Flumethasone
Flumethasone is a highly potent, long-acting **fluorinated glucocorticoid** utilized in veterinary medicine for its profound anti-inflammatory and immunosuppressive properties. Key pharmacological features include: * **High Potency**: It is approximately 15 to 30 times more potent than hydrocortisone. * **Lack of Mineralocorticoid Activity**: It exhibits virtually no appreciable mineralocorticoid (sodium-retaining) effects, reducing the risk of edema and hypertension compared to older steroids. * **Clinical Utility**: It is highly effective for acute inflammatory reactions (e.g., insect bite hypersensitivity, vaccine reactions, shock), musculoskeletal inflammation (bursitis, myositis, osteoarthritis), and various acute or chronic dermatoses. > **Clinical Pearl**: The overarching goal of flumethasone therapy—as with all systemic corticosteroids—is to use *as much as is required, and as little as possible, for as short an amount of time as possible* to minimize the risk of iatrogenic hyperadrenocorticism (Cushing's syndrome) and adrenal axis suppression.
กลไกการออกฤทธิ์: Flumethasone exerts its effects via classic genomic and non-genomic steroid pathways: 1. **Genomic Pathway**: Free flumethasone crosses the cell membrane and binds to cytosolic **glucocorticoid receptors (GR)**. 2. The receptor-ligand complex translocates to the nucleus and binds to **glucocorticoid response elements (GREs)** on DNA. 3. **Transactivation**: Upregulates the expression of anti-inflammatory proteins, notably **lipocortin-1 (annexin A1)**. Lipocortin-1 inhibits **phospholipase A2** → blocking the release of arachidonic acid from membrane phospholipids → profoundly decreasing the synthesis of pro-inflammatory **prostaglandins** and **leukotrienes**. 4. **Transrepression**: Downregulates the expression of pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF-alpha) by inhibiting transcription factors like **NF-κB** and **AP-1**. 5. **Non-genomic Pathway**: Rapid physicochemical interactions with cellular membranes provide immediate effects, which is particularly beneficial in shock or acute hypersensitivity states.
ขนาดยาตามชนิดสัตว์
- Labeled indications (acute and chronic dermatoses) · 0.03125-0.125 mg daily in divided doses · PO · daily in divided doses · Tablets no longer marketed in the USA
- Labeled indications (acute and chronic dermatoses) · 0.03125-0.125 mg. If necessary, may repeat. · IV, IM, or SC · If necessary, may repeat
- General anti-inflammatory/immunosuppressive · 0.03-0.125 mg once daily · IV, IM, SC, or PO · once daily
- Labeled indications (musculoskeletal conditions, allergic states) · 1.25-2.5 mg daily. If necessary, the dose may be repeated. · IV, IM or intra-articular · daily · ARCI UCGFS Class 4 Drug
- General anti-inflammatory · 1-2.5 mg/450 kg · IV or IM
- Labeled indications (musculoskeletal conditions, dermatoses, allergic states, shock) · 0.0625-0.25 mg daily in divided doses · PO · daily in divided doses · Tablets no longer marketed in the USA
- Labeled indications · 0.0625-0.25 mg daily; may repeat · IV, IM, SC · daily
- Labeled indications (joint inflammation) · 0.166-1 mg · Intra-articularly
- Labeled indications (localized lesions) · 0.125-1 mg · Intra-lesionally
วิธีการให้ยา
ข้อห้ามใช้
- Last trimester of pregnancy (may induce parturition)
- Systemic fungal infections (unless used for Addison's replacement therapy)
- Idiopathic thrombocytopenia (specifically contraindicated for IM administration)
- Known hypersensitivity to the compound
- Chronic corticosteroid therapy of systemic diseases using sustained-release injectable forms
อาการไม่พึงประสงค์
- Polydipsia (PD), polyuria (PU), and polyphagia (PP)
- Weight gain and lipidemias
- Dull, dry haircoat and dermatological thinning
- Panting
- Gastrointestinal effects: vomiting, diarrhea, GI ulceration
- Hepatopathy: elevated liver enzymes (ALP, ALT)
- Pancreatitis
- Endocrine: activation or worsening of diabetes mellitus, iatrogenic hyperadrenocorticism (Cushingoid effects) with sustained use
- Musculoskeletal: muscle wasting, retarded growth in young animals
- Behavioral changes: depression, lethargy, viciousness
- Immunosuppression: increased susceptibility to infections
อันตรกิริยาระหว่างยา
- Amphotericin B · Administered concomitantly with glucocorticoids may cause hypokalemia
- Anticholinesterase agents (e.g., pyridostigmine, neostigmine) · In patients with myasthenia gravis, concomitant administration may lead to profound muscle weakness. Discontinue anticholinesterase at least 24 hours prior if possible.
- Aspirin · Glucocorticoids may reduce salicylate blood levels
- Barbiturates · May increase the metabolism of glucocorticoids and decrease flumethasone blood levels
- Cyclophosphamide · Glucocorticoids may inhibit the hepatic metabolism of cyclophosphamide; dosage adjustments may be required
- Cyclosporine · Concomitant administration may increase the blood levels of each by mutually inhibiting hepatic metabolism
- Diazepam · Flumethasone may decrease diazepam levels
- Diuretics, potassium-depleting (e.g., spironolactone, triamterene) · Administered concomitantly with glucocorticoids may cause hypokalemia
- Ephedrine · May reduce flumethasone blood levels
- Insulin · Insulin requirements may increase in patients receiving glucocorticoids
- Ketoconazole and other azole antifungals · May decrease the metabolism of glucocorticoids and increase flumethasone blood levels; ketoconazole may induce adrenal insufficiency when glucocorticoids are withdrawn
การติดตาม
- Weight, appetite, and signs of edema
- Serum and/or urine electrolytes
- Total plasma proteins, albumin
- Blood glucose
- Growth and development in young animals
- ACTH stimulation test if necessary (to assess adrenal axis suppression)
การได้รับยาเกินขนาด
Short-term administration of massive dosages of glucocorticoids is unlikely to cause harmful effects. There is one reported incidence of a dog developing acute CNS effects after accidental ingestion. If acute clinical signs occur, provide supportive treatment as required. Chronic overdosage or sustained high-dose usage leads to serious adverse effects, primarily manifesting as iatrogenic hyperadrenocorticism (Cushing's syndrome), characterized by severe polyuria/polydipsia, muscle wasting, alopecia, pot-bellied appearance, and immunosuppression.
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