Download Irritable Bowel Syndrome

Irritable Bowel Syndrome
Dr T. Ghafghazi Professor of
Pharmacology Isfahan university
of Medical Sciences and a Member
of Goldaru Scientific Department
Irritable Bowel Syndrome
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Irritable bowel syndrome (IBS) is a chronic
gastrointestinal
disorder with a range of symptoms that
significantly affect
quality of life for patients. The difficulty of
differential
diagnosis and its treatment may significantly
delay initiation
of optimal therapy.
I. B. S.
Assessment
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IBS associated with:
 abdominal
discomfort
 Bloating
 constipation
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IBS is defined as “abdominal pain or discomfort
that occurs in association with altered bowel habits
over a period of at least three months.”1 Symptoms
of IBS include abdominal pain, change in bowel
habits (diarrhea or constipation), bloating, and
incomplete defecation.2 However, symptom
presentation and severity vary.3 Since current
diagnostic criteria are based on symptoms,1
definitive diagnosis of IBS presents challenges due
to overlap in symptom presentations with other
diseases or associated conditions (e.g., lactose
intolerance, inflammatory bowel disease, celiac
sprue, small intestinal bacterial overgrowth).
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Lack of definitive diagnosis
and treatment and the chronic, debilitating nature
of IBS often compel patients to change or limit
their diets,2 seek non-prescribed pharmacological
regimens (complementary and alternative medicine
[CAM] therapies in particular), and modify
routine daily activities in order to manage
Symptoms.
Pathogenesis and Pathophysiology
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The pathophysiology of IBS is
distinguishable
from celiac disease and inflammatory
bowel
diseases (e.g., ulcerative colitis, Crohn’s
disease)
since IBS does not present with gross
organic or
biochemical abnormalities.
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Although the pathogenesis of IBS is
not known, a multi-factorial involvement
of diet, gene mutations,
psychosocial factors, and immunemediated
processes is hypothesized.
The contribution of these
factors varies and in many cases no
single cause can be determined.
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One theory regarding the pathophysiology
of IBS involves interference
of neurotransmission between
the central nervous system (CNS)
and the intestines. A number of
structures in the CNS are connected
with the gut via serotonergic and
cholinergic nerves – referred to as
the enteric nervous system
(ENS).
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Independent of the afferent connections, the
intestine uses serotonin itself to regulate gut
motility. Serotonin binds to 5-HT4 and 5-HT3
receptors, and its signaling activity is
terminated by binding to the specific serotonin
reuptake transporter. It has been shown that
the activity of this transporter is reduced in
several GI disorders (including IBS) that
present with common symptoms of dysregulated
intestinal motility caused by persistent
serotonin release at its respective receptors.
What is Irritable Bowel Syndrome(IBS)?
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A group of functional bowel disorders
Chronic abdominal complaints without a structural or
biochemical cause
Constitutes a major health problem with
gastrointestinal (GI) symptoms
The cause of IBS is unknown.
Affects up to ~20 % adults in the industrialized
world
The condition is more frequent in women.
Symptoms of IBS
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Abdominal discomfort and pain
Bloating, mucous in stools, diarrhea, constipation, or
alternating diarrhea and constipation
Depression, anxiety or stress
IBS can be subdivided into
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Diarrhea-predominant (IBS-D)
Constipation-predominant (IBS-C)
Alternating diarrhea and constipation
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Less common symptoms include: feeling sick,
headache, belching, poor appetite, feeling quickly
'full' after eating, heartburn, and bladder
symptoms (an associated 'irritable bladder').
Some people have occasional mild symptoms. Others
have unpleasant symptoms for long periods. Many
people fall somewhere in between, with flare-ups of
symptoms from time to time. IBS is common and
can affect anyone at any age. The cause of IBS is
not known. There is no test that confirms the
diagnosis of IBS. A doctor will usually diagnose IBS
from the typical symptoms.
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Stress and anxiety can trigger
symptoms, or make them worse. Some
people have found such things as
relaxation techniques, stress
counselling, cognitive behaviour therapy,
psychotherapy, and similar therapies
useful in controlling symptoms of IBS.
Serotonin is important in gut function
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GI disorders may be related to
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an imbalance of serotonin in the gut
an improper reaction of the digestive system to serotonin
a faulty communication network between serotonin in the gut
and the brain and spinal cord.
