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F. Shammas / 04
IBS – Epidemiology, Pathogenesis
Presentation and Diagnosis
F. Shammas / 04
Worldwide Prevalence of IBS
Denmark 7%Denmark 7%
New Zealand 17%New Zealand 17%
UK 22%UK 22%
Nigeria 30%Nigeria 30%
Japan 25%Japan 25%
Australia 12%Australia 12%
China 23%China 23%Germany 12%Germany 12%Netherlands 9%Netherlands 9%
France 20%
Spain 13%US
10–20%
Sweden 13%Sweden 13%Belgium 8%Belgium 8%
IBS data not includedIBS data not included
Canada12%
F. Shammas / 04
Worldwide Prevalence of IBS
0
10
20
30
40
50
60
Pre
vale
nce
(%
)
UK France New US China Nigeria DenmarkZealand
F. Shammas / 04
Prevalence of IBS Diagnosis in Primary Care and Gastroenterology Practices
Primary CarePractice
GastroenterologyPractice
All Other PC Diagnoses
88%
12%IBS
IBS
28%Other GI15%
IBD14%
Peptic20%
Liver10%
Other Functional
13%
F. Shammas / 04
Rates of self-reported IBSin the US by sex and age
Drossman D et al, Dig Dis Sci 1993;38:1569
Age (years)Age (years)
13.513.0
9.4
Female
Male
14
0
Pre
vale
nce
(%
)
15–34 35–44 >45
F. Shammas / 04
IBS Physician Visits
Physician Visits Per YearPhysician Visits Per YearV
isit
s P
er
Ye
ar
Vis
its
Pe
r Y
ea
r
• Patients with IBS tend to require medical attention more than other persons
• IBS accounts for an estimated 12% of primary care visits annually
F. Shammas / 04
US Householder Survey
4.9
13.4
0 5 10 15
Non-IBSPatients
IBS Patients
Days Missed From Work or School in Past Year
Illness-related Absenteeism in IBS vs. Non-IBS Patients
F. Shammas / 04
IBS prevalence versus other important disease states
1Camilleri M, Choi M. Aliment Pharmacol Ther 1997;11:3–152Adams P, Benson V. Vital Health Stat 1991;181:1–212
US prevalence of IBS is 10–15%1
US prevalence rates for other common diseases2
– diabetes 3%
– asthma 4%
– heart disease 8%
– hypertension 11%
F. Shammas / 04
Irritable Bowel Syndrome (IBS) Epidemiology
● Affects approximately 15-20% of the population
worldwide
● 3 times more common in females than males
● Appears in early adolescence or early adulthood. Less
common in children
● Onset declines with advancing age
● Source of suffering, embarrassment, social disability,
and increased healthcare costs
F. Shammas / 04
Other Important Facts About the Epidemiology of IBS
Only 33–50% of people with IBS seek medical attention
GI disorders of function comprise
– 50% of gastroenterology referrals in the UK
– 41% of gastroenterology visits in the US
IBS is estimated to cost the US healthcare system $8 billion per year
IBS is the second most common cause of sick leave after the common cold
F. Shammas / 04
Irritable bowel syndrome
impairs the Quality of Life
(QoL) of patients
F. Shammas / 04
Measuring Quality Of Life (SF-36)
Used extensively in clinical trials Has a well-established validity and reliability Measures 8 dimensions of health:
• physical functioning
• social functioning
• physical role
• emotional role
• mental health
• vitality (degree of energy or fatigue)
• bodily pain
• general health
F. Shammas / 04
Decreased QOL in All 8 SF-36 Domains23 (N=1000)
Domain IBS Non-IBS
Physical Functioning 84.78 93.10
Social Functioning 73.66 88.32Physical Role 71.28 87.24Emotional Role 78.01 91.37Mental Health 72.46 81.18Vitality 52.82 66.31Bodily Pain 60.54 77.42General Health 55.72 75.20
F. Shammas / 04
Comparative QoL in IBS Patients and Healthy Controls
100
80
60
40
20
0
Mea
n s
core
Physic
al
funct
ionin
g
Role p
hysic
al
Bodily p
ain
Gener
al h
ealth
Vitalit
y
Social
funct
ionin
g
Role e
motio
nal
Men
tal h
ealth
SF-36 scale
US norms
UK norms
US study sample
UK study sample
F. Shammas / 04
Measured Decrease in Patient QOL
SF-36 Results by Survey Group
30
40
50
60
70
80
90
PhysicalFunctioning
SocialFunctioning
PhysicalRole
EmotionalRole
MentalHealth
Vitality Bodily Pain GeneralHealth
IBS US General Population Migraine Asthma Female (15-34) GERD
F. Shammas / 04
Impaired QoL in IBS
100
80
60
40
20
0
Asymptomatic controlsIBSChronic heart failure
Sco
re
Physic
al
funct
ionin
g
Role p
hysic
al
Bodily p
ain
Gener
al h
ealth
