Irritable Bowel Syndrome (IBS)

• Irritable Bowel Syndrome is a common gastrointestinal disorder defined by symptoms including abdominal pain associated with defecation and altered bowel habits, excluding any organic cause
• Altered bowel habits include diarrhea, constipation, or both with symptoms that fluctuate over time in most patients
• The pathophysiology of IBS is incompletely understood and is likely multifactorial
• IBS is classified as a disorder of gut-brain interaction that may include factors related to inflammation, environment, psychological factors, dietary factors, and alterations of intestinal microbiota

Prevalence

• IBS is a common condition you will encounter in practice
• IBS impacts 3.7% of men and 7.8% of women in Canada, peaking in those 18-34 years of age
• IBS is the 4th most expensive digestive disease in Canada with an estimated economic and health-care burden exceeding $6.5 billion per year

IBD vs. IBS

• Inflammatory Bowel Disease (IBD) refers to autoimmune conditions including Crohn's Disease and Ulcerative Colitis
• Inflammatory turns into Autoimmune
• Irritable Bowel Syndrome (IBS) involves abdominal pain typically associated with constipation, diarrhea, or a mix of the two
• IBS is classified as IBS-C, IBS-D or IBS-M
• IBS is commonly confused or labelled as IBD

Rome IV Diagnostic Criteria

• Recurrent abdominal pain ≥1 day/week in the last 3 months (with onset of symptoms occurring at least 6 months before diagnosis) is associated with 2 or more criteria
• Related to defecation
• Associated with a change in stool frequency and/or form
• Recurrent abdominal pain and stool form/frequency changes are common indications of IBS

Patient Assessment

• A thorough history is conducted to identify specific Gl symptoms in the absence of other Gl diseases
• History taking may include inquiries regarding:
• Frequency of bowel movements and stool appearance
• Symptoms: abdominal pain, frequency, severity, and duration, including any associated bloating, distention, or flatulence
• Potential triggers for symptoms like personal stress, interpersonal issues and diet
• Family history of IBS or Gl disorders
• Medical history including comorbid conditions
• Medications that may be contributing to symptoms
• A physical examination in patients with IBS is usually unremarkable but mild abdominal tenderness may be present
• Consider concerning signs or symptoms that identify patients who warrant further investigations
• Conditions that share similar symptoms to IBS, especially in those with diarrhea and mixed pattern bowel habits include microscopic colitis, inflammatory bowel diseases (IBD), celiac disease, and bile acid malabsorption
• In those with predominantly constipation IBS, colorectal cancer is a common concern and may be explored for differential diagnosis

Alarm Symptoms

• Alarm Symptoms include:
• Abdominal mass
• Ascites
• Blood in stool (melena)
• Elevated white blood cell count
• Family history of colon cancer, inflammatory bowel disease, or celiac disease
• Fever
• Nocturnal diarrhea
• Symptom onset after the age of 50 years
• Severe, progressively worsening of symptoms
• Unexplained iron-deficiency anemia
• Unexplained weight loss and/or loss of appetite

Bristol Stool Chart

• The Bristol Stool Form Scale is a validated instrument that allows reporting of stool appearance on a scale of 1 to 7
• IBS subtype can be identified based on stool consistency

IBS Subtypes

• IBS with Predominant Constipation (IBS-C): stool type 1-2 is more than 25% of the time and stool type 6–7 is less than 25
• IBS with Predominant Diarrhea (IBS-D): stool type 6-7 is more than 25% of the time and stool type 1–2 is less than 25%
• IBS with Mixed Bowel Pattern (IBS-M): stool type 1-2 and stool type 6–7 are both more than 25% of the time
• People whose symptoms don't fit into any category have IBS Unclassified (IBS-U)
• IBS subtype should ideally be re-categorized as a person's bowel habits change

Goals of Therapy

• Develop a strong patient-health care practitioner relationship
• Alleviate symptoms by establishing a treatment plan tailored to the patient
• Treat psychosocial comorbidity, if present
• Improve quality of life
• Promote coping and normal social and occupational functioning

Non-Pharmacological Options

• Healthcare practitioner-patient relationship can positively impact a patient's quality of life with IBS
• Patient education is central to management like education regarding diagnosis and prognosis with acknowledgement of fears
• Multidisciplinary approach to treatment is suggested, including a physician, pharmacist, psychologist, and dietician.