Serotonin plays a major role in modulating intestinal
movement and perception of pain. Helps to soften
stools by releasing water.
Serotonin (5-hydroxytryptamine, 5HT)
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A monoamine neurotransmitter
Found in cardiovascular tissue, the
peripheral nervous system, blood cells,
and the CNS
HO
95 % resides in the GI tract
Serotonergic neurons secrete 5HT
The function of serotonin is exerted upon
its interaction with specific receptors.
14 distinct families of 5HTreceptors;
5HT1, 5HT2, 5HT3 and ….
NH2
N
H
5HT3 receptors and its antagonists
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5HT3 receptors
 A ligand-gated cation channel
 Present in the GI tract
 Control sensation, contraction of intestinal muscle
 Release of fluid into the intestines
5HT3 antagonists
 Slow intestinal transit
 Decrease intestinal secretions
 Decrease the water content of stool
 Diminish colonic pain
5HT4 receptors and its agonists
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5HT4 receptors
 G-protein-coupled receptor
 Present in the GI tract
 Mediate both relaxation and contraction of circular
smooth-muscle strips
 Induces small bowel and to a lesser extent colonic fluid
secretion
5HT4 agonists
 Accelerate gastric emptying
 Accelerate small and large bowel transit
 Increase stool water content
Treatment
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The goal of current standard pharmacological
treatment is to alleviate clinical symptoms of IBS.
Because conventional treatments typically do not
get to the root of the problem or provide anything
but symptomatic relief, patients often seek CAM
therapies, including cognitive-behavioral therapy,
herbal therapies, probiotics, mind-body therapies,
acupuncture, dietary changes, and exercise.
Iberogast Drop,Iberogol Drop
Composition:
contains ethanolic extracts of
bitter candytuft(Iberis amara),being the
mostimportant, The other ingredients are
angelica root(‫)سنبل ختایی‬,chamomile
flowers)‫(بابونه‬,carawayfruit )‫(زیره‬mary thistle
)‫(خارمریم‬balm leaves )‫(بادرنجبویه‬pepperment
leaves(‫ )نعناع فلفلی‬Greater celandine (‫)مامیران‬and
liquorice roots)‫)شیر ین بیان‬
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The active ingredients are extracts from:
Iberis amara, fresh whole plant (bitter candytuft,
blomsteriberis)flanonoides, cucurbitacins
Angelica archangelica, dried root (angelica, kvanne)furanocoumarins
Matricaria recutita, dried flower (matricaria, kamomill)bisabolol
Carum carvi, dried fruit (caraway, kummin)polysaccharides
Silybum marianum, dried fruit (milk thistle, mariatistel)flavonoides
Melissa officinalis, dried leaves (melissa, citronmeliss)rosmarinic acid
Mentha piperita, dried leaves (peppermint, pepparmynta)menthol
Chelidonium majus, dried herb (greater celandine, skelört)flavonoides
Glycyrrhiza glabra, dried root (liquorice, lakritsrot)flavonoides
Pharmacological Actions
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Binding to serotonin receptors was shown for the
active substances in Iberogast and for the
individual crude drugs Chelidonium
majus herba, Matricaria recutita flos, and to a
lesser extent Iberis amara herba recens, Mentha
piperita folium and Angelica silvestris radix. Binding
to muscarine M3 receptors was
demonstrated for Iberogast and for the individual
drugs Chelidonium majus herba, Iberis
amara herba recens, and Angelica archangelica
radix.
Acid Production
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Inhibition of acid production, as
demonstrated with isolated and enriched
guinea pig parietal
cells, has been shown for Iberogast and for
the individual crude drugs Iberis amara herba
recens, Matricaria recutita flos, Mentha
piperita folium, Chelidonium majus herba and
Glycyrrhiza glabra radix.
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Iberogast relaxes isolated stomach wall strips from the
regions corpus and fundus in the
guinea pig. On the antrum region an increase in phasic
activity was demonstrated. The
individual crude drugs had different activities on the
motility of the stomach wall regions.
Iberis amara herba recens increased the tonic and phasic
activity in all three regions, whereas
Chelidonium majus herba had an increasing effect only in
the antrum region. Angelica
archangelica radix had a relaxing effect in the fundus
area.
