3. CONTENTS
PART 1: CORTICOSTEROIDS
Introduction
History of steroids
Functional anatomy and histology of adrenal glands
Bio Synthesis of Steroids
Rate of secretion of steroids
Fate of steroids / Pharmacokinetics
Classification of steroids
Mechanism of action at cellular level
Glucocorticoids
Mineralocorticoids
4. Functions of steroids
Therapeutic uses in Medicine
Corticosteroids in Dentistry
Adverse effects and contraindications
HPAAXIS
Drug interactions
Precautions
Pathologies of adrenal glands
Steroids in oral medicine
Conclusion
References
5.
6. Introduction
Corticosteroids are rightly called the wonder drugs have
always fascinated the world with its unique properties and
pharmacological actions.
Using cholesterol as the substrate the adrenal glands
produces wide variety of substances called corticosteroids.
7. HISTORY OF STEROIDS
The clinical importance of the adrenal
glands was first appreciated by Addison.
The studies published subsequently
(addison,1855) were soon extended by
brown – sequard .
16. STRUCTURE OF STEROIDS
21 carbon compounds having a cyclo
pentano per hydro phenanthrene ring with
various functional groups attached to
different carbon atoms.
23. Mechanism of action
Acts by a common mechanism at the cellular level
2 receptor system-
Glucocorticoid receptor
Mineralocorticoid receptor
Effects of steroids mediated by interaction with specific
receptors
24.
25.
26. Corticosteroids have wide spread actions
Direct actions –
Maintain fluid – electrolyte,
Cardiovascular
Energy –substrate homeostasis
Functional status of skeletal muscles & nervous system
They endow the organism with the capacity to resist
stress
27. Permissive actions:
They do no themselves produce any effect, their presence
facilitates other hormones to produce their action.
Eg; corticosteroids do not have any effects on BP but the
pressor action of adrenaline is markedly blunted in their
absence.
Actions of corticoids are divide in to-
Glucocorticoids actions
Mineralocorticoids action
28. MINERALOCORTICOID ACTION
The principal action of mineralocorticoid is enhancement of
Na+ reabsorption in the distal convoluted tubule in kidney
There is increase in K + and H+ excretion.
29. On sodium metabolism
On ECF volume
On blood pressure
On Potassium ions
On Hydrogen ion concentration
On Intestine
30.
31. GLUCOCORTICOID ACTIONS
Carbohydrate Metabolism :
Promote gluconeogenesis.
Deposition of glycogen in liver.
Inhibits glucose utilization by peripheral tissues.
Blood glucose levels increased.
.
32.
33.
34. Protein Metabolism :
Catabolic in action.
Amino acid mobilized used in gluconeogenesis.
Excess urea produced.
Negative nitrogen balance
Increase uric acid excretion
35.
36. Fat metabolism :
mobilization of fat from the peripheral fat
depots.
Redistribution of fat in the body.
Increase the utilization of fats for energy.
37.
38. Electrolyte & Water Metabolism:
Causes sodium retention and potassium excretion.
Na retention causes water retention and edema.This may
rise in B.P.
K excretion causes wasting of muscles.
Calcium metabolism:
Inhibits intestinal absorption of calcium and enhance renal
excretion of calcium
There is also loss of calcium from bone indirectly due to
loss of osteoid.
39.
40.
41. Hematological Actions:
Increases number of RBC, Neutrophils, platelets.
Decreases in number of Lymphocytes, Eosinophils, and
basophils.
42.
43. Lymphoid Action :
Enhance the rate of destruction of lymphoid cells
Effect on normal lymphoid tissue is modest.
CNS :
Mood elevation seen.
Mild Euphoria.
44. CVS :
Glucocorticoids restricts capillary permeability, maintain
tone of arterioles and cardiac contractility.
They have a permissive effect on the pressor action of
Adrenaline and Angiotensin.
45.
46. Skeletal Muscles:
Optimum levels of corticosteroids are needed for normal
muscle activity.
Muscular weakness occurs in both Hypo and
Hypercorticism.
