irritable bowel syndrome part 1 - dr vivek baliga

Irritable Bowel Syndrome

Dr Vivek BaligaConsultant, Internal MedicineBaliga Diagnostics, Bangalore

Brian E. Lacy et al. The treatment of irritable bowel syndrome. Ther Adv Gastroenterol (2009) 2(4) 221–238

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


IBS Symptoms

• Symptom onset at least 6 months before patient 1st seen for formal evaluation

• Abdominal pain/discomfort1. Present at least 3 days/month for 3 months2. Associated with >2 of the following:

I. Improvement with defecationII. Onset associated with change in stool frequencyIII. Onset associated with a change in stool formRecurrent abdominal pain or discomfort is the hallmark difference that

distinguishes patients with functional chronic constipation from constipation-dominant IBS (IBS-C)


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


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


IBS Treatment GoalsImprove 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


IBSTREATMENT

Abdominal Pain & Discomfort

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 RegimenI. 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


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


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


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


OTCs: Probiotics

• Live microorganisms , administered in adequate amounts ameliorate IBS symptoms

1. Stimulating immune response2. Reducing inflammation3. 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#3Significant improvement global relief of IBS symptomsAbdominal pain & bloating also improved


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 day2. 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


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


Tegaserod• Aminoguanidine indole, acts as a specific 5-HT4 (serotonin-type-

4) receptor agonist1. Stimulate gastrointestinal peristalsis2. Increase intestinal fluid secretion3. 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

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


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 symptomsPromising results resulted in large phase III clinical trial


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 levels3. 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


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 USDicyclomine Hydrochloride- Improved abdominal pain,

tenderness, global functioning, & bowel habits

- 68% suffered side effects when given high doses


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

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

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 painBinds to α2δ subunit of voltage dependent calcium channel in central nervous systemThus decrease calcium influx into nerve terminal and affects subsequent release of neurotransmitters

Pregabalin (Lyrica)Targeted for visceral hypersensitivity syndromesDemonstrated blunted visceral pain perceptionIncrease sensory distension thresholds to normal levels in those with rectal hypersensitivity, decrease pain & improve rectal compliance


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 symptomsMeta-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

AcupunctureStudy found benefit no better than

placebo

Cognitive behavioral therapyConsidered as an adjunct


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 Avoid1. High fat food - mayonnaise, margarine, salad dressings2. All batter-fried foods - fried chicken, chips, crackers3. Most dairy products - butter, ice cream, cheese 4. Some tolerate low-fat yogurt5. Alcohol6. Caffeine7. Chocolate 8. Sodas & carbonated drinks 9. Red meat10. Decrease your consumption

How to Eat?• Several smaller

meals or snacks throughout day

• In relaxing environment

• No rushing

DO & DON’T

THANK YOU...

irritable bowel syndrome part 1 - dr vivek baliga

Health & Medicine