Chemical

Glucocorticoid – Natural, Short Acting

Use

  1. Glucocorticoid insufficiency
  2. Allergy & Anaphylaxis
  3. Asthma
  4. Autoimmune disease
  5. Eczema & dermatitis

Presentation

Tablets

IV soln for injection

Glucocorticoid Potency

1.0

Mineralocorticoid Potency

1.0

Dose

100-500mg qid

Route

PO/IV

Onset

Peaks 1-2hrs

DoA

t1/2 8-12h

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

PK

A

OBA 50%

D

90% PPB

Albumin &

Corticosteroid-binding hormone (most)

Vd 0.3-0.5L/kg

M

Liver to inactive glucuronide and sulphate metabolites

CYP3A4

E

Metabolites in urine

Adverse Effects

Cushing’s syndrome (acute withdrawal)

Proximal myopathy

Cataracts
Altered glucose tolerance

­ ↑peptic ulcer disease

Thyroid dysfunction