Vitalit
y
Social
funct
ionin
g
Role e
motio
nal
Men
tal h
ealth
SF-36 scale
F. Shammas / 04
IBS Impact on Quality of Life (QOL)
Decrease patient QOL
Interfere with daily activities, work, and leisure time
Impact sleep, diet, ability to travel, and sexual functioning
Affect ability to function in family- and work-related roles
Contribute to lost productivity and work absenteeism
F. Shammas / 04
Irritable Bowel Syndrome (IBS)Pathogenesis
• Altered intestinal motility
• Abnormal visceral perception/sensitivity
The cause of IBS is poorly understood. However,
improvements in assessment of gut functioning, have
improved the understanding of the syndrome, which is
now considered to be through:
F. Shammas / 04
PathogenesisAltered Motility
Hypomotility
Bowel movements
Hypermotility
C-IBS D-IBS
F. Shammas / 04
PathogenesisAbnormal Visceral Perception/Sensitivity
Physiologicstimuli
Noxiousstimuli
IBS
Physiologicstimuli
Filteringmechanism
Noxiousstimuli
Normal
GI tractGI tract
F. Shammas / 04
Possible Mechanisms of Visceral Hypersensitivity
Altered sensation
AbnormalCNS motor
control
Abnormal GIsmooth muscle
activity
AbnormalCNS sensoryprocessing
Abnormal GImechanoreceptor
sensitivity
F. Shammas / 04
• Food and dietary substances• Chocolate, Dairy products, Fatty meals, Gas-producing food (beans)
• Drugs and medications• Laxatives
• Narcotics
• Calcium Channel Blockers
• Stress• Anxiety, depression, alcohol abuse, and eating disorders
• Hormones• Alteration of sex hormones (menstrual cycle)
• Inflammation and Infection
Irritable Bowel Syndrome (IBS) Trigger Factors
F. Shammas / 04
Psychologic Factors that AffectGI Function
Anxiety, panic, depression
Somatoform disorders (unexplained bodily symptoms)
Physical, sexual or emotional abuse
Alcohol or substance abuse
Eating disorders
F. Shammas / 04
Psychiatric Illness in Patients with IBS / Functional Bowel Disorders and Organic GI Diseases
100
80
60
40
20
0 McDonald Colgan Craig Ford Blanchardand Bouchier, et al., and Brown, et al., et al.,
1980 1998 1984 1987 1990
IBS/functional bowel disorder
Organic GI disease
Pat
ien
ts (
%)
F. Shammas / 04
Classification of IBS According to Predominant Symptom
Other factors to consider include duration and severity of symptoms, disease course, patient demography, referral status and psychosocial features
C-IBS D-IBSA-IBS
F. Shammas / 04
Irritable Bowel Syndrome (IBS)Diagnosis
IBS is a condition that can be diagnosed
positively on the basis of an established
series of criteria, together with limited
exclusion of organic, metabolic or
infectious diseases
F. Shammas / 04
IBS Diagnostic Criteria
• The Manning Criteria
• Rome I Criteria
• Rome II Criteria
F. Shammas / 04
The Manning Criteria (1978)
Four symptoms significantly more common in IBS than in organic disease:
– pain relieved by defecation
– more frequent stools at the onset of pain
– looser stools at the onset of pain
– visible abdominal distention
A strong trend for the following:
– passage of mucus
– sensation of incomplete bowel emptying
F. Shammas / 04
1. At least 3 months of continuous or recurrent symptoms of abdominal pain or discomfort that is
– relieved by defecation and/or– associated with a change in
frequency of stool; and/or– associated with a change in
consistency of stool
2. Two or more of the following at least25% of the time– altered stool frequency
– altered stool form– altered stool passage (straining,
urgency, feeling of incomplete evacuation)
– passage of mucus; and/or– bloating or feeling of abdominal
distention
Rome I Criteria1 Rome II Criteria2
1. At least 12 weeks, which need not be consecutive, in the past 12 months, of abdominal discomfort or pain that has two of three features
– relieved by defecation; and/or– onset associated with a change in
frequency of stool; and/or
– onset associated with a change in form (appearance) of stool
2. The following symptoms are not essential but the more of them that are present, the more confident is the diagnosis: – abnormal stool frequency – abnormal stool form – abnormal stool passage
