.
- Studies conducted by Camilleri (1999) and Bardhan (2000) found that type 3 serotonin receptors were found to address symptoms of IBS such as discomfort and urgency among women.
- Only alosetron under this class was shown to be effective in treating diarrhea caused IBS. On the hand, there are no available studies to support drugs such as granisetron and ondansetron to have the same efficacy in diarrhea for patients with IBS.
- Constipation was the only reported adverse event in a randomized controlled clinical trial by Camilleri (2001) as part of the safety analyses of the drug.
- The only drug indicated under this class is alosetron which only applicable to the female population with predominant diarrhea type of IBS.
- Not used as a drug of choice for women with predominant type of diarrhea unless conventional therapy is first applied. Failure of conventional therapy then warrants the use of this class.
- Other drugs such as ondasetron and granisetron have not been studied yet in this regard.
Some studies postulated that abdominal pain originate from colonic smooth muscle spasm. A systemic review shows that there is evidence for the efficacy of antispasmodics in IBS (Brandt, 2009). This group of drugs also attenuates the heightened baseline and postprandial contractility especially in IBS-D patients (Spiller et al., 2007).
- Blocks cholinergic transmission at parasympathetic postganglionic nerve endings and cause smooth muscle to relax.
- Advantage over placebo in global improvement (56 vs 38 %), pain (53 vs 41%), and abdominal distension (44 vs 35%t) (Hadley, 2005).
- Taken before meals to improve postprandial pain as well, as diarrhoea (Talley, 2003)
- Rationale for using antispasmodic agents is to attenuate the heightened baseline and postprandial contractility seen in patients with IBS (particularly when diarrhoea predominant) (Spiller, et al., 2007).
- Generally, most studies on the efficacy of antispasmodic drugs are of poor quality. The best evidence for efficacy among spasmolytics appears to exist for the use of antimuscarinic durgs (Brandt, 2009).
- Meta-analysis also showed that antiicholinergics have an odds ratio of 2.1 for benefit (Spiller, et al., 2007).
- Although infrequent, side effects include dry mouth, blurred vision constipation, insomnia and restlessness.
- No known drug interaction (Talley, 2003).
- Taken as needed 30-45 min before a meal to reduce the exaggerated gastro-colonic response in IBS.
Needless to say, every patient is unique, and appropriate management must be formulated on a case-by-case basis. This article serves as a guide to elucidate how IBS is managed in a unique case study, and it should not be used to self-prescribe medications. Please visit your local physicians for appropriate diagnosis and management.
- Abdul-Baki, H. (2009). A randomized controlled trial of imipramine in patients with irritable bowel syndrome. World Journal of Gastroenterology, 15(29), 3636. doi:10.3748/wjg.15.3636
- Annahazi, A., Roka, R., Rosztoczy, A, and Wittmann, T. (2014). Role of antispasmodics in the treatment of irritable bowel syndrome. World Journal of Gastroenterology 20(20): 6031-43
- Baker, D. (2007). Loperamide: A pharmacologic review. Rev Gastroenterol Disord, s11-s18.
- Baldo, B. (2001). Chemistry of Drug Allergenicity. Curr Opin Aller Immunol, 327-335.
- Bennett, P. (2010). Clinical Pharmacology. New York: Elsevier.
- Brandt, L. J. (2009). An Evidence-Based Systematic Review on the Management of Irritable Bowel Syndrome. American Journal of Gastroenterology, 104(January).
- Camilleri, M. (2005). Etiology and pathophysiology of irritable bowel syndrome and chronic constipation. Adv. Studies Med, 955–964. Retrieved from http://www.jhasim.net/files/articlefiles/pdf/XASIM_Issue_5_10B_p955_964.pdf
- Camilleri, M. A. (2009). Current and Novel Therapeutic Options for Irritable Bowel. Dig Liver Dis, 854–862.
- Chey, W. (2001). Review: smooth muscle relaxants improve symptoms and reduce pain in irritable bowel syndrome. Aliment Pharmacological Therapy, 15, 355-61.
- Chey, W. (2004). Irritable bowel syndrome: A systematic review. Clinics in Family Practice, 6(3), 647–669. Retrieved from http://www.zen-tai.com/assets/u/ibs.pdf
- Clave, P., Acalovschi, M.m Triantafillidis, J. K., Uspensky, Y. P., Kalayci, C., Shee, V., et al. (2011). Randomised clinical trial: otilonium bromide imporves frequency of abdominal pain, severity of distention and time to relapse in patients with irritable bowel syndrome. Aliment Pharmacol Ther 34(4):432-442.
