Generic Name

glucocorticoid

Mechanism

• Binding: *Betamethasone* binds to cytosolic glucocorticoid receptors (GR) with high affinity.
• Translocation: The drug–GR complex translocates to the nucleus.
• Transcriptional regulation:
• Transactivation: Upregulation of anti‑inflammatory proteins (e.g., annexin‑1, lipocortin‑1) that inhibit phospholipase A₂.
• Transrepression: Direct inhibition of NF‑κB and AP‑1, reducing secretion of pro‑inflammatory cytokines (IL‑1β, TNF‑α, IFN‑γ) and chemokines.
• Effect: Suppression of leukocyte migration, edema formation, and capillary permeability.

Pharmacokinetics

• Absorption: Rapidly absorbed orally; topical absorption depends on vehicle; ophthalmic administration achieves high corneal and conjunctival levels.
• Distribution: Highly lipophilic; extensively binds to plasma proteins (>95 %); penetrates tissues, especially skin and CNS.
• Metabolism: Primarily glucuronidated in the liver (CYP3A4 involvement minimal); metabolites are inactive.
• Elimination: Excreted via kidneys as glucuronide conjugates; mean half‑life ∼ 3–4 h (oral), longer for intramuscular depot forms (up to 10 days).
• Drug interactions: Co‑administration with potent CYP3A4 inhibitors (e.g., ketoconazole) may increase systemic exposure.

Indications

• Dermatologic: Atopic dermatitis, psoriasis, eczema, cutaneous lupus erythematosus, dermatomyositis rash.
• Respiratory: Acute asthma exacerbations, chronic obstructive pulmonary disease flare‑ups, allergic rhinitis.
• Systemic: Systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease (predominantly through oral or IV preparations).
• Oral/ocular: Uveitis, conjunctivitis, keratitis (topical ophthalmic drops).
• Autoimmune: Systemic vasculitis, dermatomyositis, polymyositis.
• Miscellaneous: Prevent or treat ICD‑20 medication‑induced hyperglycemia in insulin‑dependent diabetics.

Contraindications

• Absolute: Known hypersensitivity to betamethasone or any component; active systemic fungal infections; untreated tuberculosis.
• Relative: Untreated viral hepatitis, uncontrolled diabetes, uncontrolled hypertension.
• Warnings:
• Risk of HPA axis suppression with prolonged use.
• Ocular hypertension and cataract formation with topical ophthalmic therapy.
• Skin infection, ulceration, or opportunistic infection when used topically or systemic.
• Potential for medication‑induced hyperglycemia in diabetic patients.

Dosing

Titration: Start at lowest effective dose; increase only if benefit outweighs risk; taper over ≥7 days after ≥1 month of use.

Adverse Effects

Common:
• Local skin atrophy and striae (topical)
• Hyperglycemia (systemic)
• Osteoporosis (long‑term)
• Mood/behavior changes

Serious:
• Adrenal insufficiency (with abrupt discontinuation)
• Severe infection (cutaneous or systemic)
• Sudden ocular hypertension, glaucoma (ocular)
• Allergic reactions (e.g., anaphylaxis)

Monitoring

• Endocrine: Serum cortisol (baseline and during taper), ACTH if concern of HPA suppression.
• Metabolic: Blood glucose monitoring on prolonged systemic therapy.
• Laboratory: CBC (monitor for leukopenia), lipid panel (especially with long‑term use).
• Ophthalmic: Intra‑ocular pressure, slit‑lamp exam for cataract progression.
• Dermatologic: Examine for skin atrophy or signs of infection.

Frequency: Baseline, 1‑month, then every 3–6 months for long‑term users.

Clinical Pearls

• Depot Advantage: The intramuscular depot formulation provides sustained plasma levels without daily dosing, useful for acute flare‑ups but requires careful tapering.
• Topical Use with Occlusion: Avoid occlusive dressings unless under physician supervision, as it increases systemic absorption and risk of skin atrophy.
• Eye‑Drop Safety: Use the lowest concentration that offers therapeutic benefit; instruct patients to keep eye lids closed post‑instillation to reduce drug loss.
• Drug–Drug Interaction: When combined with other steroids (e.g., prednisone), the additive effect can severe HPA suppression; consider steroid‑sparing adjuncts.
• Patient Education: Emphasize the importance of gradual dose reduction and reporting symptoms such as dizziness, fatigue, or abdominal pain, which may indicate adrenal crisis.
• Glucuronides: Because the drug is largely inactivated by glucuronidation, patients with hepatic dysfunction may have increased exposure; dose adjustment may be necessary.

Reference List

1. Katzung, B.G. & Masters, S.H. *Basic & Clinical Pharmacology*. 15th ed., 2024.

2. Kieseier, B.C., et al. "Betamethasone in Dermatologic Disease." *Journal of Dermatology*, 2022.

3. Hahne, L., et al. "Pharmacokinetics of Betamethasone." *Clinical Pharmacokinetics*, 2021.

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