Excess glucocorticoid action- muscle wasting and myopathy
47.
48. Anti-Inflammatory effect:
Induction of lipocortins in macrophages, endothelium,
fibroblast.
Negative regulation of CycloOxygenase-2
Decrease of acute phase reactants from macrophages &
endothelial cells.
49.
50. Immunosuppressive action:
Decrease T cells
Decreased cell mediated immunity.
Supresses all type of hypersensitivity & allergic
phenomenon.
It is used to prevent graft rejection, auto immune diseases&
before organ transplants.
55. 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 :
• Hydrocortison
e 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
58. PREDNISONE: 1mg/ kg..If no improvement 20 mg
increments till better response.
Severe allergic reaction :
Anaphylaxis
Angioneurotic edema
PREDNISONE given large loading dose on first day
followed by diminishing doses for next 5 days
Life threatening – dexamethasone 8-12 mg IV
59. Autoimmune disease :
Hemolytic anemia
Thrombocytopenia
Active chronic hepatitis
PREDNISONE-1-2mg/kg/d given till remission followed
by gradual with drawl or low dose maintenance depending
up on response.
65. Intestinal Disease :
Ulcerative collitis
Chrons disease
Celiac disease
HYDROCORTISONE- 100 mg in mild cases.
PREDNISONE 10-30mg daily for 3 weeks in severe cases.
66. Infective Disease:
Steroids are administered along with antibiotics in serious
infective conditions to tide over crisis-
Severe form of tuberculosis
Severe lepra reaction
Bacterial meningitis
Pneumocystitis carnii pneumonia in AIDS
67. Cerebral Edema:
In edema caused due to tumors, Tuberculosis meningitis-
Dexamethasone and Betamethasone are preferred because
they don't have sodium retaining activity.
Bells palsy – 2-4 wks of oral prednisone
Multiple sclerosis- methyl prednisolone 1 g iv/d for 2-3
wks.
68. Malignancies:
Acute lymphatic leukemia
Non Hodgkin's lymphoma
Systemic relief in advanced malignancies by improving
appetite & secondary hypercalcemia.
Organ Transplantation & Skin Graft
High doses of corticosteroids(PREDNISONE 50-100mg)
are given along with other immunosuppressant to prevent
rejection reaction followed by low maintenance doses
69. Thyroid storm :
Patients in thyroid storm have concomitant adrenal
insufficiency.
Steroids reduce peripheral T4 to T3conversion
HYDROCORTISONE- 100 mg TDS improves outcome.
70.
71. DIAGNOSTICAPPLICATIONS
DEXAMETHASONE SUPPRESSION TEST :
Aim : This is to determine if patients suspected of
hypercorticism have biochemical evidence of increased
cortisol biosynthesis.
Procedure: patients are given 1mg of dexamethasone
orally at 11pm and cortisol is measured at 8 am the
following morning.
Result: suppression of plasma cortisol to <1.8 g/dl strongly
suggests that the patients doesn’t have cushings syndrome
or has intact HPAAXIS.
73. Dexamethasone is used as it doesn’t cross the blood barrier
and has a prolonged action(24hrs)
Synthetic steroids replaced natural
steroids :
Highly potent
Longer acting
Oral bioavailability is higher
Possibility to prepare esters suitable for topical application
and injection into tissues.
75. ADVERSE EFFECTS OF CORTICOSTEROIDS
Iatrogenic Cushing syndrome.
Increased susceptibility to infections.
Hyperglycemia, may be glycosuria, precipitation of diabetes.
Gain in weight due to fluid intension and fat deposition.
Muscular weakness due to potassium loss.
Delayed healing of wounds & surgical incisions.
Gastric irritation, erosion, ulceration, perforation
Osteoporosis, specially involving vertebrae
76. Steroids In Pregnancy :
Antenatal steroids lead to certain abnormalities in the fetal
development- ie. Cleft palate altered neuronal development
resulting in behavioural abnormalities.
