Question 3

Describe the pharmacology of hydrocortisone.

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College Answer

Hydrocortisone is a level 1 drug in the syllabus. Most answers were well structured, many used key headings. In general, detailed information specific to hydrocortisone was lacking. Answers that focused on the mechanism of action, pharmacodynamic effects and pharmacokinetics effects which were detailed and accurate scored well. It was expected that significant detail be included in the sections with relevance to clinical practice for example, the mechanism of action and pharmacodynamic effects including the side effect profile. An indication/appreciation of the timelines of such was also represented in the marking template.

Discussion

Class Glucocorticoid
Chemistry Steroid
Routes of administration IV, oral, s/c, IM, intranasal, topical, intra-articular, etc
Absorption 97% oral bioavailability
Solubility pKa=12.59; lipid soluble; available as water-soluble salts for IV injection
Distribution VOD = 0.5L/kg ; 90% protein-bound
Target receptor Glucocorticoid receptor, which is a cytoplasmic and nuclear receptor, that regulates gene transcription and protein synthesis (but some actions are also attributed to membrane-bound receptors and nongenomic pathways)
Metabolism Metabolised mainly in the liver
Elimination Free drug is reabsorbed in the distal tubule; there is minimal renal excretion of active molecules.
Time course of action Half-life 60 minutes, maximum 2 hours (with high doses)
Mechanism of action A combination of genomic effects and nongenomic effects, where some (medium and long term) activity is mediated by the regulation of protein synthesis, and some more immediate effects are mediated by the interference in cell membrane function, intracellular second messenger systems and membrane-bound glucocorticoid receptors
Clinical effects - Immunosuppression (decreased granulocyte and lymphocyte activity)
- Reduced airway oedema, bronchodilation
- Sensitisation to catecholamines, increased cardiac output
- Neuropsychiatric effects (euphoria, mania, insomnia, psychosis)
- Metabolic effects (hyperglycaemia, hyperlipidemia, decreased insulin sensitivity)
- Fatty tissue redistribution, osteoporosis, proximal myopathy
- Hypernaremia, hypokalemia, water retention
- Adrenal suppression
- Increased risk of opportunistic infections (Aspergillus, Pneumocystis, Strongyloides)
Single best reference for further information Minigh (2008)

References

Williams, Dennis M. "Clinical pharmacology of corticosteroids." Respiratory care 63.6 (2018): 655-670.

Scherholz, Megerle L., Naomi Schlesinger, and Ioannis P. Androulakis. "Chronopharmacology of glucocorticoids." Advanced drug delivery reviews 151 (2019): 245-261.

Timmermans, Steven, Jolien Souffriau, and Claude Libert. "A general introduction to glucocorticoid biology." Frontiers in immunology 10 (2019): 1545.