秋水仙鹼
秋水仙鹼是一種源自秋水仙植物（*Colchicum autumnale*）的獨特生物鹼，在人類醫學中傳統上以其抗痛風特性而聞名。在獸醫藥理學中，它主要作為**試驗性或仿單標示外療法**，用於特定的纖維化和發炎性疾病。 主要的獸醫應用包括： - **肝硬化/肝纖維化：** 用於減緩或逆轉肝臟的纖維化病變。 - **沙皮狗熱（家族性澱粉樣變性）：** 用於預防澱粉樣蛋白在腎臟中的沉積。 - **氣管支架肉芽組織增生：** 曾被實驗性地用於治療支架置入後的肉芽組織狹窄。 > **臨床重點：** 秋水仙鹼的治療指數狹窄。腸胃道不適通常是毒性的首發徵兆，一旦出現應立即重新評估病患狀況。
作用機制: Colchicine exerts its effects through several distinct mechanisms depending on the target tissue: - **Microtubule Disruption:** Binds irreversibly to **tubulin** → inhibits microtubule polymerization → interferes with sol-gel formation and the mitotic spindle → arrests cell division in **metaphase**. - **Antifibrotic Activity:** Stimulates **collagenase** activity → increases the breakdown of collagen and decreases its formation, mitigating hepatic fibrosis. - **Anti-Amyloid Effect:** Blocks the synthesis and secretion of **Serum Amyloid A (SAA)** (an acute-phase reactant protein) by hepatocytes → prevents the formation of amyloid-enhancing factor → halts amyloid deposition in tissues. - **Anti-inflammatory (Gout):** Inhibits neutrophil motility and phagocytosis of monosodium urate crystals → reduces the release of inflammatory mediators.
各物種劑量
- Fibrosis · Not recommended · PO · N/A · N/A · No evidence for its efficacy as an antifibrotic in cats.
- As an antifibrotic for the adjunctive treatment of hepatic fibrosis (Psittacines) · 0.2 mg/kg PO q12h · PO · q12h · May potentiate gout in some cases.
- Adjunctive treatment of hepatic cirrhosis/fibrosis · 0.03 mg/kg PO once daily · PO · q24h
- Adjunctive treatment of hepatic cirrhosis/fibrosis · 0.025-0.03 mg/kg PO once daily · PO · q24h · Probenecid-free drug. Not recommended for initial use with azathioprine, chlorambucil or methotrexate due to similar side effects. Used in many dogs and fewer cats without problems.
- Periodic fever syndrome in Shar Pei dogs · 0.03 mg/kg PO once daily · PO · q24h
- To reduce the frequency and severity of fever and prevent the development of amyloidosis in dogs with Shar Pei Fever · 0.025-0.03 mg/kg PO q24h · PO · q24h · No evidence supports use of colchicine once amyloidosis has resulted in renal failure.
- Fibrosis / Renal amyloidosis · Initial dose 0.01 mg/kg, increase in incremental amounts every 3-4 days to a maximum dose of 0.03 mg/kg · PO · q24h initially, up to q12h · Long-term · Increase dose only if no adverse GI effects occur.
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
禁忌症
- Serious renal dysfunction
- Serious gastrointestinal dysfunction
- Serious cardiac dysfunction
- Pregnancy (unless benefits strictly outweigh risks)
- Pregnancy
- Severe renal impairment
不良反應
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Anorexia
- Bone marrow suppression (with prolonged use)
- Neutropenia (rare)
- Severe local irritation/thrombophlebitis (if extravasated IV)
- Diarrhoea
- Renal damage (rare)
- Bone marrow suppression (rare)
- Myopathy (rare)
- Peripheral neuropathy (rare)
- Increased serum ALP
- Decreased platelet counts
藥物相互作用
- Bone Marrow Depressants (e.g., antineoplastics, immunosuppressants, chloramphenicol, amphotericin B) · May cause additive myelosuppression when used concurrently with colchicine.
- Ciclosporin · Possible increased risk of nephrotoxicity and myotoxicity · major
- NSAIDs (e.g., Phenylbutazone) · May increase the risks of thrombocytopenia, leucopenia, or bone marrow depression · major
- Anticancer chemotherapeutics · May cause additive myelosuppressive effects · major
監測
- Clinical efficacy
- Adverse effects (especially GI signs as early indicators of toxicity)
- CBC (to monitor for bone marrow suppression)
- Gastrointestinal signs (vomiting, diarrhea)
- Complete Blood Count (platelets, WBCs)
- Liver enzymes (ALP)
- Renal function parameters
- Urinalysis
過量
### Toxicity Profile Colchicine has a **narrow therapeutic index** and can be highly toxic even after relatively small overdoses. In humans, ingestion of as little as 7 mg has been fatal, with 65 mg considered a lethal dose in adults. ### Clinical Signs of Overdose - **Early Signs:** Severe gastrointestinal distress (anorexia, vomiting, bloody diarrhea, paralytic ileus). - **Advanced Signs:** Renal failure, hepatotoxicity, pancytopenia, ascending paralysis, shock, and vascular collapse. ### Management - **No specific antidote exists.** - **Decontamination:** Gut removal techniques should be employed when applicable. Due to extensive **enterohepatic recycling**, administering **repeated doses of activated charcoal** along with a saline cathartic is highly recommended to interrupt systemic reabsorption. - **Supportive Care:** Aggressive fluid therapy, symptomatic management, and potentially peritoneal dialysis.
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