Irritable bowel disease/syndrome

I am professionally pharmacist. These slides for clinical based those students who study in pharmacy program. These students get more benefits about it.

1. Irritable Bowel
Disease/Syndrome

2. Introduction
•Two idiopathic diseases
of the GIT
•Closely related clinical
presentations.

•Diseases are
–Ulcerative colitis (UC) and Crohn disease (CD) .

•UC
–chronic recurring mucosal inflammation of the colon..
•CD
–chronic recurring trans mural inflammation of the GIT
from the mouth to the anus. CD most commonly affects the
small bowel and colon.

3. Definition-

“a functional bowel disorder
in which abdominal pain or discomfort is associated
with defecation
or
changes in bowel habits
with features of disordered defecation”

5. IBD vs IBS
IBD IBS
chronic inflammation of the gastrointestinal
tract .

Involves …..UC and CD.
characterized by symptoms of abdominal pain
or discomfort
that is associated with disturbed defecation
patterns.
It includes:
Proctitis. Inflammation of the rectum.

Pancolitis. Disease affecting the entire colon

Backwashileitis. Inflammation of the terminal
ileum

Ileocolitis. (affecting the ileum and colon)
Ileitis. (affecting the i leum)

Crohn disease.(affecting the stomach and
duodenum)

Jejunoileitis. (inflammat ion of the jejunum and
i leum)
Involves
constipation predominant( IBS-C)

diarrhea predominant ( IBS-D)

type with patients alternating between the two
( IBS-A)

7. Epidemiology
•CD is higher in urban areas.
•UC is higher in rural areas.
•IBD rates higher in developed countries compared to less
developed countries.
•Asians appear to be at lower risk for developing IBD than
whites.
•IBD is more common in young adults than older patients.
•Men and women are at similar risk of developing IBD.
•IBS is more common in women than men.
•IBS appears to be as common in Asia/India as in
Western countries.

8. Manifestations
IBD IBS
UC
increasing stool urgency and
frequency.
bloody stool and mucus in the stool.
varied disease intensity
interspersed with asymptomatic
periods.
pain relieved by defecation.
alternating bowel habits.
abdominal distention.
mucus in the stool.
sensation of incomplete defecation.
CD
patterns of symptoms relate to
disease location and type
(e.g. , inflammatory, fibrostenotic,
fistulizing)
that can be useful in determining
therapy decisions.
Constipation-predominant IBS
Pain/periodic constipat ion alternating with normal
periods.
Pain(periodic, and/or a continuous dull ache)
eating can commonly trigger symptoms.
Other common symptoms are bloating, nauseas,
dyspepsia, flatulence, and heartburn.
Diarrhea-predominant IBS
characterized by precipitous diarrhea
occurring during meals or immediately postprandial.
pain, bloating, rectal urgency, and incontinence.

9. Causes
IBD IBS
Environmental factors Exact cause of IBS is unknown
Genetic factors
IBD occurs 30-100 times more frequently in first
-degree relatives of IBD patients
Comorbid factors.
Viral gastroenteritis.
emotional health,.
Diet.
environment .
concur rent drug therapy, and hormones
Anxiety disorders.
Panic disorder .
Major depressive disorder
Emotional conflict.
Possibility of sexual or physical abuse.
Abnormal immune response
overly vigorous and abnormally long immune
response.
immune system activation with subsequent
infiltration of the tissue by lymphocytes,
macrophages, and other cells.
Virus or bacterial infect ion, dietary antigens or
inappropriate immune response to normally
non-antigenic microbes
Clostridium difficile, fungal protozoal viral ,
and helminthic pathogens.
Drug- induced enterocolitis can induce IBD- like
symptoms.
Non-steroidal ant i - inflammatory drugs (NSAIDs) ,
Gold compounds, oral contraceptives, enteric
potassium supplements, pancreatic enzymes

10. Pathophysiology
IBD IBS
UC.
edema followed by loss of fine vascular
pattern and increased mucosal friability.

Ulceration may also be present .

Colon may begin to become featureless and
tubular in nature.
Constipation:
Abnormality in intestinal motility
Under lying muscle dysfunction as well as
hyperactive response to factors, such as food.


Abnormal increases in frequency of contractions
can lead to functional constipation.
CD.
Inflammation and subsequent injury of
tissue known as cryptitis.
leads to crypt abscess and subsequently
focal aphthoid-ulceration.
Influx and proliferation of macrophages and
other inflammatory cells.
May lead to lymphedema and bowel wall
thickening.
This thickening can lead to fibrosis.
Diarrhea
Diminished motor function of the under lying
musculature can lead to diarrhea.
Pain of IBS may be caused by abnormally strong
contraction of the intestinal smooth muscle.

