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an overall overview in corticosteroids and its application in oral and maxillofacial diagnostic medicine and pathology drawing to the conclusions of the limitations and drawbacks of these medicines. i have also included the precautions to be taken in dental therapeutic procedures fo

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  1. 1. CORTICOSTEROIDS Presented by : Joe Dsilva
  2. 2. CONTENTS • Introduction • History • Functional anatomy and histology of adrenal glands • Biosynthesis of steroids • Fate of steroids • Mineralocorticoids • Glucocorticoids
  3. 3. • Mechanism of action • Classification of steroids • Uses in medicine • Steroids in dentistry • Adverse effects • Drug interaction • Precautions
  4. 4. Introduction  The adrenal gland is the source of a diverse group of hormones essential for metabolic control, regulation of water and electrolyte balance, and regulation of body’s response to stress.  Using cholesterol as a substrate, the adrenal cortex produces a large number of substances collectively known as corticosteroids.
  5. 5. History  By the middle of 19th century it was demonstrated that adrenal glands were essential for life  Later, it was appreciated that the cortex was more important than the medulla  A number of steroidal active principles were isolated and their structures were elucidated by kendall and his coworkers in the 1930s.
  6. 6.  However, the gate to their great therapeutic potential was opened by Hench (1949) who obtained striking improvement in rheumatoid arthritis by using cortisone.  The nobel prize was awarded the very next year to kendall and Hench.  Currently, corticosteroids are drugs with one of the broadest spectrum of clinical utility.
  7. 7. Functional anatomy and histology of adrenal glands
  8. 8. Biosynthesis of steroids Cholesterol Pregnenolone Progesterone 11- Deoxy corticosterone Corticosterone Aldosterone 17α Hydroxy pregnenolone 17α Hydroxy progesterone 11 Desoxyhydro cortisone Hydrocortisone Dehydroepiandrosterone Androstenidione Testosterone
  9. 9. Rate of secretion of the principal steroids Glucorticoids 10-20 mg daily Mineralocorticoids – 0.125 mg daily
  10. 10. FATE OF CORTICOSTEROIDS Degraded mainly in liver Conjugated to form glucuronides and to a lesser extent form sulphates 25% - excreted in bile and feces 75% - excreted in urine
  12. 12. Mineralocorticoids  Source : Zona glomerulosa  Functions: 90% of mineralocorticoid activity is provided by aldosterone  Aldosterone – life saving hormone
  13. 13. Action on EEFECT Sodium metabolism Increases sodium reabsorption from renal tubules On ECF Sodium reabsorption, stimulates water reabsorption thus in term increases ECF volume Blood pressure Increases Potassium ions Increases in excretion of potassium ion s from renal tubules Hydrogen ion Tubular secretion of hydrogen ion , essential to maintain acid base balance. Essentials Of Medical Physiology 3rd Edition, K Sembulingam
  14. 14. Regulation of Aldosterone Secretion Increase in K+ concentration Decrease in Na+ Concentration Decrease in ECF volume Decrease in K+ concentration Increase in Na+ Concentration Increase in ECF volume Juxtaglomerular apparatus Excretion of K+ Retention of Na+ Retention of water Lungs kidneys Adrenal cortex Aldosterone angiotensinogen Angiotensin - 1 Angiotensin - 2 Stimulation Renin Converting Enzyme ACE Feedback inhibition Essentials Of Medical Physiology 3rd Edition, K Sembulingam
  15. 15. Glucocorticoids Source : zona fasciculata Functions: Cortisol – Life protecting hormone
  16. 16. Action ACTION ON EFFECT On carbohydrate metabolism Increases blood glucose level by gluconeogenesis, inhibits glucose uptake and utilization by peripheral cells Protein metabolism Promotes catabolism of protein and increases plasma amino acid and protein content Fat metabolism Metabolism of fatty acid from adipose tissue increases in concentration of fatty acid , increase utilization of fat for energy. Mineral metabolism Enhances sodium retention, potassium excretion. Water metabolism Excretion of water
  17. 17. Muscles Increases the release of amino acid from muscles by catabolism of protein Blood vessel Decreases the release of eosinophil in RES, decrease the number of lymphocytes, increase in number of neutrophils , RBC and platelets . Vascular response These are essential for constrictor action of adrealine and noradrenaline CNS Essential for normal functioning, insufficiency causes irritability and loss of concentration
  18. 18. Permissive action • Action of some hormones are executed only in presence of glucocorticoids. This is called permissive action. Examples are : • Calorigenic effect of glucagon. • Lypolytic effect of catecholamines. • Pressor effect of catecholamines. • Bronchodilation by catecholamines.
