Crohns disease
Short half life so not worried recent use prior to surgery
- Thiopurines
- Mechanism of action Inhibit cytotoxic t-cells and natural killer cells
- Clinical response ranges from a few days to up to eight weeks
- Must check Thiopurine methyltransferase enzyme (TPMT) activity
- Low TPMT activity have been associated with an increased risk of myelotoxicity, especially in Caucasians
- High TPMT activity are called “hypermethylators” or “non-responders” because they mainly produce methylated inactivated products of AZA
- Side effects: Bone marrow suppression, pancreatitis, hepatitis, fever and rash
- Methotrexate + 1mg folic acid
- Folic acid antagnonist
- Mechanism of actions - inhibits t-cell activation and b cell and inhibt methyl transferase
- Side effects: hepatic toxicity, ulcerative stomatitis, bone marrow suppression, fatigue, pulmonary fibrosis , kidney failure, teratogenic
Transplant
- Stops lymphocyte proliferation and clonal expansion
- Azathioprine
- Converted in liver to active metabolite: 6-mercaptopurine
- Blocks purine metabolism - thereby inhibits cellular proliferation
- Mycophenolate Mofetil (MMF)
- Newer and has now replaced azathioprine as the agent of choice in many centres
- Converted to its active metabolite, mycophenolic acid
- Inhibits enzyme which is the rate-limiting enzyme in purine nucleotide synthesis
- Lymphocytes do not have a salvage pathway for purine synthesis ⇒ Ability to proliferate selectively impaired
- Azathioprine
- Main side effects:
- Bone marrow suppression
- Gastrointestinal symptoms