The first few days of menstruation can lead to
transiently elevated prostaglandin
E2 (PGE2 ) , resulting in increased pain and
diarhea.

11. Clinical presentation/Sign n Symptoms
UC.
Altered stool frequency.
Bowel sensation, and abdominal pain.
Begin as mild disease,worsens as the disease
progresses.
Patients may suffer from continuous or
intermittent attacks.
Hematochezia(blood in stool), Tenesmus,
Lower left quadrant pain.
Nausea, vomiting, and weight loss.
Aphthous ulcers, Iritis and uveitis
IBS
Abdominal pain
(crampy, localized to the lower left abdomen)

Alteration of bowel habits.

Diarrhea, constipation, and alternating diarrhea
and constipation.

Bloating, gas, belching, heartburn, reflux
disease,

Achalasia, early feeling of fullness on eating
Nausea.

Painful menstruation, sexual dysfunction, and
frequent or urgent urination.
CD.
Symptoms mimicking appendicitis or
intestinal obstruction.

Abdominal pain,Diarrhea,Weight loss,Fever.
Arthralgias,Acute peripheral arthritis

Ankylosing spondylitis, peripheral arthritis
Iridocyclitis, uveitis, and episcleritis.

12. Clinical evaluation/Diagnosis
IBD (Table 53-1. CPR) IBS
UC
Patient symptoms. Most common.
Severity of symptoms correlates with
disease severity.
Increased C- reactive protein.
Platelet count , erythrocyte
sedimentation rate (ESR).
Decrease in hemoglobin.
Serum albumin can fall quickly in
severe disease
Sigmoidoscopy can be useful for
assessing disease
Identifying positive symptoms by medical history/Physical exam .
Routine blood testing.
Sigmoidoscopy and colonoscopy are done to visualize the bowel
Guided by Rome II & I I I cr i ter ia.
Rome II diagnostic criteria
Pain relieved by defecation;
Pain associated with a change in frequency and form of stool.
Abnormal stool frequency.
Abnormal stool form.
Abnormal stool passage.
Passage of mucus.
Bloating.
CD
Elevated ESR,C- reactive protein.
Hypo-albuminemia, anemia, and
leukocytosis.
Right lower quadrant pain.
Malabsorption.
Dietary deficiency, electrolyte
imbalances, coagulopathy, and
increased risk of bone fractures.
low-grade fever.
Rome III diagnostic criteria
Improvement with defecation
Onset associated with a change in form & frequency of stool.
Criteria fulfilled for the last 3 months.
Discomfort (an uncomfortable sensation not described as pain)

13. Disease classification
Ulcerative Colitis Chron’s Disease
Mild UC…less than four stools per day
with/without blood,normal ESR.

Moderate UC ..more than four stools per
day but minimal signs of toxicity fever ,
tachycardia, anemia, elevated ESR.

Severe UC…more than six bloody stools
per day, evidence of toxicity(fever ,
tachycardia, anemia, elevated ESR)

Fulminate..more than ten bowel
movements, continuous bleeding,
toxicity, abdominal
tenderness/distension, need for blood
transfusion,.
Mild to moderate disease
patients who are ambulatory,are able to take food orally;have no
symptoms of dehydration, no signs of toxicity , no abdominal
tenderness/painful mass/ obstruction; have weight loss > 10%.

Moderate to severe disease
failed to respond to therapy for mild to moderate disease.Fever ,
significant weight loss, abdominal pain , intermittent nausea or
vomiting , anemia.

Severe to fulminant disease
persisting symptoms despite therapy with steroids.
high fever , persistent vomiting, obstruction, rebound
tenderness, evidence of abscess.

Remission
patients who have responded to acute medical therapy or who
have had surgical intervention

14. COMPLICATIONS
Musculoskeletal Arthralgias(joint pain).
Peripheral arthritis pain.
Ankylosing spondylitis.
CD fistulas and abscessInflammation may progress into penetrating disease, abscess
formation, and fistula formation.
Hemorrhage Severe bleeding tends to occur early in the course of disease.
Strictures narrowing of the colon or rectum.
Toxic megacolon occurs when the inflammatory process causes the colon to dilate,
with subsequent bowel wall thinning.
bowel becoming more fragile.
major risk is bowel perforation.
Cancer . colorectal cancer
Related to duration and extent of UC as well as patient -specific risk
factors.
Primary sclerosing
cholangitis.
Hepatobiliary complication of IBD.
Osteoporosis diminished bone density

15. Treatment objectives
•Induce remission with control of acute inflammatory
flare.

•Maintain remission as long as possible.

