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IBS Background
Functional constipation
What is IBS?
A common functional GI disorder manifested by a group of symptoms
Abdominal pain/discomfort Bloating/distention Constipation and/or diarrhea
No known structural or biochemical abnormalities Symptoms may be exacerbated by eating, stress and some pharmacologic agents Significantly affects quality of life
Thompson WG et al. Gut 1999;45(Suppl. 2):437
IBS History
. . . occasional pain in the intestines and derangement of their powers of digestion, with flatulence . . .
Powell, 1818
. . . spasmodic stricture of the colon an occasional cause for confinement of the bowels . . .
Howship, 1830
. . . the bowels are at one time constipated, at another time lax, in the same person . . . how the disease has two such different symptoms I do not profess to explain . . .
Cumming, 1849
Historical Perspective
Long dismissed as a psychosomatic condition
No clear etiology Predominantly affects women 2 (~70% of sufferers are women) Condition not fatal
1
Prevalence (%)
50 40 30 20 10 0
UK1
USA2
New Zealand3
1
France4
China5
Nigeria6
Denmark7
Heaton K et al. 1992; 2Longstreth G, Wolde-Tsadnik P 1993 3 Welch G, Pomare W 1990; 4Bommalaer G et al. 1986 5 Bi-zhen W, Qi-Ying P 1988; 6Olubuyide O et al. 1995; 7Kay L et al. 1994
Male
15 Female
10
<45
>65
Camilleri M, Choi M. Aliment Pharmacol Ther 1997;11:315 2 Adams P, Benson V. Vital Health Stat 10 1991;181:1212
Not GI (22)
~75% Nonconsulters1
~70% Female2
1
~30% Male2
Drossman D, Thompson WG. Ann Intern Med 1992;116(Pt 1):100916 2 Sandler S. Gastroenterology 1990;99:40915
Productivity Burden
14 12
10 8
6
4 2
p=0.0001
IBS
Non-IBS
Drossman D et al. Dig Dis Sci 1993;38:156980
Patients with some missed workdays Average number missed workdays* Patients who cut back some days Average number days cut back*
*Over the previous 4 weeks
Drossman DA et al. Dig Dis Sci 1993;38:156980 AGA Teaching Unit in IBS, 1997
IBS sufferers incur 74% more direct healthcare costs than non-IBS sufferers
IBS patients have more physician visits for both GI and non-GI complaints
Abdominal pain
Psychologic factors
Drossman D. Aliment Pharmacol Ther 1999;13(Suppl. 2):314 2 Thompson WG et al. Gut 1999;45(Suppl. 2):9437 3 Hahn B et al. Digestion 1999;60:7781
IBS
30
Nearly one in 20 reported being hospitalized in the previous year 25% reported being hospitalized for IBS in the past
71% reported more abdominal or intestinal surgeries than women without IBS (58% versus 34%)
Rates of reported gallbladder operations, hysterectomies and appendectomies were higher
Pathophysiology of IBS
1970s
An anticholinergic drug shown to reduce mealstimulated sigmoid motility in IBS patients3
1
Kumar D, Wingate DL 1985; 2Camilleri M, Phillips SF 1989; 3 Kellow JE, Phillips SF 1987; 4Quigley EM et al. 1984
Brain-gut interaction2
Visceral hypersensitivity2
Abnormal motility2
1950
2000
Prior A, Read N. Aliment Pharmacol Ther 1993;7:17580 Drossman D. Aliment Pharmacol Ther 1999;13(Suppl. 2):314
Hypermotility
Constipation
Diarrhea
Visceral Sensitivity
Visceral hypersensitivity
Can be induced in normal subjects Is more prevalent in IBS patients1,2
IBS Normal
Colonic distention
Contains many neurotransmitters, including 5-HT, substance P, VIP (vasoactive intestinal peptide), and CGRP (calcitonin gene-related peptide)
GI tract 95%
Enterochromaffin cells Neuronal
Sensory neuron
Enterochromaffin cells
Sensitivity
Psychology
Life stress Psychologic state Coping Social support
Eating disorders
IBS or Functional GI Disorder (FGID) and Organic GI Disease Patients with Psychiatric Illnesses
100 80 Patients (%) 60 40 IBS/FGID Organic GI
20
0 McDonald and Bouchier 1980 Colgan et al. 1998 Craig and Brown 1984 Ford et al. 1987 Blanchard et al. 1990
Early life
Genetics Environment
Outcome
Medications MD visits Daily function Quality of life
Physiology
Motility Sensation
Diagnosis of IBS
Drossman D. Aliment Pharmacol Ther 1999;13(Suppl. 2):314 2 Thompson WG et al. Gut 1999;45(Suppl. 2):437
Urgency
Straining
Bloating (fullness/swelling)
Passage of mucus
Rome I Criteria
Rome II Criteria
At least 12 weeks, which need not be consecutive, in the last 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
Thompson WG et al. Gastroenterol Int 1992;5:7591 2 Thompson WG et al. Gut 1999;45(Suppl. 2):437
Drossman D. Aliment Pharmacol Ther 1999;13(Suppl. 2):314 2 Moore J et al. Br J Obstet Gynaecol 1998;105:13225
Blood work Thyroid function tests Stools (e.g. occult blood) Fiberoptic sigmoidoscopy
1 2
Hammer J, Talley NJ. Am J Med 1999;107(5A):5S11S Schmulson MW, Chang L. Am J Med 1999;107(5A):20S6S
1,2
Management of IBS
Pharmacotherapy of GI symptoms
Set realistic goals Monitoring and modification
Psychologic treatments
Antidepressants Referral to pain management
AGA Teaching Unit on IBS, 1997
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
Bloating
Antispasmodics Antiflatulents
Altered bowel motility Loperamide Cholestyramine Psyllium Methylcellulose Tegaserod Calcium polycarbophil Lactulose 70% sorbitol PEG solution
Altered motility
Altered sensation
Camilleri M, Choi M-G. Aliment Pharmacol Ther 1997;11:315
Medical management
Diet Psychologic or behavioral options
Psychotherapy Stress management
Drossman D. Aliment Pharmacol Ther 1999;13(Suppl. 2):314
Conclusion
Current treatment of symptoms of IBS often requires use of more than one medication to control the multiple symptoms
Current medical therapies for symptoms of IBS have been insufficiently effective and there is a need for novel approaches to treatment