OIA2004 PHARMACOLOGY OF CORTICOSTEROIDS

Cortisol

A glucocorticoid hormone produced diurnally by the adrenal cortex; secretion is stress-sensitive and regulated by the HPA axis.

HPA axis

Hypothalamus releases CRH → pituitary releases ACTH → adrenal cortex releases cortisol.

ACTH (Adrenocorticotropic Hormone)

Stimulates adrenal glands to produce glucocorticoids.

Negative feedback regulation

Circulating cortisol suppresses CRH and ACTH release to maintain homeostasis.

Anti-inflammatory actions

↓ Proinflammatory cytokines, ↓ eicosanoids via PLA₂ inhibition, stabilizes mast cells & basophils.

Immunosuppressive effects

↓ Circulating lymphocytes, eosinophils, and monocytes.

Metabolic effects

↑ Gluconeogenesis, protein catabolism, and lipolysis; may cause hyperglycemia and muscle wasting.

Vascular support

Enhances vasoconstrictor effects of catecholamines — important for maintaining BP.

Oral corticosteroids

Readily absorbed; e.g. prednisolone, hydrocortisone.

Parenteral forms

IV (e.g. methylprednisolone), IM, intra-articular — used for acute or severe conditions.

Topical and inhaled corticosteroids

Provide local action; still risk systemic effects due to partial absorption.

Intranasal corticosteroids

Used in allergic rhinitis; e.g. fluticasone, mometasone.

Protein binding

90% of absorbed corticosteroids are bound to plasma proteins.

Liver metabolism

Impaired hepatic function prolongs half-life and may enhance side effects.

Asthma management

Inhaled corticosteroids (ICS) are first-line long-term control therapy for persistent asthma.

Systemic corticosteroids in asthma

Used during exacerbations or status asthmaticus (e.g. oral prednisone or IV methylprednisolone).

ICS mechanism in asthma

Reduce airway inflammation and hyperresponsiveness over months of regular use.

ICS benefit

Reduce need for systemic corticosteroids and prevent exacerbations.

Other uses (Corticosteroids)

Autoimmune disorders, allergic reactions, skin diseases, IBD, transplant rejection.

Use regularly (ICS)

Daily use is necessary for sustained anti-inflammatory effects.

Onset of effect (ICS)

Anti-inflammatory benefits take weeks to months to become fully effective.

Inhaler technique importance

Proper technique ensures optimal drug deposition and efficacy.

Oropharyngeal candidiasis

Common ICS side effect due to local immune suppression.

Prevention of candidiasis

Rinse mouth after use (swish-and-spit method) to prevent fungal growth.

Hoarseness (dysphonia)

Due to deposition on laryngeal mucosa; another local side effect.

Adverse effects overview

Generally dose-related and reflect exaggerated physiological actions.

Osteoporosis

Most common long-term side effect; caused by ↓ Ca²⁺ absorption and ↓ bone formation.

Muscle wasting

Due to protein catabolism, especially in chronic high-dose users.

Hyperglycemia

From gluconeogenesis; caution in diabetics.

Hypertension

Resulting from fluid retention and enhanced vasopressor response.

Peptic ulcers

Due to reduced protective prostaglandins in gastric mucosa.

Psychiatric effects

Mood swings, insomnia, euphoria, depression, psychosis.

Adrenal suppression

Prolonged use suppresses endogenous cortisol production → risk of adrenal crisis if withdrawn abruptly.

Tapering corticosteroids

Gradual dose reduction required after long-term use to allow HPA axis recovery.

Infection risk

Immunosuppression increases risk of infections, including TB reactivation.

Cushingoid features

Moon face, buffalo hump, central obesity — due to chronic exposure.

Short-acting steroids

Hydrocortisone — t½ ~8–12 hrs; mimics endogenous cortisol best.

Intermediate-acting steroids

Prednisolone, methylprednisolone — commonly used in asthma, arthritis.

Long-acting steroids

Dexamethasone — potent, long t½; preferred in cerebral edema, chemotherapy protocols.

Relative potency

Dexamethasone > methylprednisolone > prednisolone > hydrocortisone.