18 - IBS Flashcards
1
Q
Definition of IBS
A
- 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
2
Q
Features of IBS
A
- 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
3
Q
Characterization of IBS
A
- 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
4
Q
Pathophysiology of IBS
A
- 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
5
Q
Alarm features of IBS
A
- Weight loss ( >5 kg)
- Bloody stools
- Severe diarrhea
- Recurring fever
- Onset > 50 y/o
- Family history of colon cancer, IBD
6
Q
Psychologic disorders
A
- 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
7
Q
IBS therapy
A
- Location, severity, previous response to therapy involved in selection process
- IBS subtypes are highly unstable
- Predominant sx guide most therapeutic plans
8
Q
Non-drug therapy for IBS
A
- 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)
9
Q
Behavioural therapies for IBS
A
- Relaxation
- Biofeedback
- Hypnotherapy
- Cognitive behavioural (CBT)
- Psychotherapy
- Evidence that these are more effective than placebo for some sx of IBS
10
Q
CBT for IBS
A
- 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
11
Q
Drug therapy for IBS
A
- 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
12
Q
Problems w/ IBS studies
A
- 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
13
Q
Pharm options for IBS w/ constipation
A
- Fiber based products
- Osmotic and salt laxatives
- Stimulant laxatives
- Prucalopride
- Linaclotide, lubiprostone
14
Q
Fiber based products for IBS w/ constipation
A
- 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
15
Q
Osmotic and salt laxatives
A
- Lactulose -> gas, bloating, and taste a problem
- Magnesium -> poorly absorbed, act as osmotic laxative
- Phosphate
- PEG based
16
Q
Stimulant laxatives
A
- Senna based and Bisacodyl
- Quicker onset (< 24 h)
- SE = cramping
17
Q
Approach w/ laxatives for IBS
A
- 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
18
Q
Prucalopride (Resotran)
A
- 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
19
Q
Linaclotide (Constella, Linzess)
A
- 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
20
Q
IBS w/ constipation – summary
A
- 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
21
Q
Pharm options for IBS w/ diarrhea
A
- Loperamide
- Cholestyramine
- Alosetron
- Fiber
- Newer agents = eluxadoline, rifaximin
22
Q
Loperamide - MOA, SE, dose
A
- 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
23
Q
Cholestyramine
A
- 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
24
Q
Eluxadoline (viberzi, truberzi)
A
- Mu opioid agonist and delta opioid receptor antagonist
- Minimally absorbed, acts locally for IBS w/ diarrhea
25
Q
Alosetron (Lotronex)
A
- 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
26
Q
Fiber for IBS w/ diarrhea
A
- Used to increase stool consistency
- Target fiber intake usually around 30 g/day but start lower and gradually increase to reach target
27
Q
IBS w/ diarrhea – summary
A
- 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
28
Q
IBS w/ bloating and gas
A
- 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
29
Q
Recommendations for IBS w/ gas
A
- Some foods associated w/ increased gas formation (ex: beans, onions, celery)
- Gas expulsion stimulated w/ food and exercise (go for a walk after meals)
30
Q
Antispasmodics
A
- 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
31
Q
IBS and pain
A
- Behaviour and aversion techniques can be employed
- Antidepressants and NSAIDs used in refractory cases
- Narcotic analgesics usually not successful
32
Q
Antidepressants for IBS
A
- 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
33
Q
Antibiotics and probiotics for IBS
A
- 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
34
Q
What are probiotics and which are most studied?
A
- 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
35
Q
Probiotics in IBS
A
- 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)
