18 - IBS

Question 1

Definition of IBS

Answer 1

• Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months associated w/ at least 2 features:
• • Improvement w/ defecation
• • Onset associated w/ a change in stool frequency
• • Onset associated w/ a change in stool form (appearance)
• Criteria need to be met for at least 3 months w/ onset at least 6 months prior to making the diagnosis

Question 2

Features of IBS

Answer 2

• Other supporting features = mucous in stool, bloating and distention
• Key features = abdominal pain or discomfort associated w/ altered bowel pattern
• ROME III provides subtyping of IBS based on predominant stool pattern:
• • W/ constipation
• • W/ diarrhea
• • Mixed
• • Unsubtyped

Question 3

Characterization of IBS

Answer 3

• Characterized in terms of multiple physiological determinants contributing to a common set of sx
• A group of disorders rather than a single disease
• Difficult to generalize as sx vary among people
• IBS px have higher rates of non-GI sx including headache, back pain, fatigue, myalgia

Question 4

Pathophysiology of IBS

Answer 4

• Nervous system (brain gut interactions)
• • CNS and enteric NS
• Gut flora issues -> post infectious, bacterial overgrowth
• “Its all in your head”
• • Altered sensitivity to gut distension
• • Altered signaling processes in CNS
• • Altered motor response (ex: hormones)
• • Other perception issues include genetics and psychosocial

Question 5

Alarm features of IBS

Answer 5

• Weight loss ( >5 kg)
• Bloody stools
• Severe diarrhea
• Recurring fever
• Onset > 50 y/o
• Family history of colon cancer, IBD

Question 6

Psychologic disorders

Answer 6

• Present in minority of all IBS px
• Present in majority of IBS seeking subspecialist care
• IBS sx aren’t manifestations of psychological disorders but comorbidity increases likelihood to seek subspecialist

Question 7

IBS therapy

Answer 7

• Location, severity, previous response to therapy involved in selection process
• IBS subtypes are highly unstable
• Predominant sx guide most therapeutic plans

Question 8

Non-drug therapy for IBS

Answer 8

• Look for sources of constipation and diarrhea
• Constipation -> low fiber diet, lack of exercise, medications, muscular atony or decreased abdominal pressure, metabolic abnormalities
• Diarrhea -> foods, lactose, sorbitol, fructose
• Establish “therapeutic” relationship w/ pt
• Regulate dietary fiber intake
• Avoid precipitants (ex: foods that trigger abdominal pain)
• Avoid excesses (ex: caffeine, fruit intake, carbonated drinks, gum)

Question 9

Behavioural therapies for IBS

Answer 9

• Relaxation
• Biofeedback
• Hypnotherapy
• Cognitive behavioural (CBT)
• Psychotherapy
• Evidence that these are more effective than placebo for some sx of IBS

Question 10

CBT for IBS

Answer 10

• Short term intervention oriented toward change, especially developing strategies to cope
• Describes how thoughts, emotions, events and physiologic responses are interlinked
• Education, monitoring of thoughts, emotions and how they are related, testing assumptions, stress management, and planning activities
• Best for those w/ some medical intervention, still distressed and open to active involvement in CBT

Question 11

Drug therapy for IBS

Answer 11

• Has been very difficult to find new drugs that work
• Difficult to see a good response to a single drug in most people
• Very high placebo response rate
• Only a minority of those w/ IBS need extended drug therapy
• Consider when IBS sx are impacting QoL
• Short term response over a few weeks reported w/ many therapies
• Generally, need 3-4 weeks to assess efficacy; antidepressants may be a bit longer

Question 12

Problems w/ IBS studies

Answer 12

• Hard to compare pt populations between studies
• Lack of reproducibility
• Need to develop better definitions of functional bowel conditions to lead to better controlled data to interpret clinical studies

Question 13

Pharm options for IBS w/ constipation

Answer 13

• Fiber based products
• Osmotic and salt laxatives
• Stimulant laxatives
• Prucalopride
• Linaclotide, lubiprostone

Question 14

Fiber based products for IBS w/ constipation

Answer 14

• May provide beneficial effects through a number of mechanisms:
• • Increase stool bulk and frequency
• • Improve GI transit time
• • Reduce gas/bloating by binding bile salts
• No evidence of benefit over placebo relieving global IBS sx
• Best benefit likely in abdominal pain and constipation
• Can get through diet or manufactured agents
• Bloating more likely on high doses; may increase gas produced in intestines

Question 15

Osmotic and salt laxatives

Answer 15

• Lactulose -> gas, bloating, and taste a problem
• Magnesium -> poorly absorbed, act as osmotic laxative
• Phosphate
• PEG based

Question 16

Stimulant laxatives

Answer 16

• Senna based and Bisacodyl
• Quicker onset (< 24 h)
• SE = cramping

Question 17

Approach w/ laxatives for IBS

Answer 17

• Often start w/ a regimen as a regular routine and build or subtract from there
• Ex: start w/ senokot 2 tabs HS, after 3 days if no improvement, add on something else or increase to 4 tabs HS

Question 18

Prucalopride (Resotran)

Answer 18

• Serotonin 4 receptor agonist
• Much lower affinity to hERG channel than cisapride
• Labelled indication for chronic idiopathic constipation in adult females w/ inadequate response to laxatives
• Primary action is via stimulation of colonic transit
• Renal clearance
• Not recommended in pregnancy
• SE = nausea, diarrhea; may be dose related
• Not covered by plans, about $3/day

