IBD AW

IBD

-Inflammatory bowel disease

-Disorders associated with chronic relapsing inflammation of the GI tract

-Persistent inflammation and can result in severe symptoms and complications

-Includes both UC and CD

UC and CD

-Ulcerative colitis

-Crohn's disease

IBD etiology

-Genetic susceptibility

-Environmental exposures

-Intestinal microbiota changes

IBD risk factors

-Family hx

-Exposure to certain medications: antibiotics, oral contreceptives)

-GI infections

-Poor lifestyle habits (diet)

-Vitamin D deficiency

-Concomitant immune-mediated diseases

-Smoking (only for CD)

UC pathophys

-Alterations i the epithelial cell function and intestinal bacterial composition lead to an increased intake of luminal antigens and microbiota imbalance

-Th2 cells are activated, producing inflammatory cytokines like interleukins

CD

-Release of Th1 and Th17 cells, which shape the intestinal mucosal immune environment by secreting cytokines such as TNF-alplha and IL12 and IL23

-Those cytokines have been linked to fibrosis development

General presentation of IBD

-Similar symptoms with UC or CD

-Undistinguished UC or CD is described as having "indeterminate colitis"

-Insidious and subacute

Common signs and symptoms in both UC and CD

-Diarrhea

-Rectal bleeding

-Abdominal pain/cramping

-Weight loss/malnutrition

-Tachycardia

-Fever

-Dehydration

UC signs and symptoms

-Blood is more common

-Bowel urgency

-Tenesmus: feeling of needing to pass stools even if bowels are empty

CD signs and symptoms

-Weight loss/malnutrition more common in CD than UC

-Fatigue/malaise

-Abdominal mass and tenderness

-Perianal fissure

-Abscess or fistula

UC presentation

-Continuous pattern through the affected areas of the GI tract and is superficial, not extending below the submucosal layer of the GI tract

-Colon and rectum

-Categorized based on extent

Categorizations of UC

-Rectum: proctitis

-Rectum and sigmoid colon: proctosigmoiditis

-Rectum to splenic flexure: left sided colitis

-Entire colon: pancolitis

CD presentation

-Any part of the entire GI tract from the mouth to the amus

-Mostly terminal ileum (last part of small intestine) and colon

-Small intestine, anus, mouth

-Discontinuous inflammation, patches of disease intermixed with areas of normal GI mucosa (skip legions, cobblestone pattern)

Complications of IBD

-Known as extraintestinal manifestations (EIM)

-Joints, eyes, skin, liver, kidneys, bones

-Gallstone formation: CD

-Primary sclerosing cholangitis: UC

Nonpharm

-Nutritional support

-Surgery

Medication classes for IBD

-Corticosteroids

-Aminosalicylates

-Immunomodulators

-Biologics

-Small molecules

-Antibiotics

Corticosteroids

-Long term use can be dangerous

-Utilize for short period of time and as an overlap to an effective treatment that is safer long term

-Budesonide, prednisone, prednisolone, methylprednisolone, hydrocortisone

Aminosalicylates

-Work by delivering mesalamine to areas of inflammation within the gi tract by linking mesalamine to a carrier molecule or altering the formulation to release drug in response to changes in intestinal pH

-Mesalamine, sulfasalazine, olsalazine, balsalazide

Mesalamine formulations

-Oral products should not be chewed or crushed (delayed release)

-Route of administration, site of action, and insurance should influence selection of a specific product

Sulfasalazine adverse effects

-Headache

-N/V

-Fatigue

-Bone marrow suppression

-Hepatitis

-Pneumonitis

-Should be coadministered with folic acid

Aminosalicylates for distal ileum

-Sulfasalazine

-Mesalamine

Aminosalicylates for distal left colon

-Mesalamine

Aminosalicylates for colon

-Mesalamine

-Olsalazine

-Balsalazide

Immunomodulator drugs

-Azathioprine/6-Mercaptopurine (AZA/6-MP)

-Methotrexate

Limitations of immunomodulators

-Slow onset of action

-ADEs: myelosuppression, infections, pancreatitis, lymphoma, hepatotoxicity, N/V, pneumonitis, renal dysfunction, anemia

Biologic agents

-TNF-alpha agents

-A4B7 integrin blocker

TNF-alpha blocked drugs

-Infliximab

-Adalimumab

-Certolizumab

-Golimumab

TNF-alpha blocked adverse effects

-Reactivation of serious infections: TB and Hep B

-Exacerbation of HF

-Risk for lymphoma or skin cancer

A4B7 integrin blocker drug

-Vedolizumab

Vedolizumab

-Integrin inhibitor

-Humanized monoclonal antibodies that reduce inflammation by blocking the migration and adhesion of leukocytes across the endothelium

-Gut selective: less systemic immunosuppression and improved safety profile

UC treatment to induce remission

-Corticosteroids and aminosalicylates

-Oral or topical aminosalicylates

-Oral or topical budesonide: induction of remission

-Oral prednisone

-Rectal steroids

-Cyclosporine

-Biologics necessary if no treatment response to steroids

-Biologics and corticosteroids may be used at the same time

Treatment for proctitis

-Mesalamine suppositories

-Combo of oral and topical

Treatment for left sided UC

-Enemas

Treatment for proctosigmoiditis

-Combo of oral and topical mesalamine

UC treatment for maintenance of remission

-The medication used to successfully induce remission can be continued to maintain remission (exception: corticosteroids)

-Typically biologic

CD treatment to induce remission

-Systemic corticosteroids: controlled-release budesonide

-Immunomodulators: delayed onset

-Biologics

Ileal, ileocolonic, or colonic CD

-Sulfasalazine or mesalamine are not recommended (limited efficacy)

Moderate to severe CD

-High dose prednisone

-Biologic should be initiated

-Immunomodulator only if in combo with an anti-TNF-alpha

Treatment for perianal fistulizing disease

-Anti-TNF (specifically infliximab)

-Fluids and electrolyte replacement

CD treatment for maintenance of remission

-Minimal benefits from oral mesalamine, but may consider continuation if they have a clinically relevant response

-Careful with aminosalicylates long term (per adverse effects of infections and malignancy)

-Biologics are good

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