3. Inflammatory Bowel Disease (IBD) is commonly used to
describe 2 idiopathic diseases of GIT with closely related
presentations, these diseases are ULCERATIVE
COLITIS(UC) and CROHN’S DISEASE(CD)
Ulcerative colitis is a Chronic inflammation condition of
GIT mucosa and is primarily found in rectum and colon
where as Crohn’s Disease is a transmural inflammation
of GI mucosa and can be found throughout the GIT from
mouth to the anus and normally CD affects the small
bowel and colon
COMPREHENSIVE PHRARMACY REVIEW ,7TH EDITION , P g.no 1143
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5. Epidemiology
Ulcerative colitis
Age:15-40 yrs (Young adults)
Sex: No variation between men and women or
between socioeconomic group
High incidence areas: USA and northern-western
Europe
Clinical medicine, kumar and clarks
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6. contd..
CROHN’s disease
Age:1st peak 15-30 years of age, 2nd peak around 60
years
Sex Marginally more common in females
High incidence areas: North America, UK,northern
Europe
Clinical medicine, kumar and clarks
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7. etiology
• DIET:
• Fat intake
• Fast food ingestion
• Milk and fibre consumption
• Total protein and energy intake
• DRUGS:
• NSAIDS: DICLOFENAC
• Antibiotics: may precipitate the relapse
• Oral contraceptives increase the risk of developing CD
• Smoking is protective against UC but increases the risk
of CD
Clinical pharmacy and therapeutics, roger walker andcate whittlesea
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8. CONTD..
GENETICS:
• If a patient has IBD, the lifetime risk that a first-degree
relative will be affected is ~15%.
• If two parents have IBD, each child has a 36% chance
of being affected.
• In twin studies , 58% of monozygotic twins are
concordant for CD and 6% are concordant for UC,
whereas 4% of dizygotic twins are concordant for CD
and none are concordant for UC.
• Mutations of gene CARD15/NOD2 on chromosome 16
is associated with SI CD 2 other genes – OCTN1,
DLG5
ETHNIC: Jews are more prone to IBD than non jews.
STRESS: Increase the relapse of IBD
Clinical pharmacy and therapeutics, roger walker andcate whittlesea 8
9. CONTD..
INFECTION:
Mycobacterium paratuberculosis : CD
Diarrhoea :Ulcerative colitis
Clinical pharmacy and therapeutics, roger walker andcate whittlesea
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14. Bacterial antigens are taken up by specialized M cells, pass
between leaky epithelial cells or enter the lamina propria
through ulcerated mucosa
After processing they are presented on type 1 T-helper cells by
antigen presenting cells (APC) in the lamina propria.
T-cell activation and differentiation results in Th1 T cell
mediated cytokine response
With the secretion of cytokines including gamma interferon
(IFNƴ)
14
15. Further amplification of T cells perpetuates the inflammatory
process with activation of non immune cells and release of the
important cytokines.
Eg: IL-12, IL-23, IL-1, IL-6 and tumor necrosis factor (TNF)
These pathways occur in all normal individual exposed to
inflammatory insults and this is self limiting in healthy subjects
In genetically predisposed persons, dysregulation of innate
immunity may trigger inflammatory bowel disease.
15
18. DISTINGUISHING CHARACTERISTICS OF CROHN’s disease AND Ulcerative
colitis
Characteristic Feature Ulcerative Colitis Crohn’s Disease
Abdominal tenderness May be present Common
Abdominal wall and internal fistulas Common Absent
Abdominal pain Uncommon Common
Fever , Malaise Uncommon Common
Bloody Diarrheoa Frequent Occasional
Location Only colon GIT
Anatomic distribution Continuous, begins distally Skip lesions
Weight loss Occasional Frequent
ComprEhensive pharmacy review –LEON shargel, CLINICAL PHARMACY AND THERAPEUTICS- ROGER WALKER,
pHARMACOTHERAPY a pathophysiologic appraoch josepht. dipiro
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19. Characteristic Feature Ulcerative colitis Crohn’s disease
Palpable mass Rare Common
Intra-abdominal abscess Rare Common
Bowel Obstruction Rare Common
Antibiotic response Rare Frequent
Skip lesions Rare Frequent
Effect of smoking Often improves Often worsens
Serologic markers
ASCA +
P-ANCA +
15%
70%
65%
20%
Iron deficiency anaemia, raised
CPR/ ESR, hypoalbuminaemia
Common Common
Recto vaginal fistula Rare Frequent
Perianal Fistula Rare Frequent
ComprEhensive pharmacy review –LEON shargel, CLINICAL PHARMACY AND THERAPEUTICS- ROGER WALKER,
pHARMACOTHERAPY a pathophysiologic appraoch josepht. dipiro 19
20. PATHOLOGIC FEATURES OF CD AND UC
Characteristic feature Crohn’s disease Ulcerative colitis
Transmural Inflammation Common Uncommon
Granulomas Common Rare
Fissures Common Rare
Fibrosis Common No
Sub mucosal inflammation Common Uncommon
Rectal involvement Rare Common
Ileal involvement Very Common Rare
Strictures Common Rare
Crypt abcess Rare Very common
Linear clefts Common Rare
Cobblestone appearance Common Absent
ComprEhensive pharmacy review –LEON shargel, CLINICAL PHARMACY AND THERAPEUTICS- ROGER WALKER, pHARMACOTHERAPY a pathophysiologic
appraochjosepht. dipiro
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21. RADIOLOGIC features of ibd
Crohn’s disease Ulcerative colitis
Nodularity
Granularity
Collar button ulcers
21
37. INVESTIGATIONS
Crohn’s disease Ulcerative colitis
Blood Test
•CP with morphology: Normocytic
normocromic anemia of CROHNic disease
•Serum B12 level may be low.
