In this presentation, Dr Vivek Baliga discusses the important aspects of irritable bowel syndrome - a common medical problem in clinical practice. For more articles, visit http://baligadiagnostics.com/author/drbvb/

1. Irritable Bowel
Syndrome
Dr Vivek Baliga
Consultant, Internal Medicine
Baliga Diagnostics, Bangalore

2. Irritable Bowel Syndrome (IBS)
• Highly prevalent disorder that reduces quality of life &
imposes a significant economic burden
• Viewed as static disorder that is hard to define, difficult
to diagnose and impossible to treat
• Definition evolved over past decade to incorporate new
information about this complex disorder
• Rome III Committee
• Either
– Constipation [IBS-C]
– Diarrhea [IBS-D]
– Mixed/alternating [IBS-M]
IBS as chronic disorder characterized by abdominal pain or discomfort associated
with disordered defecation
Brian E. Lacy et al. The treatment of
irritable bowel syndrome. Ther Adv
Gastroenterol (2009) 2(4) 221–238

3. IBS Symptoms
• Symptom onset at least 6 months before
patient 1st seen for formal evaluation
• Abdominal pain/discomfort
1. Present at least 3 days/month for 3 months
2. Associated with >2 of the following:
I. Improvement with defecation
II. Onset associated with change in stool frequency
III. Onset associated with a change in stool form
Recurrent abdominal pain or discomfort is the hallmark difference that
distinguishes patients with functional chronic constipation from
constipation-dominant IBS (IBS-C)
Brian E. Lacy et al. The treatment of
irritable bowel syndrome. Ther Adv
Gastroenterol (2009) 2(4) 221–238

4. Initial Approach to IBS
• Careful history to differentiate
functional symptoms from
organic disorders
• Warning signs that signal the
presence of a serious underlying
disorder
• Abdominal pain/discomfort is
cardinal symptom of IBS
– Related to defecation
– Its absence is incompatible with
IBS diagnosis
– Presence of overlapping
disorders, both gastrointestinal &
nongastrointestinal in nature,
increases pretest of IBS
probability
• Pain related to urination,
menstruation, or exertion
suggests an alternative diagnosis
Brian E. Lacy et al. The treatment of
irritable bowel syndrome. Ther Adv
Gastroenterol (2009) 2(4) 221–238

5. IBS Examinations
• All suspected IBS should undergo a careful physical
exam
– Mild tenderness over sigmoid colon
• IBS once considered a ‘diagnosis of exclusion’
• Mandatory lab/radiologic testing is not necessary
– In younger patients who meet criteria
– Normal physical examination without identifiable ‘red flags’
• Goals of testing
– Establish diagnosis as early as possible
– Initiate treatment based on predominant symptom
– Avoid expensive & unnecessary tests
Brian E. Lacy et al. The treatment of
irritable bowel syndrome. Ther Adv
Gastroenterol (2009) 2(4) 221–238

6. IBS Treatment Goals
Improve individual symptoms of IBS
•Abdominal pain/discomfort, bloating, constipation, & diarrhea)
Ameliorate global symptoms of IBS
Prevent complications of IBS
•Unnecessary surgery, risky diagnostic procedures & adverse
medication side effects from poly-pharmacy
Reduce impact of IBS on individuals by improving
quality of life & minimize impact on health care costs
Clinicians
should
focus on 4
major
goals
Brian E. Lacy et al. The treatment of
irritable bowel syndrome. Ther Adv
Gastroenterol (2009) 2(4) 221–238

7. IBS
TREATMENT
Abdominal Pain &
Discomfort
Brian E. Lacy et al. The treatment of
irritable bowel syndrome. Ther Adv
Gastroenterol (2009) 2(4) 221–238

8. Lifestyle Modifications
• Many initiate treatment for
IBS & constipation with
lifestyle modifications
– Changes in fluid intake,
exercise & diet
• Unfortunately, data to support
this is limited
– "Drink lots of water" no
scientific data available to
support claim
– "Exercise" - no data exists to
support notion
• Bowel training & education
– Constipation develops as
urge ignored to bowel
movement
– Urge occurs upon
awakening/shortly after
eating
– Many, especially with
overlapping pelvic floor
dysfunction note
improvement if they re-
establish set time to use
bathroom
Bowel Regimen
I. Getting up at same time each day
II. Eating breakfast (help initiate gastro colic reflex)
III. Using bathroom at routine, scheduled time, 30–45 min after meal
Brian E. Lacy et al. The treatment of irritable bowel syndrome. Ther Adv Gastroenterol (2009) 2(4) 221–238

