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Clinical Pharmacology of Corticosteroids

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Presentation on theme: "Clinical Pharmacology of Corticosteroids"— Presentation transcript:

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

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