Dr. SmijalPG Its yearDepartment of Periodontics

INTRODUCTION

• Adrenal corticosteroids are necessary regulators of homeostatic life processes.

• Natural hormones include

GlucocorticoidMineralocorticoidSex hormones

HISTORY• Hench (1949) -improvement in

rheumatoid arthritis by using cortisone

• In 1950 Nobel Prize -Kendall and Reichstein and Hench, for developing corticosteroids

• Currently, drugs with one of the broadest spectrum of clinical utility.

CHEMICAL STRUCTURE• 4 cycloalkane rings • 3 cyclohexane rings • 1 cyclopentane ring .• Gonane is the simplest steroid• Vary by the configuration of the side

chain, the number of additional methyl groups, and the functional groups attached to the rings

ADRENAL GLAND

Covered with thick CT capsule from which trabeculae extend into parenchyma, blood vessels and nerves

OUTER YELLOWISH CORTEX• corticosteroid secreting• 90% of the gland by weight• Partly controlled by anterior pituitary gland• Regulate metabolism & maintain normal electrolyte

balance

DARK INNER MEDULLA• Catecholamine secreting• Forms the center of the gland• Richly innervated by

preganglionic sympathetic fibers

ZONA GLOMERULOSA ZONA FASICULATA ZONA RETICULARIS

Mineralocorticoids Glucocorticoids Androgens

SYMPATHETIC GANGLIONIC

CELLS

CHROMAFFINCELLS

Catecholamines

Functional anatomy and histology of adrenal glands

Corticosteroid Hormones

• Epinephrine• Norepinephrine• Dopamine

Regulating salt and water

• Suppress inflammation and immunity

• Breakdown of fats, carbohydrates, and proteins,

• Resistance to stress

•Mineralocorticoids Aldosterone

•Glucocorticoids Cortisol

•Adrenal androgens Dehydroepiandrosterone

NORMAL ADULT DAILY PRODUCTION•Cortisol 20 mg/ day •Corticosterone 02 mg / day •Aldosterone 0.125 mg/day •Dehydroepiandrosterone 30 mg/day.

Biosynthesis of steroids

Cholesterol

Pregnenolone

Progesterone

11- Deoxy corticosterone

Corticosterone

Aldosterone

17α Hydroxy pregnenolone

17α Hydroxy progesterone

11 Desoxyhydro cortisone

Hydrocortisone

Dehydroepiandrosterone

Androstenidione

Testosterone

Mineralocorticoid Glucocorticoid Androgens

PITUTIARY

HYPOTHALAMUSSTRESS

release Corticotropin-releasing hormone (CRH)Adrenocorticotr

opic hormone (ACTH)

cortisol

GLUCOCORTICOIDS

PHYSIOLOGY

24-30mg of cortisol

300mg of cortisol

Sanghavi J, Aditya A. Applications of Corticosteroids in Dentistry. J Dent Allied Sci 2015;4:19-24

GLUCOCORTICOIDSSource : zona fasciculata

Cortisol – Life protecting hormone

• Most potent• Provides 95% of glucocorticoid

activityCortisol

• Most potent• Provides 95% of glucocorticoid

activityCorticosterone

• Secreted in minute quantities• Provides 1% of glucocorticoid

activityCortisone

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

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 adrenaline and noradrenaline

CNS Essential for normal functioning, insufficiency causes irritability and loss of concentration

Permissive action • Action of some hormones are executed only in presence of

glucocorticoids.. Examples are :

• Calorigenic effect of glucagon.

• Lypolytic effect of catecholamines.

• Pressor effect of catecholamines.

• Bronchodilation by catecholamines.

Anti-inflamma

tory Action

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

Immunosuppresive action

• Suppresses immune system of body by decreasing

number of circulating T lymphocytes.

• Prevent release of IL2 by T cells

Emotion, stress, trauma

Hypothalamus

Corticotropin releasing factor

Anterior pituitary

ACTH

Adrenal cortex

Cortisol

Feed

back

inhi

bitio

n

Regulation of Cortisol Secretion

MINERALOCORTICOIDS

Source : Zona glomerulosa

Aldosterone – life saving hormone

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.

