曲洛司坦
曲洛司坦（Trilostane）是一種合成的類固醇類似物，目前是治療犬隻腦下垂體依賴型及腎上腺依賴型腎上腺皮質機能亢進（庫興氏症候群）的**標準藥物**。 與會導致腎上腺皮質壞死的舊型療法（如 Mitotane）不同，曲洛司坦能可逆地抑制類固醇生成。這使其通常更安全且效果更可預測，但仍需密切監測以防止醫源性腎上腺皮質機能低下（愛迪生氏症）。 **主要臨床用途：** * **犬：** 腦下垂體依賴型及腎上腺依賴型庫興氏症候群；X 脫毛症（Alopecia X，特別是博美犬和阿拉斯加雪橇犬）。 * **貓：** 貓腦下垂體依賴型庫興氏症候群（仿單標示外使用）。 * **馬：** 馬庫興氏症候群 / 腦下垂體中葉機能異常 (PPID)（仿單標示外使用，儘管 Pergolide 通常是 PPID 的第一線治療藥物）。 > **臨床要點：** 當用於患有腎上腺腫瘤的犬隻時，曲洛司坦能控制庫興氏症的臨床症狀，但**不會**使腫瘤縮小。事實上，在治療期間，腎上腺可能會因失去負回饋機制而發生代償性肥大並增加體積。
作用機制: Trilostane acts as a competitive, reversible, and dose-dependent inhibitor of the enzyme **3-beta hydroxysteroid dehydrogenase (3β-HSD)**. * **Pathway Blockade:** Pregnenolone → **[3β-HSD Blocked]** → Progesterone * By blocking this crucial early step in the adrenal steroidogenesis pathway, trilostane effectively reduces the downstream synthesis of **cortisol**, **aldosterone**, and **adrenal androgens**. * Because the inhibition is competitive and reversible, the suppressive effects on cortisol production wane within 10 to 20 hours, necessitating daily or twice-daily dosing.
各物種劑量
- Hyperadrenocorticism · 7 mg/kg/day divided and given twice daily · PO · q12h · Doses of up to 60 mg per cat per day have been used.
- Hyperadrenocorticism · 15 mg (total dose) PO once daily to 60 mg (total dose) PO q12h · PO · q24h to q12h · Titrate dose with ACTH stimulation tests. Cats typically remain diabetic despite clinical improvement.
- Hyperadrenocorticism · 10-30 mg/cat p.o. q12-24h · PO · q12h to q24h · Lifelong · Give with food.
- Equine Cushing's syndrome · 0.4-1 mg/kg (total dose 120-240 mg) PO once daily · PO · q24h
- Hyperadrenocorticism (HAC) - Label Dose · 2.2-6.7 mg/kg PO once a day with food · PO · q24h · Adjust dose based on ACTH stimulation test 10-14 days post-initiation. May require twice daily dosing if clinical signs are not controlled for the full day.
- Hyperadrenocorticism (HAC) - Alternative Protocol · 2-10 mg/kg PO once daily · PO · q24h · Doses of up to 50 mg/kg/day divided twice daily have been given. Adjust based on ACTH stim test 4-6 hours post-dose.
- Hyperadrenocorticism (HAC) - Low Dose Protocol · 1 mg/kg PO once daily · PO · q24h · Recheck in 1 week. Adjust based on clinical response, UCCR, and ACTH stimulation test.
- Alopecia X (Alaskan Malamutes) · 3-3.6 mg/kg PO twice a day · PO · q12h · 4-6 months
給藥途徑
禁忌症
- Hypersensitivity to trilostane
- Pregnancy (reduces progesterone synthesis)
- Use with caution in patients with renal impairment
- Use with caution in patients with hepatic impairment
- Renal insufficiency
- Hepatic insufficiency
不良反應
- Lethargy
- Inappetence
- Vomiting
- Diarrhea
- Mild electrolyte abnormalities (hyponatremia, hyperkalemia)
- Iatrogenic hypoadrenocorticism (Addisonian crisis)
- Adrenal necrosis (rare but potentially fatal)
- Mild gastrointestinal signs
- Mild increases in serum potassium, bilirubin, and calcium
- Clinical hypoadrenocorticism (Addisonian crisis)
- Adrenal necrosis
- Adrenal hyperplasia (with prolonged treatment)
- Prolonged adrenal suppression after drug withdrawal
藥物相互作用
- ACE Inhibitors (e.g., benazepril, enalapril) · Could increase risk for hyperkalemia
- Aminoglutethimide · May potentiate the effects of trilostane and lead to hypoadrenocorticism
- Ketoconazole · May potentiate the effects of trilostane and lead to hypoadrenocorticism
- Mitotane · May potentiate the effects of trilostane and lead to hypoadrenocorticism · major
- Potassium-sparing diuretics (e.g., spironolactone) · Could increase risk for hyperkalemia
- Potassium supplements / High potassium foods · Could increase risk for hyperkalemia
- Itraconazole · Concurrent suppression of adrenal function · moderate
監測
- Clinical signs (water intake, urination, appetite, energy level)
- Adverse effects (vomiting, diarrhea, lethargy)
- Serum electrolytes (Sodium and Potassium)
- Urinalysis (Specific gravity, glucose, urine cortisol:creatinine ratio [UCCR])
- ACTH stimulation tests (conducted 4-6 hours post-pill)
- Clinical signs (water intake, urination, appetite, hair coat)
- ACTH stimulation test (3 hours post-pill)
- Pre-pill baseline cortisol
- Serum electrolytes (potassium, calcium)
- Liver parameters (bilirubin)
過量
Acute overdoses are unlikely to be life-threatening, and severe clinical signs are not typically expected immediately. * **Monitoring:** Assess blood pressure, hydration status, and electrolyte balance (Na/K). * **Treatment:** If the animal is stressed or showing signs of hypoadrenocorticism, consider administering exogenous corticosteroids short-term. * Because the drug's effects are relatively short-lived, monitoring of uncomplicated patients is usually only required for a few days post-ingestion.
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