Flashcards in Inflammatory Bowel Disease Treatment Deck (50):
What is UC?
mucosal inflammatory condition confined to rectum & colon
What is Crohn's?
transmural inflammation from mouth to anus
What does therapy for UC or Crohn's depend on?
Anatomic location, the severity, responsiveness, goal of therapy, & drug toxicity
Malaise & fever are uncommon in what form of IBD?
What is the distribution of UC vs Crohn's?
Crohn's = discontinuous
UC = continuous
Aphthous or linear ulcers are common in which form of IBD?
What features are common in Crohn's?
What feature is common in UC?
What is the goal of pharmacologic therapy for IBD?
Relieve the inflammatory process & induce remission
What is the action of azo compounds (end in "salazine")?
Reduce absorption of the parent drug from the small intestine
Azo compounds: Where are high concentrations of active drug made available?
Terminal ileum & colon
What are examples of mesalamine compounds?
Asacol & apriso
Rowasa (enema), canasa (suppositories)
What does pentasa act on?
What does anacol & apriso act on?
distal ileum & proximal colon
What does lialda act on?
What does rowasa & canasa act on?
rectum & sigmoid colon
5-ASA is derived from what 2 pathways?
Cyclooxygenase & lipoxygenase
What is the MOA of 5-ASA?
Interferes w/ production of inflammatory cytokines
Inhibit cellular functions
What is the efficacy of 5-ASA on UC vs Crohn's?
UC: induces & maintains remission, considered 1st line for mild-mod disease
Crohn's: efficacy unproven (many still use as 1st line for mild-mod disease involving the colon or distal ileum)
What is the action of the controlled-release oral formulation of budesonide?
Releases in the distal ileum & colon, where it is absorbed
How do you treat mod-severe active IBD?
Have higher doses of glucocoricoids been shown to be more efficacious?
What is a con of glucocorticoids?
Not useful for maintaining remission
- Aminosalicylates or immunosuppressive agents should be used
Purine antimetabolites have ___________ properties
6-mercaptopurine undergoes biotransformation via...
competing catabolic enzymes - xanthine oxidase & thiopurine methyltransferase
Active 6-thioguanine nucelotides are concentrated in cells resulting in...
prolonged 1/2 life
Prolonged kinetics of 6-thioguanine nucelotide results in a delay of...
17 weeks before onset of therapeutic benefit from oral azathioprine or 6-MP
What are ADEs of azathioprine & 6-mercaptopurine (purine analogs)?
Bone marrow depression
Increased risk of lymphoma
Describe the drug interaction w/ allopurinol
Reduces xanthine oxide catabolism of the purine analogs --> increased active 6-thioguanine nucleotides
What has an important role in the pathogenesis of IBD?
Fungi & viruses
What is the role of abx on IBD?
Treats micro abscesses
Decreases bacterial translocation
Treats septic complications
What has been hypothesized to have a role in the development of Crohn's?
What is the MOA of methotrexate?
Inhibit dihydrofolate reductase enzyme
Interfere w/ interleukin
Stimulate release of adenosine
Stimulate death of T lymphocytes
What are ADEs of methotrexate?
Bone marrow depression
Peripheral neuropathy when used for prolonged periods
Hepatic damage in pts w/ psoriasis
What reduces the risk of ADEs of methotrexate?
Those on methotrexate & who have renal insufficiency, are at increased risk for what?
Hepatic accumulation & toxicity
What is the MOA of anti-tumor necrosis factor?
Dysregulation of helper T cell type 1 response & regulatory T cells
What is an example of anti-tumor necrosis factor therapy?
Monoclonal antibodies to human TNF
Anti-tumor necrosis agents prevent the cytokine from binding to...
Anti-tumor necrosis agents: the Fc portion of human IgG1 promotes...
What fraction of pts will eventually lose response despite higher doses or more frequent injections of anti-tumor necrosis agents?
What causes the loss of response in anti-tumor necrosis agents?
May be due to development of antibodies to the TNF antibody
What are ADEs of anti-tumor necrosis agents?
Risk of serious infections increased w/ concomitant coricosteroids
Antibodies to the antibody (less likely in concomitant therapy w/ immunomodulators)
Delayed serum sickness-like rxn
Concomitant treatment w/ anti-TNF agents & immunomodulators may increase the risk of what?
What are integrins?
Adhesion molecules on the surface of leukocytes
Integrins may interact w/ what?
Selectins (another class of adhesion molecules, on the surface of the vascular endothelium)
What is the MOA of integrins?
Allows circulating leukocytes to adhere to the vascular endothelium & move through the vessel wall into the tissue
What is anti-integrin therapy (natalizumab) used for?
Mod-severe Crohn's who have failed other therapies through a carefully restricted program
What are ADEs of anti-integrin therapy (natalizumab)?
acute infusion rxns
small risk of opportunistic infections