Increase in K+ concentrationDecrease in Na+ ConcentrationDecrease in ECF volume

Decrease in K+ concentrationIncrease in Na+ ConcentrationIncrease in ECF volume

Juxtaglomerular apparatus

Excretion of K+

Retention of Na+

Retention of water

kidneysLungs

Aldosterone Adrenal cortex

angiotensinogen

Angiotensin - 1

Angiotensin - 2

Renin

Converting Enzyme ACE

Stimulation Feedback inhibition

Regulation of Aldosterone Secretion

Essentials Of Medical Physiology 3rd Edition,K Sembulingam

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

27

ROUTES OF ADMINISTRATION OF CORTICOSTEROIDS

1. Topical steroid for use topically on the skin, eye, and mucous membranes.

2. Inhaled steroids for use to treat the nasal mucosa, sinuses, bronchii, and lungs.

3. Oral forms - such as prednisone and prednisolone.

4. Systemic forms - available in injectable for use intravenously and parenteral routes

28

Classes of corticosteroids •Corticosteroids are generally grouped into four classes, based on chemical structure.

•Allergic reactions to one member of a class typically indicate an intolerance of all members of the class.

"Coopman classification"

•Group A• (short to medium acting glucocorticoids) Hydrocortisone, Hydrocortisone acetate, Cortisone acetate, Tixocortol pivalate, Prednisolone, Methylprednisolone, and Prednisone.

•Group B•Triamcinolone acetonide, , Mometasone, Amcinonide, Budesonide, Desonide, Fluocinonide, Fluocinolone acetonide, and Halcinonide.

•Group C•Betamethasone, Betamethasone sodium phosphate, Dexamethasone, Dexamethasone sodium phosphate, and Fluocortolone.

•Group D•Hydrocortisone-17-butyrate,Betamethasone valerate, Betamethasone dipropionate, Prednicarbate and Fluprednidene acetate

Classification of steroids based on their relative activity:GLUCOCORTICOIDS

ADRENAL INSUFFICIENCY•Endocrine disorder • Inadequate production of adrenal androgens, mineralocorticoids and glucocorticoids by the adrenal cortex

•Primary AI•Secondary AI

PRIMARY ADRENAL INSUFFICEINCY

• Addison disease• Progressive destruction of the adrenal cortex • Idiopathic nature (most commonly autoimmune) • Weakness, fatigue, loss of appetite, weight loss and

patchy hyperpigmentation of the skin and oral mucosa.

SECONDARY ADRENAL INSUFFICEINCY

Failure to produce cortisol

Hypothalamic/ Pituitary disease

Chronic administration of exogenous

corticosteroids

Inhibition of feedback loop-

pituitary and adrenal glands

Failure of production of

adrenocorticotropin

•2-3 Times more common•Selectively causes glucocorticoid deficiency

•Mineralocorticoid function is better maintained than in primary AI and the condition is less likely to cause acute adrenal crisis

ADRENAL CRISIS•Rare, potentially lethal event •Precipitated by stress • In patients with chronic AI. •Primary AI > Secondary AI•Susceptible patients have diminished adrenal reserve and are unable to secrete sufficient amounts of the steroid the body requires during a stressful event.

•Fever, gastrointestinal complaints, hypotension, tachycardia and electrolyte disturbances.

•Hypovolemic shock and cardiovascular failure can ensue.

•Few cases have been reported during dental care

RISK FACTORS OF ADRENAL CRISIS• Significant and unrecognized AI• Poor health status and stability at the time of dental

treatment (acute illness, fever)• Pain• Infection• Extractions or invasive procedures that caused

bleeding and discomfort• Use of general anesthetic containing a barbiturate.

Management Of Adrenal Crisis

• Intravenous fluids (in the form of 5% dextrose in normal saline). • Primary adrenal insufficiency: Start on 20-25 mg hydrocortisone

per 24 h.• Secondary adrenal insufficiency: 15-20 mg hydrocortisone per

24 h; if borderline fails in cosyntropin test considers 10 mg or stress dose cover only.

• Hydrocortisone should initially be given intravenously.

• If there is an improvement within 24 h, the hydrocortisone dose can be reduced.

• Changed to an oral formulation whenever the patient is stable. • The dose declined by one-third to one-half the doses daily until

a maintenance dose of 20 mg in the morning and 10 mg in the afternoon or at night is attained.

• The condition that precipitated the crisis should be treated.• Patients will not need mineralocorticoid replacement because

the renin angiotensin-aldosterone axis is intact.

Arlt W. The approach to the adult with newly diagnosed adrenal insufficiency. J Clin Endocrinol Metab 2009;94:1059-67.

SUPPLEMENTATION•Supplementation dose level for the day -minor to moderate surgery -25 to 75 mg hydrocortisone equivalent.

•Higher doses of 100 to 150 mg -major surgery and the following day.