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Iberogast acts tonicising on relaxed ileum and
relaxing on contracted ileum. Anti-ulcerogenic
effect measured as effects on prostaglandin E2
and leukotriene levels in the gastric mucosa has
been demonstrated for Iberogast and for Iberis
amara herba recens, Carum carvi fructus,
Angelica archangelica radix, Mentha piperita folium,
Glycyrrhiza glabra radix and Matricaria
recutita flos.
Anibacterial Effect
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Antibacterial activity on Helicobacter pylori was
exerted by Iberogast. Angelica archangelica
radix, Chelidonium majus herba, Matricaria recutita
flos, Mentha piperita folium, Melissa
officinalis folium and Glycyrrhiza glabra radix all
contributed to this effect.
It has been shown that each of the 9 crude drugs
contained in Iberogast is of importance for
the overall effect.
The pharmacological Effects of Iberogast
IBEROGAST—a safe and effective standard in the
treatment of functional gastrointestinal disorders
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Functional dyspepsia (FD) and irritable bowel
syndrome (IBS) are frequent disorders affecting
quality of life. They often require long-term
treatment. Abdominal symptoms of both disorders
can overlap, making differential diagnosis and
treatment challenging. The extracts of the herbal
combination preparation (Iberogast) exert
pharmacological effects in different gastrointestinal
regions and can address symptoms of both FD and
IBS.
The multi-herbal drug (Iberogast) has prosecretory
action in the human intestine
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There is growing evidence that (Iberogast, fixed
combination of hydroethanolic herbal extracts),
besides being effective in functional dyspepsia, also
improves symptoms in irritable bowel syndrome
(IBS).. Clinical data indicate that modulation of
mucosal secretion is a promising approach to treat
intestinal disorders associated with IBS
Iberogast
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Due to the 5-lipoxygenase inhibition the drug
can exert anti-inflammatory effects.It also
exhibits an antibacterial effect, as is able to
inhibit the growth of certain disease-causing
bacteria, such as Helicobacter pylori several
subspecies, and other pathogenic intestinal
inhabitants.There is also a carminative action
for Iberogast.
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Clown’s mustard (Iberis amara) (a.k.a. wild or bitter
candytuft) is believed to contain the most active
components (Glucosinolates and cucurbitacins) in having
specific actions on GI tract tone - although components in
its other herbs also play a role:
Clown's mustard seems to increase slow wave frequency
and amplitude in the small intestine - which causes
peristaltic movement. Its extract has a long history of use
for normalizing tension and spasms in the gastrointestinal
tract and relieving heartburn. It reduces inflammation,
triggers fullness and reduces discomfort in the upper
abdomen.
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Iberogast has been studied in over 15 clinical studies.
The results from all of the studies indicate that >
80% of people with IBS, GERD, Non-ulcer dyspepsia
(NUD) and drug-induced dyspepsia will experience
significant relief without side effect.
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The extracts of the herbal combination preparation
(Iberogast) exert pharmacological effects in
different gastrointestinal regions. Safety and
efficacy data of 12 clinical trials using this drug in FD
and IBS since 1990 were evaluated . Double-blind and
randomized studies versus placebo or active control
found statistically significant effects on patients’
symptoms with a comparable efficacy to a standard
prokinetic. Non-interventional and retrospective
studies confirmed these effects.
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IBEROGAST
, placebo or cisapride. One placebo controlled study (308
patients) was
conducted over a treatment period of eight weeks. In the
placebo controlled studies,
IBEROGAST
showed a significantly superior efficacy vs. placebo for
the main outcome
criterion. In the study versus Cisapride, an equivalent
efficacy for IBEROGAST
Was determined
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Results suggest that Iberogast is a
secretogogue in the human intestine by direct
epithelial actions and through activation of
enteric neurons. The prosecretory effect is
due to increased epithelial Cl− fluxes via Cadependent ClCa channels. Iberogol may be a
novel option to treat secretory disorders
associated with IBS and constipation.
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Four main mechanisms have been identified:
Stimulation of digestive secretions - through interactions with the
bitter receptors on the taste buds of the tongue.
Regulation of peristalsis (the rhythmic contraction of the
intestines) - by exerting either a relaxing or stimulating effect on the
intestinal smooth muscle.
Protecting the lining of the stomach and intestines - by stimulating
the production of mucus by mast cells (mucus-producing cells of the
stomach and intestines) as well as preventing the formation of
inflammatory substances within the intestinal tract.
