Glucocorticoids-2

1. Glucocorticoids-2 Dr. Alia Shatanawi 26-2-2013

2. Chronic Primary Adrenocortical Insufficiency(Addison’s Disease) Defficiency in corticosteroid production Symptoms: muscular weakness, low BP, depression, anorexia, loss of weight, hypoglycemia, GI disturbances. Minor noxious stimuli may be fatal. Etiology: autoimmune, destruction of gland by chronic inflammatory conidtions (e.g., TB) or discontinuation of chronic glucocorticoid treatment Treatment: 20-30mg cortisol/day + mineralocorticoid, AM, to mimic circadian rhythm.

3. Acute Primary Adrenocortical Insufficiency Cause:Waterhouse-Friderichsensyndrome, sudden withdrawal of long-term corticosteroid therapy and stress in patients with underlying chronic adrenal insufficiency Aim of therapy:correct fluid and electrolyte imbalance. Treatment: 100mg cortisol iv q8h until pt stable reduce to maintenance within 5 days. resume mineralocorticoid when cortisol at 50mg/day.

4. Waterhouse-Friderichsen syndrome Adrenal gland failure due to bleeding into the adrenal glands, caused by severe bacterial infection Most commonly the meningococcusNeisseria meningitidis Massive blood invasion, organ failure, coma, low blood pressure and shock, disseminated intravascular coagulation (DIC) with widespread purpura, rapidly developing adrenocortical insufficiency and death.

5. Congenital Adrenal Hyperplasia Familial disorder of cortisol synthesis enzyme deficiency Excessive ACTH production Most common due to 21 hydroxylase deficiency. Treatment: Cortisol (12-18 mg/m2/day, po) or alternate day prednisone or predinisolone Fludrocortisone (0.05-0.2 mg/day, po); salt. (moderate glucocorticoid potency and much greater mineralocorticoid potency) Over production of Androgens: virilization, accelerated growth and early epiphysial fusion

6. Cushing’s Syndrome Excess glucocorticoid production due to bilateral adrenal hyperplasia secondary to pituitary adenoma. Symptoms: euphoria, buffalo hump, moon face, easy bruising, poor wound healing, hypertension, cataracts, thinning of skin, increased abdominal fat, thin arms and legs, muscle wasting,osteoporosis, increased susceptibility to infection, obesity. Treatment: remove or irradiate tumor or resect AG 300mg cortisol iv on surgery day. reduce to replacement levels.

7. Buffalo Hump

8. Moon Face

9. Non-adrenal disorders Anti-Inflammatory – potency related to half-life. Immunosuppression – myasthenia gravis, rheumatoid arthritis, lupus, organ transplantation. Cause lymphatic tissue atrophy and reduce macrophage activity. Allergic disorders - asthma, bee stings, allergic rhinitis, contact dermatitis, hay fever. Cerebral edema – dexamethasone after brain/spinal cord trauma Eye disease - conjuctivitis, choroiditis, optic neuritis. Dexamethasone to reduce inflammation. GI disorders - Inflammatory bowel disease (Crohn’s), sprue, ulcerative colitis.

10. Non-adrenal disorders Leukemia - lymphocytic leukemia. Neurological - multiple sclerosis. Pulmonary - pneumonia, prevention of IRDS Renal - nephrotic syndrome. Rheumatic carditis - alter function of NE receptors. Septic Shock – Dermatological - eczema, dermatitis (topical steroids). Thyroid - malignant exophthalmos, subacute thyroiditis Collagen - giant cell arteritis, temporal arteritis

11. Anti-inflammatory and Anti-immunologic Therapy • Steroids are potent drugs for interrupting events triggered at the cell membrane (prostaglandins, phospholipase, etc.), and cell mediated immunity (antigen recognition, cell migration, etc.) • Steroids are NOT effective inhibitors of antibody synthesis. • Dosing To Reduce inflammation • various "protocols" lead to success • Discontinuing therapy • Cold turkey if glucocorticoid therapy of less than 2 weeks duration • Taper off if Glucocorticoid therapy of greater than 2 weeks duration. • Rate of taper should be proportional to duration of prior therapy. • The longer the original therapy, the slower the rate of dose reduction.

12. Glucocorticoids: unwanted efffects • Cushing’s disease • Conn’s disease • GI: peptic ulcer, fatty liver, pancreatitis, N&V. • Metabolic: hyperglycemia, protein wasting, hyperlipidemia, obesity. • Musculoskeletal: myopathy, growth failure, osteopenia. • Ocular: cataracts, glaucoma. • CNS: insomnia, nervousness, depression, bipolar disorder, schizophrenia. • Endocrine: suppression of HPA axis, increased PTH secretion, antagonism with insulin, PTH, TH.

13. Primary Aldosteronism(Conn’s Syndrome) Excess mineralocorticoid production due to hyperactivity ortumor of the adrenals. Suppressed levels of PRA and angiotensin II Symptoms: hypertension, weakness Treatment: spironolactone.

14. Glucocorticoids: unwanted efffects • Fluid & Electrolyte balance: Na+ retention, K+ loss, negative Ca++ balance, glycosuria. • Skin: thinning of the skin, striae, purpura, ecchymoses, acne, hirsuitism. • General: Cushingoid appearance with truncal obesity increased risk for bacterial, fungal, viral infections.

