1. DH206: Pharmacology Chapter 18: Adrenocorticosteroids Lisa Mayo, RDH,BSDH Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

2. Chapter 19 Outline A&P Review Hormone Secretion Classification Route of Administration Mechanism of Action Pharmacological Effects Adverse Rxns

3. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adrenocorticosteroids Use in dentistry  Topically or systemically  Treatment of oral lesions associated with inflammatory disorders Long-term therapy: asthma or arthritis

4. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. A&P Review http://www.youtube.com/watch?v=fF_3mJV3Yh0

5. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. A&P Review Adrenal glands located on upper surface of each kidney Outer (next slide) & Inner layer Inner layer (adrenal medulla) Secretes catecholamine’s during fight- or-flight response Epi is ONLY produced from the adrenal medulla = responsible for converting stored glycogen to glucose (glycogenolysis)

6. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. A&P Review Outer part: adrenal cortex has 3 layers Each layer secretes steroid hormones 3 layers of the cortex Layer of Cortex LocationHormone released Function GlomerulosaOuterAldosterone (mineralcortic o-steroid) Acts on kidney to ↑ absorption Na +, dump K + & H + FasciculataMiddleCortisolSignals to body to ↑ glucose through gluconeogenesis or glycogenolysis Body secretes 20mg/day ReticularisInnerSex androgens (testosterone) Male secondary characteristics Women’s only source of androgens

7. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. A&P Review Deficiency/Adrenal gland not working properly: Addison’s disease Effects from the 3 layers of the adrenal gland 1. Aldosterone deficiency: Increase K +, metabolic acidosis (H + ↑ ), ↓ Na + 2. Cortisol deficiency: Inadequate secretion of glucocorticoids, decrease glucose – when needed for flight or fight – will not have) 3. Testosterone deficiency Summary of what will happen to patient Hyperkalemia ( ↑ K + ) Low BP (due to Na drop) Metabolic acidosis (H + ↑ ) Hypoglycemia (decrease glucose)

8. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. A&P Review Too much hormone production from adrenal gland: Cushing’s Disease Too much ACTH hormone from pituitary Your book sometimes calls this Cushing’s syndrome: syndrome and disease are very different. Syndrome usually occurs due to exogenous steroid use Will see the opposite effects as Addison’s Aldosterone: Decrease K +, H +, ↑ Na + ( ↑ BP) Cortisol: Hyperglycemia Testosterone ↑ (secondary male characteristics) – exogenous steroids can do this as well

9. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. A&P Review Hypothalamic-Anterior Pituitary Axis A complex set of direct influences & feedback interactions among 3 endocrine glands 1. Hypothalamus 2. Pituitary gland 3. Adrenal gland Pituitary gland  Often called the “master gland” of the endocrine system  Controls many other glands  2 lobes  Located in the brain, attached to the hypothalamus Hypothalamus controls the pituitary gland: connected by the portal system called Hypothalamic-Ant Pit Axis (see net slide)

10. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. A&P Review Hypothalamic-Anterior Pituitary Axis Hypothalamus releases hormone CRH ↓ Acts on Pituitary gland ↓ ACTH hormone released ↓ Influence adrenal gland ↓ Adrenal gland releases its 3 hormones (aldosterone, cortisol, androgens) Can also have a NEGATIVE FEEDBACK to help regulate hormone levels SUMMARY: corticosteroids from adrenal gland controlled by hypothalamus & pituitary gland

11. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

12. Hormone Secretion Key Points More cortisol & CRH are secreted during waking hours When stressed – body needs more cortisol to cope When level of cortisol rises above normal: ACTH/CRH release is inhibited: called NEGATIVE FEEDBACK Steroids act like endogenous cortisol – they inhibit release ACTH/CRH Long-term steroid use – ACTH release is suppressed for long periods thus atrophy occurs to adrenal gland If steroid is stopped abruptly – relative steroid deficiency result – leads to adrenal crisis

13. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

14. DRUG CLASSIFICATION Mineralocorticoids Glucocorticoids

15. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Classification 1. Glucocorticoids Stimulate gluconeogenesis (make glucose) & lipolysis (fat breakdown) Inhibit glucose uptake by cells (to increase blood plasma glucose) Tx of inflammatory or allergic conditions (Book focuses on this category) – NEXT SLIDE Drugs called corticosteroids 2. Mineralocorticoids (Aldosterone) Affect kidney: water & electrolyte composition Act on kidney in Loop of Henle Useful for patient with kidney issues Protype: fludrocortisone(Florinef)

16. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Glucocorticoid Uses MEDICAL USESDENTAL USES AsthmaOral lesions RAAphthous stomatitis LupusTMD Addison’sPost-op surgery AllergyBurning tongue Transplant rejectionLichen planus GI disorders (ulcerative colitis, Crohns, IBD)

17. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Glucocorticoid Uses Antiinflammatory Suppress immune responses Palliative rather than curative

18. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Glucocorticoid Administration Topical Useful for dental lesions Oral Parental (IM, IV)

19. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Mechanism of Action Corticosteroids Most potent antiinflammatory agents available Almost every cell in the body has glucococortoid receptors located in the cytoplasm Cortisol (glucococortoid hormone) is hydrophobic – requires active transport into a cell by a protein Once inside the cell – travels to nucleus & binds to DNA See next slide for picture

20. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Active Transport

21. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Mechanism of Action Corticosteroids Once inside cell 1. Controls rate of PRO synthesis 2. Controls release of histamine Immunological Effects ↑ neutrophils ↓ inflammatory agents (prostaglandin, leukotriene, macrophages)

22. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Corticosteroid Drugs Classified by duration of action – need to know which drugs fall into each category p. 217, Table 18-2 Do NOT use this list, use next slide drugs..mistake in your book with Prednisone (listed as short-acting but is intermediate)

23. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Corticosteroid Drugs Short-Acting Cortisone(Cortone) Hydrocortisone(Cortisol, Cortef) Intermediate-Acting (Useful in Dentistry) Methylprednisolone(Medrol) Prednisolone(Orapred, Prelone) Prednisone(Meticorten, Deltasone) 1 st line drug Triamcinolone(Aristocort, Kenacort) Long-Acting Betamethasone(Celestone) Dexamethasone(Decadron) No contraindications for EPI in LA

24. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Rxns Rare in short-term use Long-term has many side effects due to suppression of adrenal gland function Metabolic changes (NBQ) Moon face Buffalo hump Obesity, Weight gain

25. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Rxns Hyperglycemia (NBQ) Hypertension Osteoporosis Mood/behavior changes Poor-delayed healing Immune suppression: Candidiasis, etc… Peptic ulcers Corticosteroids ↑ production of stomach acid & pepsin No Aspirin & NSAIDs

26. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Rxns Adrenal crisis Adrenal suppression with prolonged use (adrenal gland told not to release ACTH/CRH because patient getting from external source) Body cannot respond correctly to stressful situation Ex: dental phobia – steroid user body will not produce enough cortisol to respond to pt’s increased anxiety – crisis could occur Pt may need additional steroids day of appt to accommodate for this issue (Prednisone most commonly given)

27. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Drug Interactions Drug interactions due to liver metabolism by the CYP3A4 enzyme 1) Insulin drugs 2) Carbamazepine(Tegretol) 3) Phenytoin(Dilantin) 4) Rifampin (TB drug) 5) Phenobarbital