Flashcards in Pathophys & Pharm: IBD Deck (30):
Which gene pathways are involved in both Crohn's disease and ulcerative colitis?
The IL-23 and IL-12 gene pathways, which are both involved in Th17 regulation.
Why is it believed that the enteric flora plays a role in the development of IBD?
(1) Mouse models have shown that colitis will not develop in a germ-free environment.
(2) Some patients with Crohn's develop antibodies to proteins of certain enteric bacteria.
(3) The most common location for Crohn's is the ileum and colon, where enteric flora is most prevalent.
What are functions of Th17 cells?
(1) Regulate Th1 and Th2 cells.
(2) Produce cytokines that activate a number of cell lineages (epithelial cells, macrophages, fibroblasts).
What environmental factors affect the risk of IBD?
(1) Higher socioeconomic status
(3) Smoking in Crohn's disease (protective for ulcerative colitis)
J: In Crohn's disease, this refers to an area of inflammation with surrounding normal mucosa.
What is a skip lesion?
J: In Crohn's disease, this refers to a coalescence of ulceration with deep, serpiginous ulceration and heaped, edematous mucosa adjacent.
What is cobblestoning?
In Crohn's disease, to where can a fistula form?
Bladder, skin, elsewhere in bowel, genitourinary organs.
Perianal fistulae are frequently seen (along with skin tags, abscesses).
Describe the formation of a stricture in Crohn's disease.
(1) Chronic inflammation results in a TGF-B-driven attempt to heal.
(2) This results in a deposition of type 3 collagen.
(3) Fibrosis can lead to a stricture.
What is the gross appearance of ulcerative colitis?
Hyperemia, edema and a granular appearance. The disease extends only into the mucosa.
What is the clinical presentation of IBD?
(1) abdominal pain
(2) RLQ tenderness
(3) urgent diarrhea
(5) constitutional symptoms
(6) weight loss, malabsorption
What are the noted extraintestinal manifestations of IBD?
(1) erythema nodosum
(2) pyoderma gangrenosum
(3) primary sclerosing cholangitis
What is primary sclerosing cholangitis?
Chronic inflammation of intra- and extrahepatic ducts of the biliary tree with beading irregularity and stricturing of the ducts. It is frequently associated with ulcerative colitis and increases risk of colorectal cancer and cholangiocarcinoma.
Is Crohn's disease curable? Is ulcerative colitis?
What is the medical therapy for mild IBD?
(1) short course of glucocorticoids for remission induction
(2) 5-ASAs for ulcerative colitis
(3) budesonide for Crohn's disease
(4) topical steroids for distal disease
What is the medical therapy for severe IBD?
(2) anti-TNF agents
(3) anti-a4 inhibitors
What is the mechanism of action of aminosalicylates?
(1) inhibition of T cell activation
(2) inhibition of antigen presentation
(3) inhibition of adhesion
(4) decreased TNF production
What are adverse effects of aminosalicylates?
(1) paradoxical diarrhea
(2) interstitial nephritis
Are aminosalicylates used for Crohn's disease? Ulcerative colitis?
What is the mechanism of action of glucocorticoids as a therapy for IBD?
(1) Inhibition of pro-inflammatory cytokines and adhesion molecules
(2) Inhibition of proteases, like elastase, collagenase
(3) Regulation of NF-kB
(4) Decreased phagocytosis by neutrophils
(5) Apoptosis of lymphocytes
J: This steroid is used to treat IBD and is noted for its high first-pass metabolism in the liver.
What is budesonide?
What are the thiopurines used in IBD therapy? What is the mechanism of action?
(1) Inhibition of DNA synthesis
(2) Inhibition of purine synthesis
(3) Induction of apoptosis
What are adverse effects of thiopurines?
(1) leukopenia, marrow suppression
(5) 3-5 fold increased risk of non-Hodgkin lymphoma
What is the mechanism of action of methotrexate?
(1) Folate antagonist
(2) Inhibition of some interleukins, anti-inflammatory
What are adverse effects of methotrexate?
(2) hepatic fibrosis
(4) mild leukopenia
How is cyclosporin A used in treatment of IBD?
In fulminant cases of ulcerative colitis, it is used as a bridge until thiopurines kick in.
What anti-TNF agents are used to treat IBD?
What is the mechanism of action of anti-TNF agents?
(1) Bind and inhibit free and cell-bound TNF-a.
(2) Induction of apoptosis of lymphocytes in the lamina propia.
(3) Decrease secretion of IL-1, IL-6, IL-18 and INF-y.
What are the adverse effects of anti-TNF agents?
(1) transfusion reactions
(2) drug-induced lupus
(4) malignancies (lymphoma, hepatosplenic T cell lymphoma, non-melanomatous skin cancer
What is the mechanism of action of anti-a4 inhibitors (natalizumab)?
Binds to the a4 subunit of surface integrins on leukocytes, inhibiting adhesion