– passage of mucus – bloating or feeling of abdominal
distention
F. Shammas / 04
Rome II Criteria for Diagnosis of IBS
Abdominal pain or discomfort for at least 12 weeks (not necessarily consecutive) in the preceding 12 months, that has at least two of the following features
– Relieved by defecation
– A change in stool frequency
– A change in stool form or appearance
F. Shammas / 04
Rome II Criteria for Diagnosis of IBS
The following symptoms are not essential, but the more of them that are present, the more confident is the diagnosis
–Abnormal stool frequency (>3/day or <3/week)–Abnormal stool form (lumpy/hard or loose/watery stool)–Abnormal stool passage (straining, urgency or feeling
of incomplete evacuation)–Passage of mucus–Bloating or feeling of abdominal distention
F. Shammas / 04
Irritable Bowel Syndrome (IBS)Recognizing IBS
Careful interpretation of the
pain and stool characteristics
is the most important step in
recognizing IBS
F. Shammas / 04
Irritable Bowel Syndrome (IBS)Bristol Stool Form Scale
Separate hard lumps, like nuts (hard to pass). Results from slow transit
Sausage-shaped but lumpy
Like a sausage but with cracks on its surface
Like a sausage or snake – smooth and soft
Soft lumps with clear cut edges (easy to pass)
Fluffy pieces with ragged edges
Watery, no solid pieces. Results from very fast transit
Stool Form Appearance Type
1
2
3
4
5
6
7
Tru
e c
on
stip
atio
nT
rue
dia
rrhe
aId
ea
l n
orm
al
F. Shammas / 04
The positive diagnosis of IBS:a symptom-based approach
Identify current primary symptoms
Initiate a treatment plan based on symptoms
Look for ‘Red Flags’ based on:● history● physical examination● laboratory tests
Follow up in 3–6 weeks
Perform selected diagnostic tests to rule out organic disease
Make a positive diagnosis
IBS with constipation● abdominal pain/discomfort● bloating● constipation
IBS with diarrhea● abdominal pain/discomfort● bloating● diarrhea
F. Shammas / 04
Identify ‘Red Flags’
History
Unintentional weight loss
Onset in older patient (>50 years)
Family history of cancer or IBD
Initial labs
↓ HGB
↑ WBC
↑ ESR
Abnormal chemistry
↑ TSH
Physical
Abnormal exams
Rectal bleeding/obstruction
Positive Flexible sigmoidoscopy or colonoscopy (>50 years)
Red Flags
F. Shammas / 04
Irritable Bowel Syndrome (IBS)Investigations
• Endoscopy (sigmoidoscopy)
• Stool analysis
• Occult blood
• Parasites
• Leukocytes
• Excessive fat
• Radiography
• Hematology
• RBC and WBC counts
• ESR
• C-reactive protein
• Thyroid function tests
F. Shammas / 04
Further Evaluation Based on Symptom Subtype
Constipation Diarrhea Pain/gas/bloating
No Lactose-H2 breath testAdditional tests:
Plain abdominal X-ray
If intractable, consider:
Small bowel X-ray Trial of amitriptyline
Other carbohydrate-H2
breath test GI manometry
? Balloon distention test
Colonic transit testAnal manometry +balloon expulsion
Measure rectoanal angleRectal sensation and emptying
Defecating protography
Stool OSM, ELEC, LaxativesJejunal aspirate for O and PTransit test: SB and colon
Rectal sensation75SeHCAT test/cholestyramine
Predominant symptoms
F. Shammas / 04
Differential diagnosis of IBS
Hyper/hypothyroidism
Inflammatory bowel disease (IBD)
Colorectal cancer
Infectious diarrhea
Lactose malabsorption
F. Shammas / 04
IBS is a stable diagnosis
No change in IBS diagnosis: 97%
Evidence suggests that clinicians can be confident once an IBS diagnosis is made
After an initial diagnosis of IBS, there was no change over time in the diagnosis of 97% of patients (median follow up: 29 years) from Olmsted County, Minnesota
F. Shammas / 04
Irritable Bowel Syndrome (IBS)Principals of Management
• General principles
• Lifestyle modification (dietary changes)
• Psychotherapy/hypnotherapy
• Drug therapy
F. Shammas / 04
Irritable Bowel Syndrome (IBS)Management – General Principles
• Establishing confidence
• Educating the patient about IBS
• Patient reassurance that IBS could be treated
• Dispelling the patient’s fears and misconceptions
• Individualizing a treatment plan based on the patient’s need
