Endo Pharm – Glucocorticoids

Master answer

Prednisolone

Pharmacokinetics

• Absorption:
  • PO and Rectal
  • Rapidly and completely absorbed by both routes – 80–100%.
• Distribution:
  • reversibly bound to albumin and a specific corticosteroid-binding globulin
  • Protein binding: 80–90% (at low conc), 60-70% (at higher conc.)
  • VD: 0.35-0.7 L/kg
• Metabolism:
  • liver – hydroxylation with subsequent conjugation.
• Excretion:
  • 11–14% unchanged in the urine
  • Dose-dependent clearance: 170 to 200 ml/min
  • Elimination half-life: 2.6–5 hours

Effects

• CVS
  • positive effect on myocardial contractility
  • causes vasoconstriction by increasing the number of alpha-1adrenoreceptors and beta-adrenoreceptors and stimulating their function.
  • In the absence of corticosteroids, vascular permeability increases; small blood vessels demonstrate an inadequate motor response, and the cardiac output decreases.
• Renal
  • weak mineralocorticoid effects and produces sodium retention and increased potassium excretion
  • urinary excretion of calcium is also increased
  • increases the glomerular filtration rate and stimulates tubular secretory activity.
• Metabolic
  • profound effects on carbohydrate, protein, and lipid metabolism.
  • stimulates gluconeogenesis and inhibits the peripheral utilization of glucose
  • cause a redistribution of body fat, enhance lipolysis, and also reduce the conversion of amino acids to protein.
• Haematological
  • increases red blood cell, neutrophil, and haemoglobin concentrations
  • depresses other white cell lines and the activity of lymphoid tissue.
• Immunological
  • potent anti-inflammatory agent which inhibits all stages of the inflammatory process
  • inhibits neutrophil and macrophage recruitment, blocking the effect of lymphokines
  • inhibits the formation of plasminogen activator.
• CNS
  • increases the excitability of the CNS
  • absence of glucocorticoid leads to apathy, depression, and irritability.
• GIT
  • increases the likelihood of peptic ulcer disease
  • decreases the gastrointestinal absorption of calcium.

Source: Drugs in Anaesthesia and Intensive care 5th Edition