Clinical Pharmacology of Corticosteroids

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Clinical Pharmacology of Corticosteroids

• Joe Collier

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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

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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

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Examples ofCorticosteroids available

• hydrocortisone
• prednisolone
• dexamethasone
• beclomethasone
• budesonide
• fluticasone

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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)

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Unwanted Effects

• Metabolic
• growth suppression
• diabetes mellitus
• muscle wasting
• osteoporosis
• fat redistribution
• skin atrophy
• hirsutism
• acne

• hypertension
• hypokalaemia
• menstrual irregularities
• adrenal suppression

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Unwanted Effects

• Other
• infection
• emotional disturbances (psychosis, depression,
  mania)
• cataract, glaucoma
• GI bleeding, perforation
• Withdrawal
• Addisonian crisis
• raised intracranial pressure
• arthralgia/myalgia
• pustular rash

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How corticosteroids work

• Gross (metabolic) actions
• glucose diabetogenic
• (?glucose uptake and utilisation
  ?gluconeogenesis)
• fat Cushings syndrome
• (redistribution, lipolysis)
• protein muscle wasting
• (?catabolism, ?anabolism)
• minerals hypertension (mineralocorticoid effect)

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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!
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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

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Avoiding unwanted effectsof corticosteroids

• 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

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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