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Steroidal anti-inflammatory drugs

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Lecture DetailsEdit

Wayne Hodgson; Week 6 MED1022; Pharmacology

Lecture ContentEdit

Glucocorticoids are synthesised by the zona fasciculata in the adrenal cortex. Glucocorticoids affect carbohydrate and protein metabolism (stress response); hydrocortisone (cortisol) and has an anti-inflammatory activity in high doses. Indications for treatment are adrenal insufficiency (Addison's) in conjunction with mineralocorticoid; inflammatory conditions (inhibit early and late manifestations of inflammation and reverse inflammatory reaction).

Pharmacokinetics are multiple routes of administration; systemic or topical. Interactions are less likely with topical than systemic, generally induce CYP3A4. E.g. inflammation of eye treated with fluorometholone, loteprednol, dexamethasone. Arthritis treated with dexamethasone, methylprednisolone, triamcinolone.

Allergic diseases can also be treated with steroids. Hay fever, asthma, skin conditions, allergic drug reactions and beestings. They act via glucocorticoid receptor which enters the lipid membrane, binds to receptor which binds to transcription factors, decreasing protein synthesis. Endogenous glucocorticoids are hydrocortisone, cortisone. They possess some mineralocorticoid activity. Synthetic glucocorticoids are dexamethasone, betamethasone. Administered as prednisone which is converted in vivo to prednisolone. If hydrocortisone has an effect of 1, prednisolone is 4 and dexamethasone/betamethasone are 30. Stronger agents may result in withdrawal Addisons. A single large dose is pretty harmless but a longer regime may be detrimental. Onset can be delayed 4-6 hours.

Anti inflammatory actions are decreased vasodilation/oedema, decreased number/activity of leukocytes, decreased fibroblast function (collagen), decreased eicosanoid production, decreased NO and cytokines, decreased histamine release.

Side effects are increased susceptibility to hyperglycaemia, growth suppression in children, osteoporosis, hypertension, increased risk of infection. Cushings is due to excess glucocorticoids; redistribution of body fat to neck, face and abdomen.

ReadingsEdit

Rang anti-inflammatory; local hormonesEdit

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