Metyrapone
Metyrapone is an **adrenal steroid synthesis inhibitor** primarily utilized in veterinary medicine for the management of feline hyperadrenocorticism (Cushing's syndrome). * **Clinical Utility**: It is most frequently used as a short-term medical stabilization therapy prior to surgical intervention (adrenalectomy). * **Concurrent Diabetes**: Feline hyperadrenocorticism is rare and often presents with concurrent, insulin-resistant diabetes mellitus. By resolving the hypercortisolism, metyrapone reduces insulin antagonism, which can significantly decrease or even eliminate the need for exogenous insulin therapy. * **Species Specificity**: While clinical experience is limited, it appears well-tolerated in cats. It may also have potential utility in ferrets and small mammals (e.g., hamsters), though pharmacokinetic and safety data in these species are lacking. * **Human Use**: In human medicine, it is used diagnostically to evaluate hypothalamic-pituitary-adrenal (HPA) axis function and off-label for Cushing's syndrome.
Mecanismo: Metyrapone exerts its effects by directly interfering with the steroidogenic pathway within the adrenal cortex: * **Enzyme Inhibition**: It reversibly inhibits the enzyme **11-β-hydroxylase** (CYP11B1). * **Pathway Blockade**: **11-deoxycortisol** → [Blocked by Metyrapone] → **Cortisol**. This prevents the final hydroxylation step, leading to a rapid reduction in circulating cortisol and corticosterone levels. * **Feedback Loop**: The sudden drop in cortisol removes negative feedback on the pituitary gland, leading to a compensatory surge in **ACTH** secretion. Over time, this ACTH surge can override the enzymatic blockade, limiting the drug's long-term efficacy. * **Mineralocorticoid Effects**: It can also suppress aldosterone synthesis, causing mild natriuresis. However, long-term use leads to the accumulation of 11-desoxycorticosterone (a precursor with mineralocorticoid activity), which prevents Addisonian crises but can induce hypertension.
Dosificación por especie
- Hyperadrenocorticism · 65 mg/kg PO every 8 to 12 hours · PO · q8-12h · Alternatively, dosages ranging from 195-250 mg/cat/day (divided) have been used without observed toxicity (Bruyette 2010).
Las dosis son una referencia clínica para médicos veterinarios. Confirme siempre con la información vigente del producto y el paciente individual.
Vías de administración
Contraindicaciones
- Known hypersensitivity to metyrapone
- Primary adrenal cortical insufficiency (Addison's disease)
Efectos adversos
- Nausea
- Vomiting
- Abdominal pain
- Headache (reported in humans)
- Dizziness (reported in humans)
- Sedation (reported in humans)
- Allergic rash (reported in humans)
- Bone marrow depression (rare)
Interacciones farmacológicas
- Acetaminophen · Increased risk for acetaminophen toxicity. Note: Acetaminophen is strictly contraindicated in cats due to fatal methemoglobinemia and hepatotoxicity.
- Corticosteroids · Decreases the efficacy of metyrapone by suppressing ACTH and interfering with the diagnostic or therapeutic intent.
Monitoreo
- Blood glucose levels (critical in diabetic cats)
- Clinical signs of hyperadrenocorticism (to assess efficacy)
- Clinical signs of hypoadrenocorticism/Addisonian crisis (lethargy, vomiting, collapse)
- Electrolytes (sodium, potassium)
Sobredosis
Acute toxicity data indicates an oral LD50 in rats of 521 mg/kg. **Clinical Signs of Overdose**: * Gastrointestinal distress (severe vomiting/nausea) * **Acute adrenocortical insufficiency (Addisonian crisis)** * Hypoglycemia, hyponatremia, hypochloremia, hyperkalemia * Cardiac arrhythmias, hypotension, dehydration, and altered mentation **Treatment**: * No specific antidote exists. * Standard gastrointestinal decontamination protocols if ingestion is recent. * Intravenous fluid therapy (saline) supplemented with **glucose**. * Administration of **intravenous hydrocortisone** or dexamethasone to replace depleted corticosteroids. * Intensive monitoring and supportive care for several days may be required.
La referencia de fármacos de VetSheet está destinada a médicos veterinarios como apoyo a la decisión clínica; no sustituye el juicio profesional ni la información vigente del fabricante.