Prevention of excessive flatulence - by reducing the formation of
intestinal gases.
Iberogast has been very successfully
used to treat IBS and other GI
diseases – for several years in Germany
 Ammon, H., P. et al. Spasmolytic and
tonic effect of Iberogast in intestinal
smooth muscle. Phytomedicine. 13 Suppl
5: 67-74, 2006
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Arnim, U. et al.Iberogasta phytopharmacon for patients
with functional dyspepsia: results of a multicenter,
placebo-controlled double-blind study. Am J
Gastroenterol. 102 (6): 1268-75, 2007
-In one study , 20 patients diagnosed with chronic
functional disorders for 1- 20 years were given Iberogast
for 3 to 32 days – Patients also stopped taking medications
( E.g. antacids, anti-spasmodic agents, motility inducing
substances) used to treat abdomenal pressure/pain,
belching, heartburn, vomiting, nausea, fullness, lack of
appetite, constipation, and diarrhea.
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Abdominal pressure and pain - was the most common
experienced symptom, with 11 of the patients rating it as
severe. After 6 days of treatment, only 6 of the patients
continued to rate their abdominal pain and pressure as
severe. After 2 weeks, this symptom had completely
resolved for 16 patients.
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Diarrhea - rated as severe in five of the patients,
but after 2 weeks, only one patient continued to have
moderate diarrhea.
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Anti-Emetic Effect of
Iberogast
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The previously reported anti-emetic effects of Iberogast
were studied objectively in a clinical study of 18 inpatients aged between 32 and 84 years. Most had severe
underlying disorders characterized by moderate to
marked nausea. Patients received the recommended dose
of 20 drops 3 times a day for up to 14 days. A clear effect
was observed after two days' treatment. After 5 days'
treatment there was no further vomiting or nausea,
except in one patient who had some residual symptoms.
The experience of previous studies--that Iberogast is
extremely well tolerated--was confirmed
Contraindications
IBEROGAST
 must not be taken in case of known
allergies to the active ingredients
 Patients with pre-existing liver disease
should consult their doctor prior to
commencing
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Pregnancy and lactation
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From a toxicological perspective no
evidence of concern regarding the
administration of
IBEROGAST
during pregnancy and lactation can be
determined from the available data on
reproductive toxicity (embryotoxicity,
teratogenicity, peri- and postnatal
toxicity).
Interactions with other medicinal
products
No interactions were known at the time
of printing.
 Adverse Reactions : In very rare
cases, less than one in 10,000,
hypersensitivity reactions such as
exanthema,
 pruritus and dyspnea could occuring.
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Toxicology
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Product-specific investigations of single-dose
and repeat-dose toxicity have shown a very low
toxicity forIberogast .
In vivo genotoxicity studies on the productspecific extract have been performed. No
genotoxicity could be found for Iberogol in the
tests performed. Nor are there any reports in
the literature of genotoxicity for the individual
crude drugs
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Extensive investigations with IBEROGAST
in two animal species were performed assessing
acute, subchronic and chronic toxicity at 3 and 6
months, in the areas of reproductive
toxicity, fertility, embryonic, pre-and post-natal
development and mutagenicity. There is no
evidence for any acute or chronic-toxic,
reproductive - or embryo-toxic potentials, even
when
doses of up to 1200 times the recommended daily
dose were tested.
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Various studies evaluated the
tolerability profile of this preparation:
the incidence of adverse drug reactions
was 0.04 %. The worldwide spontaneous
reporting system confirmed this profile.
It has a favorable tolerability which is
relevant for long-term treatment.
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Dosage and Administration
Unless otherwise prescribed, IBEROGAST
is taken before or with meals in some liquid as
following:
Adults and children over 12 years Take 20 drops 3 times a day
(1.0 mL)
Children 6 to 12 years Give 15 drops 3 times a day (0.75 mL)
Children 3 to 6 years Give 10 drops 3 times a day (0.5 mL)
Children 3 months to 3 years Give 8 drops 3 times a day (0.4 mL)
Children under 3 months Give 6 drops 3 times a day (0.3 mL)
Duration of use depends on the kind, severity and course of the
disease.
Shake the bottle before use.
Overdose
In acute oral toxicity testing of IBEROGAST in various animal
species and during longterm
therapeutic experience in humans, no toxic signs of overdose
were observed.