U2i: Understand the pharmacology of glucocorticoids

Common properties:

Uses:

1. Glucocorticoid insufficiency
2. Allergy & Anaphylaxis
3. Asthma
4. Autoimmune disease
5. Eczema & dermatitis
6. Dexa – prevention chemo-induced nausea, cerebral oedema

MoA: Glucocorticoids diffuse into cells → react with cytoplasmic receptors to form a complex → promote gene transcription → ­ ↑mRNA synthesis and ribosomal translation

PD:

• Metabolic
  • Carbohydrate
    • Anti-insulin effect
      • Hyperglycaemia
        • ­↑gluconeogenesis
        • ↓ glucose utilisation by all cells
        • ↓ glucose uptake
        • ­↑ protein catabolism to ­ ↑gluconeogenesis
  • Protein
    • ­ ↑catabolism
    • ­ ↑aminoacid transport into hepatocytes →↑ ­ gluconeogenesis
  • Fat
    • ­ ↑lipolysis
    • ↓fatty acid synthesis
• CNS Feedback inhibition
  • Hypothalamus to ↓ CRH
  • Anterior pituitary to ↓ ACTH
• Neuro
  • ­ ↑excitability of CNS ↓ absence causes depression, apathy, Irritability
• Haematological
  • ­↑RBC, platelets, neutrophils
  • ↓ lymphocytes, eosinophils
• GIT
  • ↑­acid, pepsin secretion → peptic ulceration
  • ↓ prostaglandin synthesis to maintain mucosal barrier
• CVS:
  • ­ reactivity of peripheral blood vessels to catecholamines. ­ ↑no of a1 adrenoreceptors. ­ ↑contractility, ­ ↑vasoconstriction
• Bone:
  • ­ ↑osteoporosis: ↓ collagen synthesis by osteoblast + ­ ↑collagen breakdown
• Immune:
  • Antiinflammatory effect via
    • Stabilising lysosomal membranes → ↓ proteolytic enzymes
    • ↓ capillary permeability → ↓ capillary leakage and diapedesis → ↓ bradykinin + ↓ histamine release
  • Inhibition of phospholipase A2 → ↓prostaglandin, ↓thromboxane, ↓leukotrienes

AE: cushing’s syndrome (acute withdrawal), proximal myopathy, cataracts, altered glucose tolerance, ­ ↑peptic ulcer disease, thyroid dysfunction