9. OTCs: Stool Softeners
• Emollients which soften &
lubricate stool
• In usual doses, docusate
may increase fluid content
of stool by 3–5%
• Though safe &
inexpensive, stool
softeners rarely helpful
• Typical agents
– Magnesium hydroxide (Milk of
Magnesia), magnesium sulfate, or
magnesium citrate
• Recommend use only on
intermittent basis to treat mild
constipation
• Do not cause abdominal bloating or
distention
• Though may cause abdominal
cramps & spasms
• Avoided in renal dysfunction
Brian E. Lacy et al. The treatment of irritable bowel syndrome. Ther Adv Gastroenterol (2009) 2(4) 221–238

10. OTCs: Natural Products
1.Directly stimulate colon & increase colonic
contractions
2.Increase fluid secretion in intestinal tract
• Aloe vera
– Symptom improvement at 4-week trial was similar to placebo
• Other agents not been prospectively studied & used on needed basis
only
• Senna, cascara, aloe, castor oil & bisacodyl
Caution:
Excessive use leads to chronic watery diarrhea & electrolyte disturbances
Brian E. Lacy et al. The treatment of irritable bowel syndrome. Ther Adv Gastroenterol (2009) 2(4) 221–238

11. OTCs: Fibers
• 12 fiber studies
– 4 showed improvement in stool frequency
(polycarbophil,ispaghula husk)
– 1 showed improvement in stool evacuation
– None demonstrated improvement in abdominal pain
• 30–50% treated will have increase in gas, bloating &
abdominal distention
• Fiber supplementation, reasonable treatment
option for constipation-IBS
• Patient needs be told, fiber will not solve abdominal
pain
Brian E. Lacy et al. The treatment of irritable bowel syndrome. Ther Adv Gastroenterol (2009) 2(4) 221–238

12. OTCs: Probiotics
• Live microorganisms , administered in
adequate amounts ameliorate IBS symptoms
1. Stimulating immune response
2. Reducing inflammation
3. Altering gut flora
• Occur naturally in fermented foods
– Yogurt, buttermilk, sour poi, and miso
• Pure + mixed, cultures of potentially
beneficial organisms added to foods or
ingested in tablets, capsules, or liquids
• Improvement in symptoms of abdominal
pain/discomfort & bloating in setting of a
normalized IL-10/IL-12 ratio
Efficacy of B. Infantis
- At dose of 1x108 cfu,
improved abdominal pain &
discomfort
- Bloating, passage of gas,
straining, bowel satisfaction,
& feelings of incomplete
evacuation was significantly
better
Efficacy of VSL#3
Significant improvement
global relief of IBS symptoms
Abdominal pain & bloating
also improved
Brian E. Lacy et al. The treatment of irritable bowel syndrome. Ther Adv
Gastroenterol (2009) 2(4) 221–238

13. Prescription Medications:
PolyEthylene Glycol (PEG)
• High-molecular-weight osmotic agent
• FDA-approved for the treatment of chronic
constipation
– Not currently approved for IBS-C
• Trail with
1. 17 g PEG each day
2. 17 g PEG + 6mg tegaserod twice daily
– Stool frequency increased in both groups
– Abdominal pain improved only in the PEG-tegaserod
group
– No adverse events were reported
Confirms hypothesis that PEG solutions may improve constipation in IBS, but do not
alleviate abdominal pain/bloating
Brian E. Lacy et al. The treatment of irritable bowel syndrome. Ther Adv Gastroenterol (2009) 2(4)
221–238

14. Prescription Medications:
Lactulose
• Synthetic disaccharide composed of galactose & fructose
• Not metabolized by small intestine, so passes unchanged
into colon where it is consumed by colonic bacteria
• Several studies show lactulose improves chronic
constipation
– Not formally evaluated for IBS + constipation & not FDA
approved
• Major side effect
– Gassiness, bloating and distention
– Unlikely to improve symptoms of abdominal pain in IBS-C
– Worsens symptoms of bloating
Brian E. Lacy et al. The treatment of irritable bowel syndrome. Ther Adv Gastroenterol (2009) 2(4) 221–238

