1. Chapter 19: Adrenocorticosteroids Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

2. 2 Chapter 19 Outline  Adrenocorticosteroids  Mechanism of release  Classification  Definitions  Routes of administration  Mechanism of action  Pharmacologic effects  Adverse reactions  Uses  Corticosteroid products  Dental implications

3. 3Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adrenocorticosteroids  Haveles (p. 241)  A group of agents secreted by the adrenal cortex  Use in dentistry: used topically or systemically for treatment of oral lesions associated with inflammatory disorders  Long-term therapy: prescribed for patients with chronic systemic diseases such as asthma or arthritis

4. 4Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Mechanism of Release  Haveles (pp. 241-242) (Fig. 19-1)  Adrenocorticosteroids are naturally occurring compounds secreted by the adrenal cortex; release is triggered by a series of events  A stimulus such as stress causes the hypothalamus to release corticotropin-releasing hormone (CRH)  CRH acts on the pituitary gland cont’d…

5. 5Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Mechanism of Release  The pituitary gland releases adrenocorticotropic hormone (ACTH), which stimulates the adrenal cortex to release hydrocortisone  Hydrocortisone acts on the pituitary and the hypothalamus to inhibit the release of CRH and ACTH This mechanism is called negative feedback This mechanism is called negative feedbackcont’d…

6. 6Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Mechanism of Release  Exogenous steroids act in the same way as hydrocortisone; they also inhibit the release of CRH and ACTH  With long-term administration of steroids, ACTH release is suppressed  Adrenal crisis may occur if exogenous steroids are abruptly withdrawn

7. 7Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Classification  Haveles (pp. 241-242)  Adrenocorticosteroids are divided into two major groups  Glucocorticoids: affect intermediate carbohydrate metabolism  Mineralocorticoids: affect water and electrolyte composition of the body  The major glucocorticoid present in the body is cortisol (hydrocortisone)

8. 8Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Definitions  Haveles (p. 242)  Addison disease: disease/condition produced by deficiency of adrenocorticosteroids  Adrenocorticosteroids/corticosteroids/steroids: glucocorticoids and mineralocorticoids released from the adrenal cortex  ACTH: secreted by pituitary, causes release of hormones from the adrenal cortex  Cushing syndrome: disease/condition caused by excess of adrenocorticosteroids  Glucocorticoids: adrenocorticosteroids primarily affecting carbohydrate metabolism  Mineralocorticoids: adrenocorticosteroids that affect the body’s sodium and water balance

9. 9Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Routes of Administration  Haveles (p. 242) (Table 19-1)  Glucocorticoids are available a wide variety of dose forms  May be used topically, orally, intramuscularly, and intravenously  Systemic effects are common when the drug is administered orally or parenterally, but topical administration may rarely cause systemic effects

10. 10Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Mechanism of Action  Haveles (pp. 242-243)  Steroids bind to a specific receptor and form a steroid-receptor complex  The complex translocates into the nucleus and alters gene expression to regulate many cell processes  There is a lag time in the action of steroids, and the relationship between their effects and blood level is poor cont’d…

11. 11Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Mechanism of Action  Antiinflammatory action of glucocorticoids results from profound effects on the number, distribution, and function of peripheral leukocytes and to their inhibition of phospholipase A  Use of steroids results in an increase in the concentration of neutrophils and decrease in lymphocytes, monocytes, eosinophils, and basophils  Inhibition of phospholipase A decreases production of prostaglandins and leukotrienes  Steroids also inhibit interleukin-2, migration inhibition factor, and macrophage inhibition factor

12. 12Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Pharmacologic Effects  Haveles (pp. 243-244) (Box 19-1)  Effects for which they are used include antiinflammatory action and suppression of allergic reactions  They suppress the immune response  Corticosteroids are palliative rather than curative

13. 13Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Reactions of Glucocorticoids  Haveles (pp. 243-244)  Proportional to the dose, frequency, and time of administration, and duration of treatment  Metabolic changes: moon face, buffalo hump, truncal obesity, weight gain, and muscle wasting produce Cushing syndrome appearance  Hyperglycemia may be aggravated  Infections: corticosteroids decrease resistance to infection  Central nervous system effects: changes in behavior and personality, including euphoria (with increasing dose), agitation, psychoses, and depression (with decreasing dose) behavior cont’d…

14. 14Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Reactions of Glucocorticoids  Peptic ulcer: corticosteroids stimulate an increase in production of stomach acid and pepsin  Impaired wound healing and osteoporosis: catabolic effects resulting from impaired synthesis of collagen can impair wound healing  Ophthalmic effects: corticosteroids can increase intraocular pressure, may exacerbate glaucoma Cataracts are associated with steroids Cataracts are associated with steroidscont’d…