- Curtiss, F. R. (2008). Irritable bowel syndrome and antidepressants. Journal of Managed Care Pharmacy : JMCP, 14(9), 882–5. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19006445
- Dekel, R., Drossman, D. a, & Sperber, A. D. (2013). The use of psychotropic drugs in irritable bowel syndrome. Expert Opinion on Investigational Drugs, 22(3), 329–39. doi:10.1517/13543784.2013.761205
- El-Salhy, M. (2012). Irritable bowel syndrome: diagnosis and pathogenesis. World Journal of Gastroenterology : WJG, 18(37), 5151–63. doi:10.3748/wjg.v18.i37.5151
- Gatcheco, F. N. (2004). Epidemiology of dyspepsia, irritable bowel srndrome and functional abdominal pain among Filipino children. Journal of Pediatric Gastroenterology & Nutrition 39: S375-6.
- Gershon, M. (1999). Roles played by 5-hydroxytryptamine in the physiology of the bowel. Aliment Pharmacol Ther, 1315- 1330.
- Grundfast, M. B., & Komar, M. J. (2001). Irritable bowel syndrome. The Journal of the American Osteopathic Association, 101(4 Suppl Pt 1), S1–5. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11392210
- Gunn, M., Cavin, A., & Mansfield, J. (2003). Management of irritable bowel syndrome. Postgrad Med J, (August 2002), 154–159.
- Hillila, M. (2010). Irritable bowel syndrome in the general population: epidemiology, comorbidity and societal costs. Helsinki: Helsinki university Print.
- Hulisz, D. (2004). The burden of illness of irritable bowel syndrome: current challenges and hope for the future. Journal of Managed Care Pharmacy, 10(4), 299–309. Retrieved from http://www.amcp.org/data/jmcp/subject review-299-309.pdf
- Ibhanesebhor, O. (2010). REVIEW OF THE ROLE OF LOPERAMIDE AND CODEINE IN. WHO.
- Karim, A., Ranney, R., & Evensen, K. e. (1972). Pharmacokinetics and metabolism of diphenoxylate in man. Clin Pharm Ther, 407-419.
- Keszthelyi, D., Troost, F. J., & Masclee, a a. (2012). Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Methods to assess visceral hypersensitivity in irritable bowel syndrome. American Journal of Physiology. Gastrointestinal and Liver Physiology, 303(2), G141–54. doi:10.1152/ajpgi.00060.2012
- Lacy, B. E., Weiser, K., & De Lee, R. (2009). The treatment of irritable bowel syndrome. Therapeutic Advances in Gastroenterology, 2(4), 221–38. doi:10.1177/1756283X09104794
- Longo, D., Fauci, A., kasper, D., Hauser, S., Jameson, J. L., and Loscalzo, J. (2012). Harrison's Principles of Internal Medicine. New York: McGraw Hill.
- Mertz, H. R. (2003). Irritable bowel syndrome. The New England Journal of Medicine, 349(22), 2136–46. doi:10.1056/NEJMra035579
- Morgan, V., Pickens, D., Gautam, S., Kessler, R., & Mertz, H. (2005). Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome. Gut, 54(5), 601–7. doi:10.1136/gut.2004.047423
- Olden, K. W. (2012). Targeted therapies for diarrhea-predominant irritable bowel syndrome. Clinical and Experimental Gastroenterology, 5, 69–100. doi:10.2147/CEG.S29023
- Parrish, C. R. (2008). Opioid Analgesics and the Gastrointestinal Tract. Practical Gastroenterology, 41-50.
- Rahimi, R. (2009). Efficacy of tricyclic antidepressants in irritable bowel syndrome: A meta-analysis. World Journal of Gastroenterology, 15(13), 1548. doi:10.3748/wjg.15.1548
- Spiller, Q. A., Aziz, Q., Creed, F., Emmanuel, A., Houghton, L, Hungin, L., et al. (2007). Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut, 1770–1798.
- Talley, N. J. (2003). Evaluation of drug treatment in irritable bowel syndrome. Minnesota.
- Tytgat, G. N. (2007). Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17547475#.