Clinical Pharmacology of Corticosteroids - PowerPoint PPT Presentation

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Clinical Pharmacology of Corticosteroids

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

  7. Unwanted Effects • Other: • 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 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

  11. 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

  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