Lifestyle Interventions

• Promoting increased physical activity and reduction of alcohol/caffeine is part of Lifestyle interventions
• A study with a 12-week intervention followed by a continued moderate increase in physical activity demonstrated long-term positive effects on IBS and associated psychological symptoms
• Symptoms related to drinking pattern, but not moderate or light alcohol intake, have been associated to increased GI symptoms, particularly among females with IBS-D
• Caffeine, particularly caffeinated coffee, increasing gastric acid secretion and colonic motor activity in healthy individuals

Dietary Interventions

• Occurrence of bloating and abdominal pain in more than 60% of patients with IBS is related to ingestion of wheat and fermentable carbohydrates
• Low FODMAPs diet: multiple studies and systematic reviews evaluate the effect of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) in IBS
• Gluten-free diet (GFD): celiac disease should be ruled out first
• Fibre: start at a lower dose and gradually titrate upward during several weeks to a total daily intake of 20-30 g and elimination diet

Gut Microflora

• Prebiotics are food components that remain undigested which stimulate either the growth or the activity of intestinal bacteria that improves host health
• Minimal evidence of prebiotics in IBS, except 1 trial with guar gum improved IBS symptoms, including bloating and excess gas
• Probiotics are live that may affect composition or function of the gut microbiota
• A 2017 review provided international consensus that supports the use of probiotics to reduce overall symptoms and abdominal pain
• Minimal evidence to suggest they reduce symptoms of constipation, gas, or diarrhea, however, moderate evidence promotes use reduce bloating/distention and improve the frequency/consistency
• Can be expensive with ++ financial burden Fecal transplantation needs controlled studies for any recommendation

Psychological Interventions

• Cognitive behavioural therapy (CBT), hypnosis, and mindfulness-based therapies have been designed and implemented effectively in IBS
• CBT is the most widely studied psychotherapy and is currently a first-line treatment for IBS
• A prospective study comparing standard CBT with home-based CBT demonstrated that minimal-contact CBT combined with self-guided therapy improved Gl symptoms at 2 weeks sustained at 12 months of follow up

Pharmacotherapy

• Soluble Fibre can improve global IBS symptoms
• MOA: Water-soluble fibre (e.g. psyllium) has a high water-holding/gel-forming capacity preserved throughout the large bowel, acts as bulking agent to firm loose/liquid stools with diarrhea
• Potential ADRs: bloating, flatulence, abdominal discomfort, allergic reactions (rare), esophageal and colonic obstruction (rare)
• Take with plenty of fluids (≥250 mL) to prevent obstruction and/or impaction
• Start low and slowly titrate up based on symptoms
• Can be used long term
• Advise patient not to take within 2h of any other medications

IBS-C Treatments

• Antidepressants: Pain, depression
• Antispasmotics: Pain and may worsen constipation
• Linaclotide: Pain, discomfort, stool consistency, straining
• Prucalopride: Constipation
• Osmotic laxatives: Improve stool consistency and increase frequency e.g. polyethylene glycol
• Soluble fibre: Improve overall IBS symptoms

Laxatives

• Osmotic laxatives (e.g., polyethylene glycol, lactulose) may increase the frequency of bowel movements
• Polyethylene glycol is recommended over lactulose in IBS
• Stimulant laxatives (bisacodyl, senna) are commonly used in IBS-C for symptomatic management
• Polyethylene glycol is typically dosed as 17g (1 capful) mixed in 250ml of beverage and drank once daily in adults
• Onset is ~24-96 hours

Antispasmodics

• Antispasmodics can help patients with pain predominance by inducing muscular relaxation of the wall of the Gl tract and provide symptomatic short-term relief
• Dicyclomine (anticholinergic): can be dosed from once to four times daily. ADRs include dizziness, dry mouth, nausea, blurred vision and drowsiness. Avoid use with other anticholinergics.
• Pinaverium (gastrointestinal calcium antagonist) [Dicetel®]: dosed TID. It can cause esophageal irritation, so should be taken with water and food and swallowed whole without lying down
• Trimebutine (spasmolytic): dosed TID. Should be taken before meals whose ADRs include dry mouth, diarrhea, dyspepsia, nausea, constipation, drowsiness, and headache
• Hyoscine (anticholinergic/antimuscarinic): reduces acetylcholine binding at muscarinic receptors to induce smooth muscle relaxation and can worsen constipation

Antidepressants

• Patient preferences is important with this consideration option
• Selective serotonin re-uptake inhibitors (SSRIs) choice for patients with IBS-C due to the prokinetic effects
• SSRIs are prescribed at dosages standard for treating mental health conditions
• SSRIs useful for psychological comorbidities like Citalopram and fluoxetine
• Potential ADRs: nausea, nervousness, diarrhea, dry mouth, insomnia and sexual dysfunction
• Tricyclic antidepressants (TCAs) treat abdominal pain and less likely to cause constipation when administered at low dosage
• TCAs increased colonic transit time and more effective for IBS-D like amitriptyline, desipramine, and imipramine
• Potential ADRs: drowsiness, constipation, dry mouth

Linaclotide

• Brand Name: Constella®
• Guanylate Cyclase-C Agonist increases the production of cyclic guanosine monophosphate
• Proposed to reduce constipation by increasing fluid secretion and accelerating intestinal transit, and to target abdominal pain by reducing visceral hypersensitivity
• Systemic drug-drug interactions are not expected
• Avoid taking with a high-fat meal because it may result in looser stools and higher stool frequency

