Dexamethasone | Pharmacology Mentor

Generic Name

Dexamethasone

Mechanism

Corticosteroid Receptor Binding
Diffuses into cells → binds cytoplasmic glucocorticoid receptor (GR) (α and β subtypes).
Induces conformational change → nuclear translocation.
Gene‑Regulatory Effects
Transactivation: ↑ expression of anti‑inflammatory proteins (e.g., annexin‑1, lipocortin, IL‑1 receptor antagonist).
Transrepression: ↓ transcription of pro‑inflammatory genes (IL‑1, IL‑6, TNF‑α, COX‑2, 5‑LOX).
Metabolic Actions
↑ gluconeogenesis & ↓ peripheral glucose uptake → hyperglycemia.
Induces lipolysis and proteolysis → catabolic state.

The net result is potent suppression of inflammation, immune cell trafficking, and cytokine production.

Pharmacokinetics

Parameter	Value	Key Points
Bioavailability	Oral 80‑100 % (dose‑dependent).	Excellent for enteral use.
Distribution	Protein‑bound ~65 % to albumin and α1‑acid glycoprotein.	Large volume of distribution (~5 L/kg).
Metabolism	Hepatic (CYP3A4 mainly) to inactive glucuronide conjugates.	Minimal renal excretion of parent drug.
Half‑life	3–4 h (clinical effect up to 12 h due to genomic actions).	Allows once‑daily dosing in many regimens.
Metabolite	Dex‑1‑O‑glucuronide (inactive).	No active metabolites.

Indications

Inflammatory/Autoimmune:
Severe asthma exacerbations, COPD flare‑ups
Rheumatoid arthritis, systemic lupus erythematosus
Acute graft‑versus‑host disease
Endocrine:
Adrenal insufficiency (acute crisis), congenital adrenal hyperplasia
Oncology:
Palliative care for CNS tumors or brain metastases
Chemotherapy‑associated nausea/vomiting
Lymphoma and leukemic remission induction (combination regimens)
Neurology/ENT:
Meningitis prophylaxis, intracranial hypertension
Severe allergic reactions (anaphylaxis adjunct)
Other Uses:
Sickle cell crisis, mast cell activation syndrome
Rhabdomyolysis management
COVID‑19 (high‑dose oral or IV in progressive disease)

Contraindications

Absolute Contraindications:
Active systemic fungal infection, uncontrolled bacterial infection, non‑sealed perforated viscus.
Warnings & Precautions:
Infection risk – immunosuppression; screen for TB, hepatitis.
Metabolic derangements – hyperglycemia, electrolyte imbalance.
Ocular effects – glaucoma, cataract progression.
Skeletal effects – osteoporosis, osteonecrosis (especially with chronic use).
Endocrine suppression – adrenal crisis in tapering.
Drug interactions – CYP3A4 inducers/inhibitors modify levels.

Dosing

Scenario	Route	Dose (adult) Frequency	Notes
Acute asthma/COPD flare	Oral/IV	4–6 mg PO or 8 mg IV (single dose)	3–4 h repeated if needed	Adjunct to β₂ agonist.
Adrenal insufficiency	PO	8–10 mg PO (single dose)	24 h	Follow with fludrocortisone.
Neuropathic pain/brain edema	IV	4 mg IV every 8 h	t.i.d.	Max 10 mg/day to avoid CNS depression.
Oncologic nausea	PO	2–4 mg PO daily	qd	Often combined with ondansetron.
Long‑term systemic therapy	PO	2.5–10 mg/day	qd or divided	Taper over 4–6 weeks.
Intra‑articular injection	IA	0.25–0.5 mg/mL	Single dose	Avoid in septic joints.

Glucocorticoid‑challenge tests may be used to determine adrenal reserve if symptoms persist after taper.

Adverse Effects

Class	Adverse Effect	Frequency	Comments
Gastrointestinal	Dyspepsia, gastritis	Common	Prophylaxis with PPIs in high‑risk patients.
Metabolic	Hyperglycemia, dyslipidemia	Common	Monitor fasting glucose; adjust insulin/OGTT.
Central Nervous System	Mood lability, insomnia	Common	Avoid high bedtime doses; consider TID schedule.
Immune	Increased infection risk, secondary fungal infection	Rare–moderate	Screen for TB/viral hepatitis before chronic or high‑dose use.
Orthopedic	Osteoporosis, avascular necrosis	Rare–chronic	Dual‑X‑ray absorptiometry, calcium/vit D supplementation.
Dermatologic	Acne, cystic lesions	Rare	Use lowest effective dose.
Hematologic	Leukocytosis (neutrophil count rise)	Common	Can mask infection; check differential.
Cardiovascular	Hypertension, fluid retention	Common	Adjust antihypertensives; diuretics.
Endocrine	Suppression of HPA axis, adrenal insufficiency in withdrawal	Common in chronic use	Gradual taper essential.
Serious	Steroid‑induced psychosis, ptosis, steroid myopathy, severe GI bleeding	Rare	Manage promptly; consider alternative agents.

Monitoring

Baseline: CBC, CMP (liver enzymes, electrolytes), fasting glucose, CRP/ESR
During Therapy:
Infection: CBC (neutrophil ratio), clinical signs
Metabolic: glucose fasting, HbA1c yearly, lipid panel quarterly
Bone: DEXA every 12‑18 mo if >3 mo use; calcium/vit D levels
CNS: mood assessment with validated scales if high dose >1 mo
Ophthalmology: visual acuity and intra‑ocular pressure for long‑term use
Pituitary imaging: if adrenal insufficiency suspected after taper
Post‑taper: Monitor for adrenal crisis symptoms and consider ACTH stimulation test if prolonged >3 mo therapy.

Clinical Pearls

Taper Wisely: A 10‑mg/day prednisone equivalence can usually be cut in half every 2 weeks; abrupt withdrawal after ≥1 month triggers adrenal crisis.
Use Low‑dose to Minimize Metabolic Impact: 0.75–1 mg PO BID can provide anti‑inflammatory benefit with less hyperglycemia.
Intramuscular Dexamethasone in MRSA: A single 8‑mg IM dose can blunt cytokine storm in severe sepsis (studies ongoing).
Avoid in Dental Extraction in SEPSIS: Even one oral dose can worsen peri‑implant infection.
CO₂ Retention Awareness: In COPD patients, low‑dose dexamethasone may induce hypercapnia; monitor arterial blood gases.
Fetal Safety: Category C → avoid during 1st trimester; use only if benefit outweighs risk.
Drug Interaction Survival Kit:
CYP3A4 inhibitors (ketoconazole, clarithromycin) → ↑ levels, consider dose reduction.
CYP3A4 inducers (rifampin, carbamazepine) → ↓ efficacy.

By integrating these high‑yield facts and monitoring strategies, clinicians can maximize therapeutic benefits while mitigating risks of dexamethasone therapy.