•Normalize bowel function when possible.

•Maintain nutritional status

•Improve quality of life (QOL).

•Alleviate discomfort.

16. Drugs Used
IBDAminosalicylatessulfasalazine:1st choice …………………… (dosing details Table 53-2 CPR)
At higher concentrations they inhibit prostaglandins and prostacyclins.
Disadvantages.. increased incidence of adverse events
Steroids. Systemic corticosteroids.
Topical and non-systemic steroids(enemas, suppositories, and ileal release
formulations).
Budesonide has been shown to be effective in IBD.
Azathioprine Disrupting the inflammatory response seen in IBD.
Effective at inducing and maintaining remission in IBD.
Response is slow and may take months to be fully effective.
Methotrexate Given parenterally is an effective treatment.
with multiple modes of ant i - inflammatory effects.
Cyclosporine. Potent immunosuppressive agents.
used for severe IBD.
potent inhibitors of T lymphocyte activation.
Biologics. Infliximab, adalimumab and certolizumab.
preventing the cytokine from binding to cell surface receptors and subsequently
decreasing inflammation due to activated T lymphocytes and monocytes.
(Table 53-3 CPR)
Antibiotics. Metronidazole (Flagyl ) and ciprofloxacin
If.. increased risk of perforation or bacteremia.

17. Probiotic and
prebiotic
therapy.
Exogenously administered bacteria such as Lactobacillus GG,
Saccharomyces boulardii , and nonpathogenic E. coli .
Normalizes the intestinal environment flora and thus decrease
inflammatory triggers.
facilitating growth of commensal gut flora to displace possible
antigenic microorganisms.
Antispasmodics
and
Anti-diarrheals.
to treat cramping or discomfort in IBD inflammation.

Anti-depressants
and anxiolytics
use as adjuvant therapy.
Analgesics. Narcotics are to be avoided in UC therapy.
NSAID medications should be avoided because they have been implicated in
inducing IBD flares.

18. Drug Therapy for IBD/UC
based on anatomic disease extent
Distal disease…. treated effectively with topical therapy-Extensive disease…. requires systemic therapy.
Severity is generally defined as mi ld, moderate, severe, or fulminate.
mild to
moderate
distal disease.
oral and topical amino-salicylates.
Topical Steroids.(Topical mesalamine is superior.)
Topical mesalamine plus oral amino-salicylate is superior to either alone.
oral 5-ASA drugs tend to work in 2-4 weeks and are effective in a high
percentage of patients.
Budesonide has been effective in UC treatment
Mild to
moderate
extensive
disease.
Oral 5-ASA (sulfasalazine in regard to efficacy)
Oral steroids
Higher doses for longer periods increase risk of corticosteroid-associated risk.
Patients receiving corticosteroids for > 3 months should be evaluated/dual -energy x- ray
absorptiometry (DEXA) bone -testing.
Corticosteroid- induced osteoporosis…. bisphosphonates, calcium supplementation at 1-
1.5 g per day, and vitamin D supplementation at 800 mg per day.
Moderate to
severe disease.
may require hospitalization.
Infection with enteric pathogens should be ruled out .
indication for surgical resection or alternate intravenous therapy such as with cyclosporine.
Total parenteral nutrition is used when oral feeds are not tolerated.

19. Doses/UC
Moderate distal disease. Maintenance therapy
Oral
5-ASA
doses
Sulfasalazine 4-6 g/day in 4 divided doses
Mesalamine 2-4.8 g /day in 3 divided doses
Balsalazide 6.75 g /day in 3 divided doses
Olsalazine 1.5-3 g / day in divided doses

Mesalamine suppositories 500 mg twice a
day.
Mesalamine enemas 1-4 g per day.
Balsalazide 3-6 g/ day
Mesalamine Eudragrit -S 3.2 g/day
Mesalamine suppository 500 mg every day or twice
a day
Mesalamine enema 2-4 g daily, every other day, or
every third day
Olsalazine 1 g /day
Sulfasalazine 2 g /day.
Mesalamine 1.6 g orally /day plus 4-g enemas twice
weekly
Oral
CS
Budesonide
Topical therapy generally induces
remission more quickly.
Hydrocortisone enema 100 mg per day
Corticosteroids, topical/oral , are not effective
and should not be used.
Mild to moderate extensive diseaseMaintenance therapy
Oral
5-ASA
Sulfasalazine 4-6 g/day in 4 divided doses.

