Trilostane
Trilostane is a synthetic steroid analog and currently the **standard of care** for managing pituitary-dependent and adrenal-dependent hyperadrenocorticism (Cushing's syndrome) in dogs. Unlike older therapies such as mitotane, which cause targeted necrosis of the adrenal cortex, trilostane works by reversibly inhibiting steroidogenesis. This makes it generally safer and more predictable, though careful monitoring is still required to prevent iatrogenic hypoadrenocorticism (Addison's disease). **Key Clinical Uses:** * **Dogs:** Pituitary-dependent and adrenal-dependent hyperadrenocorticism; Alopecia X (especially in Pomeranians and Alaskan Malamutes). * **Cats:** Feline pituitary-dependent hyperadrenocorticism (off-label). * **Horses:** Equine hyperadrenocorticism / Pituitary Pars Intermedia Dysfunction (PPID) (off-label, though pergolide is more commonly the first-line treatment for PPID). > **Clinical Pearl:** When used in dogs with adrenal tumors, trilostane will control the clinical signs of Cushing's but will *not* shrink the tumor. In fact, the adrenal glands may undergo compensatory hypertrophy and increase in size during treatment.
กลไกการออกฤทธิ์: 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.
ขนาดยาตามชนิดสัตว์
- 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
วิธีการให้ยา
ข้อห้ามใช้
- 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
อาการไม่พึงประสงค์
- 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
อันตรกิริยาระหว่างยา
- 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
การติดตาม
- 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)
การได้รับยาเกินขนาด
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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