15. Glucocorticoids inhibit some portions of the immune response, they are used in treatment of a large number of diseasesThe following list includes some of the established uses of systemic corticosteroids.: • acute, severe allergic reactions • arthritis, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and gouty arthritis • adrenocortical insufficiency • allergic conjunctivitis • allergic rhinitis • anemia • (acquired hemolytic and congenital hypoplastic) • ankylosing spondylitis • asthma • beryliosis • bursitis • corneal ulcers • Crohn'sdisease • dermatitis (atopic, contact, exfoliative, and seborrheic) • dermatomyositis • erythema multiforme • erythroblastopenia • herpes zoster of the eye • hypercalcemia secondary to cancer • hypersensitivity reactions • idiopathic thrombocytopenic purpura • leukemia • lupus erythematosis • lymphoma • multiple myeloma • multiple sclerosis, acute exacerbations • mycosis fungoides • optic neuritis

16. Cont…. • pemphigus • pneumonitis (aspiration) • rheumatic carditis • Stevens-Johnson syndrome • thrombocytopenia • trichinosis with nerve or heart involvement • tuberculosis, disseminated and fulminating • tuberculous meningitis • ulcerative colitis

17. Prednisolone Predominant glucocorticoid and low mineralocorticoid activity useful for the treatment of a wide range of inflammatory and auto-immune conditions. Prednisolone acetate: ophthalmic suspension (eye drops) is an adrenocortical steroid product, prepared as a sterile ophthalmic suspension and used to reduce swelling, redness, itching, and allergic reactions affecting the eye. Prednisolone can also be used as an immunosuppressive drug for organ transplants and in cases of adrenal insufficiency (Addison's).

18. Dexamethasone Used in many inflammatory and autoimmune conditions It is also given in small amounts (usually 5-6 tablets) before and/or after some forms of dental surgery, such as the extraction of the wisdom teeth, an operation which often leaves the patient with puffy, swollen cheeks

19. Corticosteroids: synthesis inhibitors Metyrapone: blocks 11-hydroxylase increases ACTH synthesis SE: Na+, H2O retention, hirsuitism Aminoglutethimide: blocks conversion of cholesterol to pregnenalone Used in Cushing’s syndrome Ketoconazole: Inhibit steroid synthesis at high doses Used in Cushing’s syndrome

20. Glucocorticoids: antagonists • Mifepristone (RU486) • progesterone antagonist, abortifacient • powerful glucocorticoid receptor antagonist • high affinity for GR • orally administered • only used when other treatments have failed. Used in Cushing’s syndrome.

21. Dental uses of corticosteroids • Topical use: non-infections, ulcerative diseases in oral cavity. Inhibit the inflammatory reaction, redness and edema • Systemic use: third molar extraction, pre-prosthetic surgery, reconstructive oral surgery, orthognatic surgery , also in immune or inflammatory conditions.

22. Condition Administration

23. Triamcinolone acetonide oral gel (Kenalog) • Acute and chronic oral lesions • 0.1% triamcinolone acetonide 3.5 g/ tube (17.5 mg cortisol/tube) • apply a small dab (about ¼into to the lesion at bed time or 2-3/day after meals • Nystatin/ Triamcinolone Acetonide (Mycogen): Candidiasis

24. Dexamethasone ointment • Indication: inflammation in oral cavity 0.1% dexamethasone 5g / tube

25. Autoimmune disease:Lupus erythematous

26. Pemphigus vulgaris

27. Erythema Multiforme Target Lesions Steven-Johnson Syndrome

28. Management of corticosteroid-use dental patientsPrevent adrenal crisisAcute adrenal crisis is a life-threatening condition that occurs when there is not enough cortisol, a hormone produced by the adrenal glands

29. Adrenal crisis( acute adrenal insufficiency) • Hypotension • Severe weakness • Progressive mental confusion • Nausea and vomiting • Abdominal, lower back or leg pain • Hyperthermia • Hypoglycemia • Hyperkalemia • Loss of consciousness • Coma • death

30. Dental patient taking steroid supplementation not required • Patient taking low dose (<20 mg of cortisol daily) • Patient taking large dose: for less than 2 weeks for minor dental procedure with minimal stress

31. Dental patient taking steroid supplementation required • Patient taking large dose: for greater than 2 weeks for extensive major or stressful dental procedure ＃ Double usual daily dose on the day before, the day of, and the day after surgery ＃Appt in the morning ＃ Good pain control ＃ Resume normal maintenance dose post-op 2 days.

32. Dental patient taking steroid supplementation required • If the patient received at least 20mg of cortisol for more than 2 weeks within past year ＃60mg cortisol(or equivalent) the day before and the day of surgery at morning ＃ On first 2 post-op days, 40mg cortisol ＃ Then take 20mg cortisol thereafter, until post-op 6 days.

33. Management of adrenal crisis • Place the patient in a supine position with leg elevated • 200 mg hydrocortisone IV stat repeated as necessary • Oxygen and CPR if necessary • Transportation to a medical facility as soon as possible

34. Compound Topical Anti-Inflammatory Na+ Retention Equivalent Oral Dose (mg) Forms Available Short Acting GC Cortisol Cortisone Prednisone Prednisolone Methylprednisolone 1 0 0.3 0.3 0 1 0.8 4 5 5 1 0.8 0.3 0.3 0 20 25 5 5 4 o,i,t o,i,t o o,i,t o,i,t Intermediate Acting GC Triamcinolone Fluprednisolone 5 7 5 15 0 0 4 1.5 o,i,t o Long Acting GC Betamethasone Dexamethasone 10 10 25-40 30 0 0 0.6 0.75 o,i,t o,i,t Mineralocorticoids Fludrocortisone Desoxycorticosterone Acetate 10 0 10 0 250 20 2 o,i,t i, pellets

35. Drug Interactions • Anticonvulsant drugs (phenytoin and carbamazepine): potent inducer of glucocorticoid metabolism.