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CORTICOSTEROIDS (Adverse effects (Iatrogenic Cushing's (Clinical signs…

- - - - PUPD
      - Polyphagia
      - Elevated liver enzymes
      - Pot-bellied appearance
- - - - Allergy
    - - Osteoarthritis
  - - - hypercalcaemia #
  - - - Clinical signs
        
        Collapsed
        
        Bradycardic
        
        Hyperkalaemic
        
        Hyponatraemic
        
        Dehydrated
- - - - Carbohydrate
        
        Increase GNG
        
        Inhibit glucose utilisation
        
        Hyperglycaemia
        
        Increased insulin release
        
        Increased glycogen storage
      - Protein
        
        Breakdown and reduced synthesis
  - - - Act on all stages of inflammation
      - Affects all types of inflammatory reactions
      - Blood vessels, inflammatory mediators and cells # #
      - Inflammatory cells
        
        DECREASE
        
        action of T helper cells
        
        chemotaxis and diapedesis
        
        activity of macrophages
        
        fibroblast function
        
        osteoblasts
      - Inflammatory mediators
        
        DECREASE
        
        production of prostanoids
        
        generation
        
        histamine release
        
        INHIBIT
        
        COX
        
        PLA2 via lipocortin
  - - - Inhibit cellular response
        
        Lymphocytes
        
        Eosinophils
        
        Monocytes
        
        Basophils
      - Increase in neutrophils
    - - Inhibit humoral response
  - - - Very lipid soluble
    - - Complex
        
        Translocate to nucleus
        
        Increase/ Decrease transcription
        
        Up/Down regulate gene expression
        
        Transcription activator protein
        
        Enhancer of gene expression
    - - Induced
        
        ACE
        
        RAAS
        
        mineralocorticoid
        
        beta-2 adrenoreceptor
        
        Gs
        
        cAMP
        
        Increase calcium
        
        bronchodilator
        
        Vasodilator
      - Inhibited
        
        Cytokines
        
        Collagenase
        
        COX enzymes
- - - - Short
        
        Prednisolone
        
        Prednisone
        
        Methyprednisolone
      - Long
        
        Triamcinolone
        
        Dexmethasone
        
        Betamethasone
      - Fludrocortisone
        
        High mineralocorticoid activity
  - - - Mineralocorticoids
        
        Zona Glomerulosa
    - - Zona Fasiculata and Reticularis
        
        cortisol/hydrcortisone
        
        corticosterone
      - Structure Function
        
        4 ring
        
        21 carbon
        
        Double bond C4-5
        
        Ketone C3
        
        Substitutions increase gluconeogenic potency, decrease mineralocorticoid activity
    - - as required
      - from cholesterol
    - - Needed for
        
        Stress
        
        Regulation of normal physiological situations
- - - - i/v
      - phosphate salts and soluble esters
    - - acetate
      - Phenylprioprionate
  - - - Methylprednisolone acetate
      - Triamcinolone acetonide
- - - - albumin
      - corticotrophin binding globulin (CBG)
        
        high affinity
        
        low capacity
        
        Endogenous only EXCEPT prednisolone
  - - - Reduction in double bond C4-5
      - Sulphation/ Glucoronidation
    - - Hydrocortisone and prednisolone