• Scheduling appointments for return visits
F. Shammas / 04
Patient Education in IBS
Education and reassurance are essential elements of clinical management
Patients need information about the nature of their condition, such as its high prevalence, the causes, triggers, symptoms, and disease course
Patients should be made aware of the available treatment options e.g. pharmacologic and non-pharmacologic therapies
F. Shammas / 04
Dietary and Lifestyle Modification in IBS
Stress management/reduction techniques have been shown to improve patient well being
Diet diaries may be used to identify dietary factors that tend to trigger IBS symptoms. Elimination or reduction in intake of these foods may reduce the frequency and severity of symptoms
F. Shammas / 04
• Dietary measures
• avoid foodstuff that may cause symptoms as legumes, caffeine, artificial
sweeteners, dairy products, chocolate, fat-rich diets
• encourage high-fiber diets
• prescribe wheat bran
• Avoid drugs that disturb bowel function
Dietary and Lifestyle Modification in IBS
– Drugs causing constipation
• Opiates, Anticholinergics• Tricyclic anti-depressants
• 5-HT3 antagonists• Calcium channel blockers
– Drugs causing diarrhea• Misoprostol• Cisapride
• Antacids containing MgOH• Herbal teas containing senna• Alcohol, caffeine
F. Shammas / 04
Psychotherapy/Hypnotherapy in IBS
Stress management
Interpersonal psychotherapy
Cognitive behavioral therapy
Relaxation techniques to reduce anxiety
Hypnotherapy may also be useful for treating both psychologic and physical symptoms
F. Shammas / 04
Other Complementary Therapies
Herbal medicine (ex: peppermint, ginger, etc…)
Traditional Chinese medicine (herbs, acupuncture)
Traditional Japanese medicine (Kampo)
Traditional Indian medicine (ayurveda)
‘Probiotics’
F. Shammas / 04
Drug Therapy in IBS - Highlights
• There is currently no cure for IBS
• Current treatments for IBS are mainly
symptomatic (end-organ treatments)
• There is a profound placebo response to any
IBS treatment
• Most treated patients end up receiving a
combination of different drugs
F. Shammas / 04
The IBS Prescription Market
Antidiarrheals 5%
Anticholinergics/Antimuscarinics/Antispasmodics
51%
Other (eg, sucralfate) 4%
Cisapride 3%
PPIs8%
H2RAs19%
Antiemetics (including metoclopramide) 3%
Carhartics and Laxatives 7%
F. Shammas / 04
Multiple Prescription Therapies Used
One-year Data for Continuously Enrolled Patients Who Used GI Drugs
Switch22%
Augment42%
Single18%
Continuous7%
Intermittent11%
64%
• 64% of IBS patients switched or augmented their initial prescriptions
F. Shammas / 04
Irritable Bowel Syndrome (IBS)End-Organ Drug Therapy
Predominantsymptom
Treatment Increase fiberOsmotic laxative
Bulk laxative
Antidiarrheal Antispasmodic agentsAntidepressants
DiarrheaConstipation
Abdominal pain/distension
(post-prandial/chronic)
Altered bowel function
F. Shammas / 04
Drug Therapy
LaxativesAnti-Diarrheal AgentsAntispasmodicsAntidepressantsAnxiolyticsOther Medications
F. Shammas / 04
Irritable Bowel Syndrome (IBS)Drug Therapy - Laxatives
LaxativeLaxative MembersMembers Mode of ActionMode of Action
Stimulants Phenolpthalein, bisacodyl,
senna, castor oil
Increase intestinal motility (peristalsis)
Decrease absorption of water and electrolytes
Saline/osmotic Magnesium salts, sodium
phosphate, lactulose,
sorbitol
Retain water in intestinal lumen (osmosis)
Increase intestinal motility (peristalsis)
Bulk-forming Bran, psyllium,
methylcellulose
Cause intestinal distension induce peristalsis
Fecal softeners Docusate, mineral oil,
glycerin
Lower surface tension intestinal fluids penetrate
fecal mass soft, easily passed stools
F. Shammas / 04
Irritable Bowel Syndrome (IBS)Anti-Diarrheal Agents
• Loperamide (Imodium)
- Acts on the circular and longitudinal muscles of the gut- Decrease GI motility and reduce mucosal secretion.- can have a constipating effect and can lead to dependence
• Diphenoxylate (Lomotil)
F. Shammas / 04
Irritable Bowel Syndrome (IBS)Antispasmodics
• Anticholinergics
• Buscopan (hyoscine), Fybogel (mebeverine), dicyclomine
