IBD DR. J Flashcards
In IBD what two factors are involved to cause a chronic state of dysregulated mucosal immune function?
- Exogenous
- Endogenous
Transmural inflammation of any part of the GI Tract.
Crohn’s disease
Confluent mucosal inflammation of the colon starting at the anal verge and extending proximal for a viable extent
Ulcerative colitis
Which disease can affect any part of the GI tract from the mouth to the anus?
CD
What part of the GI Tract is often spared in CD?
Rectum
Which disease is limited to the mucosa and superficial submucosa, with the deeper layers unaffected except in fulminant disease?
UC
What cells reside at the base of the crypts and give rise to all absorptive and secretory cells making up the epithelial layer?
Intestinal stem cells
Cells that produce the mucus layer
Goblet cells
Cells that produce antimicrobial peptides
Paneth cells
Cells that synthesize IgA which prevents invasion by pathogenic organisms and helps to maintain a homeostatic balance
Plasma cells
_____ cells and innate immune cells detect micro iota using pattern recognition receptors
Epithelial
Commensals in IBD are recognized as what?
Pathogenic
TNF alpha and INF gamma are ___inflammatory with ____ effects on barrier function
Pro; negative
CD1d, RIPK1 and IL-10 are ____inflammatory with ______ effects.
Anti; protective
The CD the cytokine profile is representative of what mediated inflammatory response?
T-helper1 (TH1)
The UC inflammatory response is mediated by what pathway?
TH2 pathway
What is the TH2 pathway mostly under control of?
IL-4
TNF alpha exists in a _____
Stable homotrimer
Both ___+_____ TNF can perform their biological function by binding to their receptors
Membrane; soluble
What does TNF trigger?
Apoptosis and breaks epithelial barrier
What does TNF drive?
Adaptive immune response
What produces TNF? What does TNF recruit?
Immune cells
What does TNF modulate?
Immune cell function
What is the MOA of anti- TNF Biologics?
Bind to homotrimeric TNF alpha to neutralize TNF alpha mediated pro-inflammatory signaling
Fully human antibody against IL-12/23 that binds to the p40 subunit
Ustekinumab
Small molecule inhibitor of JAK activity that prevents JAK dependent phosphorylation of STAT proteins
Tofacitinib
What is sulfasalazines site of delivery?
Colon
What are the 3 anti-inflammatory pro drug formulations?
- Sulfasalazine
- Olsalazine
- Balsalazide
What are the 3 key factors for drug delivery
- Mucus
- pH
- Commensals
The prodrugs all contain what bond?
Azo bond
What is the therapeutic moeity of sulfasalazine?
5- ASA
5-ASA acts _____ in the colon; ____ absorbed in the mucosa
Topically; poorly
5-ASA is highly ____phobic
Lipo
What mechanism makes 5- ASA active?
N-acetylation
Pentasa has a ________ release
Time dependent
Eudragit and Asacol have _____ dependent release
pH
Where is Asacol released?
Terminal ileum and cecum
What is 5-ASA incorporated into for a time delayed release?
Microparticles of lipophilic matrix dispersed within a hydrophilic matrix
The core of 5-ASA microparticles are coated with what?
A pH dependent gastric acid resistant polymer
Each APRISO capsule has what type of release dosage form?
Delayed and extended
What problems can immunosuppressants cause?
They can increase the risk of infection and malignancies
Glucocorticoids are quickly______
Absorbed
What is essential for both MC and GC activity?
3-one-4-ene
Where does cyclosporine act?
At an early stage in antigen receptor induced differentiation of T cells and blocks their activation
What does cyclosporine bind to?
Cyclophilin
What does cyclophilin form?
A complex that inhibits the cytoplasmic phosphates calcineurin
What does cyclosporine inhibit?
Gene transcription
What is the key excipient in sandimmune?
Cremophor
Immunosuppressant macrolide antibiotic
Tacrolimus
What does tacrolimus bind to?
FK binding protein
Living food supplements or components of bacteria that have been shown to have beneficial effects on human health
Probiotics
