Mechanism of Action of Hydrocortisone Injection
Hydrocortisone injection works by binding to intracellular glucocorticoid receptors, which then translocate to the cell nucleus to modify gene transcription, resulting in profound metabolic effects and modulation of the body's immune response to diverse stimuli. 1
Molecular and Cellular Mechanisms
Hydrocortisone is structurally identical to cortisol, the naturally occurring glucocorticoid produced in the zona fasciculata of the adrenal cortex. 2
The drug acts as an adrenocortical steroid that exerts both glucocorticoid and mineralocorticoid effects, though it is primarily used for its glucocorticoid properties when given parenterally. 1
At the cellular level, hydrocortisone causes profound and varied metabolic effects including regulation of carbohydrate, protein, and lipid metabolism. 1
The compound modifies the body's immune response to diverse stimuli, providing potent anti-inflammatory and immunosuppressive actions. 1
Pharmacological Properties of Injectable Formulation
Hydrocortisone sodium succinate is the highly water-soluble ester form used for injection, which permits immediate intravenous administration of high doses in a small volume of diluent. 1
When given parenterally in equimolar quantities, hydrocortisone sodium succinate has the same metabolic and anti-inflammatory actions as hydrocortisone itself, making them equivalent in biologic activity. 1
This formulation is particularly useful where high blood levels of hydrocortisone are required rapidly, such as in adrenal crisis or perioperative stress coverage. 1
Onset and Duration of Action
Following intravenous injection of hydrocortisone sodium succinate, demonstrable effects are evident within one hour and persist for a variable period. 1
Excretion of the administered dose is nearly complete within 12 hours, which explains why the plasma elimination half-life is approximately 90 minutes. 2, 1
If constantly high blood levels are required, injections should be made every 4 to 6 hours due to this relatively short half-life. 1
The preparation is also rapidly absorbed when administered intramuscularly and is excreted in a pattern similar to that observed after intravenous injection. 1
Clinical Relevance of Mechanism
The lipophilic nature of cortisol means it is highly protein-bound in plasma (60-80% to cortisol-binding globulin and 15-35% to albumin), with only about 5% existing as the free active fraction. 2
Continuous infusion is superior to intermittent bolus dosing for maintaining physiologic cortisol concentrations during stress responses, as it provides more stable therapeutic levels. 3
The mechanism explains why dexamethasone (which has no mineralocorticoid activity) is inadequate as glucocorticoid stress cover in patients with primary adrenal insufficiency, despite having longer duration of action. 2
Common Pitfalls Related to Mechanism
Never assume a single dose provides prolonged coverage - the short half-life necessitates either continuous infusion (200 mg/24 hours) or repeated dosing every 4-6 hours for sustained effect. 3, 1
Cortisone acetate should not be used intramuscularly as it is not effective in elevating plasma cortisol levels when given by this route, unlike hydrocortisone hemisuccinate. 4
The volume of distribution may be increased in critically ill patients, potentially requiring higher doses in obese adults or those taking CYP3A4 inducers. 2