• Probanthine (propanthalene)
• Smooth Muscle Relaxants
• Duspatalin (mebeverine)
• Spasmo-canulase
• Spasmonal (alverine)
• Dicetel, Eldicet (pinaverium bromide)
F. Shammas / 04
Irritable Bowel Syndrome (IBS)Drug Therapy – Centrally-Acting Agents
• Antidepressants
• TCA: Tofranil (imipramine), Desipramine
• Elavil (amitriptyline)
• SSRI: Prozac (fluoxetine)
• Anxiolytics
• Librax (benzodiazepine)
F. Shammas / 04
Irritable Bowel Syndrome (IBS)Drug Therapy – Other Medications
• Opioid Agonists (Fedotozine)
• Somatostatin (Sandostatin-octreotide)
• Cholecystokinin (CCK) antagonists (Loxiglumide)
• Selective Muscarinic M3 Antagonists
(zamifenacin and darifenacin - Pfizer)
F. Shammas / 04
Treatment of C-IBS
Currently there is no approved drug treatment on the market that has consistently proved to be more effective than placebo in the management of ALL symptoms of C-IBS
There is a need for new effective treatments that are well tolerated and target each individual symptom of C-IBS
F. Shammas / 04
Irritable Bowel Syndrome New Therapeutic Approaches
The 5-HydroxyTryptamine (5-HT) Modulators
F. Shammas / 04
New Therapeutic Approaches in IBS
Psychosocialfactors
Alteredsensation
Alteredmotility
Sympathetic
S2, 3, 4
Vagal nuclei
F. Shammas / 04
Alteration of 5-HT (serotonin)
function has been implicated in
the pathogenesis of IBS,
namely in the altered motility
and visceral hypersensitivity…
F. Shammas / 04
Serotonin (5-hydroxytryptamine)
• Serotonin is an important neurotransmitter in both the CNS
and ENS. It is found in 3 main areas in the body; intestinal
wall, blood vessels and CNS
• Approximately 90% of the body’s 5-HT is found in the GIT
• The remainder acts as a neurotransmitter in the myenteric
plexus
• Serotonin has various effects on the intestine, including:
• Inhibition of gastric acid secretion
• Stimulation of synthesis and release of gastric and colonic mucus
• Contraction or relaxation of the GI smooth muscles
F. Shammas / 04
CGRP5-HT4
receptor
Enterochromaffin cells5-HT
Grider JR et al. Gastroenterology 1998;115:370–80
Release ofCGRP, VIP, SP
ACh/SPMotorneurons
VIP/PACAP/NOSMotor neurons
5-HT triggers the peristaltic reflex in Humans
F. Shammas / 04
GI Serotonin (5-HT)Actions
Food reaches the gut
Intestinal distension
stimulates peristalsis
Release of 5-HT from the intestinal mucosa
modulates visceral sensitivity
Stimulates ions and water secretion in the lumen of small intestine & colon
F. Shammas / 04
The GI Serotonin Receptors
• Receptors for serotonin are located on the
afferent neurons and interneurons in the
ENS
• They are involved in the perception of
abdominal pain and GI motility
F. Shammas / 04
The Serotonin Receptors Subtypes
• Approximately 15 subtypes of 5-HT receptors have
been identified in the body
• Only 2 receptors are involved in GI motility and
abdominal pain
• Subtype 3 (5-HT3)
• Subtype 4 (5-HT4)
F. Shammas / 04
The Serotonin Receptors Subtypes
• Subtype 3 (5-HT3)
• Mediate visceral pain
• Reduces colonic transit (induces peristalsis)
• Increases intestinal secretions
• Subtype 4 (5-HT4)
• Stimulates peristalsis
• Involved in modulation of intestinal absorption/secretions
that influences stool consistency and visceral sensitivity
F. Shammas / 04
Role of 5-HT in the GI Tract
5-HT has multiple roles in GI physiology with its effects being due to different mechanisms and different receptor subtypes
5-HT3 receptor activation increases intestinal secretion, motility and colonic tonus
5-HT4 receptor activation leads to peristalsis and increased water/chloride secretion. It can also result in inhibition of intestinal tone and enhanced visceral sensitivity
95% of body’s serotonin in GIT
• 90% in EC cells• 10% in enteric neurons
F. Shammas / 04
The 5-HydroxyTryptamine (5-HT)
Receptors
Agonists & Antagonists
F. Shammas / 04
5-HT4
receptor
Partial agonist
Full agonist
antagonist
The 5-HydroxyTryptamine (5-HT) Receptors
Agonists, Partial Agonists & Antagonists
F. Shammas / 04
5-HT3 Antagonists
5-HT3 antagonists cause constipation and increase colonic transit time.
