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SYNTHETIC CORTICOSTEROIDS
Synthetic corticosteroidsare chemically modified analogs of natural
glucocorticoids (like cortisol) designed to:
• Enhance anti-inflammatory potency
• Extend duration of action
• Reduce mineralocorticoid effects (in most cases)
EXAMPLES
Intermediate Type Prednisone
12–36 hours is half life
Clinical Use; Asthma, autoimmune diseases
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Pharmacokinetics of SyntheticCorticosteroid
Absorption
• Well-absorbed orally
• IV and IM formulations available for rapid effect
• Topical, inhalational, and intra-articular forms also in use
Distribution
• Widely distributed
• Bind to plasma proteins:
• ~90% to corticosteroid-binding globulin (CBG) and albumin
• Cross the placenta and enter breast milk
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Pharmacokinetics of SyntheticCorticosteroid
Metabolism
• Hepatic metabolism via reduction and conjugation
• Prednisone is a prodrug, converted to active prednisolone in the
liver
• Dexamethasone less extensively metabolized
Excretion
• Renal elimination of inactive metabolites
• Half-life does not always correlate with biological duration of action
due to receptor-binding effects
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CLINICAL PHARMACOLOGY
Chronic AdrenocorticalInsufficiency (Addison’s Disease)
•Primary adrenal insufficiency due to destruction or dysfunction of adrenal cortex
Causes
•Autoimmune adrenalitis (most common)
•Tuberculosis
•Metastatic cancer
Clinical Features
•Weakness, fatigue, weight loss
•Hypotension, hyponatremia, hyperkalemia
•Hyperpigmentation (due to elevated ACTH)
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Diagnosis
•ACTH stimulation test:
• No cortisol rise in Addison’s disease
• Serum cortisol: Low
• Plasma ACTH: Elevated
Treatment
• Glucocorticoid replacement:
• Hydrocortisone (15–25 mg/day in divided doses)
• Mineralocorticoid replacement:
• Fludrocortisone (0.05–0.2 mg/day)
• Dose adjustment during stress (illness/surgery)
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Acute Adrenocortical Insufficiency (Adrenal Crisis)
Life-threatening emergency due to rapid cortisol deficiency
Common causes
•Abrupt withdrawal of steroids
•Stress (infection, trauma) in Addison's disease
•Bilateral adrenal infarction/haemorrhage
Clinical Presentation
•Sudden hypotension, shock
•Severe dehydration, vomiting, abdominal pain
•Hypoglycemia, hyponatremia, hyperkalemia
Diagnosis
•Based on clinical suspicion
•Do not wait for lab confirmation — treat immediately
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CLINICAL PHARMACOLOGY
Treatment
• ImmediateIV hydrocortisone:
• 100 mg bolus, then 50–100 mg IV every 6–8 hours
• IV fluids:
• 5% dextrose in normal saline
• Electrolyte correction
• Switch to oral maintenance dose after stabilization
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Cushing’s Syndrome
A condition caused by prolonged exposure to excess
glucocorticoids.
Clinical Features
• Central obesity, moon face, buffalo hump
• Muscle wasting, thin skin, easy bruising
• Osteoporosis, glucose intolerance, hypertension
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CLINICAL PHARMACOLOGY
Treatment
•Exogenous cause: Gradual tapering of corticosteroids to
prevent adrenal crisis
• Cushing’s disease: Transsphenoidal surgery (first-line)
• Adrenal tumours: Surgical resection
• Medical therapy (if surgery contraindicated or pending):
• Ketoconazole, Metyrapone (steroid synthesis inhibitors)
• Mifepristone (glucocorticoid receptor antagonist)
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CLINICAL PHARMACOLOGY
DiagnosticUse of Glucocorticoids
Purpose
• Evaluate Cushing’s syndrome and differentiate causes of hypercortisolism.
Low-Dose Dexamethasone Suppression Test (LDDST)
• Protocol
• 1 mg dexamethasone orally at 11 PM → Measure serum cortisol at 8 AM
• Normal Response
• Suppression of morning cortisol (<5 mcg/dL)
• Abnormal Response
• No suppression → Suggests Cushing’s syndrome
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CLINICAL PHARMACOLOGY
DiagnosticUse of Glucocorticoids
High-Dose Dexamethasone Suppression Test (HDDST)
• Helps distinguish Cushing’s disease (pituitary) from ectopic ACTH or adrenal
tumours
• Protocol
• 8 mg dexamethasone at night → Check cortisol next morning
• Interpretation
• Suppression: Suggests Cushing’s disease
• No suppression: Suggests ectopic ACTH or adrenal tumour.
