IBS Drugs Flashcards
What are the differences between Ulcerative Colitis and Crohn’s Disease?
Ulceritive colitis is continous but only affects the mucosa/submucosa. Crohns is patchy, so usually not curative by surgery, and affects all 3 layers. UC is associated with IL13, Th2 mediated, with limited clonal expansion and normal T cell apoptosis. Whilst CD is Th1 mediated, so associated with TNFa, florid T cell (CD8+) expansion and impaired T cell apoptosis.
Name 3 environmental factors of IBD?
Smoking and obseity (esp Crohns) and the gut microbiome.
Describe how the microbiome could cause AI disease (4 steps)
1) Compelx interplay between host and gut microbiome 2) DISRUPTED innate immunity and IMPAIRED clearance. 3) PRO-INFLAMMOTRY compensatory response. 4) GRANULOMA formation and physical DAMAGE.
Name 3 supportive and 3 symptomatic pharmacological therapies for IBD. Which are better for UC and which are better for CD?
Supportive: nutritional support, fluids, blood. Symtpomatic treatment: Glucocorticoids, Aminosalicylates and Immunosupressives.
Aminosalicylates (and probiotics!) are better for UC and Glucocortocoids and Immunosupressants are better for CD.
What are mesalazine and olsalazine and whats the difference between them? What’s their main role and name 3 mechanisms?
They are both aminosalicyltaes- mesalazine is one molcule of 5-aminosalicylic acid and olsalazine is two molecules of 5-aminosalicylic acid. They are anti-inflammartry- they inhibit IL1, TNFa and PAF as well as other cytokines, they decrease antibody secretion and they inhibit macrophage migration.
Describe the metabolism and absorption of mesalazine and olsalazine. Describe optimal administration.
Mesalazine is not metabolised, directly absorbed by the small bowel and colon. Olsalazine is metabolised by colonic flora and abosorbed in the colon. Optimal administration is combined oral and topical.
What are glucocorticoids, like prednisolone, mainly used for?
INDUCING remission in CROHNS disease (ASAs preferable for UC, side effects with long ter steroid use)
How do glucocorticoids, like prenisolone and budesonide, inhibit inflammation?
Glucocoroticoids increase synthesis of annexin 1, which via an extracellular receptor, inhibits phosplipase A2, hence inhibiting production of prostaglandins and leukotrienes.
Name 3 ways to limit side effects of steroids
1) Use topically or via a foam enema. 2) Administer with another drug to lower the steroid dose (e.g. odensatron and steroids used for emetogenic chemotherapy, e.g. use glucortocids with azathioprine). 3) Used a steroid with extnesive first pass metabolism (budesonide is an example) , limiting systemic effects.
Compare a standard glucocorticoid e.g. prednisolone, with budesonide.
Prednisolone is more effective at inducing remission in Crohns but has more side effects, so budesonide is preffered if the disease is mild.
Describe the use of azathioprine. What can it be used with?
No better than placebo in ACTIVE CD but good at MAINTAINING remission. Methotrexate has a similar effect bu inhibiting thymidine synthesis.
Describe 5 effects 6MP/azathioprine has on the immune system.
Inhibits antibody synthesis, leukocuyte proliferation, monocyte infiltration and cell/amtibod immune mediated responses, whilst enhancing T cell apoptosis.
Name 4 side effects of azathiprone
Hepatotoxiity, bone marrow supression, increased skin cancer and lymphoma risk, pancreattis.
What are the two active metabolites of azathioprine and what do they do?
6-TeMPN (inhibits de no purine synthesis) and 6-TGN (intercaltes with DNA, prevents cell replication)
What is the drug interaction between allopurinol (a gout drug) and azathioprine?
Alloupurinol inhibits xanthine oxidase which usually converts 6MP to 6-TU, an inactive form. Hence allopurinol may increase the proportion of 6-MP converted to an active form G-MeMPN or 6-TGN, increasing potency.
