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Dr.

Smijal
PG Its year
Department of Periodontics
INTRODUCTION
• Adrenal corticosteroids are necessary regulators of
homeostatic life processes.
• Natural hormones include

Glucocorticoid
Mineralocorticoid
Sex 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 DARK INNER MEDULLA


• corticosteroid secreting • Catecholamine secreting
• 90% of the gland by weight • Forms the center of the gland
• Partly controlled by anterior pituitary gland • Richly innervated by
• Regulate metabolism & maintain normal electrolyte preganglionic sympathetic
balance fibers
ZONA GLOMERULOSA ZONA FASICULATA ZONA RETICULARIS CHROMAFFIN SYMPATHETIC
CELLS GANGLIONIC
Mineralocorticoids Glucocorticoids Androgens CELLS
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.
Cholesterol
Biosynthesis of
steroids Pregnenolone

Progesterone 17α Hydroxy Dehydroepiandrosterone


pregnenolone

11- Deoxy corticosterone 17α Hydroxy Androstenidione


progesterone

Corticosterone Testosterone
11 Desoxyhydro
cortisone
Aldosterone
Hydrocortisone

Mineralocorticoid Glucocorticoid Androgens


release Corticotropin-
HYPOTHALAMUS
S Adrenocorticotr PITUTIARY
releasing hormone
(CRH)
T opic hormone
(ACTH) GLUCOCORTICOIDS
R
E
S
S cortisol
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
GLUCOCORTICOIDS
Source : zona fasciculata

Cortisol – Life protecting hormone


• Most potent
Cortisol • Provides 95% of glucocorticoid
activity

• Most potent
Corticosterone • Provides 95% of glucocorticoid
activity

• Secreted in minute quantities


Cortisone • Provides 1% of glucocorticoid
activity
ACTION ON EFFECT
On carbohydrate Increases blood glucose level by
metabolism gluconeogenesis, inhibits glucose uptake
and utilization by peripheral cells
Promotes catabolism of protein and
Protein metabolism increases plasma amino acid and protein
content
Metabolism of fatty acid from adipose
Fat metabolism 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-
inflammatory
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


Regulation of Cortisol Secretion
Emotion, stress, trauma

Hypothalamus

Feedback inhibition
Corticotropin releasing factor

Anterior pituitary

ACTH

Adrenal cortex

Cortisol
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.
Regulation of Aldosterone Secretion
Increase in K+ concentration Decrease in K+ concentration
Decrease in Na+ Concentration Increase in Na+ Concentration
Decrease in ECF volume Increase in ECF volume
Feedback
Stimulation inhibition

Juxtaglomerular Excretion of K+
angiotensinogen Renin
apparatus Retention of Na+
Retention of water

Angiotensin - 1 Converting kidneys


Enzyme ACE Lungs

Angiotensin - 2 Adrenal cortex Aldosterone

Essentials Of Medical Physiology 3rd Edition,


K Sembulingam
FATE OF CORTICOSTEROIDS
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
27
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"

28
• 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.

29
•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

30
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
Inhibition of
Hypothalamic/ feedback loop-
Pituitary disease pituitary and adrenal
glands
Failure to
Chronic produce cortisol
administration Failure of production
of exogenous of
corticosteroids 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 therapy
Mineralocorticoids:
• 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 alkalosis
CNS:
 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 bone
Eyes:
 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  Osteoporosis
 Diabetes mellitus  Psychosis
 Hypertension  Epilepsy
 Pregnancy  Renal failure
 Herpes simplex
keratitis
 Tuberculosis
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 stomatitis
Topical
• 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 ulceration


Scully 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

• 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
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

• Clobetasol propionate
• 20 -40 mg/day is most effective for the
treatment.

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


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
Lupus erythematosus

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


• Tapered gradually
STEROIDS IN THE TREATMENT OF
BENIGN LESIONS
CENTRAL GIANT
CELL GRANULOMA

• 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
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
• 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


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
injections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.
Protocol for Supplementation
of Patients on Glucocorticoid
Therapy Who Are Undergoing
Dental Care (Burket’s 10th ed)
Dental Previous Systemic Current Daily Current
Procedure Steroid Use Systemic Steroid alternating topical
Use Systemic Systemic
Steroid Use Steroid Use

Routine If prior usage lasted No Treat on No


procedures for > 2 weeks and supplementation steroid dosage supplementati
ceased < 14–30 days needed day; no further on needed
ago, give previous supplementati
maintenance dose on needed

If prior usage ceased


> 14–30 days
ago, no
supplementation
needed
Dental Previous Systemic Current Systemic Daily alternating Current topical
Procedure Steroid Use Steroid Use Systemic Steroid Systemic Steroid
Use Use

Extractions, If prior usage lasted Double daily dose Treat on steroid


surgery, or > 2 weeks and on day of dosage day, and
extensive ceased < 14–30 procedure give double daily
procedures days ago, give dose on day of
previous procedure
maintenance dose No
supplementation
If prior usage Give normal daily needed
ceased > 14–30 Double daily dose dose on first
days ago, no on first postoperative day
supplementation postoperative day when pain is
needed when pain is anticipated
anticipated
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

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