Prucalopride

• Marketed under the brand name Resotran®
• Serotonin 5-HT4 Receptor Agonist with prokinetic properties helps Gl tract moves food during digestion
• Indicated for chronic constipation, reserved for when laxatives don't work
• Potential ADRs: nausea, abdominal pain, diarrhea or headache, typically occurring with first couple days of treatment

IBS-D Treatments

• Antidepressants: Pain, depression
• Cholestyramine: Diarrhea
• Diphenoxylate/atropine: Diarrhea
• Eluxadoline: Diarrhea, pain
• Loperamide: Diarrhea (no effect on pain)
• Rifaximin: Diarrhea, pain
• Soluble fibre: Improve overall IBS symptoms

Loperamide

• Loperamide is a µ-opioid receptor agonist which improves diarrhea by decreasing peristalsis, prolonging Gl transit time, and reducing fluid secretion in the intestinal lumen
• Although loperamide is an effective anti-diarrheal agent, its use for IBS-D treatment is not as strong as that of therapies and has no shown to improve overall IBS symptoms
• ADRs: abdominal cramps, constipation, bloating, and nausea
• Unlike other options, this is available OTC.
• Common first choice for diarrhea patients, because it's the cheapest.
• Loperamide can be used prophylactically when a patient anticipates diarrhea
• Brand name: Imodium®

Cholestyramine

• Evidence supports a role for bile acids in the pathophysiology of IBS-D, with some patients proposed to have bile acid malabsorption
• Bile salt sequestrants, cholestyramine or colesevelam may be effective against diarrheal symptoms in some patients with IBS-D
• Powder (for oral suspension) and tablet formulations
• Bile acid sequestrants should be considered after other therapies targeting diarrhea have been unsuccessful
• Potential ADRs: constipation, stomach/abdominal pain, gas, nausea, vomiting
• Administer other drugs 1h before or 4-6h after resin to limit possible reduced absorption in the Gl tract
• Cholestyramine is marketed as Olestyr® and colesevelam as Lodalis®

Diphenoxylate/atropine

• Diphenoxylate is an opioid agonist that acts on the presynaptic opioid receptors (predominantly mu receptors) in the enteric nervous system
• Atropine is added in a fixed dose of 0.025 mg, which is a competitive inhibitor of acetylcholine receptors to prevent patients from misusing diphenoxylate:
• By acting on presynaptic opioid receptors, it blocks the release of acetylcholine in the synaptic cleft, thus its inhibits motility and secretory action of the enteric nervous system
• This action leads to a decrease in segmental contractions and prolongation of gastrointestinal transit time
• Reduces the epithelial secretion of fluid and electrolytes and enhances active absorption by mild action on delta receptors
• Geriatric patients are more susceptible to the antimuscarinic effects of atropine, agitation, drowsiness, increased intraocular pressure
• This medication does not have the analgesic effects of morphine at standard doses, but it can lead to central nervous system effects, like euphoria at higher doses

Eluxadoline

• Eluxadoline (Vibrezi®) mixed µ-opioid receptor agonist, 8- opioid receptor antagonist, and к-opioid receptor agonist peripherally acting in the gut with minimal oral bioavailability
• Reduces visceral hypersensitivity without completely disrupting intestinal motility, suggesting that peripheral 8-opioid receptor antagonism may reduce μ-opioid receptor-mediated constipation
• Take with food and avoid concomitant administration with alcohol, opioid analgesics, and anticholinergics
• Potential ADRs: constipation, nausea, vomiting, abdominal pain, and drowsiness
• Discontinue if severe constipation develops (>4 days without BM) and has Psychological dependence
• Contraindicated in patients who have undergone cholecystectomy (gallbladder removal surgery)

Rifaximin

• Small intestinal bacterial overgrowth has been suggested to be associated with IBS
• Rifaximin is an oral, minimally absorbed, broad-spectrum antimicrobial agent that targets the GI tract and is associated with a low risk of clinically relevant bacterial antibiotic resistance
• Two weeks of rifaximin treatment may provide adequate relief of global IBS symptoms and loose stools, abdominal pain, and bloating
• This effect gradually disappears and re-treatment is necessary in a large proportion of patients to retain symptom improvement
• May be repeated for up to 3 treatment courses

IBS-M Treatment

• Soluble fibre is used to improve global IBS symptoms
• See treatments for IBS-C and IBS-D

Summary

• A common condition is IBS with which the audience will encounter in their future careers
• Patients can present with IBS-D, IBS-C, or a mix of the two!
• Patients need to be provided with self-management on lifestyle interventions, non-pharmacological strategies and identification of triggers
• The treatment of symptoms from IBS with pharmacotherapy has to be individualized