Pharmacology
Immunosuppressants
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Get access- Ciclosporin A (calcineurin inhibitor) and Tacrolimus:
- Inhibit IL-2 production
Do not cause bone marrow suppression
- SEs: nephrotoxicity, tremor, hirsutism and gingival hypertrophy
- Contraindicated in uncontrolled hypertension (dose-related increase in BP)
- Purine antagonists: azathioprine and MMF
- Blocks RNA and DNA synthesis
- Azathioprine is metabolised to 6-mercaptopurine
Azathioprine toxic by-products are metabolised/inactivated by thiopurine methyltransferase (TPMT)
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TPMT activity levels are checked prior to commencement of azathioprine as the risk of myelosuppression is increased in patients with reduced activity due to bone marrow toxicity. Allopurinol interacts with TPMT so a lower dose of azathioprine is required.
- Side effects of azathioprine
- Bone marrow suppression
- Hepatotoxicity (FBC and LFT monitoring is needed)
- Mycophenolate mofetil: inhibits purine metabolism
Side effects: bone marrow suppression, GI upset, secondary malignancies, congenital malformations, spontaneous abortions
Requires weekly FBC then fortnightly after 4 weeks then monthly after 8 weeks for the first year
- Must be taken on an empty stomach (antacids will reduce absorption)
- Methotrexate: folic acid antagonist
- Inhibits dihydrofolate reductase to suppress DNA synthesis
- Used as a steroid-sparing agent eg for scleritis and uveitis
- Renally excreted
- Side effects
- Bone marrow suppression
- Deranged LFTs
- Oral ulceration
- Myalgia
- Pneumonitis
- Alkylating agents: cyclophosphamide, chlorambucil
- Cross-link DNA strands to prevent transcription of mRNA
- Profoundly suppresses function of T and B cells
Toxicity: bone marrow suppression, hemorrhagic cystitis (usually discontinued after 6-12 months to reduce the risk of bladder malignancy. Urine dipstick should be performed to screen for toxicity)
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Cyclophosphamide is dosed intravenously according to the patient's body surface area
- Biologics
- anti-VEGF agents
- anti-TNF alpha agents eg. infliximab and etanercept
- anti-CD20: rituximab
- CD20 is present on B lymphocytes
- Binding of rituximab causes cell lysis/apoptosis by complement-mediated cytotoxicity
- B cells and IgG/IgM levels are reduced for 6-12 months after therapy
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Infliximab is contraindicated in SLE as it can cause a lupus-like syndrome