Interstitial Lung Dz
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- Cyclophosphamide (Cytoxan)
- Azothioprine (Imuran)
- Methotrexate (Trexall, Rheumatrex)
MoA (Chemotherapy drugs)
- Metabolically cytochrome P450 activated to phosphoramide mustard - inactive otherwise
- Forms DNA crosslinks both between and within DNA strands leads to cell death
- Inhibits dihydrofolate reductase (DHFR)
- Inhibits thymidine synthase (TS)
- Inhibits de novo purine nucleotide synthesis
- Metabolized into the active 6-mercaptopurine, itself a purine synthesis inhibitor.
- 6-Mercaptopurine impedes DNA synthesis and thus inhibits the proliferation of cells, especially the fast-growing lymphocytes.
- T-cells and B-cells are particularly affected by the inhibition of purine synthesis.
SEs (Chemotherapy drugs)
- Acrolein is one prominent metabolite responsible for major toxicities
- Hemorrhagic cystitis,
- Cardiac toxicity
- Myelosuppression with neutropenia and thrombocytopenia
- Uncommon but include nausea
- Hair loss
- BM supression- susceptible to infection
MoA (Anti-inflammatory drugs)
- Arrests mitosis in metaphase by binding to tubulin & prevents mitotic spindle formation in granulocytes & other motile cells.
- Inhibits migration of granylocytes into inflamed areas & ↓ their metabolic & phagocytic activities.
- Prevents elaboration of urate-induced glycoprotein in joints.
Indication (Anti-inflamm. drugs)
- Prevention & treatment of gout.
- No analgesia.
- Give within 24 hrs.
SEs (Anti-inflamm. drugs)
- GI upset from chronic exposure to drug & its metabolites
- Due to enterohepatic circulation (↑ turnover of jejunal mucosal cells)
- Long-term use:
- Hair loss
- Bone marrow depression
- Peripheral neuritis
- Myopathy (↑ CPK)
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