托芬那酸
托芬那酸 (Tolfenamic acid) 是一種屬於**滅酸類 (fenamate)** 的非類固醇消炎止痛藥 (NSAID)，化學結構上與甲氯芬那酸 (meclofenamic acid) 相關。主要用於鎮痛、抗發炎和解熱。 **主要臨床特徵：** * **雙重作用：** 與許多傳統 NSAID 不同，滅酸類藥物不僅能抑制前列腺素的合成，還能直接阻斷前列腺素受體，從而提供更佳的鎮痛效果。 * **脈衝式給藥：** 對於犬隻的慢性疾病，通常採用獨特的「脈衝式」給藥計畫（例如每週連續給藥 3-5 天），以在維持療效的同時，將胃腸道和腎臟毒性降至最低。 * **血小板影響：** 具有顯著的抗血栓素活性，會損害血小板凝集功能。因此，**不建議在手術前使用**。 * **藥物取得：** 雖然在加拿大、歐洲和澳洲廣泛核准用於小動物和大型動物，但目前在美國並未上市。 > **臨床要點：** 與食物一起服用會增加腸肝循環，進而提高其生物利用度，但與空腹狀態相比，也可能造成吸收上的變異性增加。
作用機制: Tolfenamic acid exerts its effects through multiple pathways in the inflammatory cascade: * **Cyclooxygenase (COX) Inhibition:** It is a potent inhibitor of the **COX** enzyme, which prevents the conversion of arachidonic acid → **prostaglandins (PGs)** and **thromboxanes (TXA2)**. This reduces inflammation, pain, and fever. * **Direct Receptor Antagonism:** Uniquely among NSAID classes, fenamates directly block the binding of synthesized prostaglandins to their respective tissue receptors (e.g., EP receptors), providing a secondary mechanism of action against pain and inflammation. * **Anti-thromboxane Activity:** By inhibiting TXA2 synthesis, it significantly impairs platelet aggregation and normal clotting function.
各物種劑量
- Acute pain · 4 mg/kg · SC, IM or PO · once daily · 3-5 days (injectable suggested for first dose only)
- Pain/inflammation · 4 mg/kg · PO · once daily · 3-5 days or as recommended by the veterinarian
- Inflammation, pain, and fever · 4 mg/kg · SC · once, may be repeated once after 24 hours · 1-2 days · Do NOT give IM to cats. Treatment starts with a single injection on day 1.
- Inflammation, pain, and fever · 4 mg/kg · PO · sid · 3 days · Treatment starts with a single injection on day 1, followed by 3 days PO. Repeated dosing on a weekly basis is NOT recommended in cats.
- Metritis-mastitis-agalactia (MMA) · 2 mg/kg · IM · once · Once · Meat withdrawal = 6 days.
- Pneumonia · 2 mg/kg · IM · Treatment may be repeated once only after 48 hours · Up to 2 doses · Inject high in the neck. Meat withdrawal = 10 days.
- Mastitis · 4 mg/kg · IV · single injection · Once · Meat withdrawal = 4 days; Milk withdrawal = 12 hours (1 milking).
- Acute pain · 4 mg/kg · SC, IM or PO · once daily · 3-5 days (injectable suggested for first dose only)
給藥途徑
禁忌症
- Hypersensitivity to tolfenamic acid or other fenamates (e.g., meclofenamic acid)
- Active gastrointestinal bleeding or ulceration
- Pre-surgical administration (due to anti-thromboxane/platelet effects)
- Dehydrated, hypovolemic, or hypotensive patients
- Patients with gastrointestinal disease
- Patients with blood clotting problems
- Pregnant animals
- Animals under 6 weeks of age
- Intramuscular (IM) administration in cats
不良反應
- Vomiting
- Diarrhea
- Gastrointestinal ulceration (at high doses)
- Platelet dysfunction/prolonged bleeding time
- Potential nephrotoxicity (especially in dehydrated patients)
- Gastrointestinal signs (vomiting, diarrhea, anorexia)
- Gastrointestinal ulceration and bleeding
- Renal toxicity (especially during hypotension)
- Potential precipitation of cardiac failure (rare/unknown risk in animals)
藥物相互作用
- Aspirin · May increase the risk of gastrointestinal toxicity (e.g., ulceration, bleeding, vomiting, diarrhea).
- Corticosteroids · Concomitant therapy may increase the occurrence of gastric ulceration; avoid concurrent use.
- Digoxin · NSAIDs may increase serum levels of digoxin.
- Fluconazole · May increase plasma levels of NSAIDs; potentially affects tolfenamic acid levels in dogs.
- Furosemide · NSAIDs may reduce the saluretic and diuretic effects of furosemide.
- Methotrexate · Serious toxicity has occurred with concomitant NSAID use; use together with extreme caution.
- Nephrotoxic Drugs (e.g., aminoglycosides, amphotericin B) · May enhance the risk of nephrotoxicity.
- Other NSAIDs · May increase the risk of gastrointestinal toxicity (e.g., ulceration, bleeding, vomiting, diarrhea). · major
- Warfarin · Tolfenamic acid is 98-99% protein-bound; may displace highly protein-bound drugs like warfarin, increasing bleeding risk. Monitor closely.
- Glucocorticoids · Increased risk of gastrointestinal ulceration and bleeding. Do not administer concurrently or within 24 hours. · major
- Aminoglycosides · Increased risk of nephrotoxicity. · major
監測
- Clinical efficacy (pain scores, resolution of inflammation)
- Adverse effects (vomiting, diarrhea, anorexia)
- Renal function (BUN, Creatinine, SDMA, USG) with prolonged use
- Signs of GI bleeding (melena, pale mucous membranes)
- Clinical signs of gastrointestinal toxicity (vomiting, diarrhea, melena, anorexia)
- Renal parameters (BUN, creatinine, USG), especially in perioperative or hypotensive patients
- Liver enzymes in patients receiving prolonged therapy
過量
Acute toxicity data is limited. Experimental studies in dogs and cats did not demonstrate significant renal or GI toxicity until doses exceeded 10 times the labeled dose. **Treatment Protocol:** * **Decontamination:** Empty the gut following recent oral ingestion (emesis induction, activated charcoal). * **Supportive Care:** Institute IV fluid therapy to maintain hydration and support renal perfusion. * **Seizure Control:** Use IV **diazepam** if seizures occur. * **Monitoring:** Closely monitor for signs of gastrointestinal bleeding (melena, hematemesis). Monitor electrolyte and fluid balance carefully, and manage any acute renal failure using established veterinary guidelines.
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