Mercaptopurine
**Mercaptopurine (6-MP)** is a thiopurine antineoplastic and immunosuppressive agent. **Clinical Pearls & Pharmacology:** * It is closely related to **azathioprine**, which is actually a prodrug that is rapidly converted to mercaptopurine in the body. * While rarely used as a first-line agent in veterinary medicine, it serves as a valuable adjunctive therapy for **lymphosarcoma**, **acute leukemias**, and severe immune-mediated diseases such as **rheumatoid arthritis** or refractory autoimmune conditions (e.g., unresponsive ulcerative colitis/inflammatory bowel disease). * Because it is a cytotoxic agent, it requires careful handling and rigorous patient monitoring for bone marrow suppression and hepatotoxicity.
กลไกการออกฤทธิ์: 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.
ขนาดยาตามชนิดสัตว์
- 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
ขนาดยาเป็นข้อมูลอ้างอิงทางคลินิกสำหรับสัตวแพทย์ผู้มีใบอนุญาต โปรดตรวจสอบกับฉลากล่าสุดและผู้ป่วยแต่ละรายเสมอ
วิธีการให้ยา
ข้อห้ามใช้
- Hypersensitivity to mercaptopurine
- Pregnancy (teratogenic and mutagenic)
อาการไม่พึงประสงค์
- Nausea
- Anorexia
- Vomiting
- Diarrhea
- Bone marrow suppression (leukopenia, thrombocytopenia, anemia)
- Hepatotoxicity
- Pancreatitis
- Gastrointestinal ulceration (including oral ulcers)
- Dermatologic reactions
อันตรกิริยาระหว่างยา
- 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.
การติดตาม
- 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
การได้รับยาเกินขนาด
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).
ข้อมูลอ้างอิงยาของ VetSheet มีไว้สำหรับสัตวแพทย์ผู้มีใบอนุญาตเพื่อช่วยในการตัดสินใจทางคลินิก ไม่ใช่สิ่งทดแทนการวินิจฉัยของผู้เชี่ยวชาญหรือฉลากล่าสุดของผู้ผลิต