15. Tegaserod
• Aminoguanidine indole, acts as a specific 5-HT4 (serotonin-
type-4) receptor agonist
1. Stimulate gastrointestinal peristalsis
2. Increase intestinal fluid secretion
3. Reduce visceral sensation
• FDA approved for treatment of women with IBS-C
• Pivotal studies
– Improvement in both global & individual IBS symptoms
compared with placebo
– Therapeutic gain ranged from 5%-19%
– Relative risk of noting improvement in global IBS symptoms
while on tegaserod was higher than with placebo
• Unfortunately, tegaserod removed in most markets due to
adverse cardiovascular events

16. Prescription Medications:
Lubiprostone
• Bicyclic fatty acid metabolite of prostaglandin E1
– Acts locally within trSelectively stimulates type 2 chloride channels
in epithelia thereby causing efflux of chloride into lumen
– Fluid secretion provides bolus effect that softens stool, increases
intestinal transit & improves constipation
• Act, rapidly metabolized, & has low systemic bioavailability
• FDA approved for chronic constipation in adult men & women
Safety & Efficacy Trial
• Patients treated with any dose of lubiprostone had greater improvement in
mean abdominal pain & discomfort scores
• With 24 mg b.i.d.lubiprostone had greatest improvement in symptom
• Also had greatest adverse events
8 mg twice-daily dose provided best combination of efficacy & safety
Brian E. Lacy et al. The treatment of irritable bowel syndrome. Ther Adv Gastroenterol (2009) 2(4) 221–238

17. Future Therapy:
Linaclotide
• 14-amino-acid peptide that mimics endogenous guanylin &
uroguanylin, both which activate guanylate cyclase C
receptor that stimulates cyclic GMP, which increases
electrolytes & water into lumen
• Preclinical studies
– Accelerated intestinal transit & improved visceral pain
– Showed improved symptoms in chronic constipation
• Trial randomized to 1 of 4 different daily doses(75, 150, 300,
600 mg) or placebo
– Shown to significantly improve stool frequency + symptoms of
straining, bloating & abdominal pain
– Except for bloating using 150 mg dose
More likely to report adequate relief of global IBS symptoms
Promising results resulted in large phase III clinical trial

18. Antibiotics
• Evidence which support antibiotics use
– Enteric flora may differ in IBS compared with healthy controls
– Resulting in increased hydrogen release during carbohydrate fermentation
1. Gaseous symptoms & colonic gas production
– Symptomatic patients found to have higher H2 production when compared with healthy volunteers
– Hypersensitivity to products of colonic fermentation may be responsible for generation of symptoms
2. Evaluated with lactulose hydrogen breath test + rectal barostat testing (rectal sensitivity)
– IBS patients had greater post-lactulose rectal sensitivity testing with greater discomfort even at
low/normal hydrogen production levels
3. IBS & bacterial overgrowth
– Reported that eradication of bacterial overgrowth eliminated 84% IBS symptoms
Rifaximin
• Gut-selective antibiotic not systemically absorbed, has broad-
spectrum activity against gram +ve & gram -ve
aerobes/anaerobes
• Trail rifaximin 400mg 3 times daily
• Reported improvement in global IBS symptoms + bloating
symptoms
Brian E. Lacy et al. The treatment of
irritable bowel syndrome. Ther Adv
Gastroenterol (2009) 2(4) 221–238

19. Smooth Muscle Relaxants
• Therapy for abdominal pain over 2
decades focused on smooth muscle
relaxants (Antispasmodics)
– Ample theoretical grounds for
prescribing
– Clinical experience has been
disappointing -poorly designed, poorly
controlled, and no benefits above
placebo
• Some patients do improve, particularly
with symptoms induced by meals &
complain of tenesmus
• In meal-induced symptoms,
anticholinergics prescribed 30–60 min
before meals
– Peak serum levels coincides with peak
symptoms
Recent Meta-Analysis
- All IBS subtypes included
“Antispasmodic agents
demonstrated modest
improvements in global IBS
symptoms & abdominal pain”
Available only in US
Dicyclomine Hydrochloride
- Improved abdominal pain,
tenderness, global functioning,
& bowel habits
- 68% suffered side effects
when given high doses
Brian E. Lacy et al. The treatment of
irritable bowel syndrome. Ther Adv
Gastroenterol (2009) 2(4) 221–238

