Autoimmune Meds Flashcards
Aminosalicylates
- give 2 examples
- 2 indications
- mesalazine (UC), sulfasalazine (RA)
- moderate/severe UC treatment
- rheumatoid arthritis DMARD
mesalazine is an aminosalicylates, used in the treatment of UC, how does it exert its action?
-by releasing ___ which has anti-____ and _____ effects mainly on the gut (preparations are designed to delay delivery of active ingredient to colon, in colon ____ enzymes break this link and release the molecules).
- releasing 5-ASA(aminosalicylic acid)
- anti-inflamm and immunosupressive
- bacterial enzymes
Adverse effects of aminosalicylates e.g. mesalazine, sulfasalazine
- GI upset: nausea, dyspepsia
- headache
- rarely: thrombocytopenia, leukopenia, renal impairment
- hypersensitivity reaction
- CI: ASPIRIN HYPERSENITIVITY
- mesalazine has a ph-sensitive coating so interacts with drugs that alter gut pH:
e. g. ___ increase gastric pH so may cause coating to be broken down prematurely
e. g. ____lowers stool pH and may prevent 5-ASA release in the colon
- e.g. PPIs increase gastric pH
e. g. lactulose lowers stool pH
What is the preffered route of administration of mesalazine for UC?
- enema or suppository (Ascol foam enema)
- once or 12-hrly for 4-6weeks to induce remission
Methotrexate indications, name 2
- DMARD for Rheumatoid Arthritis
- Part of Chemo e.g. for leukaemia, lymphoma, solid tumours
- Severe psoriasis (treatment resistant)
Methotrexate inhibits dihyd___ ____ which converts dietary ___ ___ to tetrahydrofolate (FH4). FH4 is required for DNA and protein synthesis so lack of FH4 prevents cellular ____.
Actively dividing cells are particularly sensitive to these effects.
Methotrexate also inhibits ______ ____ leading to its anti-inflamm and immunosupressive effects
- dihydrofolate reductase
- folic acid
- replication
- inflammatory mediators
3 SEs of methotrexate use
- mucosal damage
- bone marrow suppression –> neutropenia
- hypersensitivity reactions
- hepatic cirrhosis or pulmonary fibrosis from long-term use
As methotrexate is a once weekly tablet, if accidentally taken daily can –> overdose with severe effects like renal impairment and hepatotoxicity, what is given to treat this? Once medication rescues normal cells from the effects, supportive therapies enhance it’s excretion…
- folinic acid
- hydration
- urinary alkalinisation
2 CIs for methotrexate use:
CI: PREGNANCY (teratogenic)
CI: SEVERE RENAL IMPAIRMENT
Azathioprine is a pro-drug used for Crohon’s and UC and as a DMARD in RA and to prevent organ rejection. What is it’s main metabolite?
-6 - mercaptopurine
Azathioprine metabolised to 6-mercaptopurine has what action?
- inhibits purine, so inhibit DNA/RNA replication
- as lymphocytes rely on purines they are most affected
What metabolises azathioprine and its metabolites? what is done before starting therapy?
- Zanthine oxidase and TPMT (thiopurine methyltransferase)
- tpmt phenotype before therapy and do not prescribe if pts have absent activity, if reduced activity treat only by specialist
What is the most serious dose-related adverse effect of azathioprine?
-Bone Marrow Suppression (leukopenia and increased risk of infection)
Why is Azathioprine and allopurinol co-prescription not possible. (relates to metabolism of azathioprine)
- Allopurinol is a xanthine oxidase inhibitor
- this would reduce metabolism of azathioprine increasing the risk of toxicity
