Term
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Definition
| general supportive therapy, sulfasalazine, mesalamine, corticosteroids, immunomodulators, antibx/probiotics, infliximab, and next generation anti-TNF rxs |
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Term
| what characterizes general supportive care, as should be provided to IBD pts? |
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Definition
| general IBD supportive care doesn't affect the level of disease, it simply deals with the diarrhea via antidiarrheals (loperamide, diphenoxylate, cholestyramine - *not in severe IBD), antispasmodics for bloating/cramps (dicyclomide, hyoscyamine, propantheline), and analgesics to treat pain/depression - however toxic megacolon is a risk |
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Term
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Definition
| a compound consisting of 5 ASA w/a diazo bond and a transport component. colonic bacteria break this bond and 5 ASA is then released. it is cheap and only active in the colon - *but for some reasons crohn's pts respond to it* |
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Term
| what are side effects associated with sulfasalazine? |
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Definition
| sperm abnormalities, n/v, low grade hemolysis, hypersensitivity reaction, agranulocytosis, nephrotoxicity, and folate deficiency (supplement pts while on rx) |
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Term
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Definition
| next gen 5-ASA sulfasaline. can be adm PO or by enema. types include asacol, pentasa, dipentum, colazal, lialda. these are better b/c they can be taken less frequently - raise pts compliance. *nephrotoxicity is a concern (check creatinine 1x/yr). |
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Term
| what characterizes corticosteroids as tx for IBD? |
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Definition
| corticosteroids such as budesonide are highly effective in remission of crohns/UC, but ineffective for maintenance therapy b/c you might not be able to get them off, and long term effects (bone abnormalities/DM/fluid retention) are possible |
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Term
| what are the immunomodulators used in tx of IBD? |
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Definition
| azothioprine, methotrexate, and cyclosporine |
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Term
| what characterizes the use of azothioprine/6-mercaptopurine as immunomodulators to tx IBD? |
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Definition
| azothioprine/6-mercaptopurine have to be taken for months before they are beneficial, they can also reduce metabolism, and all immune modulators are good for getting pts off steroids - however it can be toxic, particularly to the pancreas. |
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Term
| what characterizes the use of methotrexate as an immunomodulator to tx IBD? |
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Definition
| this folate antagonist can be used for IBD maintenance, though pts need to take folate supplements and they may be subject to bone marrow suppression/hepatoxcity (need liver bx). contraindicated in pregnancy. |
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Term
| what characterizes the use of cyclosporine as an immunomodulator to tx IBD? |
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Definition
| cyclosporine is extremely renal toxic - but is quick acting (days), so good as a last resort |
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Term
| how does a breakdown product of azothioprine/6-mercaptopurine help prevent the inflammatory process seen in IBD? |
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Definition
| azo is broken down into 6-mercaptopurine and further broken down in 6-thioguanine and lastly into 6-thioguanine nucleotide and **6-thioguanine GTP**. the 6-thioguanine GTP is incorporated into the small GTPase which is Rac 1 which is essential for T-cell activation - however this incorporation prevents said activation - preventing the inflammatory process and is less toxic than cyclosporine. |
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Term
| what characterizes antibx as tx for IBD? |
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Definition
| antibx such as metronidazole and ciprofloxacin *do not affect remission rate, but can be beneficial, however there is a risk of pseudomembranous colitis |
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Term
| how can probiotics help with IBD? |
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Definition
| probiotics associate w/epithelial cells and barricade pathogens, stimulate innate immune response, increase defensines/antimicrobial compounds, improve epithelial integrity (tightening of tight junctions/promotion of mucus production), and influence T cell immune hyporesponsiveness. this is based on the face that IBD pts have empirically lower levels of lactobacillus and bifidobacterium in their feces |
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Term
| what are the anti-TNF alpha drugs? |
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Definition
| infliximab, natalizumab, adalimumab, and certolizumab pegol |
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Term
| what characterizes the use of infliximab as an anti-TNF alpha therapy to tx IBD? |
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Definition
| infliximab is a chimeric IgG1 monoclonal antibody approved for RA/AS/CD which can also *help with fistula healing. however the body can develop ab against it (up to 60%) b/c it is no 100% human-derived. CDP571 is a more humanized version, but still has murine component. |
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Term
| what characterizes the use of adalimumab as an anti-TNF alpha therapy to tx IBD? |
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Definition
| this is a recombinant monoclonal antibody for TNF alpha, 100% human derived. *when it binds to TNF alpha, receptors p75 and p55 are blocked. in the presence of complement, *adalimumab lyses surface TNF and has *no antibodies, *no reactions and *no CRP benefit. pts must be screened for TB prior to use to ensure nothing is lying dormant and it is safe and effective for 4 wks use. |
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Term
| what are next generation IBD drugs? |
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Definition
| anti- IL-2 drugs, cytokines (fontolizumab/IFN gamma), sargramostim, (targets innate immune system, granulocyte macrophage colonies), and *visilizumab - anti- CD3, causing apoptosis of activated T cells - most important cell as far as IBD is concerned. |
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