15. 15Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Reactions of Glucocorticoids  Electrolyte and fluid balance glucocorticoids with some mineralocorticoid action can produce sodium and water retention Hypertension or congestive heart failure may be exacerbated; hypokalemia may result Hypertension or congestive heart failure may be exacerbated; hypokalemia may result  Adrenal crisis: adrenal suppression with prolonged use The adrenal gland cannot respond adequately if a stressful situation arises The adrenal gland cannot respond adequately if a stressful situation arises  Dental effects: delayed healing of mucosal surfaces, more likely to have an infection, and are more friable Oral candidiasis may result with use of oral steroid inhalers Oral candidiasis may result with use of oral steroid inhalers

16. 16Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Uses of Corticosteroids  Haveles (p. 245) (Box 19-2)  Medical uses  Replacement: patients with hypofunction of the adrenal cortex (Addison disease) need replacement Patients with a hyperfunctioning adrenal cortex (Cushing syndrome) may have a majority of the gland removed and need replacement therapy Patients with a hyperfunctioning adrenal cortex (Cushing syndrome) may have a majority of the gland removed and need replacement therapycont’d…

17. 17Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Uses of Corticosteroids  Medical uses  Emergencies: used for treatment of shock or adrenal crisis  Inflammatory/allergic: treatment of a wide variety of inflammatory and allergic conditions Not curative, ameliorate symptoms Not curative, ameliorate symptoms Topical steroids are used for skin conditions which involve dermatoses or “irritations” Topical steroids are used for skin conditions which involve dermatoses or “irritations”cont’d…

18. 18Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Uses of Corticosteroids  Haveles (p. 245) (Box 19-2)  Dental uses  Oral lesions: systemically administered steroids may be effective in treatment of oral lesions  Aphthous stomatitis: triamcinolone acetonide (Kenalog in Orabase) has been advocated  Temporomandibular joint: if only the joint is affected, intraarticular injection can often decrease pain and improve joint movement  Uses in oral surgery: to reduce edema, trismus, and pain  Pulp procedures: used in pulp capping, pulpotomies, and control of hypersensitive cervical dentin

19. 19Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Corticosteroid Products  Haveles (p. 246) (Table 19-2)  May be arranged according to duration of action into short-, intermediate-, and long- acting groups

20. 20Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Selected Corticosteroids, Oral  Haveles (p. 246) (Table 19-2)  Short acting  hydrocortisone (Cortisol)  prednisone (Deltasone)  methylprednisolone (Medrol)  Intermediate acting  triamcinolone  prednisolone  Long acting  dexamethasone  betamethasone

21. 21Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Dental Implications  Haveles (pp. 246-248)  Adverse reactions  Steroid supplementation  Topical use cont’d…

22. 22Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Dental Implications  Haveles (p. 246) (Box 19-3)  Steroids suppress the immune reaction  Infections are more likely to occur and healing is delayed with chronic administration  Symptoms of infections may be masked

23. 23Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Reactions of Corticosteroids  Haveles (pp. 246-247)  Gastrointestinal effects: adrenocorticosteroids stimulate acid secretion  Blood pressure: mineralocorticoid action can exacerbate hypertension  Glaucoma: other agents that induce or exacerbate glaucoma should be used with caution  Behavioral changes: bizarre behavior may be explained by presence or withdrawal from adrenocorticosteroids  Osteoporosis: may be seen in patients taking long-term adrenocorticosteroids

24. 24Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Reactions of Adrenocorticosteroids  Haveles (p. 247)  Infection: antiinflammatory activity may mask symptoms of infection  Delayed wound healing  Adrenal crisis: with prolonged administration of steroids, suppression of the hypothalamic-pituitary-adrenal axis occurs  The body does not respond quickly to stress with release of hydrocortisone  Periodontal disease: steroids interfere with the body’s response to infection and can produce osteoporosis, which may reduce bony support for teeth

25. 25Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Steroid Supplementation  Haveles (pp. 247-248) (Fig. 19-4)  With both low and very high doses of steroid, supplementation is not needed for patients who use chronic steroids and are to undergo a stressful dental procedure  With some intermediate doses of steroids, additional steroids may be indicated if the procedure will produce severe stress  Consult with the patients physician

26. 26Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Topical Use  Haveles (p. 248)  Steroids are used in dentistry to manage oral conditions such as aphthous stomatitis, related to inflammatory or immune conditions