Origin and Mechanism of Action
The drug is an analogue of hydrocortisone (cortisol)—the primary and most potent endogenous glucocorticoid produced by the adrenal cortex.
Historical background: Corticosteroids were first isolated from the adrenal cortex in 1948 by T. Reichstein and E. Kendall. In September of that year, P. Hench first administered cortisone to a patient with rheumatoid arthritis who had been bedridden for 6 years, resulting in a rapid recovery of mobility.
Unlike modern synthetic derivatives (such as prednisolone or dexamethasone), hydrocortisone possesses not only glucocorticoid activity but also significant mineralocorticoid activity (the ability to retain sodium and water in the body). The drug exerts a dose-dependent effect on metabolism, with a predominantly catabolic orientation in target tissues (lymphoid tissue, adipose tissue, connective tissue, muscles, skin).
Pharmacological Effects
The main effects of the drug are due to its steroid nature:
- Anti-inflammatory;
- Immunosuppressive;
- Anti-shock.
Endogenous hydrocortisone levels in the body are tightly regulated by the hypothalamic-pituitary axis. For example, drugs that suppress the secretion of adrenocorticotropic hormone (ACTH), such as opioid analgesics, predictably lead to decreased levels of intrinsic hydrocortisone and testosterone.
Indications for Use
Hydrocortisone is used in various pharmaceutical formulations depending on the clinical situation:
- Acute adrenal insufficiency. In such urgent situations, the drug is administered intravenously (100 mg every 6–8 hours).
- Anaphylactic shock.
- Inflammatory joint diseases (e.g., rheumatoid arthritis). Administration of the suspension directly into the pathology site—the joint cavity (cavitas articularis)—is practiced.
- Prevention of "cytokine storm". Hydrocortisone is used as premedication before intravenous infusion of toxic drugs (e.g., the antifungal agent amphotericin B) to prevent acute reactions associated with the release of pro-inflammatory cytokines (TNF-$\alpha$ and IL-1).
- Replacement therapy during drug-induced suppression of steroidogenesis. Historically, hydrocortisone was prescribed as "coverage" when using first-generation aromatase inhibitors (aminoglutethimide) because they non-selectively suppressed the synthesis of all steroids. Modern selective drugs (anastrozole, letrozole) do not require such coverage.
Side Effects and Contraindications
The use of hydrocortisone requires caution due to the risk of systemic complications.
Absolute Contraindications:
- Systemic infections (due to potent immunosuppressive action);
- Predisposition to thrombosis;
- Acute renal failure.
Drug Interactions and Risks: Special attention should be paid to combinations with anesthetic agents. For example, etomidate (an ultra-short-acting agent) specifically inhibits steroidogenesis in the adrenal cortex. Even after a single administration of etomidate, plasma hydrocortisone and aldosterone levels drop. Prolonged administration of etomidate threatens the development of adrenocortical insufficiency (hypotension, electrolyte imbalance, oliguria).
Formulations and Administration Details
In prescription practice, Hydrocortisoni acetas is prescribed in several forms:
- Suspension in vials (2.5%, 5 ml). Applied:
- Intramuscularly: 0.125–0.250 g once daily.
- Intra-articularly: 0.005–0.025 g (corresponding to a volume of 0.1–1 ml) once a week.
- Ointment for topical use (1% — 20.0 g). Used as a topical agent in dermatology.
- Ophthalmic ointment (2.5% — 10.0 g). Used in ophthalmology to suppress local inflammation.