•Raised ESR, CRP and raised WBC count.
•Hypo albuminaemia.
•Blood culture in septicaemia.
•Fe deficiency anemia
•Raised white cell and platelet count
•Raised ESR, CRP
•Hypo albuminaemia
Serological Test
• Saccharomyces cerevisiae antibody is
usually present
•P-ANCA negative
•P-ANCA may be positive
Stool culture
•Should always be performed in both to rule out infective cause
ComprEhensive pharmacy review –LEON shargel, practicalmedicine- alagappan
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38. CONTD..
Crohn’s Disease Ulcerative Colitis
Radiography
Plain ABD. X-ray:
•Loss of haustral markings and shortening of
bowel Is seen in sever lession.
•Narrowing of bowel lumen is seen
Ultrasound:
•Thickened small bowel loops and mesentery
or abscess
•Thickening of colonic wall and presence of
free fluid in abdominal cavity
Barium Enema (contraindicated in toxic
megacolon)
•Skip lesions
•Rose thorn appearance
•String appearance
•Cobble stone appearance
•Omega sign are also seen
•Ulcerations
•Pseudopolyps
•Loss of haustration
•Shortening of bowel is seen
ComprEhensive pharmacy review –LEON shargel, practical medicine- alagappan
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39. CONTD..
Crohns disease Ulcerative colitis
Instant Barium enema
•Patchy sup. Ulceration to wide spread deep
•Cobble stone appearance and narrowing
•Superficial ulcers
•Shortened and narrowed colon in long
standing disease
Colonoscopy
•Fissures and fistulae •Pseudopolyps
•Mucosal granularity and hyperemia
High resolution USG. And spiral CT
•Radionuclide scan with gallium labeled
polymorphs or indium or technetium
labeled leucocytes
•Capsule imaging of the gut.
•Radionuclide scan used to assess colonic
inflammation
Stricture evaluation and dilation
complicated Lesser complicated
ComprEhensive pharmacy review –LEON shargel, practical medicine- alagappan
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48. truelove and witts criteria for assessing severity of
ulcerative colitis
FEATURE Mild Moderate Severe
Stool frequency per
day
<4 4-6 >6 (mostly bloody)
Pulse (beats/min) Normal Intermediate >90bpm
Rectal bleeding Little Moderate Large amounts
Heamoglobin Normal Intermeidiate <10.5g/ dL
Weight Loss (%) None 1-10 >10
Temperature Apyrexial Intermediate 38.8 0C on 2 of 4 days
ESR <20 mm/h 20-30 mm/h >30mm/h
Albumin (g/dl) Normal 3-3.5 <3
Clinical pharmacy and therapeutics– roger walker
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49. Mild ulcerative colitis
Gradual onset
Infrequent diarrhoea (<4movements/day)
Intermittent rectal bleeding
Stool may be formed or too loose in consistency
Fecal urgency ,tenesmus,left lower quadrant pain
relieved by defecation
NO significant abdominal tenderness
ComprEhensive pharmacy review –LEON shargel
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50. Moderate ulcerative colitis
More severe diarrhoea with frequent bleeding
Abdominal pain & tenderness but not severe
Mild fever , anemia & hypoalbuminemia,
tachycardia.
ComprEhensive pharmacy review –LEON shargel
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51. Severe ulcerative colitis
Severe diarrhoea with >6-10 bloody bowel
movements per day
Severe anemia , hypovolemia ,imparied nutrition &
hypoalbuminemi,ELEVATED esr
Abdominal pain & tenderness
FULMINANT COLITIS:
Subset of severe disease with rapidly worsening
symptoms & signs of toxicity
ComprEhensive pharmacy review –LEON shargel
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55. TREATMENT
Goals of therapy
Induce and maintain remission.
Ameliorate symptoms
Improve patients quality of life
Adequate nutrition
Prevent complication of both the disease and
medications
ComprEhensive pharmacy review –LEON shargel
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57. NON PHARMACOLOGICAL THERAPY
Nutrition and Diet Support :
Patients with moderate to severe IBD are often malnourished.
The nutritional needs of the majority of patients can be
adequately addressed with enteral supplementation. Patients who
have severe disease may require a course of parenteral nutrition.
