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Glucocorticoids

The Glucocorticoids influence carbohydrate and protein metabolism whereas the mineralocorticoids affect water and electrolyte balance. Glucocorticoids enter target cells by diffusion and bind to specific receptors present in the cell nucleus. Thus they regulate protein synthesis by stimulating messenger RNA formation.

Partly the metabolic effects of glucocorticoids may be due to increased synthesis of cAMP dependent kinase. Certain glucocorticoids stabilize lysosomal membranes and thereby inhibit the release of inflammatory mediators like eicosanoids, histamine, and cytosine or increase the generation of anti-inflammatory mediators.

• Glucocorticoids have a negative feedback action on hypothalamus and anterior pituitary. Due to this, the release of endogenous glucocorticoids is reduced.

• Glucocorticoids reduce vasodilatation and decrease fluid exudation.

• They cause decreased influx and activity of leucocytes in areas of acute inflammation.

• There occurs decreased activity of mononuclear cells, decreased proliferation of blood vessels and less fibrosis in areas of chronic inflammation.

• In lymphoid areas, glucocorticoids decrease clonal expansion of T and B cells and decrease action of cytokine secreting T cells.

• Clucocorticoids have significant effect on inflammatory and immune mediators such as:

— Decreased production and action of cytokines including many interleukins, tumor necrosis factor-r, and granulocytemacrophage colony-stimulating factor.

— Reduced generation of eicosanoids

— Decreased generation of IgG

Glucocorticoids

Decreased in compliment components in the blood.

• So the overall effects of glucocorticoids are reduction in chronic inflammation and autoimmune reactions. However, they also cause decreased healing and diminution in the protective aspects of the inflammatory response.

Other Effects of glucocorticoids

• They inhibit growth and cell division.

• They increase haemoglobulin synthesis.

• Euphoria occurs commonly. Sometimes there will be increased motor activity, insomnia, anxiety, or depression. Some patients treated with glucocorticoids become anxious, depressed or overtly psychotic.

• Glucocorticoids play a vital role in adaptation to stress.

• They cause feedback inhibition of CRU, ACTH and TSH while secretion of growth hormone is increased.

Disorders of corticosteroid secretion

Adrenocortical insufficiency leads to Addison’s disease and hypoaldosteronism. Similarly adrenocortical hypersecretion leads to Cushing’s syndrome and hyperaldosteronism.

Synthetic analogues of corticosteroids are betamethasone, dexamethasone, prednisolone, prednisone, and triamcinolone. All of them have more potent glucocorticoid activity. Fludrocortisone is the most potent mineralocorticoid.

Therapeutic Uses of Glucocorticoids

1. Replacement therapy: Addison’s disease and hypopituitarism are treated by hydrocortisone which has some mineralocorticoid activity or by a combination of a synthetic glucocorticoid with fludrocortisone. Deoxycorticosterone (DOCA) is also occasionally used as a replacement therapy for aldosterone deficiency.

2. Glucocorticoids are very useful in the treatment of rheumatoid arthritis, osteoarthritis, and other form of chronic arthritis.

3. Collagen diseases: Glucocorticoids therapy may prove life saving in diseases like systemic lupus erythematosus, polyarteritis nodosa, dermatomyositis, and nephrotic syndrome.

4. Hypersensitivity and allergic disorders:

Glucocorticoids are very useful in the treatment of anaphylactic shock, angioneurotic oedema, and serum sickness. Beclomethasone and budesonide are available as inhalation aerosol preparations. They are employed in chronic obstructive pulmonary disease including chronic bronchial asthma in order to minimize systemic adverse effects of glucocorticoids.

5. Glucocorticoids are also used to treat diseases having autoimmune aetiology such as haemolytic anaemia, idiopathic thrombocytopenia, ulcerative colitis and myasthenia gravis.

6. Ocular conditions: Glucocorticoids are used topically in the treatment of conjunctivitis, iritis, iridocyclitis, and keratitis. Retrobulbar or systemic therapy is employed for retinitis, uveitis and optic neuritis.

7. Clobetasol (a glucocorticoid) is used topically in pruritic skin conditions, active acute dermatoses and chronic dermatitis. To treat pemphigus, exfoliative dermatitis and Stevens-Johnson syndrome glucocorticoids are given systemically.

8. Since glucocorticoids cause lympholysis, they are used to treat acute lymphatic leukemia, lymphomas and Hodgkin’s disease.

9. Other uses: They are also used in the treatment of:

• Cerebral oedema

• Rheumatic fever (not responding to salicylates)

• Acute gout (intolerant to colchicine)

• Acute/chronic hepatitis

• Sarcoidosis

• Mountain sickness

10. Diagnostic uses:

a. Dexamethasone suppression test: If dexamethasone fails to decrease cortisol release (+ve test), the patient is having Cushing’s syndrome due to anterior pituitary cause. Test is negative (decreases cortisol release), if patient is suffering from adrenocortical tumours.

b. This test is also used to diagnose endogenous depression.

11. Uses of steroids in dentistry: The Glucocorticoids are used to treat following diseases:

• Oral ulceration and oral mucosal lesions:

For this they may be used topically or systemically depending on need, e.g.

(a) use of short course of systemic corticoids in moderate to severe erythema multiformis;

(b) use of a high potency topical steroid preparation such as fluocinonide, betamethasone, or clobetasol in severe cases of recurrent aphthous stomatitis;

(c) use of systemic corticosteroid therapy in oral manifestation of pemphigus;

(d) use of topical medication with 0.05% fluocinonide and 0.05% clobetasol in oral lichen planus;

(e) rarely use of systemic corticosteroid for brief treatment of severe exacerbations or for short period of treatment of recalcitrant cases of oral lichen planus that fail to respond to topical steroids (prednisolone 40—50 mg. daily for 10 days without tapering).

For topical application, Glucocorticoids are used in the form of paste so that they adhere to mucosa for a longer duration to have greater benefit.

• Pulp inflammation: A combination of triamcinolone plus tetracycline is used locally over exposed dental pulp. This will reduce the pain and hypersensitivity of pulp.

• Tempormandibular joint pain is treated by giving intra-articular injection of hydrocortisone or prednisolone.

• Bell’s palsy: Administer Glucocorticoids prednisolone systemically.

• Postoperative pain and swelling after surgery, e.g. after removal of impacted third molar and after orthognathic surgery. So give i.m. injection of methyl prednisolone or betamethasone just before surgery.

• For prophylactic purpose, hydrocortisone is used before any operative dental procedure in patients who are taking steroids for a month or more or who have taken them for a month or more during the previous year in order to avoid precipitation of adrenal crisis— a state of profound shock.

• A preoperative antibiotic may be indicated during dental procedures in patients on large doses of glucocorticoids for longer periods because such patients are liable to have delayed wound healing and a decreased resistance to infections.

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