硫唑嘌呤
**硫唑嘌呤 (Azathioprine)** 是一種強效的嘌呤拮抗型免疫抑制劑，在獸醫學中廣泛用於犬隻，以治療多種免疫介導和自體免疫性疾病（例如：免疫介導性溶血性貧血 [IMHA]、炎症性腸病 [IBD]、重症肌無力及天皰瘡）。 **臨床關鍵要點：** * **減少類固醇用量 (Steroid-Sparing Effect)：** 通常與皮質類固醇（如潑尼松或潑尼松龍）合併使用。這種組合允許逐漸減少類固醇的劑量，從而在維持疾病緩解的同時，將長期的類固醇副作用降至最低。 * **起效緩慢：** 硫唑嘌呤並非速效藥物。通常需要 **2至6週** 才能達到完全的免疫抑制臨床療效。因此，它不適合單獨用於急性、危及生命的自體免疫危機。 * **物種敏感性：** **貓對硫唑嘌呤極度敏感**，容易引發骨髓抑制，這是因為貓體內的硫嘌呤甲基轉移酶 (TPMT) 濃度天生較低。在貓科動物中使用此藥極具爭議，通常應避免使用。 * **毒性風險：** 最顯著的副作用是 **骨髓抑制**（白血球低下、貧血、血小板低下）。在犬隻中，肝毒性和急性胰臟炎也是值得注意的風險。
作用機制: Azathioprine is a **prodrug** that must be metabolized to exert its effects. * **Pathway:** Azathioprine is rapidly converted in the body (primarily in erythrocytes and the liver) to **6-mercaptopurine (6-MP)**. * 6-MP is further metabolized into active thioguanine nucleotides (TGNs). * **Mechanism:** These active metabolites act as **purine antagonists**. They are falsely incorporated into cellular DNA and RNA, which **inhibits purine metabolism, RNA/DNA synthesis, and cellular mitosis**. * **Immunological Effect:** Because lymphocytes (T-cells and B-cells) lack a salvage pathway for purine synthesis and rely heavily on *de novo* synthesis, they are profoundly affected. This leads to a marked suppression of **delayed hypersensitivity** and **cellular immunity**, with a lesser effect on humoral antibody responses.
各物種劑量
- Inflammatory bowel disease · Initially 2 mg/kg PO once daily for 2 weeks, then tapered to 2 mg/kg PO every other day for 2-4 weeks, then 1 mg/kg PO every other day. · PO · q24h then tapered · Long-term · May take 2-6 weeks before beneficial effects are seen.
- Immune-mediated anemia, colitis, immune-mediated skin disease, and acquired myasthenia gravis · 2 mg/kg PO once daily (q24h); long-term therapy 0.5-1 mg/kg PO every other day · PO · q24h then q48h · Long-term · With prednisolone administered on the alternate days.
- Adjunctive therapy in myasthenia gravis in non-responsive patients · Initially, 1 mg/kg PO once daily. If neutrophil and platelet counts are normal after 2 weeks, dose is increased to 2 mg/kg PO once daily. · PO · q24h · Until clinical remission · Taper to every other day when clinical remission occurs. Discontinue if WBC <4,000 cells/mcL or neutrophils <1,000 cells/mcL.
- Lymphoplasmacytic enteritis (if poor response to prednisolone) · 2 mg/kg PO once daily for 5 days, then on alternate days to prednisolone · PO · q24h then q48h · Long-term
- Severe cases of immune-mediated hemolytic anemia (IMHA) · 2.2 mg/kg PO once daily (q24h) · PO · q24h · Long-term · In addition to prednisone. Tapered gradually.
- Acute immune-mediated hemolytic anemia (IMHA) with glucocorticoids · 1-2 mg/kg PO once daily · PO · q24h · Long-term maintenance · Used for long-term maintenance as steroid side effects become intolerable.
- Severe and refractory inflammatory bowel disease · 2.2 mg/kg PO once daily · PO · q24h · Long-term · A lag time of 3-5 weeks is expected before clinical improvement is noted.
- Adjunctive treatment of ocular fibrous histiocytomas · 2 mg/kg PO daily for 2 weeks, reevaluate, and reduce to 1 mg/kg every other day for 2 weeks, then 1 mg/kg once weekly for 1 month · PO · Tapering schedule · 10 weeks
給藥途徑
禁忌症
- Known hypersensitivity to azathioprine
- Cats (generally contraindicated due to severe, potentially fatal myelotoxicity)
不良反應
- Bone marrow suppression (leukopenia, anemia, thrombocytopenia)
- Gastrointestinal distress (vomiting, diarrhea, anorexia)
- Acute pancreatitis
- Hepatotoxicity
- Poor hair growth
- Increased susceptibility to secondary infections
- Increased risk of neoplastic illnesses with long-term use
藥物相互作用
- ACE Inhibitors (e.g., benazepril, enalapril) · Increased potential for hematologic toxicity
- Allopurinol · Decreases hepatic metabolism of azathioprine; significantly increases toxicity risk. Dose of azathioprine must be reduced to 1/4 to 1/3 of the usual dose if used concurrently. · major
- Aminosalicylates (e.g., sulfasalazine, mesalamine, olsalazine) · Increased risk for azathioprine toxicity
- Non-depolarizing muscle relaxants (e.g., pancuronium, tubocurarine) · Neuromuscular blocking activity may be inhibited or reversed by azathioprine
- Corticosteroids · Often used together intentionally, but carries a greater potential risk for overall toxicity development · moderate
- Drugs affecting myelopoiesis (e.g., trimethoprim/sulfa, cyclophosphamide) · Increased potential for hematologic toxicity (additive bone marrow suppression)
- Warfarin · Potential for reduced anticoagulant effect
- Aminosalicylates · Increased risk of azathioprine toxicity. · moderate
- ACE inhibitors · May increase the potential for haematological adverse events (e.g., severe anaemia or leucopenia). · major
監測
- Hemograms (CBC including platelets): Monitor closely; initially every 1-2 weeks, then every 1-2 months on maintenance therapy. Reduce dose by 25% if WBC drops to 5,000-7,000 cells/mcL. Discontinue if WBC < 5,000 cells/mcL until resolved.
- Liver function tests (ALT, AST, ALP, Bilirubin)
- Serum amylase/lipase (if pancreatitis is suspected)
- Clinical efficacy and signs of secondary infection
過量
There is limited specific information regarding acute overdose of azathioprine in veterinary patients. * **Decontamination:** If ingestion was recent, use standard protocols to empty the GI tract (emesis induction, activated charcoal). * **Treatment:** Provide aggressive supportive care. Monitor hematologic parameters closely for delayed bone marrow suppression. * **Consultation:** Contact an animal poison control center for the most up-to-date guidance.
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。