미토탄

부신 세포독성제 / 항종양제

미토탄(o,p'-DDD로도 알려짐)은 수의학에서 주로 개의 **뇌하수체 의존성 부신피질기능항진증(PDH)**(쿠싱 증후군)의 내과적 치료에 사용되는 부신 세포독성제입니다. 살충제인 DDT와 구조적으로 유사합니다. 부신피질의 표적 괴사를 유발하여 과도한 코르티솔 생성을 효과적으로 감소시킵니다. 또한 사람과 개의 부신암에 대한 고식적 치료에도 사용됩니다. **임상 요점:** 치료는 일반적으로 *유도기*(임상적 목표에 도달할 때까지 매일 투여하여 증식된 부신 조직을 빠르게 파괴)와 *유지기*(부신피질의 재성장을 방지하기 위해 주 1~2회 투여)의 두 단계로 나뉩니다. 과도한 치료는 의인성 부신피질기능저하증(애디슨병)을 유발할 수 있으므로 철저한 모니터링이 필수적입니다.

작용 기전: Mitotane acts as a targeted **adrenocortical cytotoxic agent**. * It causes severe, progressive necrosis and atrophy of the **zona fasciculata** and **zona reticularis** of the adrenal gland → drastically reducing the synthesis of glucocorticoids (cortisol). * It relatively spares the **zona glomerulosa**, meaning mineralocorticoid (aldosterone) synthesis is usually unaffected, though clinically significant effects on aldosterone production can occasionally occur. * The exact intracellular mechanism of cytotoxicity is not fully understood, but it is believed to involve metabolic activation within the adrenal mitochondria, leading to irreversible binding to cellular macromolecules and subsequent cell death.

동물 종별 용량

Cats

Hyperadrenocorticism · 30-50 mg/kg · PO · q24h · to effect · Efficacy in cats is very variable, with many showing no response at non-toxic levels. Not recommended.

Ferrets

Medical treatment of hyperadrenocorticism · 50 mg per ferret PO once daily for one week, then 50 mg PO 2-3 times per week · PO · q24h then 2-3 times/week · Long-term · Have a compounding pharmacy make 50 mg capsules. Can be coated with Nutrical.

Dogs

Pituitary-dependent hyperadrenocorticism (Induction - Protocol A) · 25 mg/kg twice a day, PO with food · PO · q12h · Until clinical endpoints occur (usually 4-9 days) · Reduce food by 1/3 the day before. Stop therapy if water consumption approaches 60 mL/kg/day, appetite reduces, vomiting, listlessness, or diarrhea occurs.
Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol A) · 25-50 mg/kg per week · PO · Divided in as many doses as possible weekly · Long-term · Adjust based on ACTH stimulation test results.
Pituitary-dependent hyperadrenocorticism (Induction - Protocol B) · 30-50 mg/kg/day PO with a meal once daily or divided q12h · PO · q24h or q12h · 7-10 days · Goal is basal and post-ACTH cortisol between 1-5 micrograms/dL.
Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol B) · 35-50 mg/kg per week in 2-3 divided doses · PO · Divided weekly · Long-term
Pituitary-dependent hyperadrenocorticism (Induction - Protocol C) · 50 mg/kg divided q12h · PO · q12h · Until water consumption decreases to <100 mL/kg/day or adverse signs observed (usually 3-7 days) · Max 5-7 days prior to ACTH stim test if water consumption cannot be monitored.

투여 경로

금기

Known hypersensitivity to mitotane
Pregnancy (FDA Category C in humans; Class D in veterinary medicine - embryotoxic/teratogenic)
Patients that are not eating well (should never be administered to anorexic animals)
Not recommended in cats (trilostane is more effective and mitotane efficacy is highly variable)

이상반응

Lethargy
Ataxia
Weakness
Anorexia (loss of appetite)
Vomiting
Diarrhea
Neurologic signs (uncommon)
Liver changes (congestion, centrolobular atrophy, fatty degeneration)
Iatrogenic hypoadrenocorticism (requiring long-term glucocorticoid/mineralocorticoid replacement in ~5% of dogs)
Anorexia
Diarrhoea
Acute-onset neurological signs (2-3 weeks post-initiation)
Iatrogenic hypoadrenocorticism

약물 상호작용

CNS Depressants · Additive depressant effects may be seen if used concomitantly. · moderate
Insulin · Diabetic dogs receiving insulin may have their insulin requirements rapidly decreased when mitotane therapy is instituted. · major
Phenobarbital · Can induce enzymes and reduce the efficacy of mitotane; conversely, mitotane can induce hepatic microsomal enzymes and increase the metabolism of phenobarbital.
Spironolactone · Has been demonstrated to block the action of mitotane in dogs; an alternate diuretic is recommended. · major
Barbiturates · Increases the hepatic metabolism of mitotane · moderate
Corticosteroids · Increases the hepatic metabolism of mitotane · moderate

모니터링

Physical exam and history (especially water consumption, food consumption, and weight)
ACTH response test (crucial for dose adjustment)
Serum electrolytes (Na+/K+)
BUN
CBC
Liver enzymes
Blood glucose
Appetite (daily during induction)
ACTH stimulation test (to monitor treatment efficacy)
Blood glucose (in diabetic patients)
Clinical signs of weakness, vomiting, or neurological changes

과용량

Because of the drug's toxicity and very long half-life, acute overdosage should be managed aggressively. * **Decontamination:** Emptying the stomach and administering activated charcoal and a cathartic should be considered after a recent ingestion. * **Monitoring & Treatment:** The patient must be closely monitored. Administer systemic glucocorticoids (e.g., dexamethasone or prednisone) and IV fluids if signs of acute hypoadrenocorticism (Addisonian crisis) develop.

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