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TOXICITY OF GLUCOCORTICOIDS
1.Hyperglycemia& Diabetes
• ↑ Gluconeogenesis and insulin resistance
• Can unmask or worsen Type 2 diabetes
2. Muscle Wasting
• Protein catabolism in skeletal muscles
• Leads to weakness and thinning of limbs
3. Osteoporosis
• Inhibition of osteoblasts, increased bone resorption
• Decreased calcium absorption from gut
• Major long-term risk, especially in older adults
4. Fat Redistribution
• Central obesity, “moon face,” “buffalo hump”
• Result of altered lipid metabolism and fat deposition
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CONTRAINDICATIONS OF
GLUCOCORTICOIDS
Absolute Contraindications
Systemicfungal infections
→ Risk of uncontrolled spread due to immunosuppression
Known hypersensitivity to the drug or formulation components
Peptic ulcer disease
→ ↑ Risk of GI bleeding and ulcer perforation
•Hypertension & cardiovascular disease
→ Sodium/water retention may worsen BP and heart failure
•Diabetes mellitus
→ Hyperglycemia and insulin resistance exacerbation
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CONTRAINDICATIONS OF
GLUCOCORTICOIDS
•Osteoporosis
→ Acceleratesbone loss, especially in elderly/postmenopausal women
•Psychiatric disorders
→ May provoke mood swings, psychosis, or insomnia
•Glaucoma & cataracts
→ Increased intraocular pressure and lens opacities
•Active infections (especially viral or latent TB)
→ Suppression of immune response may lead to reactivation
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SPECIAL PRECAUTIONS
General Precautions
•Avoid abrupt withdrawal after long-term use → Adrenal crisis risk
• Taper dosage gradually to allow HPA axis recovery
• Adjust dose during stress (e.g., surgery, trauma)
• Use the lowest effective dose for the shortest duration
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DOSAGE AND DOSAGEFORMS OF
GLUCOCORTICOIDS
Dosage
•Varies by drug and condition
•Hydrocortisone (replacement): 15–25 mg/day in 2–3 divided doses
•Anti-inflammatory doses (Prednisone): 5–60 mg/day depending on severity
Dosage Forms
•Oral: Prednisone, Hydrocortisone, Dexamethasone
•Parenteral (IV/IM): Hydrocortisone sodium succinate, Methylprednisolone
•Topical: Betamethasone, Clobetasol
•Inhaled: Fluticasone, Budesonide (for asthma)
•Intranasal: Beclomethasone, Fluticasone (for rhinitis)
•Intra-articular: Triamcinolone
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MINERALCORTICOID
Physiological Effects
• Principalaction: Sodium retention & potassium excretion
• Acts on distal renal tubules and collecting ducts:
• ↑ Na reabsorption
⁺
• ↑ K and H excretion
⁺ ⁺
• Maintains ECF volume and blood pressure
Pharmacological Use
• Rarely used due to short half-life
• No routine clinical use — Fludrocortisone preferred for replacement
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MINERALCORTICOID
Deoxycorticosterone (DOC)
Metabolism
• Intermediatein adrenal steroidogenesis
• Synthesized from progesterone
• Converted to corticosterone → aldosterone
• Low ACTH sensitivity; levels increase in congenital adrenal hyperplasia
Physiological Effects
• Mild mineralocorticoid activity:
• Na retention
⁺
• K and H loss
⁺ ⁺
• Minimal glucocorticoid action
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MINERALCORTICOID
Fludrocortisone – SyntheticMineralocorticoid
Metabolism
• Synthetic analog of cortisol with fluorine substitution
• Potent mineralocorticoid and some glucocorticoid activity
• Long half-life; orally active
• Metabolized in the liver
Physiological & Pharmacological Effects
• Strong sodium-retaining effect → ↑ ECF volume, ↑ BP
• Promotes renal K excretion
⁺
• Minimal anti-inflammatory effect (not used for glucocorticoid therapy)
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MINERALCORTICOID
Fludrocortisone – SyntheticMineralocorticoid
Therapeutic Use
• Drug of choice for mineralocorticoid replacement
• Addison’s disease
• Congenital adrenal hyperplasia
• Typical dose: 0.05–0.2 mg/day orally
