Hydrocortisone

Hydrocortisone
IUPAC name	(8R,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
CAS number	50-23-7
DrugBank	DB00741
PubChem	5754
ChemSpider	5551
UNII	WI4X0X7BPJ
ATC prefix	D07
ATC suffix	AA02
Synonyms	Cortisol

Hydrocortisone. It is a steroid hormone produced by the adrenal cortex and is the primary glucocorticoid in humans. As a medication, it is a cornerstone of replacement therapy for conditions like Addison's disease and adrenal insufficiency, and is widely used for its potent anti-inflammatory and immunosuppressive effects. Its applications range from treating severe allergic reactions and asthma exacerbations to managing inflammatory bowel disease and various skin conditions.

Medical uses

Hydrocortisone is essential in managing adrenal crisis, a life-threatening complication of Addison's disease, often administered via intravenous therapy. In allergic emergencies like anaphylaxis, it is used alongside epinephrine to mitigate delayed inflammatory responses. Topical formulations are first-line treatments for eczema, psoriasis, and contact dermatitis, while rectal foams and enemas treat ulcerative colitis affecting the distal colon. Ophthalmic preparations are used for uveitis and allergic conjunctivitis, and joint injections can provide relief in rheumatoid arthritis or osteoarthritis. It is also a critical component of chemotherapy regimens to prevent certain side effects.

Adverse effects

Systemic use, especially long-term, carries significant risks, including iatrogenic Cushing's syndrome, characterized by moon face and central obesity. It can induce or worsen diabetes mellitus by promoting gluconeogenesis and insulin resistance. Other serious concerns include osteoporosis, increased susceptibility to infections like pneumonia, peptic ulcer disease, avascular necrosis of the femoral head, and psychosis. Topical use may cause skin atrophy, telangiectasia, and, if used near the eyes, glaucoma or cataracts. Abrupt withdrawal after prolonged therapy can trigger an adrenal crisis.

Pharmacology

Hydrocortisone exerts its effects by diffusing across the cell membrane and binding to the glucocorticoid receptor in the cytoplasm. This complex translocates to the cell nucleus, where it modulates gene transcription, leading to the synthesis of proteins that inhibit phospholipase A2 and subsequent arachidonic acid metabolism. This action suppresses the production of key inflammatory mediators like prostaglandins, leukotrienes, and cytokines such as interleukin-1 and tumor necrosis factor-alpha. It also stabilizes lysosomal membranes and reduces capillary permeability. Its biological half-life is approximately 8-12 hours.

Chemistry

Hydrocortisone is a naturally occurring corticosteroid and is chemically known as 11β,17α,21-trihydroxypregn-4-ene-3,20-dione. It is a derivative of pregnane and shares the characteristic four-ring steroid nucleus. The presence of hydroxyl groups at the 11β, 17α, and 21 positions is critical for its glucocorticoid activity. It is the synthetic pharmaceutical form of the endogenous hormone cortisol. In the laboratory, it is a white, crystalline powder that is sparingly soluble in water but soluble in organic solvents like ethanol and acetone.

History

The therapeutic potential of adrenal extracts was pursued following Thomas Addison's 1855 description of Addison's disease. The isolation of adrenal corticosteroids was a major focus in the early 20th century, with key work conducted at the Mayo Clinic and by researchers like Edward Calvin Kendall. Kendall successfully isolated Compound E (cortisone) in the 1930s and 1940s, work for which he later shared the Nobel Prize in Physiology or Medicine in 1950 with Philip Showalter Hench and Tadeus Reichstein. Reichstein's group in Switzerland also made seminal contributions to synthesizing and understanding these compounds. Hydrocortisone (cortisol) was identified and synthesized soon after, becoming a fundamental tool in endocrinology and immunology.

Society and culture

Hydrocortisone is on the World Health Organization's List of Essential Medicines. It is available globally under numerous brand names, including Cortef and Solu-Cortef. Its development revolutionized the treatment of inflammatory and autoimmune diseases, reducing reliance on institutions like the National Hospital for Neurology and Neurosurgery for certain conditions. The mass production of corticosteroids, including hydrocortisone, following World War II marked a turning point in pharmaceutical manufacturing. Its role in enabling organ transplantation by suppressing rejection and its use in space medicine, studied by agencies like NASA, further underscore its cultural and scientific impact.

Category:Drugs