Origin and Mechanism of Action
The drug is an analogue of hydrocortisone (cortisol), the primary and most active 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 the same year, P. Hench first administered cortisone to a patient with rheumatoid arthritis who had been immobilized for 6 years, leading to a rapid restoration of mobility.
Unlike modern synthetic derivatives (such as prednisolone or dexamethasone), hydrocortisone exhibits not only glucocorticoid but also marked mineralocorticoid activity (the ability to retain sodium and water in the body). The drug has a dose-dependent effect on metabolism, having a predominantly catabolic orientation in target tissues (lymphoid, adipose, connective tissue, muscles, skin).
Pharmacological effects
The main effects of the drug are due to its steroid nature:
- Anti-inflammatory;
- Immunosuppressive;
- Anti-shock.
The level of endogenous hydrocortisone in the body is strictly regulated by the hypothalamic-pituitary system. For instance, drugs that inhibit adrenocorticotropic hormone (ACTH) secretion, such as opioid analgesics, naturally lead to a decrease in endogenous hydrocortisone and testosterone levels.
Indications for use
Hydrocortisone is used in various dosage forms 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 focus—the articular 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 with "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);
- Tendency to thrombosis;
- Acute renal failure.
Drug interactions and risks: Special attention should be paid to combinations with anesthetics. 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).
Dosage forms and administration features
In prescription practice, Hydrocortisoni acetas is prescribed in several forms:
- Suspension in vials (2.5%, 5 ml). Used:
- 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.
- Topical ointment (1% — 20.0 g). Used as a topical agent in dermatology.
- Eye ointment (2.5% — 10.0 g). Used in ophthalmology to suppress local inflammation.
Briefly: answers to topical questions
What is the molecular mechanism of the anti-inflammatory action of hydrocortisone?
The molecular mechanism of the anti-inflammatory action of hydrocortisone is implemented primarily through genomic effects and influence on arachidonic acid metabolism.
- Induction of lipocortins — proteins inhibit phospholipase A2, blocking the release of arachidonic acid and stopping the synthesis of prostaglandins and leukotrienes.
- Suppression of cyclooxygenase-2 — drugs repress the gene responsible for enzyme synthesis, reducing the production of pro-inflammatory mediators.
- Inhibition of adhesion molecule synthesis — impedes the penetration of leukocytes and other inflammatory cells into tissues.
- Repression of cytokine genes — additionally suppresses the synthesis of pro-inflammatory factors.
What systemic side effects are characteristic of long-term hydrocortisone use?
With long-term use of glucocorticoids, the following may occur:
- adrenal cortex atrophy and withdrawal syndrome;
- iatrogenic hypercorticism (Cushing's syndrome), especially in case of overdose;
- in pharmacological doses — apoptotic death of lymphocytes, suppression of their activation, and attenuation of cytokine secretion.
Hydrocortisone is the BASE (natural hormone). It works everywhere: from shock (systemically) to joints (intra-articular) and skin (ointment), but unlike fluorinated synthetics, it strongly retains water (mineralocorticoid effect).
Class and exam questions
Why is hydrocortisone prescribed before amphotericin B infusion?
For the prevention of acute reactions ("cytokine storm"). Amphotericin B causes a sharp release of pro-inflammatory cytokines (TNF-$\alpha$ and IL-1), and hydrocortisone suppresses this immune response, preventing chills and hypotension.
What is the main difference between hydrocortisone and synthetic glucocorticoids (e.g., dexamethasone)?
Hydrocortisone is an analogue of a natural hormone and has pronounced mineralocorticoid activity (retains sodium and water). Synthetic fluorinated drugs have enhanced anti-inflammatory action and are practically devoid of mineralocorticoid effect.
Which anesthetic drug causes a decrease in hydrocortisone levels?
Etomidate. It specifically inhibits steroidogenesis in the adrenal cortex, lowering hydrocortisone and aldosterone levels, which with prolonged use can lead to acute adrenal insufficiency.
What else to study on this topic
- Synthetic non-fluorinated glucocorticoids (prednisolone, methylprednisolone)
- Fluorinated glucocorticoids (dexamethasone, triamcinolone)
- Topical glucocorticoids in dermatology (betamethasone, clobetasol)
- Mechanisms of development and relief of acute adrenal insufficiency
- Complications of long-term glucocorticoid therapy
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