Dexamethasone
**Dexamethasone** is a highly potent, long-acting synthetic glucocorticoid widely used in veterinary medicine for its profound anti-inflammatory and immunosuppressive properties. * **Potency:** It is approximately 25-30 times more potent than hydrocortisone (cortisol) and lacks any significant mineralocorticoid (water-retaining) activity. * **Formulations:** It is available as an alcohol base or as a phosphate derivative (suspensions, solutions, or ointments). The anti-inflammatory efficacy of the alcohol form is generally superior to that of the phosphate derivative. > **Clinical Pearl:** Because of its long biological half-life (>36-72 hours) and lack of mineralocorticoid activity, dexamethasone is excellent for high-dose immunosuppressive therapy, acute allergic reactions, or diagnostic testing (e.g., low/high-dose dexamethasone suppression tests). However, it is **not** suitable for alternate-day maintenance therapy due to the high risk of profound hypothalamic-pituitary-adrenal (HPA) axis suppression.
Mecanismo: Dexamethasone exerts its effects by diffusing across cell membranes and binding to specific cytosolic **glucocorticoid receptors (GR)**. * **Transactivation:** The receptor-ligand complex translocates to the nucleus → binds to glucocorticoid response elements (GREs) on DNA → upregulates the expression of anti-inflammatory proteins like **lipocortin-1** (annexin A1). Lipocortin-1 inhibits **phospholipase A2**, thereby blocking the release of arachidonic acid and the subsequent synthesis of inflammatory prostaglandins and leukotrienes. * **Transrepression:** It inhibits transcription factors such as **NF-κB** and **AP-1** → downregulates the production of pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF-α).
Vías de administración
Contraindicaciones
- Systemic fungal infections
- Active viral infections
- Corneal ulcers (especially for ophthalmic preparations)
- Concurrent use of NSAIDs
- Known hypersensitivity to the drug
Efectos adversos
- Polyuria (PU) and Polydipsia (PD)
- Polyphagia (increased appetite)
- Panting (especially in dogs)
- Gastrointestinal ulceration or bleeding
- Iatrogenic hyperadrenocorticism (Cushing's syndrome) with chronic use
- Secondary infections due to immunosuppression
- Delayed wound healing
- Muscle wasting and weakness
Interacciones farmacológicas
- NSAIDs (e.g., carprofen, meloxicam) · Significantly increased risk of severe gastrointestinal ulceration and bleeding.
- Insulin · Dexamethasone induces insulin resistance, antagonizing the hypoglycemic effect of insulin and increasing requirements in diabetic patients.
- Phenobarbital · May induce hepatic enzymes, increasing the metabolism and clearance of dexamethasone.
- Diuretics (potassium-depleting) · Increased risk of hypokalemia.
Monitorización
- Clinical signs of disease resolution
- Water intake and urination (PU/PD)
- Appetite and body weight
- Blood glucose levels (especially in predisposed patients)
- Signs of gastrointestinal bleeding (melena, hematemesis)
- ACTH stimulation test (if assessing HPA axis suppression)
Sobredosis
Acute overdose is rarely life-threatening but may cause significant gastrointestinal upset, profound PU/PD, and panting. Chronic overdosage leads to **iatrogenic hyperadrenocorticism (Cushing's syndrome)**, characterized by alopecia, pot-bellied appearance, muscle wasting, and immunosuppression. Treatment is supportive and requires gradual tapering of the drug.
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