IBD Pathophys and Pharm Flashcards
Review: What gene to people really like to talk about in IBD?
NOD2 - intracellular bacteria sensing and Paneth cell function
(apparently this is more for CD than UC)
4 processes involving bacteria that when dysregulated may contribute to IBD?
Pathogenic bacteria
Abnormal microbial composition
Defective host containment of commensals
Defective host immunoregulation
What kind of T cells are thought to be involved in UC and CD?
Th17
Weird relationship between CD, UC, and smoking?
CD: smoking -> increased risk of CD flare.
UC: smoking may be protective.
“Skip lesions” and “cobblestoning” are buzzwords for…
Gross appearance of CD.
What does the transmural inflammation of CD often lead to?
Fistulae and strictures.
Strictures in CD might be driven by…?
An attempt to heal, mediated by TGF-beta -> fibrosis.
Is perianal disease more common in CD or UC?
CD
Big picture about extra intestinal manifestations of IBD?
Lots of systems.
Lots of inflammatory things.
Some things are products of impaired absorption?
How can IBD contribute to kidney stones?
More oxalate gets absorbed. Secretion in kidneys -> kidney stones.
2 derm manifestations related to IBD?
Pyoderma Gangrenosum (purulent, autoimmune skin lesion) Erythema Nodosum (red, itchy skin rash)
What’s primary sclerosing cholangitis? Is it more commonly associated with CD or UC?
Why is it bad?
Inflammation of biliary tree -> stricturing / beading irregularity.
Iincreases risk of colorectal cancer and cholangiocarcinoma.
How can you cure UC?
Colectomy (usually not the best option though)
4 treatments for mild IBD?
Short-course glucocorticoids..
5-aminosalicylates (5-ASAs) - for UC
Budesonide - for CD
Topical steroids - (hydrocortisone enema).
3 types of medical therapies in more severe IBD?
Immunomodulators (thiopurines, methotrexate)
Anti-TNF agents
Anti-alpha4 agents
What’s the MoA of aminosalicylates? (4 things)
Is it more useful in CD or UC?
Inhibit T cell prolifeation. Inhibit Ag presentation. Inhibit adhesion (of immune cells?) Decrease TNF production. Seems to be more useful in UC than CD.
2 adverse effects of 5-ASAs?
Paradoxical diarrhea
Interstitial nephritis.
Main utility of corticosteroids in IBD?
Induction of remission - they don’t seem to be useful for maintenance.
What is budesonide?
Which IBD is it more for?
A glucocorticoid formulation designed to be released in the colon.
Meant for CD.
How do azathioprine and 6MP work?
Inhibition of DNA synthesis.
Is cyclosporin used for IBD much anymore?
No.
Effects of TNF inhibition?
Anti-inflammatory
Apoptosis of T cells and lymphocytes (only if the mAb includes the Fc portion)
3 anti-TNF drugs?
Infliximab
Adalimumab
Certolizumab (PEGylated Fab’)
What’s one reason antibody-based drugs can stop working?
Patients develop antibodies that neutralize the antibodies.
How do anti-alpha4 drugs work? Drug that does this?
Blocking integrins and thus adhesion of leukocytes.
Natalizumab does this.
What’s the major adverse effect of anti-alpha4 Abs? How can it be avoided?
Progressive multifocal leukoencephalopathy (PML) - Caused by JC Virus.
Screen people for JCV Abs in serum prior to giving natalizumab.
Why are ABx more useful for CD than UC?
ABx help with the complications of transmural inflammation - abscesses, fistulae present in CD.
These don’t happen in UC.
What’s the first-line therapy for CD?
Budesonide
What’s the first-line therapy for UC?
5-ASAs
