(GIT Pharm6) Drug Treatment For Irritable Bowel Syndrome (20th September 2023)
(GIT Pharm6) Drug Treatment For Irritable Bowel Syndrome (20th September 2023)
(GIT Pharm6) Drug Treatment For Irritable Bowel Syndrome (20th September 2023)
SYNDROME
Presented By:
Dr.H.S.Imran-ul-Haque
Asst.Prof
DIMC
• IBS is a disorder of the GI tract that interferes with the normal
functions of the colon.
• IBS is described as a functional disorder, which means that it involves
symptoms that cannot be attributed to a specific injury, infection, or
other physical problem.
• IBS is one of the most common disorders seen in primary care and
the most common reason for referral to gastroenterologists.
• In GI-related problems 15% to 20% suffer from IBS.
• IBS affects women about twice as often as men.
• IBS can occur at any age but is most common between 20 and 50
years.
• There is a strong association between emotional distress and IBS.
• Psychosocial trauma (eg, a history of abuse, recent death of a close
relative or friend, or divorce) is more likely to be found in patients
presenting with IBS than in the general population.
• An increased prevalence of psychiatric disorders such as anxiety,
depression and personality disorders occurs among adults with IBS.
• Some people show first evidence of IBS after contracting
gastroenteritis (sometimes referred to as postinfectious IBS).
• Menstrual periods may trigger symptoms in some women.
PATHOPHYSIOLOGY
• Enteric nerves control intestinal smooth muscle action and are
connected to the brain by the autonomic nervous system.
• IBS is thought to result from dysregulation of this “brain–gut axis.”
• The enteric nervous system and the central nervous system (CNS) are
interconnected and interdependent.
• A number of neurochemicals mediate their function, including
serotonin (5-hydroxytryptamine or 5-HT), acetylcholine, substance P,
and nitric oxide, among others.
• Serotonin is particularly important because the GI tract contains the
largest amounts in the body.
• Two 5-HT receptor subtypes, 5-HT3 and 5-HT4 , are involved in gut
motility, visceral sensitivity, and gut secretion.
• The 5-HT3 receptors slow colonic transit and increase fluid
absorption,
• 5-HT4 receptor stimulation accelerates colonic transit.
• Studies suggest that the colon of IBS sufferers is abnormally sensitive
to normal stimuli.
• Enhanced visceral sensitivity manifests as pain, especially related to
gut distention
• Some IBS patients demonstrate sensitivity to common foods such as
wheat, beef, pork, soy, and eggs.
CLINICAL PRESENTATION AND DIAGNOSIS
• The diagnosis of IBS is made by symptom-based criteria and the
exclusion of organic disease.
• Patients should be questioned about the frequency, consistency,
color, and size of stools.
• Because of the functional nature of IBS, a patient may present with
symptoms of upper GI problems such as gastroesophageal reflux
disease or with excessive flatulence.
• Patients should also be questioned about diet to establish any
symptom relationship to meals or specifically after consumption of
certain foods
• The Rome III diagnostic criteria define IBS as occurring when
symptoms of recurrent abdominal pain or discomfort exist for at least
3 days/month in the last 3 months associated with two or more of the
following:
• (a) improvement with defecation,
• (b) onset associated with a change in the frequency of stool, and/ or
(c) onset associated with a change in the form (appearance) of stool.
• These criteria should be fulfilled for the previous 3 months with
symptom onset at least 6 months prior to diagnosis.
TREATMENT
• The principal goal of IBS treatment is to reduce or control symptoms.
• A standard treatment regimen is not possible because of the
heterogeneous nature of the IBS patient population.
• Patients suffering from IBS can benefit from clinician support and
reassurance.
Treatment
Non-
Pharmacological
Pharmacological
Nonpharmacologic Therapy
Diet and Other General Modifications:
• Dietary modification is a standard therapeutic modality.
• Food hypersensitivities and adverse effects have been associated with IBS,
especially IBS-D.
• Elimination diets are the most commonly used strategy, usually focusing on
milk and dairy products, fructose and sorbitol, wheat, and beef.
• Flatulence may be controlled by reducing gas-causing foods (beans, celery,
onions, prunes, bananas, carrots, and raisins).
• Response to elimination diets varies widely, but they may be useful in
individual patients.
• Care should be taken to avoid nutritional deficits while attempting to
eliminate offending foods.
• The low FODMAP (fermentable oligosaccharides, disaccharides,
monosaccharides and polyols) diet is said to control IBS symptoms in
some patients.
• FODMAPS are carbohydrates that are poorly absorbed and quickly
fermented (by bacterial action).
• The gas byproduct of the bacterial action is thought to contribute to
IBS symptoms.
• Probiotics may also be an option for some patients with IBS.
• Bifidobacterium infantis is one product used for its effect in
constipation, diarrhea, gaseousness, bloating, and abdominal
discomfort.
• It has not been associated with significant untoward effects.
