別嘌醇
**別嘌醇 (Allopurinol)** 是一種強效的**黃嘌呤氧化酶抑制劑**，廣泛應用於獸醫學中。 主要臨床應用包括： * **尿酸鹽結石：** 主要用於犬隻（特別是易感品種如大麥町犬）以溶解和預防尿酸結石。必須結合低嘌呤飲食使用，以防止黃嘌呤結石的形成。 * **犬利什曼原蟲症：** 作為抑制利什曼原蟲的藥物。通常與葡甲胺銻 (meglumine antimoniate) 或米替福新 (miltefosine) 聯合使用進行長期管理。 * **鳥類與爬蟲類醫學：** 用於控制高尿酸血症及治療鳥類和爬蟲類的痛風。 *臨床提示：* 由於別嘌醇會增加黃嘌呤的尿液排泄，若長期高劑量使用且未限制飲食中的嘌呤，反而可能導致黃嘌呤結石的形成。
作用機制: Allopurinol and its primary active metabolite, **oxypurinol** (alloxanthine), competitively inhibit the enzyme **xanthine oxidase**. * **Normal Pathway:** Hypoxanthine → **xanthine oxidase** → Xanthine → **xanthine oxidase** → Uric Acid * **Inhibition:** By blocking this enzyme, allopurinol prevents the conversion of oxypurines to uric acid. This decreases serum and urine concentrations of uric acid, while increasing the levels of the more water-soluble precursors (hypoxanthine and xanthine). **In Leishmaniasis:** Allopurinol acts as a purine analogue. *Leishmania* organisms mistakenly incorporate allopurinol metabolites into their RNA, which disrupts protein synthesis and inhibits parasite multiplication.
各物種劑量
- Urate uroliths (dissolution) · 15 mg/kg PO q12h; only in conjunction with low purine foods. · PO · q12h
- Urate uroliths (prevention) · 10-20 mg/kg/day · PO · Daily · Preferable to minimize recurrence with dietary therapy to avoid xanthine uroliths.
- Urate uroliths (dissolution and prevention) · 7-10 mg/kg PO three times daily · PO · TID · Goal is to reduce urine urate:creatinine ratio by 50%.
- Leishmaniasis (First line treatment) · 10 mg/kg PO twice daily · PO · BID · 6-12 months · Used plus Meglumine antimoniate 75-100 mg/kg once daily for 4-8 weeks.
- Leishmaniasis (Second line treatment) · 10 mg/kg PO twice daily · PO · BID · 6-12 months · Used plus Miltofosine 2 mg/kg PO once daily for 4 weeks OR allopurinol alone.
- Leishmaniasis · 20 mg/kg PO q12h · PO · q12h · 9 months · With Meglumine antimoniate (100 mg/kg/day SQ) until resolution.
- Leishmaniasis (Alternate protocol alone) · 10 mg/kg PO q8h or 10-20 mg/kg PO q12h · PO · q8h or q12h · 1-4 months
- Leishmaniasis · 10 mg/kg PO twice daily · PO · BID · If possible use with meglumine antimoniate, if not, use alone.
- Leishmaniasis (with renal insufficiency) · 5 mg/kg PO twice daily · PO · BID
- Leishmaniasis · 15 mg/kg PO twice daily · PO · BID · months
給藥途徑
禁忌症
- Known hypersensitivity to allopurinol
- Red-tailed hawks (anecdotal reports of severe toxicity)
不良反應
- Xanthine urolithiasis (especially with high doses or non-restricted diets)
- Hypersensitivity reactions (rash, erythema)
- Lethargy
- Gastrointestinal upset
- Hepatotoxicity (rare)
- Bone marrow suppression (rare)
藥物相互作用
- Chlorpropamide · May increase risks for hypoglycemia and hepato-renal reactions
- Cyclophosphamide · Increased bone marrow depression may occur
- Cyclosporine · Allopurinol may increase cyclosporine levels
- Diuretics (Furosemide, Thiazides, Diazoxide) and Alcohol · Can increase uric acid levels, antagonizing allopurinol's effect
- Oral Anticoagulants (e.g., Warfarin) · Allopurinol may reduce the metabolism of warfarin thereby increasing its effect
- Trimethoprim/Sulfamethoxazole · Thrombocytopenia has occurred in a few human patients when used concurrently
- Uricosuric Agents (e.g., Probenecid, Sulfinpyrazone) · May increase the renal excretion of oxypurinol and thereby reduce xanthine oxidase inhibition; additive effects on blood uric acid may be beneficial
- Urinary Acidifiers (e.g., Methionine, Ammonium Chloride) · May reduce the solubility of uric acid in the urine and induce urolithiasis
- Azathioprine · Allopurinol inhibits the metabolism of azathioprine, leading to severe, potentially fatal myelosuppression. · major
- Mercaptopurine · Allopurinol inhibits the metabolism of mercaptopurine, significantly increasing toxicity risk. · major
- Amoxicillin / Ampicillin · Concurrent use increases the risk of cutaneous rash. · moderate
監測
- Urine uric acid (for urolithiasis)
- Adverse effects (rash, lethargy)
- Periodic CBC, liver and renal function tests (e.g., BUN, Creatinine, liver enzymes); especially early in therapy
過量
Information on acute overdosage in veterinary species is limited. Massive overdoses may cause gastrointestinal distress (vomiting, diarrhea). Treatment should consist of supportive care and monitoring of renal function. Adequate hydration is important to promote diuresis and excretion.
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。