  19. 19. Antiinflammatory Action
  20. 20. Effects on resistance to stress Physical or mental stress Increases ACTH Increase in glucocorticoid secretion High resistance to body against stress
  21. 21. Anti allergic action • Suppresses all type of hypersensitivity reaction and allergic reaction. • Suppresion of recruitment of leucocytes at the site of contact with antigen and inflammatory response to immunological injury
  22. 22. Immunosuppresive action • Suppresses immune system of body by decreasing number of circulating T lymphocytes. • Prevent release of interleukin 2 by T cells
  23. 23. Regulation of Cortisol Secretion Emotion, stress, trauma Hypothalamus Corticotropin releasing factor Anterior pituitary ACTH Adrenal cortex Cortisol Feedback inhibition
  24. 24. Classification of steroids based on their relative activity: GLUCOCORTICOIDS Short acting (t1/2 < 12 hr) • Hydrocortisone • Cortisone Intermediate acting: (t1/2 12 – 36) • Prednisole • Methyl prednisole • Triamcinolone Long acting: (t1/2 > 36 hrs) • Paramethasone • Dexamethasone • Betamethasone
  25. 25. Mineralocorticoids • Desoxycorticosterone acetate(DOCA) • Fludrocortisone • Aldosterone
  26. 26. Uses In Medicine Replacement therapy Acute adrenal insufficiency • Hydrocortisone or dexamethasone are given i.v, first as a bolus injection and then as infusion along with istonic saline and glucose solutions. Chronic adrenal insufficiency • Hydrocortisone given orally is the most commonly used drug with adequate salt and water allowance Congenital adrenal hypoplasia • 0.6 mg/kg daily in divided doses round the clock
  27. 27. Pharmacotherapy: • Single dose (even excessive) is not harmful can be used to tide over mortal crisis even when benefit is not certain. • Short courses (even high doses) are not likely to be harmful in the absence of contraindications. Starting doses can be high in severe illness
  28. 28. • Long term use is potentially hazardous: keep the dose to minimum which is found by trial and error, even partial relief may have to be tolerated. • No abrupt withdrawal after a corticoid has been given for > 2 to 3 weeks: may precipitate adrenal insufficiency
  29. 29. • Arthritis • Collagen diseases • Severe allergic reactions • Autoimmune disorders • Bronchial asthma • Infective diseases • Eye diseases • Skin diseases • Intestinal diseases
  31. 31. Steroids in oral surgery • Prevention of post operative pain, edema and trismus after 3rd molar surgery • Prevention of post operative edema after orthognathic surgery • Prevention of alveolar osteitis
  32. 32. Steroids in endodontics • steroid-antibiotic combinations like Ledermix • Steroids like hydrocortisone are also mixed with zinc • oxide eugenol to be used as root canal sealers. It appears • that the action of steroids on root resorption is chemistry • dependent. International Journal of Pharmaceutical Sciences Review and Research
  33. 33. Steroid in oral medicine
  34. 34. Ulcerative Vesiculoerosive diseases  Immunologically mediated diseases that affect the oral mucosa present with inflammation and loss of epithelial integrity, through cellular and/or humoral immunity-mediated attack on epithelial connective tissue targets.  The main clinical features are ulceration and reddening, with pain that can be severe and debilitating.