5-HT3 antagonists have potential use in nausea and vomiting as well as in D- IBS
Ondansetron (Zofran) and Granisetron (Kytril) are currently used to treat chemotherapy-induced nausea and vomiting
Alosetron (Lotronex) and Cilansetron (Calmactin) are being developed for use in D-IBS patients
F. Shammas / 04
5-HT3 Antagonists in D- IBS
Alosetron (Lotronex) approved for treatment of D-IBS in female patients (not effective in men)
– Relieves abdominal pain / discomfort within 1-4 weeks– Decreases fluid secretion in small intestine– Relieves stool frequency and bowel urgency within 1
week– Principal side effect: constipation in 20–30% of patients
Cilansetron (Calmactin) decreased colonic contractile responses to distention
F. Shammas / 04
5-HT4 Receptor Effects
Enhances esophageal clearance and gastric emptying, and hastens intestinal and colonic transit
Mediate reflexes controlling GI motility and secretion
Mediate perception of visceral pain
F. Shammas / 04
5-HT4 Receptor Agents
5-HT4 partialagonists
Zelmac®
• A selective 5-HT4 receptorpartial agonist
• Normalizes bowel function and rapidly relieves abdominal pain/discomfort, and bloatingin IBS patients
5-HT4
antagonists
Prucalopride
Enterokinetic activity
• Being evaluated inpatients with chronicconstipation (phase III trials)
Piboserod
• Alleviates symptoms of D-IBS
• In phase II trials
5-HT4
agonists
F. Shammas / 04
Combined 5-HT3 antagonists/5-HT4 agonists
Cisapride (Prepulsid® - Janssen)
– Gastroprokinetic agent
– Approved for use in GERD
– Off-label use in IBS
– Withdrawn from US market in July 2000 due to cardiac safety concerns (80 fatalities)
F. Shammas / 04
The 5-HydroxyTryptamine (5-HT) Receptors
Agonists, Partial Agonists & Antagonists
Product Mode of Action Indication Principal Claims
Alosteron (Lotronex)
GSK
Selective 5-HT3 antagonist
Women with D-IBS ♦ Relieves abdominal pain / discomfort within 1-4 weeks
♦ Decreases fluid secretion in small intestine
♦ Relieves stool frequency within 1 week
♦ Relieves bowel urgency within 1 week
Prucalopride
Phase III - Janssen
Selective 5-HT4 full agonist
♦ Chronic constipation ♦ IBS (pipeline)
♦ Enhances intestinal motility ♦ Normalization of stool frequency,
consistency and completeness of evacuation
Cisapride
Prepulsid - Janssen
5-HT3 antagonist / 5-HT4 agonist
♦ GERD
♦ IBS (off-label)
♦ Promotes gastric motility
♦ Reduces heartburn due to GERD
Tegaserod
Zelmac - Novartis
5-HT4 partial agonist
♦ C-IBS ♦ A new GI sensorimotor modulator
♦ Normalizes altered motility in IBS ♦ Rapid relief of abdominal pain,
bloating and constipation ♦ Excellent cardiac safety profile
F. Shammas / 04
Targeting the 5-HT4 Receptor
Should Benefits
the
Constipation- Predominant
IBS Patients
