Describe the pharmacology of hydrocortisone.
Hydrocortisone is listed as a Class A drug in the syllabus and as such knowledge of its pharmacokinetics is expected. No marks were awarded for generic pharmacokinetic statements such as: "average bioavailability", "moderate protein binding", "bioavailability 100% for IV preparation" etc
|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)|
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.