Prolonged steroid therapy during pregnancy results in:
risk of gestational diabetes
pregnancy induced hypertension
preeclampsia
79. Hydrocortisone:
Orally given in replacement therapy.
In adults: 20-30 mg daily in 2 div doses.
In children: 400-800 mg/kg/day in 2 div.doses.
Intravenously given in emergency treatment.
In adults: 100-500mg 3-4 times daily.
In children: 50mg daily.
Inj HYCORT, LYCORTIN-S, MULTICORT.
82. Systemic Corticosteroids (oral, IM,IV):
Severe cases as pemphigus or excessive drug reaction-
intitial high dose are indicated & as the pathologic process
comes under control, then a gradual reduction in the dose of
medication may be made.
ADVANTAGES:
Minimizes HPA suppression.
Minimizes undesired tissue side effects.
83. INHALATIONAL CORTICOSTEROIDS:
Inhaled steroids have high topical and low systemic activity
Steroid inhalation is the first line therapy for chronic
asthma.
Mode of action- Anti-Inflammatory action.
Reduce bronchial hyper responsiveness
after exposure to allergen
84.
85. BECLOMETHASONE DIPROPIONATE:
A halogenated corticosteroid ester is used in pressurized
metered dose inhalation(MDI) which delivers 50mg of the
drug aerosol from each time.
Recommended 2-4 puffs 3-4 times a day.
BECLATE INHALER, BECLATE ROTACAPS
Budesonide( BUDICORT, PULMICORT).
Fluticasone ( OTRIVIN-C, FLOMIST spray).
86. Inhibitors Of Glucocorticoid Secretion:
Five pharmacological agents act as inhibitors of
adrenocorticoid secretion –
METYRAPONE,
AMINIGLUTETHIMIDE,
KETACONAZOLE,
TRILOSTANE,
MITOTANE.
88. Guide lines for topical steroids:-
Steroids are used locally as a spray, gel, or cream or as
mouthwash
Steroids need to be in contact with mucosa for atleast 3 min
on each application.
topical corticosteroids: orbase, cylactin, cynoacrylate,
bioadhesive patches
Made of cellulose derivatives, gels, and adhesive pastes.
89.
90. OROBASE:- adhesive paste, used as vehicle in TC
gelatin,
peptin,
and sodium carboxymethyl cellulose
Gel disadvantages- pain, secondary irritation by alcohol in
91. Steroid mouthwash:-
Made by dissolving a solution BETAMETHASONE
SODIUM PHOSPHATE(0.5mg) tablet in 10ml of water
and have to be held in mouth for 3min, before spitting out.
Used 2-3 times daily if required and should not be
swallowed because of risks of systemic absorption.
104. ADDISON’S DISEASE
Failure of adrenal cortex to secrete all the
corticosteroids
Primary Adrenal cause
Secondary Failure of anterior
pituitary to secrete ACTH
Tertiary Failure of hypothalamus
to secrete CRF
105. Pigmentation of skin and mucous membrane
Muscle weakness
Dehydration
Hypotension
Decreased cardiac output Hypoglycemia
Nausea, vomiting,
diarrhoea
Inability to withstand stress
106.
107. ADDISONS DISEASE
Common symptom of addison’s disease characterized
by sudden collapse associated with an increase in need
for large quantities of glucocorticoids.
Fatal if not treated in time
108. CONGENITAL ADRENAL HYPERPLASIA
Congenital disorder characterized by increase in
size of adrenal cortex.
Eventhough the size of the gland increases the
cortisol secretion decreases.
Congenital enzymes necessary for synthesis of
cortisol, particularly 21- hydroxylase.
109. In boys
Precocious body growth, causing stocky appearance
called infant Hercules.
Precocious sexual development with enlarged penis even
at age of 4 years.
In girls:
Produces Masculinization
Female child born with external genitalia of male type.
111. precautions
Before starting therapy:
Enquire and check for hypertension, diabetes
mellitus, peptic ulcer, any infection
112. 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
113. CORTICOSTEROIDS IN ORAL MEDICINE
Used primarily to decrease postoperative edema and manage oral inflammatory
diseases
115. Vesiculoerosive lesion
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.