The dosages used are a minimum of 2
g/Day

maximum of 4.8 g/day
Balsalazide 3-6 g/ day
Mesalamine 2-4 g /day
Olsalazine 1 g/day
Sulfasalazine 2-4 g/ day
6-MP and azathioprine 100-250 mg/ day, maximum
of 2.5 mg/kg/day
Oral CsPrednisone 40-60 mg/day….followed by a dose taper of 5-10 mg weekly until a daily dose of 20
mg is reached.

20. Moderate to severe disease. Remmission maintenance Therapy.
IV steroid therapy.
Prednisolone (40-60 mg) , hydrocortisone
(300 mg) , or methylprednisolone (32-48
mg/day
Empiric broad-spectrum antibiotics are of
little use.
narcotics, anti-diarrheals, and
anticholinergics should be avoided.
Intravenous cyclosporine at 2-4 mg/kg /
day.
5-ASA should be stopped in the acute
settings.
azathioprine or 6-MP can be beneficial
when added for maintenance.
Sulfamethoxazole/ trimethoprim should be
added as prophylaxis against

Pneumocystis pneumonia for patients on
cyclosporine.
Fulminant disease.
Treated as noted for severe disease and
should not take anything by mouth.

Broad spectrum antibiotics are of ten used
empirically.
Immediate colectomy.

21. Drug Therapy for IBD/CD
depends on the disease location, disease severity and any complications.
Mild to
moderate
CD
5-ASA orally Mesalamine 3.2-4 g/day
Sulfasalazine 3-6 g/day.
Sulfasalazine may be more effective.
Oral
broad-spectrum
antibiotics
Metronidazole 750-1500 mg/day

Ciprofloxacin 1000 mg/ day
CS Budesonide orally 9 mg/ day for 8-16 weeks
Tapered 3 mg per week over 2-4 weeks
Moderate
to severe
CD
Systemic steroidsPrednisone 40-60 mg per day
antimetabolite
drugs
Azathioprine 2-3 mg/kg/day or
6-MP 1-1.5 mg/kg/day.
Methotrexate 25 mg/week IM, tapered to 15 mg/week IM after 16
weeks
Anti -TNF therapyFor patients who do not tolerate systemic steroids and
immunosuppressant therapy.
Infliximab 5 mg/kg at 0, 2, and 6 weeks.
concomitant dosing of azathioprine, 6-MP, or methotrexate(MTX)
Adalimumab 160 mg day one, and 80 mg day 15 followed by 40 mg
every other week starting.

22. Maintenance
Severe or fulminant CDIV fluids and bowel rest
(parenteral nutrition).

IV antibiotics with
metronidazole,
aminoglycosides, and
broad-spectrum penicillin.
IV CS.

Surgical intervention may be
required in patients who do not
respond to IV corticosteroids.
Mesalamine 2.4-4.8 g / day or
sulfasalazine 2-4 g/day

Budesonide Doses of 6-9 mg per day

Azathioprine, 6-MP, methotrexate,
and anti -TNF therapy have been
used in maintenance; but adverse
events must be weighed carefully,

Systemic steroids are normally
avoided in long- term therapy
secondary to systemic toxicity;

23. Treatment of IBS
based on the nature and severity of symptoms
Mild IBS Diet and lifestyle changes.
Moderate IBSAnti-cholinergics used as antispasmodics.
Dicyclomine 20 mg by mouth 4 times a day
Hyoscyamine 0.15-0.3 mg by mouth 4 times a day

Clidinium plus chlordiazepoxide (Librax) 2.5/5 mg 1-2 tabs by mouth before
every meal and at bed-time.

Hyoscyamine + scopolamine, atropine, phenobarbital 1-2 tablets every 6-8 hr.

Loperamide ( Imodium) 4 mg followed by 2 mg after each unformed bowel
movement up to a maximum of 16 mg /day.

Low-dose tricyclic antidepressants :
Lubiprostone…a chloride channel activator indicated for idiopathic constipation.
Polyethylene glycol…. laxative solution.
Severe IBS Selective serotonin reuptake inhibi tors.

Anxiolytic drugs, including diazepam, are occasionally used.

These drugs should be taken for only short periods of time.

24. Surgery
•Proctocolectomy with permanent ileostomy.
•Proctocolectomy with continent ileostomy.
•Colectomy with ileorectal anastomosis.
•Ileal pouch anal anastomosis ( IPAA).
•Ileostomy.
•Colectomy.

25. Patient Education/Counseling
•Education about the disease.

•Diet and lifestyle changes.

•Smaller meals are preferable.

•Decrease fatty foods, gas-producing foods.

•Decrease alcohol.

•Decrease caffeine

•Avoid dairy in lactose- intolerant patients

•Prepare strategies to handle stress.