•Postoperatively, appropriate patient monitoring that is based on the risk factors

Prolonged therapyMineralocorticoids:• Sodium and water retention• Edema• Hypokalemic alkalosis• Progressive rise in B.P• Weight gain• Fluid and electrolyte disturbance

Glucocorticoid:GIT:•Acute erosive gastritis with hemorrhage•Peptic ulcer•Intestitial perforation•Pancreatitis Metabolic effects:•Hyperglycemia•Ketoacidosis•Hyperosmolar coma•Hypophosphatemia

CVS and renal system: Hypertension Salt and water retention Hypokalemic alkalosisCNS: Influence mood, sleep pattern Insomnia Acute psychotic reactions Benign intracranial hypertension Epilepsy

Musculoskeletal effects: Proximal myopathy and osteoporosis with

compression fractures of vertebrae Acute aseptic necrosis of boneEyes: Glaucoma

Suppression of inflammation and immune response:

Latent infection may flare

Opportunistic 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.

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

Peptic ulcer Diabetes mellitus Hypertension Pregnancy Herpes simplex

keratitis Tuberculosis

Osteoporosis Psychosis Epilepsy Renal failure

PULSE THERAPY•Short term therapy

•High dose therapy -48-72 hours 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

BENEFITS•Avoids complications & side effects of long term steroid therapy

•To achieve immunosuppressive effects similar to those with higher doses of steroids

DOSE EQUIVALENT

STEROID TREATMENT CARD

Issued when• Oral/systemic corticosteroids Patients prescribed oral steroids for

periods of more than 3 weeks Or those receiving more than four short oral courses per year

• Inhaled corticosteroids (ICS) Patients receiving high dose inhaled corticosteroids

• Other forms of corticosteroid Patients receiving topical or nasal corticosteroids do not routinely require a steroid card unless systemic absorption likely to be increased i.e. Crohn’s/Ulcerative colitis flare/prolonged usage/multiple formulations prescribed/drug interactions

STEROIDS IN DENTISTRY

ORAL MANIFESTATION OF ADDISONS DISEASE• Characteristic melanin pigmentation • The skin darkens in the elbows, folds of the hands or areolas of the

breasts. • The oral mucosa can in turn develop black-bluish plaques, mainly

affecting buccal mucosa but it can also be seen on the gums, palate, tongue and lips.

STEROIDS IN ORAL SURGERY

•Post operative pain, edema and trismus after 3rd

molar surgery

•Post operative edema after orthognathic surgery

•Prevention of alveolar osteitis

Das JR, Sreejith VP, Anooj PD, Vasudevan A. Use of Corticosteroids in third molar surgery: Review of literature. Univ Res J Dent 2015;5:171-5.

PERIOPERATIVE ANTI-INFLAMMATORY•Boc and Peterson -use of steroids for orthognathic and traumatic oral surgical procedures,

•6mg of sodium dexamethasone or equivalent, given 2-3 hours before surgery

•And repeated at surgery may accomplish this purpose

CORTICOSTEROIDS IN ORTHODONTIC

TOOTH MOVEMENT•Orthodontic tooth movement is by sequential reactions of the periodontal tissue in response to biomechanical forces.

•The arachidonic acid metabolites also play an important role in the process of bone remodeling during tooth movement

International Journal of Pharmaceutical Sciences Review and Research

•Hydrocortisone at a dose of 10 mg/kg/day for 7 days on Rats

•Lower amount of tooth movement•It is essential that the patients are reviewed of their prior history of•Corticosteroids use.•Longer interval between treatments

Yamane A, Fukui T, Chiba M, In vitro measurements of orthodontic tooth movement in rats given B-amino propionitrile or hydrocortisone using a time-laps video tape recorder, Eur J Orthod, 19, 1997, 21-28.

STEROIDS IN ENDODONTICS

•Steroid-antibiotic combinations like Ledermix

•Steroids like hydrocortisone are also mixed with zinc oxide eugenol as root canal sealers.

International Journal of Pharmaceutical Sciences Review and Research

STEROID IN ORAL MEDICINE

Recurrent aphthous stomatitisTopical• Hydrocortisone hemisuccinate (pellets of 2.5 mg) • Triamcinolone acetonide (adhesive paste containing 0.1% of the

steroid).• In inaccessible areas controlled by topical dexamethasone.(0.5

mg/5 ml held over the area or applied with a saturated gauge pad to the ulcers, 4 times/day for 15 min )

• Betamethasone sodium phosphate rinse

• Major aphthous ulcers systemic treatment

• Prednisone therapy 40 mg/day for 1 week

• 1.0 mg/kg a day as a single dose in severe RAS patients and should be tapered after 7-14 days

BEHCET’S DISEASE• The mainstay of treatment for

Behcet’s disease is immunosuppressive therapy.