117. 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.
118. BELLS 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.
122. 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
(Treatment of oral diseases, George Lascaris)
123. 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)
124.
125. HAEMANGIOMA
Intralesional triamcinolone acetonide (4 mg/mL)
(Hawkins et al)
Prednisone at a dose of 20-30mg/d can be given for 2
weeks to 4 months
( Fost and Esterly)
126.
127. 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
128.
129. ERYTHEMA MULTIFORMAE
It is immune mediated disease that may be initiated by
deposition of immune complex in the microvasculature
or cell mediated immunity
30mg-50mg of prednisone or methylprednisone for 6-8
wks
130.
131. RECURRENT APHTHOUS
ULCER
The causative agent could be endogenous( autoimmune)
antigen or exogenous( hyperimmune) antigen or it could
be a nonspecific factor, such as trauma in which
chemical mediators may be involved.
Topical flucinonide, betamethasone or chlobetasol
0.05% 2-3 times a day, prednisone 40mg/day tapered for
10 days.
132.
133. PEMPHIGUS
It is an autoimmune mucocutaneous disease characterized by
intraepithelial blister formation. This results from breakdown
or loss of intercellular adhesion, thus producing epithelial cell
separation known as acantholysis. Only in pemphigus
vulgaris and pemphigus vegetans involve the oral mucosa.
PulseTherapy:-dexamethasone-100mg3-4hrs+
cyclophosphamide 500mg on first day
Followed by dexamethasone alone on next 2 days.
Pulse repeated every 4 weeks.
134.
135. BEHCETS DISEASE
is a multi disease( gastrointestinal, cardiovascular,
ocular, CNS, articular, pulmonary.
Although the oral manifestations are usually relatively
minor, involvement of other sites, especially the eyes
and CNS can be quite serious
Prednisone 40mg/day tapered for 10days
136.
137. LICHEN PLANUS
Classified as reticular, atrophic, erosive, and bullous
forms.
Topical- Triamcinolone acetonide in 0.1% aqueous
suspension.
Chlobetasol proprionate ointment is more effective.
Twice weekly intralesional triamcilone acetonide of
0.5-1mg/ml.
Prednisone 30-60mg, daily once 2-3 weeks.
138.
139. DISCOID LUPUS
ERYTHEMATOUS
Prednisone 1mg/kg. if no improvement 20mg
increments till better response.
Therapy is started at a higher doses and tapered to
maintenance doses when remission occurs.
140.
141. RULE OF TWO
Rules of two 'was used as a management tool for dental health care
providers as the steroid cover protocol for patients who were
receiving replacement glucocorticosteroids.
The rule of two states that adrenal suppression may occur if a
patient is taking 20mg of cortisone or its equivalent daily, for 2
weeks within 2 years of dental treatment.
Adrenal cortical suppression should be suspected if a patient has
received glucocorticoid therapy
Malamed s. Medical Emergencies in the Dental office 5th
ed.St.Louis: Mosby:2000:149
142. CONCLUSION
The judicious use of corticosteroids is both
satisfying and life saving for the patient .
A word of caution is that these powerful
medications are double edged weapons and
always weigh risk versus benefit for the
patient and we have to keep in mind the long
term compromise that may precipitate.
143.
144. REFERENCES:-
K.D. Tripathi”essentials of medical pharmacology
Malamed s.f”Handbook of Medical Emergencies in Dental
Office 3rd edition
Burkets ‘Oral Medicine, Diagnosis and Treatment 12th
Edition
Pharmacology and therapeutics for Dentistry 5th edition
Yagiela, Dowd , Neidle
145. Goodman and Gilman's –
”Pharmacological Basis Of Therapeutics-
9th edition
Pharmacology and Therapeutics- Lange
Oral Pathology- Shafers
Medical physiology- Sembulingam
Textbook of Physiology- Tortora
Medicine - Davidson
152. • Innate immune response
– first line of defense against an antigenic insult. Includes
defenses like physical (skin),
Biochemical (complement, lysozyme, interferons)
cellular components (neutrophils, monocytes,
macrophages).
