Transcript Clinical Pharmacology of Corticosteroids

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
 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
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
•
•
•
•
•
•
hydrocortisone
prednisolone
dexamethasone
beclomethasone
budesonide
fluticasone
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
• 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
• 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 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
• 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 corticosteroids
• Steroid Selection:
– remember, their effects can
differ with regard to their
mineralocorticoid and antiinflammatory actions and
duration of effect eg as
parenteral products
AIA NaRet
Hydrocortisone
1
1
Prednisolone
5
1
Dexamethasone
35
<1
Fludrocortisone
<<1 20
or as topical products
(creams)
• hydrocortisone - mild
• clobetasone but. moderately potent
• betamethasone - potent
• clobetasol prop. - very
potent
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