  35. 35. • Corticosteroids play a central role in the treatment of vesiculoerosive lesions. • However, the frequency and severity of the adverse effects associated with the use of systemic corticosteroids have led to the increased use of topical corticosteroids (TCs)
  36. 36. Topical corticosteroids for ulcerative vesiculoerosive lesions
  37. 37. Indications for use • Short course of TC – accelerates remission without producing adverse effects • Ulcerative disease that have tendency to remit spontaneously • Eg RAS, some cases of EM, drug induced ulceration Scully et al., 1999; Chan et al., 2002
  38. 38. TC for longer and less predictable periods • When disease is chronic • Marked tendency for recurrence • Eg. RAS, erosive OLP, apecific form of EM, MMP
  39. 39. In severe cases of ulceration • After a short course of systemic corticosteroids, a maintenance regimen of TC can be used once the disease is controlled. • This can prevent recurrence, and also avoids adverse effects assosiated with long course of systemic corticosteroids
  40. 40. Protocols for use When a TC is prescribed, especially for prolonged course is predicted  The basic rule is that a TC of a potency appropriate to the severity of the clinical symptoms should be used, at the lowest possible concentration and frequency, with maintaining the effectiveness of the treatment.  It should always be taken into account that these drugs do not cure the disease but rather control or relieve the symptoms. JDR April 2005 vol. 84 no. 4 294-301
  41. 41. The key factors • Specific diagnosis • Severity of oral disease • Presence or absence of extraoral lesion • Medical history of patient JDR April 2005 vol. 84 no. 4 294-301
  42. 42. Factors that influence the effectiveness of TCs: Intrinsic potency of drug: This can be increased by halogenation and esterification of steroid This makes drug more lipophilic and gives it greater penetrability Contact time between the drug and lesion and the Vehicle used to apply it JDR April 2005 vol. 84 no. 4 294-301
  43. 43. Concentration: which can increase its clinical effectiveness, although no additional advantage is obtained beyond certain limits. JDR April 2005 vol. 84 no. 4 294-301
  44. 44. Success of a topical medicine Depend on two main factors • Number of application per day • High potency – 2 to 3 times • Low potency – 5 to 10 times • Vehicle used JDR April 2005 vol. 84 no. 4 294-301
  45. 45. Various vehicles • Orabase • Cyanoacrylate • Bioadhesive patch made of cellulose derivatives • Gels JDR April 2005 vol. 84 no. 4 294-301
  46. 46. Patients prescribed TC in an adherent vehicle should be instructed to  Apply a small amount to the target area after meals, and  Not to eat or drink for at least 30 min.  It is best not to rub the TC in, because this can produce irritation. JDR April 2005 vol. 84 no. 4 294-301
  47. 47.  Preparations such as orabase will not adhere to wet surface so mucosa and lesion must be dried with guaze before application.
  48. 48. For small and accessible erosive lesions, or those located on the gingiva and palate, the lesions can be treated by the • Use of an adherent paste in a tray, • Which allows for accurate control over the contact time and • Ensures that the entire lesional surface is exposed to the drug. JDR April 2005 vol. 84 no. 4 294-301
  49. 49. Adhesive denture paste as vehicle for TC can avoid some of above disadvantages this provides stability and bioadhesive properties forperiod of 12 hrs after application, esp. in localized lesions,
  50. 50. • TC mouthrinses: • Contact time can be predicted • Drug is in contact with all lesions • Are released more readily to oral mucosa when aqueous solution is applied
  51. 51. • Disadvantage • Will be in contact with all mucosa wheather effected or not • This also increase the surface area of absorption thus risk of adverse effects • This can be exacerbated by presence of ulcerated surfaces and by increased pressure excerted by liquid on mucosa as a result of normal rinsing • Can be involumentary ingested
  52. 52. Thami and bhalla proposed using saliva as vehicle for TCs which they designated as chew and spit method. • Patient is directed to chew or suck betamethasone tab. Mixing it with mouth saliva keeping it without swallowing for as long as possible 10 to 15 min Disadvantage; • Cannot guaranteed that tablet is completely dissolved • Cannot be used in dry mouth
  53. 53. Systemic steroids for ulcerative vesiculobullous diseases
  54. 54. Major aphthae or severe multiple minor aphthae • Prednisone therapy should be started at 1.0 mg/kg/day in patients with severe RAU and should be tapered after 1 to 2 weeks. Natah SS, Konttinen YT. IJOMS 2004;33:221-34. • Predisone therapy 1- 2mg /kg/day after breakfast untill the disease is controlled and then maintenance dose of 2.5 to 15mg daily ( Burket 11th edition )