Probiotic formulas have been effective in maintaining remission
in ulcerativecolitis.
Supplemental fat soluble vitamins,medium supplemental
triglycerides and parenteral vitamin B12
Avoid high fibre diet in presence of diarrhoea and dysentry.
Pathology and therapeutics for pharmacists-GREEN AND HARRIS,practical medicine-alagappan
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58. Surgery:
• For ulcerative colitis, colectomy may be performed when
the patient has disease uncontrolled by maximum
medical therapy or when there are complications of the
disease such as colonic perforation, toxic dilatation
(megacolon), uncontrolled colonic hemorrhage, or colonic
strictures.
• The indications for surgery with Crohn’s disease are not
as well established as they are for ulcerative colitis, and
surgery is usually reserved for the complications of the
disease. There is a high recurrence rate of Crohn’s
disease after surgery.
Pathology and therapeutics for pharmacists-GREEN AND HARRIS,practical medicine-alagappan
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59. Pharmacological therapy of ibd
Agents used in IBD
• AMINOSALICYLATES
• STEROIDS
• AZATHIOPRINE & 6-MERCAPTOPURINE
• METHOTREXATE
• CYCLOSPORINE & TACROLIMUS
• BIOLOGIC AGENTS
• ANTI TUMOUR NECROSIS FACTOR THERAPY
• ANTIBIOTICS
• METONIDAZOLE AND CIPROFLOXACIN
• RIFAXIMIN
• PROBIOTIC AND PREBIOTIC THERAPY
• ANTI SPASMODICS AND ANTI DIARRHEALS
• ANTIDPRESSANTS AND ANXIOLYTICS
• ANALGESICS
SURGERY
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60. Management of ibd
Agents used in IBD
• AMINOSALICYLATES
• STEROIDS
• AZATHIOPRINE & 6-MERCAPTOPURINE
• METHOTREXATE
• CYCLOSPORINE & TACROLIMUS
• BIOLOGIC AGENTS
• ANTI TUMOUR NECROSIS FACTOR THERAPY
• ANTIBIOTICS
• METONIDAZOLE AND CIPROFLOXACIN
• RIFAXIMIN
• PROBIOTIC AND PREBIOTIC THERAPY
• ANTI SPASMODICS AND ANTI DIARRHEALS
• ANTIDPRESSANTS AND ANXIOLYTICS
• ANALGESICS
SURGERY
60
61. AMINOSALICYLATES
SULFASALAZINE(Salazar,Salazopyrin)
MESALAZINE( Coolgut,Cosacol)
OLSALAZINE(Dipentum)
BALSALAZINE(Balacol, Colorex)
MECHANISM OF ACTION: Salicylic acid moiety released
is absorbed and has anti-inflammatory action.
ADVERSE EFFECTS:
Nausea and vomiting
Headache
Rashes
Rarely bone marrow dyscrasias,
Liver dysfunction.
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62. STEROIDS
HYDROCORTISONE (Ciplorin,Labocort)
PREDNISONE(Deltasone, Rayos)
BUDESONIDE(Buovent,Derinide)
METHYL PREDNISONE(Alred,Biolone)
MECHANISM OF ACTION :
ADVERSE EFFECTS:
Suppression of response to infection
Growth suppression in children
Osteoporosis
Iatrogenic cushing’s syndrome
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63. IMMUNUSUPPRESANTS
AZATHIOPRINE(Azap)
CYCLOSPORINE(Graftin,Imusporin)
MERCAPTOPURINE(Empurine,6MP)
METHOTREXATE(Imutrex,Caditrex)
ADVERSE EFFECTS:
Leukopenia,
macrocytic anemia
Thrombocytopenia
alopecia ,
steatorrhea
hepatotoxicity
MECHANISM OF ACTION
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64. Biologic agents: anti-tnf
ADALIMUMAB (Humira)
INFLIXIMAB (Remicade)
CETUXIMAB(Erbitux)
NATALIZUMAB(Tysabri)
ETANERCEPT(Enbrel,Enbrol)
MOA: It is a monoclonal antibody against TNF-alpha that binds with
TNF-alpha and prevents its interaction with cell surface receptors
in inflammatory cells.
ADVERSE EFFECTS:
Upper respiratory tract infections with cough
Nausea and vomiting, reactivation of latent TB AND Hepatitis B
etc.,.
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65. antibiotics
• METRONIDAZOLE(Metrogyl)
• CIPROFLOXACIN (Ciptec,Ciproxin)
• RIFAXIMIN(Rcifax,Xifaxan)
ADVERSE EFFECTS:
GIT disturbances
Anorexia
Occasionally can cause
Dizziness
Myalgia
Ataxia
Hepatitis
Blood dyscrasias
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71. PREVENTION OF IBD
Stop smoking
Do regular exercise
Healthy diet
Do not use NSAIDs without doctor’s advice
Do not use ANTIBIOTICS unless they have been
prescribed for you by a doctor
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