酮洛芬
酮洛芬 (Ketoprofen) 是一種強效的**丙酸衍生物類非類固醇消炎止痛藥 (NSAID)**，在結構上與布洛芬 (ibuprofen)、萘普生 (naproxen) 和卡洛芬 (carprofen) 相似。在獸醫學中，它被廣泛用於其強大的**鎮痛、解熱和抗發炎**特性。 主要藥理特點： * **對映異構體特徵**：市售的酮洛芬為消旋混合物。**S(+) 對映異構體**主要負責抗前列腺素活性（以及相關的胃腸道/腎臟毒性），而 **R(-) 對映異構體**則提供鎮痛作用且無明顯的胃腸道副作用。 * **物種應用**：廣泛用於馬匹的肌肉骨骼疼痛，並被部分臨床獸醫師視為貓咪短期鎮痛的首選 NSAID 之一。它也可用於狗、牛、豬及各種特寵物種。 * **臨床要點**：雖然非常有效，但酮洛芬是一種非選擇性的 COX 抑制劑。因此，與較新的 COX-2 選擇性 NSAIDs（如 coxibs）相比，它引起胃腸道潰瘍和腎臟毒性的風險較高，特別是在小動物中。其在犬貓的使用通常限制在短期療程（例如 1 至 5 天）。
作用機制: Ketoprofen exerts its effects primarily through the inhibition of the **cyclooxygenase (COX)** enzymes. * **Arachidonic Acid Cascade**: Cell membrane phospholipids → **Phospholipase A2** → **Arachidonic Acid**. * **COX Inhibition**: Ketoprofen non-selectively blocks **COX-1** and **COX-2** enzymes. This prevents the conversion of arachidonic acid into **prostaglandin precursors (endoperoxides)**, thereby halting the synthesis of pro-inflammatory and hyperalgesic prostaglandins (e.g., PGE2) and thromboxanes. * **LOX Inhibition (Theoretical)**: Ketoprofen purportedly has inhibitory activity on **lipoxygenase (LOX)**, which would theoretically block the formation of leukotrienes. However, *in vitro* studies have not definitively confirmed this dual-inhibition activity at therapeutic doses in veterinary species. * **Central and Peripheral Action**: By reducing peripheral prostaglandins, it decreases nociceptor sensitization. It also acts centrally to reduce fever by inhibiting prostaglandin synthesis in the hypothalamus.
各物種劑量
- Antiinflammatory/analgesic · 2 mg/kg (0.2 mL/kg) SC for one day, and continue with ketoprofen tablets PO at a lower maintenance dose of 1 mg/kg once a day for four more days · SC, PO · q24h · 5 days total · In severe cases, the parenteral loading dose of 2 mg/kg can be given for up to three consecutive days.
- Antiinflammatory/analgesic · 1 mg/kg PO or SC once daily for up to 5 days, or 2 mg/kg SC as a single injection · PO, SC · q24h · Up to 5 days
- Post-operative pain control · 1-2 mg/kg IV, SC once daily for 3 days duration after surgery; or 1 mg/kg PO once daily for 3 days, after surgery · IV, SC, PO · q24h · 3 days
- Antiinflammatory/analgesic · 2 mg/kg SC once daily for up to 3 consecutive days. If preferred after one injection treatment may be followed on the next day with tablets at 1 mg/kg and continued on successive days for up to 4 days · SC, PO · q24h · Up to 5 days total
- Acute pain from musculoskeletal and other painful disorders · 2 mg/kg · SC · q24h · up to 3 consecutive days · Oral dosing for 4 days may follow a single injection of ketoprofen on day one.
- Acute pain from musculoskeletal and other painful disorders · 1 mg/kg · PO · q24h · up to 5 days · Oral dosing for 4 days may follow a single injection of ketoprofen on day one.