Question 19

Linaclotide (Constella, Linzess)

Answer 19

• Peptide guanylate cylase-C (GCC) agonist
• Indirectly activates cystic fibrosis transmembrane conductance regulator => secretion of Cl and bicarb into bowel and increased transit
• Approved for IBS C and chronic constipation
• Frequent SE = diarrhea
• Not approved for plan coverage

Question 20

IBS w/ constipation – summary

Answer 20

• Dietary measures w/ bran or psyllium usually a good place to start
• If fiber fails, consider osmotic laxative (ex: magnesium) and/or stimulant (ex: senna, Bisacodyl)
• Add on therapy w/ lactulose or PEG based products
• Linaclotide or prucalopride for refractory cases

Question 21

Pharm options for IBS w/ diarrhea

Answer 21

• Loperamide
• Cholestyramine
• Alosetron
• Fiber
• Newer agents = eluxadoline, rifaximin

Question 22

Loperamide - MOA, SE, dose

Answer 22

• Increased transit time, water and electrolyte absorption, and anal sphincter tone
• Some evidence to improve stool consistency and abdominal pain over placebo
• Lack evidence in decreasing global IBS sx
• May use Lomotil or codeine in refractory cases
• Can be used prophylactically (ex: prior to travel, stressful situation)
• SE = bloating may be worsened, abdominal pain may develop
• Dose = 2-4 mg up to QID

Question 23

Cholestyramine

Answer 23

• 3rd line in IBS w/ diarrhea
• Can be used as add on therapy w/ other agents
• Issues w/ taste and drug interactions
• Often hit or miss agent, so review benefit

Question 24

Eluxadoline (viberzi, truberzi)

Answer 24

• Mu opioid agonist and delta opioid receptor antagonist

- Minimally absorbed, acts locally for IBS w/ diarrhea

Question 25

Alosetron (Lotronex)

Answer 25

- Serotonin 3 receptor antagonist - Better than placebo in IBS w/ diarrhea, improves overall sx - Major concerns w/ ischemic colitis lead to withdrawal from US market; can still obtain via approval process

Question 26

Fiber for IBS w/ diarrhea

Answer 26

- Used to increase stool consistency | - Target fiber intake usually around 30 g/day but start lower and gradually increase to reach target

Question 27

IBS w/ diarrhea – summary

Answer 27

- Exclude lactose intolerance, celiac disease and other sources in diet for diarrhea - Antidiarrheals usually first line w/ loperamide preferred agent - Add in fiber slowly if used to increase stool consistency

Question 28

IBS w/ bloating and gas

Answer 28

- These px less likely to obtain benefit w/ drugs than IBS w/ constipation or diarrhea - Diet changes and limited fiber intake as can worsen both sx - Antidepressants have a role - Antispasmodics considered - Data on promotility agents less certain

Question 29

Recommendations for IBS w/ gas

Answer 29

- Some foods associated w/ increased gas formation (ex: beans, onions, celery) - Gas expulsion stimulated w/ food and exercise (go for a walk after meals)

Question 30

Antispasmodics

Answer 30

- Primarily act via decreasing spontaneous smooth muscle stimulated movements (directly or via anticholinergic or antimuscarinic mechanisms) - May provide relief of abdominal pain, distension or bloating (take pre-meals) - Can occasionally be used for sx management of IBD as well - Most SE are anticholinergic - Belladonna, clidinium, dicyclomine, hyoscyamine, pinaverium, propantheline, trimebutine - Used to be prescribed frequently, px often on them daily for long periods of time - Generally, not recommended for regular basis as tolerance may develop - Systematic reviews of the agents generally say no better than placebo

Question 31

IBS and pain

Answer 31

- Behaviour and aversion techniques can be employed - Antidepressants and NSAIDs used in refractory cases - Narcotic analgesics usually not successful

Question 32

Antidepressants for IBS

Answer 32

- Visceral hypersensitivity (increase pain/ discomfort vs. non-IBS for same degree of colon distension) - Increases pain threshold; may also affect GI motility - 6-12-week RCTs didn’t show improvement in abdominal pain w/ SSRIs, modest relief w/ TCAs - Response may vary amongst the agents (may try more than 1 agent) - TCAs most studied (amitriptyline, desipramine); some data w/ SSRIs - Used in chronic pain doses (low dose) rather than depression doses

Question 33

Antibiotics and probiotics for IBS

Answer 33

- Antibiotics -> data that they help/worsen IBS, bacterial overgrowth - Probiotics -> competition w/ pathogenic bacteria, anti-inflammatory effects, don’t know which ones to use and in what doses

Question 34

What are probiotics and which are most studied?

Answer 34

- Live microorganisms which when administered in adequate amounts confer a health benefit on the host - Most studied = lactobacilli and bifidobacterial alone or in different combinations

Question 35

Probiotics in IBS

Answer 35

- Problem is most of GI flora is anaerobic and many strains are difficult to capture and grow - Multiple month sampling has reported more instable intestinal flora in IBS and bacterial overgrowth px - Studies don’t find consistent findings w/ these mechanisms - Bacteria from probiotic are generally cleared from GI tract w/in 1 week after last ingestion - Real trial evidence overall still weak (most studies are small, significant placebo response in trials)