clinical pharmacology of corticosteroids
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Clinical Pharmacology of Corticosteroids

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Clinical Pharmacology of Corticosteroids. Joe Collier. Aims. The session will describe: the class of corticosteroids generally how corticosteroids bring about their effects how corticosteroids can be used to: treat patients with deficiency or to modify disease

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Presentation Transcript
slide2
Aims
  • The session will describe:
    • the class of corticosteroids generally
    • how corticosteroids bring about their effects
    • how corticosteroids can be used to:
      • treat patients with deficiency or
      • to modify disease
    • the key pharmacokinetic and pharmacodynamic properties of corticosteroids
    • the main unwanted effects of corticosteroids and ways in which these may be avoided
clinical pharmacology of c orticosteroids
Clinical Pharmacology of Corticosteroids
  • Objectives - At the end of the session you should be able to:
    • describe the actions of corticosteroids (prednisolone, hydrocortisone, betamethasone, dexamethasone),
    • explain, where possible, the pharmacokinetics and pharmacodynamics of these drugs;
    • describe and explain their interactions and unwanted effects and how these can be avoided;
    • describe, briefly, the principles of their use
examples of corticosteroids available
Examples ofCorticosteroids available
  • hydrocortisone
  • prednisolone
  • dexamethasone
  • beclomethasone
  • budesonide
  • fluticasone
slide5
Uses
  • Corticosteroids are used:
    • to reduce inflammation (asthma, arthritis) and swelling (cerebral oedema)
    • to suppress the immune response (systemic lupus erythematosis)
    • to reduce nausea and vomiting (as in cancer chemotherapy)
    • to reduce terminal pain (associated with cancer)
    • as replacement therapy (in Addisons disease)
unwanted effects
Metabolic:

growth suppression

diabetes mellitus

muscle wasting

osteoporosis

fat redistribution

skin atrophy

hirsutism

acne

hypertension

hypokalaemia

menstrual irregularities

adrenal suppression

Unwanted Effects
unwanted effects1
Unwanted Effects
  • Other:
    • infection
    • emotional disturbances (psychosis, depression, mania)
    • cataract, glaucoma
    • GI bleeding, perforation
  • Withdrawal
    • Addisonian crisis
    • raised intracranial pressure
    • arthralgia/myalgia
    • pustular rash
how corticosteroids work
How corticosteroids work
  • Gross (metabolic) actions:
    • glucose: diabetogenic
      • (glucose uptake and utilisation; gluconeogenesis)
    • fat: Cushing’s syndrome
      • (redistribution, lipolysis)
    • protein: muscle wasting
      • (catabolism, anabolism)
    • minerals: hypertension (mineralocorticoid effect)
how corticosteroids work1
How corticosteroids work
  • Cellular (nuclear)* level:
    • anti-inflammatory and immunosuppressive actions:
      •  number and activity of leucocytes,
      • proliferation of blood vessels,
      • activity of mononuclear cells,
      • activity of cytokine secreting cells,
      • production of cytokines,
      • generation of eicosanoids and PAF,
      • complement components in blood,
      • histamine release
  • *Effect through gene transcription (lipocortin synthesis, inhibition of COX-2 synthesis). THIS TAKES TIME!
avoiding unwanted effects of corticosteroids
Avoiding unwanted effectsof corticosteroids
  • Modification of dose/dose regimen
      • Use short courses/low doses if possible
      • Use steroid sparing drugs
      • Withdraw ‘chronic’ steroids slowly
      • Give dose once daily and in morning
      • Give on alternate days if possible
      • Give prophylactics if possible
      • Give product locally
      • Remember contraindications
      • Enrol help of patient
avoiding unwanted effects of corticosteroids1
Steroid Selection:

remember, their effects can differ with regard to their mineralocorticoid and anti-inflammatory actions and duration of effect eg as parenteral products

or as topical products (creams)

hydrocortisone - mild

clobetasone but. - moderately potent

betamethasone - potent

clobetasol prop. - very potent

Avoiding unwanted effectsof corticosteroids
giving products locally can still cause problems
Giving products locally can still cause problems!
  • systemic dosing can occur
  • local toxicity can develop -
    • skin: infection, thinning, bruising.
    • eye: viral infection, cataract, glaucoma.
    • inhalation: fungal infection, hoarseness
    • joints: infection, necrosis
ad