20. Tricyclic antidepressants
• Used to treat functional bowel disorders for 3 decades
• Modulate pain both centrally & peripherally
• Secondary amine TCAs (nortriptyline,desipramine)
• Better tolerated due to lower propensity for
anticholinergic, antihistaminic & alpha-adrenergic side
effects
• Side effects
– Worsening constipation in IBS + constipation can limit
therapeutic potential
– Concerns over potential cardiac arrhythmias
• Best supporting data for TCAs use - desipramine
– Significant benefits compared with placebo
Brian E. Lacy et al. The treatment of
irritable bowel syndrome. Ther Adv
Gastroenterol (2009) 2(4) 221–238

21. Selective serotonin reuptake inhibitors
(SSRIs)
• Primarily mediate pain
centrally, but also effects
enteric nervous system
• Prescribed at dosages
standard for treating mental
disorders
• Only 6 studies conducted
– Fluoxetine, Paroxetine,
Citalopram
– Most noted improvement in
overall wellbeing
– Though none showed any
benefit with bowel habits &
abdominal pain
• Selective serotonin and
norepinephrine inhibitors
(SSNRI/SNRI)
 Venlafaxine, duloxetine
 May also have a role in
treatment of IBS pain
• Duloxetine (Cymbalta) studied
& marketed for both
psychiatric disease &
neuropathic pain
 FDA approval for major
depressive disorder, diabetic
neuropathy, fibromyalgia
 Off-label for visceral
hypersensitivity syndromes

22. Anticonvulsants
• Treatment of chronic pain for 40 years
• Meta-analysis investigating anticonvulsants have suggested less
promising
– Results for treatment of both acute and chronic pain syndromes
• Anticonvulsant theoretical sense for neuropathic pain & visceral hypersensitivity
– Little data to support their use & so mostly off-label use
Gabapentin (Neurontin)
Frequently prescribed anticonvulsant for
chronic neuropathic pain
Binds to α2δ subunit of voltage dependent
calcium channel in central nervous system
Thus decrease calcium influx into nerve
terminal and affects subsequent release of
neurotransmitters
Pregabalin (Lyrica)
Targeted for visceral hypersensitivity
syndromes
Demonstrated blunted visceral pain
perception
Increase sensory distension thresholds to
normal levels in those with rectal
hypersensitivity, decrease pain & improve
rectal compliance
Brian E. Lacy et al. The treatment of irritable bowel syndrome. Ther Adv Gastroenterol (2009) 2(4) 221–
238

23. Alternative & Complementary
Medicine
• Peppermint, germanium, lavender oils & derivatives
• Act to relax smooth muscle via a cAMP-dependent mechanism
Peppermint trial reported 75%
patients with >50% reduction in total
IBS symptoms
Meta-analysis with peppermint oil
Significant benefit in overall IBS
symptoms
Carmint (coriander, lemon, mint
extracts)
Potential antispasmodic & sedative
properties
Recent trial, demonstrated
improvements in severity &
frequency of abdominal
pain/discomfort
Acupuncture
Study found benefit no better than
placebo
Cognitive behavioral therapy
Considered as an adjunct
Brian E. Lacy et al. The treatment of irritable bowel syndrome. Ther Adv Gastroenterol (2009) 2(4) 221–238

24. Soluble fibres
• Less irritating than
insoluble fibres, but
doesn’t provide all
nutrients
Insoluble fibres
• Need nutrients that only come in insoluble
fibres
• Eat a good sampling of these, but be
cautious, especially if with diverticulitis
Try to Avoid
1. High fat food - mayonnaise, margarine, salad dressings
2. All batter-fried foods - fried chicken, chips, crackers
3. Most dairy products - butter, ice cream, cheese
4. Some tolerate low-fat yogurt
5. Alcohol
6. Caffeine
7. Chocolate
8. Sodas & carbonated drinks
9. Red meat
10. Decrease your consumption
How to Eat?
• Several smaller
meals or snacks
throughout day
• In relaxing
environment
• No rushing
DO & DON’T

25. THANK YOU...