• In the acute phase, prednisone, at doses of 40-60 mg/day• It may be used alone or in combination therapy with other

immunosuppressive agents

ULCERATIVE VESICULOEROSIVE

DISEASES•Immunologically mediated diseases affecting oral mucosa

•Inflammation and loss of epithelial integrity,

•Corticosteroids central role in the treatment

•Adverse effects of systemic corticosteroids

increased use of topical corticosteroids (TCs)

TOPICAL CORTICOSTEROIDS FOR

ULCERATIVE VESICULOEROSIVE

LESIONS

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 ulcerationScully et al., 1999; Chan et al., 2002

TC for longer and less predictable periods

•When disease is chronic

•Marked tendency for recurrence

•Eg. RAS, erosive OLP, aspecific form of EM, MMP

In severe cases of ulceration

•After a short course of systemic corticosteroids,

maintenance regimen of TC

•Prevent recurrence, and avoids adverse effects

associated with long course of systemic

corticosteroids

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

Prolonged topical therapy•Can cause atrophy of epidermis, dermis•Subcutis•Disturbed wound healing•Hypertrichosis•Perioral dermatitis

Heike Scha¨cke, Wolf-Dietrich Do¨cke, Khusru Asadullah; Mechanisms involved in the side effects of glucocorticoids; Pharmacology & Therapeutics 96 (2002) 23 – 43

Major aphthae or severe multiple minor aphthae

•Prednisone therapy 1.0 mg/kg/day in patients with severe RAU and tapered after 1 to 2 weeks.

•Predisone therapy 1- 2mg /kg/day after breakfast until the disease is controlled and then maintenance dose of 2.5 to 15mg daily ( Burket 11th edition )

ERYTHEMA MULTIFORME

Indian J Ophthalmol Jan-Feb 2010;58(1):64-66

• 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

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

CICATRICIAL PEMPHIGOID• Prednisolone – 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

Bullous pemphigoid

JIAOMR, April-June 2011;23(2):128-131

• Clobetasol propionate

• 20 -40 mg/day is most effective for the

treatment.

Lichen planus

Burkit’s Oral Medicine, 11th editionJIAOMR, April-June 2011;23(2):128-131

• Prednisolone - 1mg/kg/d for <7 days

• Tapered to 10-20mg per day for 2 weeks

Lupus erythematosus

• Prednisolone – 20 - 30 mg/day for 2- 6 weeks

• Tapered gradually

STEROIDS IN THE TREATMENT OF BENIGN

LESIONS

CENTRAL GIANT CELL GRANULOMA

J Med Assoc Thai 2008; 91 (Suppl 3): S90-6

• 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.

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)

STEROIDS IN SALIVARY GLAND

DISORDERS

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)

STERIODS IN NEURALGIA

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

STEROIDS FOR TMJ DISORDERS

ARTHRITIS

Oral Surgery Volume 1 Issue 2, Pages 88 - 95

• Rheumatoid arthritis - Intraarticular injection – 10 to 40

mg/ml

• Osteoarthritis - Intraarticular injection – 20 mg/ml(2

injections 14 days apart)

BELL’S PALSY • Prednisolone is started within

72 hours of symptom onset• May prevent denervation,

autonomic synkinesis and progression of paresis to palsy.

STEROID TAPPERING DOSE• Fagan recommends

•60 mg x 3 days •40 mg x 3 days •20 mg x 3 days •10 mg x 3 days •5 mg x 3 days

ORAL SUBMUCOUS FIBROSIS•The initial symptomatic relief the anti-inflammatory action of the steroids

•Clearing the juxta epithelial inflammatory reaction.

• Biweekly submucosal injectionscombination 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.

Protocol for Supplementation of Patients on Glucocorticoid Therapy

Who Are Undergoing Dental Care (Burket’s 10th ed)

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 daysago, no supplementation needed

No supplementation needed

Treat on steroid dosage day; no further supplementation needed

No supplementation needed

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 supplementation needed

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.

References • Risk of adrenal crisis in dental patients Results of a systematic search; May/June 2014

• 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

• Murthy, J. M. K., and Amrit B. Saxena. “Bell’s Palsy: Treatment Guidelines.” Annals of

Indian Academy of Neurology 14.Suppl1 (2011): S70–S72. PMC. Web. 23 Jan. 2017.

Thank You