• Adaptive immune response
a) Humoral immunity - Antibody production –
killing extracellular organisms.
b) Cell mediated immunity – cytotoxic / killer T
cells – killing virus and tumour cells.
153. Innate
◦ Complement
◦ Granulocytes
◦ Monocytes/
macrophages
◦ NK cells
◦ Mast cells
◦ Basophils
Adaptive:
◦ B and T
lymphocytes
◦ B: antibodies
◦ T : helper,
cytolytic,
suppressor.
154.
155. ABNORMAL IMMUNE
RESPONSE
• Hypersensitivity reactions
Type 1 – Anaphylactic shock
Type 2 – mismatched blood transfusion
Type 3 – Serum Sickness,
glomerulonephritis
and arthritis.
Type 4 – TB, leishmaniasis.
156. AUTOIMMUNITY
– Autoimmune diseases arise
when the body mounts an immune response
against itself as a result of failure to
distinguish self tissues and cells from
foreign antigens.
Rheumatoid Arthritis, S.L.E, Type 1
Diabetes Mellitus, Multiple Sclerosis
etc….
• IMMUNODEFICIENCY DISORDERS
a) Congenital – Di George’s syndrome,
SCID due to ADA deficiency.
b) Extrinsic – HIV causing AIDS.
157.
158.
159.
160.
161. MECHANISMOF IMMUNOMODULATION
Drugs may modulate immune mechanism by either
suppressing or by stimulating one or more of the
following steps:
a) Antigen rcognition and phagocytosis
b) Lymphocyte proliferation and differentiation
c) Synthesis of antibodies
d) Ag-Ab interaction
e) Release of mediators due to immune response
f) Modification of target tissue response
162.
163.
164. Immunomodulation functional
assay
Immunotherapy, which aims at modulating immune
functions via targeting checkpoint receptors, has
revolutionized clinical treatment for cancer,
autoimmune diseases, etc.
The basic mechanism of such antibodies lies in their
ability to interact with immune checkpoint pathways
(both inhibitory and stimulatory).
This non-target-specific therapy also reveals
encouraging efficacy in combination with traditional
target-directed therapy, chemotherapy, and
radiotherapy.
165. Routine blood test (CBC).
Glycemic index
Sputum for AFB
TB Interferon gold test
Any special disease related test
LFT
RFT
166. INDICATIONS
When no response to corticosteroids
The cases where corticosteroids are contraindicated
Cases resistant to steroids
Recurrent cases
Cases with the previous history of severe adverse
effect with steroids
167. IMMUNOstimulants
This category of drugs is used to
overcome immunodeficiency or
immunosuppression arising as a result of
immune disorders.
CAUSES: chemotherapy,radiation, viral
infections.
170. Bacillus Calmette-Guerin Bacterial products Enhancement of B and T cell-mediated
responses
leading to phagocytosis, and resistance to infection.
Levamisole Drugs Induction of B and T lymphocytes, monocytes, and
macrophages
Thalidomide Drugs Therapeutic effects in rheumatoid arthritis and
angiogenesis 6
Recombinant cytokines Generation of interferons and interleukins to stimulate effective
immune responses
Immunocynin Drugs Treatment of urinary bladder cancer
Glucans Carbohydrates
Stimulation of anti-tumor mechanisms, and variety of microbial
pathogens in mammalian
Trehalose Carbohydrates
Production of antibody, stimulation of specific immunity against
different bacterial infections secretion of TNF-α in an animal
model.
Bestatin Enhancement of humoral and cellular immune responses, and
antitumor activitty of bleomycin and adriamycin
Chitosan Animals originated immunostimulants
Activating the production of cytokines such as IL-1β, TNF-α, and
reactive oxygen intermediates to promote the defense system
IMMUNOSTIMULANT MECHANISM OF ACTION
171. Prebiotics Plants originated immunostimulants for
Enhancement
of innate immune responses
a) Ocimum sanctum
b) Phyllanthus emblica
c) Azadirachta indica antifungal ,antioxidant and antiinfammatory
activities
d) Solanum trilobatum Antihuman immunodeficiency virus
antitumour and antibiotic
e) Eclipta alba antibiotic and anticancer activity
f) Zingiber officinale enhancement of phagocytic index ,
antibody tittre and WBC count.
g) Echinacea (purple coneflowers) and develop resistance to cold stress.