  55. 55. Erythema multiforme • Minor EM – 20 to 40 mg/day for 4 to 6 days • Severe or rapidly progressing lesions – 60 mg/day slowly tapered by 10mg/day over 6 weeks Indian J Ophthalmol Jan-Feb 2010;58(1):64-66
  56. 56. Pemphigus Vulgaris • Mainstay 1-2mg/kg/d. • Initial dose of treatment – 0.5 mg/kg/day to 3 mg/kg/d • Dose that achieves clinical control is maintained for 2- 3 weeks and then gradually tapered. Burket’s Oral Medicine, 11th edition
  57. 57. Pulse therapy • Also called short term therapy • High dose therapy involves a 48-72 hrs course of intensive steroid administration • Single i.v injection of a supra-physiological dose of steroid • Dose of 0.5-2g of prednisolone or equivalent
  58. 58. Benefits • Avoids complications & side effects of long term steroid therapy • To achieve immunosuppressive effects similar to those with higher doses of steroids
  59. 59. Cicatricial pemphigoid Predisolone – 30 to 60 mg/day 2 to 3 weeks to stop new bullae formation. Tapered by 20% every 2 to 3 weeks until the dose of 10 mg is reached • Then maintained on alternate day and reduced by 5 mg every 2 week then stopped
  60. 60. Bullous pemphigoid Clobetasol propionate 20 -40 mg/day is more effective for the treatment. JIAOMR, April-June 2011;23(2):128-131
  61. 61. Lichen planus Prednisolone - 1mg/kg/d for <7 days Tapered to 10-20mg per day for 2 weeks Burkit’s Oral Medicine, 11th edition JIAOMR, April-June 2011;23(2):128-131
  62. 62. Lupus erythematosus Predisolone – 20 - 30 mg/day for 2- 6 weeks Tapered gradually
  63. 63. Steroids in the treatment of benign lesions
  64. 64. CGCG Intralesional injection of triamcinolone can be given in a dose of 1 to 2 mg/kg/d (maximum of 60 mg). The treatment interval at 4 to 6 weeks. J Med Assoc Thai 2008; 91 (Suppl 3): S90-6
  65. 65. Hemangioma Prednisone at a dose of 20-30 mg/d can be given for 2 weeks to 4 months Intralesional triamcinolone acetonide (4 mg/mL)
  66. 66. Steroids in salivary gland disorders
  67. 67. Mucocele  0.05% clobetasol propionate 3 times a day for 4 weeks in a mucosal adhesive base.  Intralesional injections have also been tried with success. (JOMS 2008;66:1737-9)
  68. 68. Steriods in neuralgia
  69. 69. Post herpetic neuralgia To reduce incidence of post herpetic neuralgia:  Prednisolone 20 to 30 mg/day for 7 – 10 days tapered to 10 mg/day for 1 week
  70. 70. Steroids for TMJ disorders
  71. 71. Arthritis Rheumatoid arthritis - Intraarticular injection – 10 to 40 mg/ml Osteoarthritis - Intraarticular injection – 20 mg/ml(2 injections 14 days apart) Oral Surgery Volume 1 Issue 2, Pages 88 - 95
  72. 72. Bell’s palsy  Significant improvement can be achived when Prednisolone is started within 72 hours of symptom onset  1 mg/kg body weight (maximum 70 mg) in divided doses with meals for six days, and the dose can be reduced gradually over the next four days.
  73. 73. OSMF Predisolone – 20 - 30 mg/day for 2 – 4 weeks then gradually taper to discontinue in 1 to 2 months
  74. 74. Injections of triamcinolone 10mg/ml diluted in 1 ml of 2% lidocaine with hyaluronidase 1500 IU, biweekly for 4 weeks.
  75. 75.  Biweekly submucosal injections of a combination of dexamethasone (4mg/ml) and two parts of hyaluronidase, diluted in 1.0 ml of 2% xylocaine by means of a 27 gauge needle, not more than 0.2ml solution per site, for a period of 20 weeks.  Significant relief of burning sensation (88%) and improvement of trismus (83%) can be seen in most patients.
  76. 76. Adverse effects Due to extention of pharmacological action occuring with prolonged therapy Mineralocorticoids:  Sodium and water retention  Edema  Hypokalemic alkalosis  Progressive rise in B.P  Weight gain  Fluid and electrolyte disturbance
  77. 77. Glucocorticoid: GIT:  Acute erosive gastritis with hemorrhage  Peptic ulcer  Intestitial perfortion  Pancreatitis Metabolic effects:  Hyperglycemia  Ketoacidosis  Hyperosmolar coma  Hypophosphatemia
  78. 78. Cushingoidism: Prolonged therapy causes  Central obesity with moon face  Buffalo hump  Pink florid striae are liable to appear on the abdomen, hips and pectoral region and skin may become friable
  79. 79. CVS and renal system:  Hypertension  Salt and water retention  Hypokalemic alkalosis CNS:  Influence mood, sleep pattern  Insomnia  Acute psychotic reactions  Benign intracranial hypertension  Epilepsy
  80. 80. Musculoskeletal effects:  Proximal myopathy and osteoporosis with compression fractures of vertebrae  Acute aseptic necrosis of bone Eyes:  Glaucoma
  81. 81. Suppression of inflammation and immune response:  Latent infection may flare  Oppurtunistic infection with low grade pathogens Retardation of linear growth:  Occurs in children who receive more than 50 mg of cortisone per m2 of body surface per day.
