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Treatment of Inflammatory Bowel Disease (5-aminosalicylates (Drugs: …
Treatment of Inflammatory Bowel Disease
Corticosteroids
Drugs:
Budesonide, Hydrocortisone, Prednisolone
Mechanism of action:
Binds to glucocorticoid receptor in the cytoplasm of many cells which increases or decreases synthesis of specific proteins
This leads to anti-inflammatory and immunosuppressive effects via increased anti-inflammatory factors and decreased inflammatory mediators and decreased action of inflammatory cells
Adverse effects:
Long term HPA axis suppression and Cushing's syndrome
Clinical use:
Induction of remission in active IBD
5-aminosalicylates
Drugs:
Balsalazide, Mesalazine, Olsalazine, Sulfasalazine
Mechanism of action:
Active ingredient is 5-aminosalicylic acid (5-ASA)
All drugs (apart from mesalazine) have 5-ASA cleaved by bacteria in the intestine to release 5-ASA
Exact mechanism of action of 5-ASA is unknown but has local anti-inflammatory effects by scavenging reactive oxygen species, inhibiting inflammatory mediators and decreasing neutrophil chemotaxis
Pharmacokinetics:
Very little 5-ASA is absorbed, acts locally in intestines
Adverse effects:
Nausea, rash, headache, diarrhoea (diarrhoea more common with olsalazine)
Sulfasalazine can cause vomiting, reversible male infertility and haemolysis
Clinical use:
Ulcerative colitis (not as effective in Crohn's as effects are localised to the colon)
Azathioprine & Mercaptopurine
Mechanism of action:
Azathioprine is converted to mercaptopurine which is an immunosuppressant with potent anti-inflammatory properties
Inhibits purine synthesis for DNA replication and proliferation of cells thus suppressing T and B-cell production
Adverse effects:
Myelosuppression, infection, alopecia, diarrhoea, anorexia, nausea, vomiting, mouth ulceration, oesophagitis
Liver dysfunction (less common)
Clinical use:
Inflammatory bowel disease and other immune mediated diseases
Drug interactions:
Allopurinol inhibits metabolism of mercaptopurine which increases risk of bone marrow toxicity
Monitoring:
FBC and LFTs
Methotrexate
Mechanism of action:
Competitively inhibits dihydrofolate reductase thereby inhibiting synthesis of tetrahydrofolate
Tetrahydrofolate is required for purine synthesis, DNA synthesis and cell division
Therefore methotrexate inhibits cell proliferation
Clinical use:
Crohn's disease and ulcerative colitis refractory to standard treatment
Also used for other immune-mediated diseases and some cancers
Adverse effects:
Myelosuppression, nausea and vomiting, oral mucositis, pulmonary toxicity, hepatotoxicity, photosensitivity
Monitoring:
FBC and LFTs
TNF-alpha antagonists
Mechanism of action:
Monoclonal antibodies that act against TNF-alpha thus inhibiting its inflammatory action
Clinical use:
Moderate to severe IBD where other treatment does not work
Also used in other immune mediated diseases
Adverse effects:
Infections, rash, itch, headache, autoantibodies
Precautions:
Infection
Malignancy
Drugs:
Infliximab, Adalimumab
Vedolizumab
Mechanism of action:
Monoclonal antibody against alpha-4-beta-7 integrin on T cells
This inhibits adhesion of T-cells to MAdCAM-1 expressed in the GIT
This inhibits migration of T-cells across the endothelium into inflamed GI tissue and inhibits GI inflammation
Clinical use:
Moderate to severe IBD unreponsive to conventional treatments or TNF-alpha antagonists
Adverse effects:
Common: Arthralgia, headache, cough, infections
Rare: Autoantibodies
A relatively new drug, so there may be other adverse effects not yet recorded