아자티오프린

면역억제제 - 퓨린 길항제

**아자티오프린(Azathioprine)**은 수의학에서 주로 개를 대상으로 면역 매개성 용혈성 빈혈(IMHA), 염증성 장질환(IBD), 중증 근무력증, 천포창 등 다양한 면역 매개성 및 자가면역 질환을 치료하는 데 널리 사용되는 강력한 퓨린 길항제 계열의 면역억제제입니다. **핵심 임상 정보:** * **스테로이드 절약 효과:** 코르티코스테로이드(프레드니손 또는 프레드니솔론 등)와 함께 투여되는 경우가 많습니다. 이 병용 요법을 통해 질병의 관해를 유지하면서 스테로이드 용량을 점진적으로 줄일 수 있어 장기적인 스테로이드 부작용을 최소화할 수 있습니다. * **지연된 약효 발현:** 아자티오프린은 속효성 약물이 아닙니다. 완전한 면역억제 임상 효과를 얻으려면 일반적으로 **2~6주**가 필요합니다. 따라서 급성으로 생명을 위협하는 자가면역 위기 상황에서 단독 제제로 사용하는 것은 적합하지 않습니다. * **종 특이적 민감성:** **고양이는 아자티오프린에 매우 민감**하여 골수 억제가 쉽게 발생합니다. 이는 고양이가 선천적으로 티오퓨린 메틸트랜스퍼라제(TPMT) 효소 수치가 낮기 때문입니다. 고양이에게 이 약을 사용하는 것은 논란의 여지가 많으며 일반적으로 피해야 합니다. * **독성 위험:** 가장 심각한 부작용은 **골수 억제**(백혈구 감소증, 빈혈, 혈소판 감소증)입니다. 개에서는 간 독성과 급성 췌장염도 주의해야 할 위험 요소입니다.

작용 기전: 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.

동물 종별 용량

Dogs

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

투여 경로

POIV

금기

Known hypersensitivity to azathioprine
Cats (generally contraindicated due to severe, potentially fatal myelotoxicity)

이상반응

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

약물 상호작용

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

모니터링

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

과용량

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.

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