Corticosteroid

CORTICOSTEROIDS
Presented by :
Joe Dsilva

CONTENTS
• Introduction
• History
• Functional anatomy and histology of adrenal glands
• Biosynthesis of steroids
• Fate of steroids
• Mineralocorticoids
• Glucocorticoids

• Mechanism of action
• Classification of steroids
• Uses in medicine
• Steroids in dentistry
• Adverse effects
• Drug interaction
• Precautions

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.

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.

 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.

Functional anatomy and histology
of adrenal glands

Biosynthesis of steroids
Cholesterol
Pregnenolone
Progesterone
11- Deoxy corticosterone
Corticosterone
Aldosterone
17α Hydroxy
pregnenolone
17α Hydroxy
progesterone
11 Desoxyhydro
cortisone
Hydrocortisone
Dehydroepiandrosterone
Androstenidione
Testosterone

Rate of secretion of the principal
steroids
Glucorticoids
10-20 mg daily
Mineralocorticoids – 0.125 mg
daily

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

Mineralocorticoids
 Source : Zona glomerulosa
 Functions: 90% of mineralocorticoid activity is provided
by aldosterone
 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.
Essentials Of Medical Physiology 3rd Edition,
K Sembulingam

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

Glucocorticoids
Source : zona fasciculata
Functions:
Cortisol – Life protecting hormone

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

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

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.

Effects on resistance to stress
Physical or
mental stress
Increases
ACTH
Increase in
glucocorticoid
secretion
High
resistance
to body
against
stress

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 interleukin 2 by T cells

Regulation of Cortisol Secretion
Emotion, stress, trauma
Hypothalamus
Corticotropin releasing factor
Anterior pituitary
ACTH
Adrenal cortex
Cortisol
Feedback inhibition

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

Mineralocorticoids
• Desoxycorticosterone acetate(DOCA)
• Fludrocortisone
• Aldosterone

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

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

• 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

• Arthritis
• Collagen diseases
• Severe allergic reactions
• Autoimmune disorders
• Bronchial asthma
• Infective diseases
• Eye diseases
• Skin diseases
• Intestinal diseases

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

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

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.

• 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)

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, apecific form of EM, MMP

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

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

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

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

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

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

Various vehicles
• Orabase
• Cyanoacrylate
• Bioadhesive patch made of cellulose derivatives
• Gels
JDR April 2005 vol. 84 no. 4 294-301

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

 Preparations such as orabase will not adhere to wet
surface so mucosa and lesion must be dried with guaze
before application.

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

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,

• 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

• 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

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

Systemic steroids for ulcerative
vesiculobullous diseases

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 )

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

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

Benefits
• Avoids complications & side effects of long term steroid
therapy
• To achieve immunosuppressive effects similar to those
with higher doses of steroids

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

Bullous pemphigoid
Clobetasol propionate
20 -40 mg/day is more 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
Predisolone – 20 - 30 mg/day for 2- 6 weeks
Tapered gradually

Steroids in the treatment of benign
lesions

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

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)

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

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
 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.

OSMF
Predisolone – 20 - 30 mg/day
for 2 – 4 weeks then gradually
taper to discontinue in 1 to 2
months

Injections of triamcinolone 10mg/ml diluted in 1
ml of 2% lidocaine with hyaluronidase 1500 IU,
biweekly for 4 weeks.

 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.

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

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

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

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
 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.

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

• 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

• 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.

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

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.

Contraindications:
 Peptic ulcer
 Diabetes mellitus
 Hypertension
 Pregnancy
 Herpes simplex keratitis
 Tuberculosis
 Osteoporosis
 Psycosis
 Epilepsy
 Renal failure

Drug interactions
Glucocorticoid dosage decreased:
 Antibiotics (Erythromycin)
 Cyclosporine
 Isoniazid
 Ketoconazole
 Estrogen
Reduce metabolic
clearance

Glucocorticoid dosage increased:
 Cholestyramine
 Antiepileptic Drugs (Barbiturates, Phenytoin,
Carbamazepine)
 Rifampicin
Glucocorticoid dosage needs adjustment:
 Antianxiety and antipsychotic drugs
 Antihypertensives
 Hypoglycemics
 sympathomimetics

Precautions during therapy
Before starting therapy:
 Enquire and check for hypertension, diabetes
mellitus, peptic ulcer, any infection

During therapy:
 Prescribe drug with food
 Diet low in calories and sodium and rich in
potassium
 Check periodically for weight gain, hypertension,
hyperglycemia

 Increase dose in case of stress
 Instruct patient not to stop abruptly
While stopping therapy:
 Taper therapy

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

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
days
ago, no
supplementation
needed
No
supplementation
needed
Treat on steroid
dosage day; no
further
supplementatio
n needed
No
supplementatio
n 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
supplementatio
n 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
• 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

Corticosteroid

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