Question 20

Last updated 15/08/2023 - 18:47
 Topic: Endocrine System
Pass rate
40%
Other SAQs in this paper:
Other SAQs in this topic:

Describe the pharmacokinetics of prednisone (50% marks). List the cardiovascular, renal, metabolic, haematological and immunological effects of prednisone (50% marks)

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College Answer

The question asked for detailed information on the pharmacokinetics and selected pharmacodynamics of prednisone. Most candidates provided unnecessary details of the mechanism of action and pharmaceutics significantly wasting time. Many provided incorrect information and general information without specifics which is represented by the low pass rate. The pharmacokinetics part was answered poorly. It was expected from the candidates to have detailed knowledge on the prednisolone  binding capacity and affinity to albumin and corticosteroid binding protein as well as the important metabolism of prednisone. 

Discussion

Pharmacokinetics:

Class Glucocorticoid
Chemistry Steroid
Routes of administration Oral
Absorption 80% oral bioavailability
Solubility pKa=12.59; poor water solubility; highly lipid soluble
Distribution VOD=1.0 L/kg; <50% protein-bound (albumin and corticosteroid-binding globulin
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 in the liver into prednisolone, which is the active form of the drug. Prednisolone is then metabolised into inactive breakdown products
Elimination Eliminated rapidly by being converted into prednisolone, which is then eliminated by hepatic metabolism. Also is a substrate for P-glycoprotein, which is an efflux pump into the lumen of the gut.
Time course of action Converted rapidly (over minutes) into prednisolone; half life of prednisolone is closer to 2-3 hrs

Effects of prednisone:

Cardiovascular:

  • Enhanced vasoconstriction 
  • Increased sensitivity to catecholamines
  • Decreased activity of ATP-sensitive potassium channels
  • Decreased induction of nitric oxide synthase
  • Increased cardiac contractility
  • Decreased myocardial sensitivity to endotoxin
  • Decreased transcription and expression of nitric oxide synthase

Renal: 

  • Mineralocorticoid-related fluid and electrolyte effects: 
  • Hypernatremia, hypokalemia, water retention

Metabolic:

  • Hyperglycaemia due to decreased peripheral insulin sensitivity and the increased gluconeogenesis in the liver
  • Skeletal muscle catabolism and redistribution of amino acids to the liver to act as metabolic substrate
  • Peripheral lipolysis and liberation of free fatty acids

Haematological:

  • Increased haemoglobin and red cell content of blood, due to impaired erythrocyte phagocytosis by the reticuloendothelial system
  • Increased granulocyte concentration (neutrophils, mainly) because of increased exit from the marrow and reduced migration into tissues
  • Lymphocyte apoptosis
  • Redistribution of  eosinophils, monocytes, and basophils out of the circulation

Immunological:

  • Dendritic cell apoptosis, immune anergy
  • Decreased B and T lymphocyte numbers and function
  • Decreased immunoglobulin synthesis

References

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

Buchman, Alan L. "Side effects of corticosteroid therapy." Journal of clinical gastroenterology 33.4 (2001): 289-294.

Fardet, Laurence, et al. "Corticosteroid-induced adverse events in adults." Drug safety 30.10 (2007): 861-881.

Poetker, David M., and Douglas D. Reh. "A comprehensive review of the adverse effects of systemic corticosteroids." Otolaryngologic Clinics of North America 43.4 (2010): 753-768.

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

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