Inflammatory Bowel Disease Flashcards
Inflammatory Bowel Disease
Family of closely related intestinal disorders
Also known as IBD
Ulcerative Colitis (UC)
Mucosal inflammatory condition confined to the rectum and colon
Crohn’s Disease (CD)
Transmural inflammation of the gastrointestinal tract that can affect any part
Etiology (7)
- Unknown
- Host susceptibilities and environmental triggers
- Infectious diseases
- Genetics (hereditary)
- Environmental
- Immune defects
- Psychologic factors
Ulcerative Colitis: Distribution of disease in GI tract Fistula, abscess, stricture Location Histology Risk of colon cancer
- Distribution of disease in GI tract – colon and rectum
- Fistula, abscess, stricture – uncommon
- Location – mucosal
- Histology – crypt abscess, cryptitis
- Risk of colon cancer – high
Crohn's Disease Distribution of disease in GI tract Fistula, abscess, stricture Location Histology Risk of colon cancer
- Distribution of disease in GI tract – mouth to anus
- Fistula, abscess, stricture – common
- Location – transmural
- Histology – tissue granuloma
- Risk of colon cancer – high
UC Disease Severity Mild (4)
- < 4 BM per day
- No or minimal blood
- No systemic symptoms
- Normal ESR
UC Disease Severity Moderate (3)
- > 4 BM per day
- Minimal blood
- Minimal systemic complications
UC Disease Severity Severe (7)
- > 6 BM per day
- Positive blood
- Evidence of systemic complications
- ESR > 30
- Hb <75% normal
- Abdominal tenderness
- Bowel wall edema
Fulminant (7)
- > 10 stools per day
- Continuous blood
- Evidence of systemic complications
- ESR > 30
- Transfusions required
- Abdominal pain
- Dilated colon
Treatment - Goal of Therapy (4)
- Reverse and prevent further destruction of inflammatory response
- Maintain disease remission
- Prevent malignancy
- Optimize quality of life
Treatment Pharmacological (3)
- Generally, consider treatment as immune modulating therapy
- Induce remission
- Maintain remission
Treatment Drugs for IBD (6)
- Aminosalicylates
- Corticosteroids
- Antibiotics
- Immunomodulatory Agents
- Immunosuppressants
- Biologics
Aminosalicylates MOA (3)
- Unknown
- Works topically to inhibit pro-inflammatory cytokines
- Inhibits inflammatory transcription of NF-kB to block prostaglandin and leukotriene production
Aminosalicylates Available Agents (6)
Mesalamine: Ascacol®, Pentasa®, Rowasa®
Sulfasalazine
Balsalazide
Aminosalicylates ADE (7)
- Headache
- Nausea
- Photosensitivity
- Diarrhea
- Colitis
- Pancreatitis
- Hepatitis
Corticosteroids MOA for IBD (4)
- Unknown
- Decreases transcription of proinflammatory cytokines
- Prevents nuclear translocation of NF-kB
- Inhibits inflammatory response
Corticosteroids Available Agents for IBD (3)
Topical – Hydrocortisone
Oral – Prednisone/prednisolone and Budesonide (Enterocort®)
Corticosteroids
Place in Therapy for IBD (3)
- Moderate to Severe
- Remission (induction)
60%-80% in moderate disease
50%-60% in severe disease - Ineffective for maintenance therapy (IV is used for acute flare)
Corticosteroids ADE (8)
- Weight gain
- Glucose intolerance
- Hypertension
- Neuropsychiatric events
- Decreased linear growth
- Bone loss
- Kyphosis
- Adrenal suppression
Antibiotics - Place in therapy for IBD
Mucosal inflammation and abscesses present
Antibiotics Available Agents for IBD (2)
- Metronidazole
- Active CD
- UC maintenance - Ciprofloxacin
- CD (perineum)
- UC
Immunomodulators Available Agents (3)
- Azithioprine (Imuran®)
- Mercaptopurine (6MP)
- Methotrexate
Immunomodulators MOA
Azathioprine and mercaptopurine (1)
Methotrexate (2)
Azathioprine and mercaptopurine
1. Inhibit inflammatory response (protein synthesis, nucleic acid metabolism, clonal expansion of lymphocytes)
Methotrexate
- Unknown
- Inhibits proinflammatory cytokins and down-regulates activated T-cells and neutrophils
Immunomodulators Place in Therapy (3)
- Prevention of clinical relapse
- Failed previous therapy
- Weaned from other therapy and now require induction - Azathioprine and mercaptopurine
- Induction of mucosal and clinical remission - Methotrexate
- Second line to azathioprine and mercaptopurine
Immunomodulators
ADE
Azathioprine and mercaptopurine (7)
- Neutropenia
- Thrombocytopenia
- Hepatotoxicity
- Infection
- Rash
- Hypersensitivity
- Malignancy
Immunomodulators ADE – Methotrexate (5)
- Neutropenia
- Thrombocytopenia
- Nausea
- Nephropathy
- Vasculitis
Immunomodulators Pearls (4)
- Thiopurine methyltransferase deficiency
- Caution with mercaptopurine
- Risk of metabolite toxicity
- Patients receiving methotrexate should receive folic acid
Immunosuppresants Available Agents (2)
- Calcineurin inhibitors
- Tacrolimus
- Cyclosporine - Antimetabolites
Antimetabolites Available Agent
Mycophenolate mofetil (Cellcept®)
Antimetabolites Place in Therapy (2)
- Suppresses T and B cell proliferation
2. Decreases lymphocyte proliferation through inhibition of DNA synthesis
Antimetabolites MOA (2)
- Alternative to mercaptopurine and azathioprine therapy
2. Used in conjunction with other agents
Biologics MOA (2)
- Neutralizes pro-inflammatory cytokine TNF
2. Activates complement-mediated cytolysis of TNF-producing monocytes
Biologics Available Agents (2)
- Humira - Adalimumab
2. Remicade - Infliximab
Biologics ADE (4)
- Infusion Related Reactions: Shortness of breath, Chest tightness
- Hypersensitivity Reactions: Fever, Facial edema
- Positive ANA titers
- Infection
Biologics Pearls (4)
- Patients may develop antibodies resulting in loss of response or infusion reactions
- Pre-medicate with corticosteroids
- Co-treat with corticosteroids - Smoking reduces response to infliximab
- Limited data for use in pediatric patients with UC
- CAUTION in heart failure patients
Adjunct Meds for IBS (3)
- Loperamide (Imodium)
- Useful for proctitis or diarrhea - Antispasmodics
- Dicyclomine (Bentyl)
- Propantheline (Pro-Banthine)
- Hyoscyamine (Levsin) - Cholestyramine (Questran)
- Bile-salt-induced diarrhea after ileal resection