  82. 82. SUPPRESSION OF HPA axis • Depend on both dose and duration of therapy • With administration of glucocorticoid, adrenal cortex atrophies • With stoppage of exogenous steroid precipitates withdrawal syndromes- Malaise • Fever • weakness • Pain in muscles • Joints • Reactivation of disease
  83. 83. • When subjected to stress these patients may undergo acute adrenal insufficiency • Any patient who has received >20 to 25 mg /day hydrocortisone or equivalent for more than 2 to 3 weeks should be put on a scheme of gradual withdrawal: 20 mg hydrocortisone/day reduction every week and then still smaller fraction once level is achieved
  84. 84. • In stressful situation these patients requires protection with exogenous steroids upto 1 year after withdrawal. • If patient on steroid therapy develops infection steriod should not be discontinued. Rather dose has to be increased to meet stress of infection.
  85. 85. Measures to minimize HPA axis suppression • Use of short acting steroids at lowest possible dose • Use of steroid at shorest period of time • Giving entire daily dose one time in morning • Switch to alternate day therapy
  86. 86. Alternate day therapy • Double dose is taken every other morning • Usually preferred for other chronic conditions. • Schedule allows rest periods so that adverse effects are decreased while anti-inflammatory effects continue. • ADT is used only for maintenance therapy • ADT can be started after symptoms have subsided and stabilized.
  87. 87. Contraindications:  Peptic ulcer  Diabetes mellitus  Hypertension  Pregnancy  Herpes simplex keratitis  Tuberculosis  Osteoporosis  Psycosis  Epilepsy  Renal failure
  88. 88. Drug interactions Glucocorticoid dosage decreased:  Antibiotics (Erythromycin)  Cyclosporine  Isoniazid  Ketoconazole  Estrogen Reduce metabolic clearance
  89. 89. Glucocorticoid dosage increased:  Cholestyramine  Antiepileptic Drugs (Barbiturates, Phenytoin, Carbamazepine)  Rifampicin Glucocorticoid dosage needs adjustment:  Antianxiety and antipsychotic drugs  Antihypertensives  Hypoglycemics  sympathomimetics
  90. 90. Precautions during therapy Before starting therapy:  Enquire and check for hypertension, diabetes mellitus, peptic ulcer, any infection
  91. 91. During therapy:  Prescribe drug with food  Diet low in calories and sodium and rich in potassium  Check periodically for weight gain, hypertension, hyperglycemia
  92. 92.  Increase dose in case of stress  Instruct patient not to stop abruptly While stopping therapy:  Taper therapy
  93. 93. Rule of 2 Adrenocortical suppression should be suspected if a patient has received Glucocoticoid therapy through two of the following methods  In a dose of 20 mg or more of cortisone or its equivalent  Via oral or parenteral route or a continuous period of 2 weeks or longer  Within 6 months -2 years of therapy Medical emergencies in dental office, Stanley F.Malamed Complications in Anesthesia - John L. Atlee; Page-132
  94. 94. Protocol for Supplementation of Patients on Glucocorticoid Therapy Who Are Undergoing Dental Care (Burket’s 10th ed)
  95. 95. Dental Procedure Previous Systemic Steroid Use Current Systemic Steroid Use Daily alternating Systemic Steroid Use Current topical Systemic Steroid Use Routine procedures If prior usage lasted for > 2 weeks and ceased < 14–30 days ago, give previous maintenance dose If prior usage ceased > 14–30 days ago, no supplementation needed No supplementation needed Treat on steroid dosage day; no further supplementatio n needed No supplementatio n needed
  96. 96. Dental Procedure Previous Systemic Steroid Use Current Systemic Steroid Use Daily alternating Systemic Steroid Use Current topical Systemic Steroid Use Extractions, surgery, or extensive procedures If prior usage lasted > 2 weeks and ceased < 14–30 days ago, give previous maintenance dose If prior usage ceased > 14–30 days ago, no supplementation needed Double daily dose on day of procedure Double daily dose on first postoperative day when pain is anticipated Treat on steroid dosage day, and give double daily dose on day of procedure Give normal daily dose on first postoperative day when pain is anticipated No supplementatio n needed
  97. 97. Conclusion • Corticosteroids play an important role in control of pain & inflammation associated with numerous disease states of oral cavity. • Currently corticosteroids are drugs with one of the broadest spectrum of clinical utility. • But it should never be used as a substitute to other treatments • Lets keep it mind that these drugs do not cure the disease but rather control or relieve the symptoms.
  98. 98. References • Burket’ s Oral Medicine 9th and 11th edition • Corticosteroids in Dentistry, Basavaraj Kallali et al JIAOMRApril-June 2011;23(2):128-131 • Steroids in Dentistry - A Review Sambandam V, Int. J. Pharm. Sci. Rev. Res., 22(2), Sep – Oct 2013; nᵒ 44, 240-245 • Steroids Application In Oral Diseases, Int J Pharm Bio Sci 2013 Apr; 4(2): (P) 829 - 834
  99. 99. Thank You