Diazoxide
Diazoxide is a non-diuretic thiazide derivative primarily utilized in veterinary medicine for the medical management of **insulinomas** (insulin-secreting islet cell tumors), particularly in dogs and ferrets. While it possesses potent direct vasodilatory properties (used intravenously in humans for hypertensive emergencies), its oral use in animals leverages its profound **hyperglycemic** side effects. By antagonizing insulin release, it helps stabilize blood glucose levels in patients with refractory hypoglycemia. **Clinical Pearls:** - It is often used in conjunction with dietary management (frequent small meals) and glucocorticoids (e.g., prednisone) when those modalities alone fail to control hypoglycemic crises. - Due to its structural similarity to thiazide diuretics, it can cause sodium and water retention, but it lacks diuretic efficacy.
Mecanismo: Diazoxide exerts its hyperglycemic and vasodilatory effects via multiple mechanisms: - **K+ ATP Channel Activation**: It binds to the sulfonylurea receptor 1 (SUR1) subunit of the **ATP-sensitive potassium (K+ ATP) channels** on pancreatic beta cells → channel opening → cellular hyperpolarization → decreased intracellular **calcium (Ca2+)** influx → **inhibition of insulin exocytosis** from secretory granules. - **Beta-Adrenergic Stimulation**: Stimulates the release of **epinephrine**, which promotes hepatic glycogenolysis and inhibits peripheral cellular glucose uptake. - **Vasodilation**: Directly relaxes arteriolar smooth muscle by opening K+ ATP channels in vascular smooth muscle cells → hyperpolarization → vasodilation → decreased peripheral vascular resistance and blood pressure.
Dosificación por especie
- Hypoglycemia secondary to insulin secreting islet cell tumors · Initially, 5 mg/kg PO twice daily; increase to a maximum of 30 mg/kg PO twice daily to control clinical signs · PO · q12h · Insulinomas are very rare in cats; little experience with this drug in this species.
- Hypoglycemia secondary to insulin secreting islet cell tumors · Begin at 5-10 mg/kg PO q12h. · PO · q12h · Add diazoxide when clinical signs cannot be controlled with prednisone alone. At same time prednisone dosage may be lowered.
- Hypoglycemia secondary to insulin secreting islet cell tumors · Initially, 5 mg/kg PO twice daily; increase to a maximum of 30 mg/kg PO twice daily to control clinical signs · PO · q12h
- Hypoglycemia secondary to insulin secreting islet cell tumors (refractory) · Initially at 10 mg/kg divided twice a day. May gradually increase dosage to 60 mg/kg/day as tolerated and add hydrochlorothiazide (2-4 mg/kg/day). · PO · Divided twice a day · Used if frequent feedings and glucocorticoids fail or cause Cushingoid appearance.
- Adjunctive therapy of hypoglycemia secondary to insulin secreting non-islet cell (extra-pancreatic) tumors · 5-13 mg/kg PO three times daily · PO · q8h · May add hydrochlorothiazide 2-4 mg/kg/day.
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
- Functional hypoglycemia
- Hypoglycemia secondary to insulin overdosage in diabetic patients
- Hypersensitivity to thiazide diuretics (unless benefits outweigh risks)
- Hypersensitivity to thiazides
- Functional hypoglycemia (non-insulinoma)
Efectos adversos
- Anorexia
- Vomiting
- Diarrhea
- Hypersalivation
- Tachycardia
- Agranulocytosis
- Aplastic anemia
- Thrombocytopenia
- Diabetes mellitus
- Cataracts
- Sodium and water retention
- Malaise (ferrets)
- Bone marrow suppression (ferrets)
- Gastrointestinal upset (anorexia, vomiting, diarrhea)
- Hyperglycemia
- Cataracts (rare)
- Bone marrow suppression (rare)
Interacciones farmacológicas
- Alpha-adrenergic agents (e.g., phenoxybenzamine) · May decrease the effectiveness of diazoxide in increasing glucose levels
- Hypotensive agents (e.g., hydralazine, prazosin) · Diazoxide may enhance the hypotensive actions of other hypotensive agents
- Phenothiazines (e.g., acepromazine, chlorpromazine) · May enhance the hyperglycemic effects of diazoxide
- Phenytoin · Diazoxide may increase the metabolism, or decrease the protein binding of phenytoin
- Thiazide diuretics (e.g., hydrochlorothiazide) · May potentiate the hyperglycemic effects of oral diazoxide. Can be used synergistically, but caution is advised as hypotension may occur
- Thiazide diuretics · Potentiate hyperglycemic and hyperuricemic effects · moderate
- Phenothiazines · May potentiate hyperglycemia · moderate
- Alpha-adrenergic blockers · May antagonize the effects of diazoxide · moderate
- Highly protein-bound drugs (e.g., NSAIDs, warfarin) · Diazoxide is highly protein-bound and may displace or be displaced by other drugs, altering free drug concentrations · moderate
Monitoreo
- Blood (serum) glucose
- CBC (at least every 3-4 months)
- Physical exam (monitor for clinical signs of adverse effects like edema, cataracts, or tachycardia)
- Blood glucose
- Electrolytes (sodium, potassium)
- Complete blood count (CBC) periodically
- Signs of fluid retention/edema
Sobredosis
Acute overdosage may result in severe **hyperglycemia** and **ketoacidosis**. - **Treatment**: Administer insulin, intravenous fluids, and correct electrolyte imbalances. - **Monitoring**: Intensive and prolonged monitoring of blood glucose and acid-base status is highly recommended.
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.