Pharmacologic Therapy
Agents for Pain and Bloating:
• Botanicals Peppermint oil is widely advocated;
• it acts as an antispasmodic agent due to its ability to relax GI smooth
muscle.
• However, it also relaxes the lower esophageal sphincter, which could
allow reflux of gastric contents into the esophagus.
Antispasmodics:
• Dicyclomine and hyoscyamine have been among the most frequently
used medications for treating abdominal pain in patients with IBS.
• Side effects include blurred vision, constipation, urinary retention,
and (rarely) psychosis.
• These drugs may be used in patients with intermittent postprandial
pain.
Antidepressants:
• Tricyclic antidepressants (TCAs) such as amitriptyline and doxepin
have been used with some success for treatment of IBS-related pain.
• They modulate pain principally through effects on neurotransmitter
reuptake, especially norepinephrine and serotonin.
• Low-dose TCAs (eg, amitriptyline, desipramine, or doxepin 10–25 mg
daily) may help patients with IBS who predominantly experience
diarrhea or pain.
The selective serotonin-reuptake inhibitors (SSRIs):
• Paroxetine, fluoxetine, and sertraline are potentially useful due to the
significant effect of serotonin in the gut.
• SSRIs principally act on 5-HT1 or 5-HT2 receptors, but they can also have
some effect on gut-predominant 5-HT3 and 5-HT4 receptors, perhaps
reducing visceral hypersensitivity.
• They may be beneficial for patients with IBS-C or when the patient
presents with IBS complicated by a mood disorder.
• Serotonin–norepinephrine reuptake inhibitors may offer some benefit in
IBS patients who also have depression or anxiety accompanied by
significant pain (Venlafaxine,Desvenlafaxine & Duloxetine).
Agents for Constipation Predominance
Bulk Producers:
• These agents may improve stool passage in IBS-C but are unlikely to
have a favorable effect on pain or global IBS symptoms.
• Psyllium may increase flatulence, which may worsen discomfort in
some patients.
• Methylcellulose products are less likely than psyllium to increase gas
production.
• Although fiber-based supplement use is common in IBS-C,
methylcellulose may be dose adjusted in diarrhea to increase stool
consistency.
Linaclotide:
• This drug is a guanylate cyclase-C (GC-C) agonist indicated for
treatment of IBS-C in adults.
• Linaclotide relieves the abdominal pain, bloating and constipation
associated with IBS-C while exhibiting a low tendency for systemic
side effects.
• However, diarrhea may prove troublesome in some patients.
• Clinical trials have demonstrated improved quality of life in treated
patients.
Lubiprostone:
• This agent is also FDA approved for treatment of IBS-C, but only in
women age 18 years and older.
• Lubiprostone is generally well tolerated in such patients.
• It is typically given in smaller doses than used in chronic idiopathic
constipation.
• However, as with treatment for constipation, nausea may be an
adverse effect that limits use
Tegaserod Maleate:
• This 5-HT4 receptor agonist was shown to be effective in IBS-C but
was withdrawn from the market because of the risk of heart attack,
stroke, and unstable angina (heart/chest pain).
• The FDA can authorize its availability and use for emergency
situations only.
Agents for Diarrhea Predominance
Eluxadoline:
• This agent is a mu-opioid receptor agonist that reduces bowel
contractions.
• In July 2015, the FDA approved eluxadoline for treatment of adults
with IBS-D.
• The most common adverse effects are constipation, nausea, and
abdominal pain.
Rifaximin:
• This is a semisynthetic antibiotic with very low systemic absorption.
• Research suggests bacterial overgrowth plays a role in producing
bloating experienced by some IBS patients.
• Rifaximin has proven to be better than placebo in relieving bloating,
and its lack of absorption reduces the likelihood of adverse effects.
• In July 2015, the FDA approved rifaximin for treatment of IBS-D in
adults
Loperamide:
• Loperamide stimulates enteric nervous system receptors, inhibiting
peristalsis and fluid secretion.
• It improves stool consistency and reduces the number of stools.
• Consequently, it is most useful in patients who have diarrhea as a
prominent symptom.
• However, it does not lessen abdominal pain and can occasionally
aggravate pain
Alosetron:
• Stimulation of 5-HT3 receptors triggers hypersensitivity and hyperactivity of the large
intestine.
• Alosetron, a selective 5-HT3 antagonist, blocks these receptors and is indicated for
treatment of women with severe IBS-D.
• To be eligible for treatment, patients should have frequent and severe abdominal pain,
frequent bowel urgency or incontinence, and restricted daily activities.
• Alosetron has been shown to improve overall symptoms and quality of life.
• It can cause constipation in some patients.
• Because of an association with ischemic colitis, alosetron can be prescribed only within
strict guidelines, including signing of a consent form by both patient and physician.
• Patients selected for treatment must exhibit severe chronic IBS symptoms and have
failed to respond to conventional therapy.
THANK YOU