- Antiinflammatory/analgesic · 3 mg/kg · IM · q24h · Up to 3 days · Withdrawal times (U.K.) for meat: 4 days
給藥途徑
禁忌症
- Known hypersensitivity to ketoprofen or other NSAIDs
- Active gastrointestinal ulceration or bleeding
- Significant renal or hepatic impairment
- Late pregnancy (due to risk of premature closure of the patent ductus arteriosus)
- Intra-arterial administration
- Dehydrated, hypovolaemic, or hypotensive patients
- Patients with pre-existing gastrointestinal disease
- Patients with blood clotting problems
- Pregnant animals
- Animals < 6 weeks of age
不良反應
- Horses: Gastric mucosal damage, GI ulceration, renal crest necrosis, mild hepatitis, injection site inflammation (IM)
- Dogs and Cats: Vomiting, anorexia, gastrointestinal ulceration, renal toxicity
- General: Masking of infection signs (inflammation, hyperpyrexia)
- Gastrointestinal signs (vomiting, diarrhea, anorexia)
- Gastrointestinal ulceration and bleeding
- Renal toxicity (especially in dehydrated/hypotensive patients)
- Hepatic accumulation (in patients with liver disease)
- Potential precipitation of cardiac failure (rare/unknown risk in animals)
藥物相互作用
- Aminoglycosides (gentamicin, amikacin) · Increased risk for nephrotoxicity.
- Anticoagulants (heparin, LMWH, warfarin) · Increased risk for bleeding.
- Aspirin · Plasma levels of ketoprofen could decrease; increased likelihood of GI adverse effects (blood loss). Concomitant use is not recommended.
- Bisphosphonates (alendronate) · May increase risk for GI ulceration.
- Corticosteroids · Concomitant administration significantly increases the risks for GI adverse effects and ulceration.
- Cyclosporine · May increase risk for nephrotoxicity.
- Fluconazole · May increase NSAID levels.
- Furosemide · Ketoprofen may reduce the saluretic and diuretic effects of furosemide.
- Highly Protein Bound Drugs (phenytoin, valproic acid, sulfonamides) · Ketoprofen is 99% protein-bound and may displace other drugs, leading to increased serum levels and duration of action.
- Methotrexate · Serious toxicity has occurred when NSAIDs are used concomitantly; use with extreme caution.
- Probenecid · May cause a significant increase in serum levels and half-life of ketoprofen.
- Other NSAIDs · Increased risk of severe gastrointestinal ulceration and renal toxicity. Do not administer concurrently or within 24 hours. · major
監測
- Clinical efficacy (reduction in pain, lameness, or fever)
- Adverse effects (monitor for vomiting, diarrhea, melena, or anorexia)
- Baseline and periodic liver and renal function tests (BUN, Creatinine, ALT, AST) are recommended with long-term therapy
- Clinical signs of gastrointestinal ulceration (vomiting, melena, anorexia)
- Renal parameters (BUN, Creatinine, USG) especially in older or compromised patients
- Hepatic enzymes
- Hydration status and blood pressure
過量
As with any NSAID, overdosage can lead to severe **gastrointestinal** and **renal** toxicity. * **Dogs**: The LD50 after oral ingestion is reported to be 2000 mg/kg, but exposures as low as **0.44 mg/kg** have caused GI ulcers. Common clinical signs of toxic exposure include vomiting. * **Cats**: Highly sensitive; have developed renal toxicity at doses as low as **0.7 mg/kg**. * **Horses**: Generally tolerate higher doses. Doses up to 11 mg/kg IV once daily for 15 days showed no toxicity. However, severe laminitis occurred at 33 mg/kg/day (15X label dose) for 5 days. At 55 mg/kg/day (25X label dose), horses developed anorexia, depression, icterus, abdominal swelling, gastritis, nephritis, and hepatitis. **Treatment**: * **Decontamination**: Emetics and/or activated charcoal are appropriate for recent oral exposures. * **GI Protection**: Use of gastrointestinal protectants (e.g., omeprazole, sucralfate, misoprostol) is strongly warranted if GI effects are expected. * **Renal Protection**: Aggressive IV fluid diuresis is warranted to support renal perfusion if renal effects are expected.
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