Immunosuppressants and biologics
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Name three anti-metabolite agents.
Azathioprine, methotrexate and mycophenolate mofetil
Azathioprine method of action?
Gets converted to 6-mercaptopurine in the body.
Purine synthesis inhibitor - prevents synthesis of adenine and guanine. Especially active in lymphocytes leading to apoptosis.
Levels must be checked of an enzyme (TPMT) that converts 6MP to toxic products.
Mycophenolate mofetil MOA?
Salvage pathway - inhibits production of guanosine monophosphate. Lymphocytes cannot convert guanine back to guanine monophosphate therefore proliferation is inhibited.
Methotrexate MOA and SE?
Depletes folic acid (dihydrofolate -> tetrahydrofolate) - dihydrofolate inhibitor.
Therefore inhibits generation of DNA building blocks
SE - GI common, leucopenia, thrombocytopenia, transaminitis, pneumonitis (methotrexate lung)
Ciclosporin MOA and SE?
Inhibits calcineurin pathway (involved with calcium metabolism and influx).
Inhibits nuclear transcription factor (NF-ATc) which activates T cells so transcription of IL-2 gene is prevented.
SE - drug interactions, toxicity, hypertension, tremor
Targets of biologic therapies and an example for each.
* Cytokine targeting - e.g. Anti-TNF - infliximab
* Anti cellular - e.g. Anti B cell - Rituximab
* Receptor targeting - e.g. Herceptin
* Endogenous product - e.g. Interferon alpha
Which antibiotic should be used for MRSA skin infection?
Vancomycin (NOT FLUCLOXACILLIN)
Where does cellulitis affect?
Dermis and subcut
Where does ersipelas affect?
SE of biologics?
- - Infections (esp first 6 months)
- - Chronic inflammation
- - Severe heart failure
- - Viral reactivation e.g. TB
- - Demyelination
- - Infusion reaction (if chimaeric)
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