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Transcript of 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 steroidsCholesterol
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
MECHANISM OF ACTION
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
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
GlucocorticoidsSource : 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.
Antiinflammatory Action
Effects on resistance to stress
Physical or mental stress
Increases ACTH
Increase in glucocortic
oid 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
Emotion, stress, trauma
Hypothalamus
Corticotropin releasing factor
Anterior pituitary
ACTH
Adrenal cortex
Cortisol
Fee
dbac
k in
hibi
tion
Regulation of Cortisol Secretion
Classification of steroids based on their relative activity:GLUCOCORTICOIDS
Short acting(t1/2 < 12 hr)• Hydrocortison
e • Cortisone
Intermediate acting: (t1/2 12 – 36)• Prednisole• Methyl
prednisole• Triamcinolone
Long acting:(t1/2 > 36 hrs)• Paramethasone• Dexamethason
e• Betamethasone
Mineralocorticoids • Desoxycorticosterone acetate(DOCA)
• Fludrocortisone
• Aldosterone
UsesIn 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 DENTISTRY
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
Steroid in oral medicine
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:
JDR April 2005 vol. 84 no. 4 294-301
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
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.
• 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 )
Natah SS, Konttinen YT. IJOMS 2004;33:221-34.
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
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
JIAOMR, April-June 2011;23(2):128-131
Clobetasol propionate
20 -40 mg/day is more 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
Predisolone – 20 - 30 mg/day for 2- 6 weeks
Tapered gradually
Steroids in the treatment of benign lesions
CGCG
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
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 effectsDue 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.MalamedComplications 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 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
• 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
Thank You