1. Clinical Pharmacology of Corticosteroids
Joe Collier

2. 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

3. 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

4. Examples of Corticosteroids available
hydrocortisone
prednisolone
dexamethasone
beclomethasone
budesonide
fluticasone

5. 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)

6. Unwanted Effects Metabolic: growth suppression hypertension
diabetes mellitus
muscle wasting
osteoporosis
fat redistribution
skin atrophy
hirsutism
acne
hypertension
hypokalaemia
menstrual irregularities
adrenal suppression

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

8. 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)

9. 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!

10. Avoiding unwanted effects of 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

11. Avoiding unwanted effects of 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

12. 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