巰嘌呤
**巰嘌呤 (Mercaptopurine, 6-MP)** 是一種硫嘌呤類抗腫瘤藥物與免疫抑制劑。 **臨床要點與藥理學：** * 它與**硫唑嘌呤 (Azathioprine)** 密切相關，硫唑嘌呤實際上是一種前驅藥，在體內會迅速轉化為巰嘌呤。 * 雖然在獸醫學中較少作為第一線藥物使用，但它可作為**淋巴肉瘤**、**急性白血病**以及嚴重的免疫介導疾病（如**類風濕性關節炎**或難治性自身免疫疾病，例如對治療無反應的潰瘍性結腸炎/炎症性腸病）的有效輔助療法。 * 由於它是一種細胞毒性藥物，需要小心處理，並嚴格監測病患是否出現骨髓抑制和肝毒性。
作用機制: Mercaptopurine is an inactive prodrug that requires intracellular activation to exert its cytotoxic and immunosuppressive effects. * Mercaptopurine enters the cell and is converted by the enzyme **hypoxanthine-guanine phosphoribosyltransferase (HGPRT)** → **thioinosinic acid (TIMP)**. * TIMP acts as a **purine antagonist**, inhibiting multiple enzymes required for *de novo* purine synthesis. * False nucleotides are incorporated into DNA and RNA → **inhibition of nucleic acid synthesis** → cell cycle arrest and apoptosis. * It primarily affects rapidly dividing cells, strongly inhibiting **humoral immunity** (B-cell function) and, to a lesser extent, cell-mediated immunity.
各物種劑量
- As an immunosuppressant in combination with corticosteroids for treating bullous pemphigoid · 2.2 mg/kg · PO · once daily (q24h), then q48h
- For erosive, immune-mediated polyarthritis in combination with corticosteroids · 2 mg/kg · PO · once daily (q24h) for 14-21 days, then q48h (every other day) · 14-21 days initially
- For treatment of immune-mediated diseases or acute lymphocytic and granulocytic leukemias · 50 mg/m2 · PO · once daily (q24h) to effect, then every other day (q48h) or as needed
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
給藥途徑
禁忌症
- Hypersensitivity to mercaptopurine
- Pregnancy (teratogenic and mutagenic)
不良反應
- Nausea
- Anorexia
- Vomiting
- Diarrhea
- Bone marrow suppression (leukopenia, thrombocytopenia, anemia)
- Hepatotoxicity
- Pancreatitis
- Gastrointestinal ulceration (including oral ulcers)
- Dermatologic reactions
藥物相互作用
- Allopurinol · Decreases hepatic metabolism of mercaptopurine via xanthine oxidase inhibition. Dose of mercaptopurine must be drastically reduced (to 1/4-1/3 of usual dose) if used concurrently.
- Aminosalicylates (mesalamine, sulfasalazine) · May increase the risk for mercaptopurine toxicity.
- Hepatotoxic drugs (halothane, ketoconazole, valproic acid, phenobarbital, primidone, doxorubicin) · Increased risk of hepatotoxicity; use cautiously together.
- Immunosuppressive drugs (azathioprine, cyclophosphamide, corticosteroids) · Increased risk of severe infection due to additive immunosuppression.
- Myelosuppressive drugs (antineoplastics, chloramphenicol, flucytosine, amphotericin B, colchicine, trimethoprim/sulfa) · Additive bone marrow depression; use with extreme caution.
- Vaccines, live · Increased risk of vaccine-induced infection; use with caution or avoid during therapy.
- Warfarin · Mercaptopurine may reduce the anticoagulant effect of warfarin.
監測
- Hemograms (including platelets): Monitor closely; initially every 1-2 weeks, then every 1-2 months on maintenance therapy. (Note: If WBC drops to 5,000-7,000 cells/mm3, consider reducing dose by 25%. If WBC drops below 5,000 cells/mm3, discontinue until leukopenia resolves).
- Liver function tests (ALT, AST, ALP, Bilirubin)
- Serum amylase (if pancreatitis is suspected)
- Clinical efficacy and signs of toxicity
過量
Toxicity may present **acutely** (severe GI effects like vomiting and diarrhea) or be **delayed** (bone marrow depression, hepatotoxicity, gastroenteritis). * **Treatment**: If ingestion was recent, use standard protocols to empty the GI tract (emesis, activated charcoal). Provide aggressive supportive care (IV fluids, antiemetics, broad-spectrum antibiotics if neutropenic, and potentially blood transfusions for severe myelosuppression).
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。