This is a presentation regarding the epidemiology, pathophysiology,clinical features,symtoms,diagnosis,treatment and management options for the disease -irritable bowel disease.
2. In OP > 30% of patients havefunctional gastrointestinal disorders.
IBSisthe most common functional bowel disorder
In 1966,DeLor coined the term to the irritable bowel syndrome (IBS) -functional
enteropathy
IBS was defined as “a functional bowel disorder in which abdominal pain is
associated with defecation ora change in bowel habits”
Younger people have ahigher prevalence of IBS
Female predominance
3.
4.
5. IBS is characterized by the presence of abdominal pain associated with disturbed defecation
Diagnostic Criteria:
Manning
Kruis
ROME IV
6. Manning: diagnostic cut off- 3 or more of the 6 symptoms
listed
In Kruis criteria, IBS is excluded if any physical finding or any
of the laboratory parameters assessed by the physician is
abnormal
ROME IV- criteria fulfilled for the previous 3 months, with
the symptom onset atleast 6 months before diagnosis
7. Clinical features
Abdominal pain- mandatory for diagnosis
either aggravated or relieved by defecation
with increase or decrease in stool frequency,
with loose or harder stools
8. Constipation and diarrhea-
Bristol stool form scale is used to measure stool form
Changes in stool form roughly correlate with colonic transit time
Classification of IBS patients according to the predominant symptom:
IBS with constipation (IBS-C), with diarrhea (IBS-D), or mixed stool pattern (IBS-
M)
9.
10. Bloating and visible distension:
Feeling of bloating in 60% of the patients, more in IBS-C
Visible distension is more in women
17. Visceral hypersensitivity
Abnormal sensitization within the dorsal horn of spinal cord or higher up in the CNS
Neurotransmitters involved- 5-HT, neurokinins, calcitonin gene related peptide
Transient receptor potential vanilloid-1 increased in rectosigmoid- mediate visceral pain
Serine proteases act as signaling molecules
18.
19. Low grade mucosal inflammation, immune
activation and altered intestinal permeability
Increased levels of pro-inflammatory cytokines and elevated mast cell counts
B- lymphocyte activation in the blood
Increased intestinal permeability and reduction in integrity of epithelial barrier
20.
21. Abnormal 5-hydroxytryptamine
metabolism
5-HT in the enterochromaffin cells of intestine released after a meal activate both intrinsic
and extrinsic primary afferent neurons
Re uptake of 5-HT by enterocytes via the serotonin transporter (SERT) and broken down in to 5-
hydroxy-indole acetic acid limiting its action
Patients with IBS-D have reduced 5-HT re-uptake; IBS-C have impaired release of 5-HT
25. Psychologic factors
Sustained stress- important for both onset and persistence of IBS
History of abuse might be present- modulates central response to pain
Psychiatric conditions co-exist in IBS
Immune activation of the intestine with elevated TNF-⍺ has been linked to anxiety and
depression
26. CNS dysregulation
Reduced inhibitory feedback on the emotional arousal network
Aberrant central processing of sensory information
Impaired activity levels of the dorsolateral prefrontal cortex
27.
28. Genetic factors
Relatives of a patient with IBS are 3 times more likely to report symptoms of
IBS
Shared disease susceptibility genes for another entity that increases risk of IBS
(e.g., lactose intolerance, depression or anxiety, somatization, or an immune
system that increases risk of infection)
MC - 5-HTT LPR polymorphism in the serotonin transporter gene (SLC6A4)
Missense mutation of SCN5A gene- implicated in IBS
Increased TNFSF15 mRNA in the rectal mucosa of IBS-D patients and an
association between SNPs in TNFSF15 and risk of IBS-D
35. Included: Six RCTs and 16 non-randomized interventions
There was a significant decrease in IBS SSS scores for those individuals
on a low FODMAP diet in both the RCTs and non-randomized
interventions
Significant improvement in the IBS-QOL score for RCTs and for non-
randomized interventions.
Following a low FODMAP diet was found to significantly reduce
symptom severity for abdominal pain, bloating and overall symptoms
in the RCTs.
36. Peppermint
Peppermint (Mentha piperita) is a natural herbal remedy for IBS
L-menthol's blockade of calcium channels and attendant smooth muscle
relaxation
modulation of transient receptor potential voltage channels with effects on
visceral sensation,
direct antimicrobial and anti-inflammatory effects,
modulation of psychosocial distress.
37. TCAs
TCAs are a class of agents, now commonly referred to as neuromodulators,
which include amitriptyline, nortriptyline, imipramine, and desipramine.
TCAs improve visceral pain and central pain by acting on norepinephrine and
dopaminergic receptors
Improves abdominal pain because of their anticholinergic effects
At higher doses, can also slow GI transit, thereby improving symptoms of
diarrhea
Twelve RCTs evaluated the efficacy and safety of TCAs for the treatment of IBS
with improvement in global IBS symptoms
Anticholinergic effects -dry mouth, dry eyes, urinary retention, constipation, and
cardiac arrhythmias.
38. Lubiprostone
Lubiprostone is classified as a secretagogue
Lubiprostone is a locally acting prostaglandin E1 analog with high affinity for
type-2 chloride channels located in the apical membranes of intestinal epithelial
cells
Activation of these receptors increases intestinal secretion and peristalsis
Lubiprostone is US FDA-approved for the treatment of adult women with IBS-C
at a dosage of 8 μg twice daily
Lubiprostone has been evaluated in 3 RCTs and a high-quality systematic
review/meta-analysis and found to be more effective than placebo for overall IBS-
C symptoms.
appropriate safety profile with the most common AEs being GI in nature
39. Guanylate cyclase-C (GC-C) agonists
Guanylate cyclase-C (GC-C) agonists target GC-C receptors residing in the apical
membranes of intestinal epithelial cells.
There are currently 2 US FDA-approved agents for the treatment of IBS-C—
linaclotide 290 μg and plecanatide 3 mg.
These agents are classified as secretagogues.
Both activate GC-C receptors, increasing intestinal fluid secretion and peristalsis,
with preclinical trials identifying reduced activation of visceral nociceptive
neurons.
These effects explain the global improvements experienced with linaclotide or
plecanatide.
Diarrhea is the most common AE experienced
40. Tegaserod
Tegaserod is the only US FDA-approved 5-HT4 receptor agonist for the
treatment of adult women younger than 65 years with IBS-C.
It is contraindicated in patients with more than 1 CV risk factors
A systematic review and meta-analysis of 11 trials treated with tegaserod were
less likely to have persistent IBS-C symptoms
In 2002, it was voluntarily withdrawn from the market because of concerns over
the risk of cardiovascular events
Additional analyses found no evidence of increased proarrhythmic risk or
platelet aggregation in these studies.
In 2019, based on this evaluation, tegaserod was approved again for treatment
of IBS-C.
