IBD Treatment Flashcards
Most important drug for the continuous treatment of IBD
5-ASA (mesalamine)
Sulfasalazine =
Sulfapyrazine + 5-ASA (active part
Mesalamine MOA
- Alters eicosanoid metabolism via inhibition of 5-lipoxygenase and suppression of leukotriene formation (anti-inflammatory)
- Immunomodulatory: suppresses chemotaxis of neutrophils and macrophages and inhibits release of cytokines
- Scavenger of free radicals
Mesalamine Dosing
High doses (3 grams QD)
Unmodified 5-ASA is ineffective and only 25% is absorbed in the colon
Can be given by enema if disease is limited to rectum and right colon
Enema Pros and Cons
Reduces systemic load
Difficult to hold the enema in place for long enough time for efficacy
Don’t go beyond the splenic flexure
Pentasa General
Pure 5-ASA but coated with a membrane which dissovles in the stomach and duodenum
60% is released in the upper small intestine and the rest in the colon
Asacol and Claversal General
Mesalamine coated with Eudragit-S or L which dissolves at a pH greater than 6-7 so most of the drug is released in the small intestine and colon
5-ASA PK and ADR
Unclear which metabolite and body compartment
Headache, skin rash and GI complications (watery diarrhea, exacerbation of colitis)
Sulfasalazine (Azulfidine)
Sulfonamide + 5-ASA GI Symptoms Hematological symptoms (neutropenia) Skin rxns Impaired folic acid absorption and male infertility
White people have more
NAT2 vs N-acetyltransferase-1
Steroids + IBD
Anti-inflammatory (suppress symptoms)
Lots of side effects (immunosuppresion, osteoporosis, etc)
Local applications are preferred for colitis
Steroids used in IBD
Prednisone or Prednisolone or Hydrocortisone
Budesonide (Entocort) + IBD
Topical GLUCOCORTICOID
Less systemic side effects
Metronidazole + IBD
Effective in killing anaerobic
Long-term = peripheral neuropathy
Ciprofloxacin + IBD
Best alternative to metronidazole if not tolerated
Azathioprine + CD
Cytostatic agent
Pro-drug of 6-mercaptopurine
Suppresses DNA replication and proliferation of lymphocytes
- Not acute due to taking several months to start working
SUPPRESS BONE MARROW
Mutagenic and TERATOGENIC
Monitoring with Azathioprine
Thiopurine methyl-transferase (TPMT deficiency increase the risk of toxicity
Methotrexate + CD
Alternative to Azathioprine
Tacrolimus + UC
Suppress IL-2
Cytostatic or Immunosuppressant drugs
Risk of infection!!! Azathioprine Methotrexate Tacrolimus Cyclosporine
Cyclosporine MOA
Blocks calcineurin from getting activated
- Ca + Calmodulin → activates calcineurin → dephosphorylate NFAT (activated T cells) → NFAT is activated and goes to the nucleus and it causes IL-2 transcription
Supportive therapies for IBD
Antidiarrheal agents and Nutrition
Antidiarrheal Use
CAUSE toxic megacolon Loperamide Diphenoxylate/atropine Anticholinergic Cholestyramine
Nutrition Therapies for IBD
Iron, folate, B12
Corrects consequences (malabsorption, etc)
TPN for severe pts