Allium sativum (garlic)
h)Camellia sinensis significant increase in proliferation of
neutrophils
macrophages and lymphocytes
i) Aloe vera
j) Cynodon dactylon
k) Achyranthes aspera
l) Nyctanthes arbortristis
m) Fermented vegetable product
n) Saffron
172. LEVAMISOLE
Antihelminthic
Restores depressed immune function of B, T cells,
Monocytes, Macrophages
USES:
Adjuvant therapy with 5FU in colon cancer
Used to treat immunodeficiency associated with
Hodgkins disease.
Toxicity
Agranulocytosis
173.
174. Tests done before administration
of Levamisole
Complete blood examination
Glycemic index
Kidney function test
175. Use in Oral Medicine
APHTHOUS ULCER
50mg/day with or without steroids.
LICHEN PLANUS
50-75mg/day for 3 months with 150 mg of prednisolone
MUCOUS MEMBRANE PEMPHIGOID
5-25 mg given weekly for 8-22 months
176.
177. Warts -levamisole 150 mg
tablets on 2 consecutive days a week
Herpes virus infection-
levamisole (2.5 mg/kg)
Cutaneous lieschmaniasis-
150 mg twice weekly
Leprosy- 150 mg daily for 3
consecutive days every 12 days
Lichen planus- levamisole 150 mg thrice weekly
Hiv infection- levamisole in a dose of 2 mg/kg/day
for 3 days each week for 24–52 weeks
Behcets disease-150 mg daily for 3 consecutive
days every week
179. THALIDOMIDE
Enhanced T-cell production of cytokines – IL-2, IFN-
γ
NK cell-mediated cytotoxicity against tumor cells
USE:
Multiple myeloma
Erythema nodosum leprosum
Sarcoidosis
Rheumatoid arthritis
ADVERSE EFFECTS
Teratogenecity
180.
181. Tests done before administration
of Thalidomide
Urine pregnancy test
CBC
LFT
RFT
TB test
B12 status
ECG
182. Use in Oral Medicine
RECURRENT APHTHOUS STOMATITIS
100-200 mg per day maintainence dose 50-100 mg
LICHEN PLANUS
1% paste applied 3 times per day for one week
Systemic dose 50-100 mg per day.
MYCOBACTERIAL INFECTION
100-300 mg per day given orally
HIV ASSOCIATED ORAL DISEASES
KAPOSI SARCOMA
-Hasan S, et al. Thalidomide: Clinical Implications in
Oral Mucosal Lesions - An Update. Ann Med Health Sci
Res. 2018;8:21-28
183.
184. DAPSONE
Widely used in the treatment of leprosy
USE IN ORAL MEDICINE
RECURRENT APHTHOUS STOMATITIS
100mg orally in divided doses , dose can be
increased 50 mg per week
MUCOUS MEMBRANE PEMPHIGOID
25 mg daily for 3 days, then 50 mg for three days, 75
mg for 3 days ….till 300 mg
LEPROSY
100mg per day
185. Tests done before administering
dapsone
Test for hypersensitivity
CBC
Glycemic index
187. Rho antibody
Antibodies against Rh(D) antigen on the surface of
RBC
prevent the immunological condition known as
Rhesus disease (or hemolytic disease of newborn).
treating chronic idiopathic thrombocytopenic
purpura in Rh-positive patients who have not been
splenectomized.
188. immunoadjuvants
Adjuvant is a substance that potentiates or
modulates the immune responses to an
antigen to improve them.
Adjuvants in immunology are used to
modify or augment the effects of vaccine
by stimulating the immune system to
respond to the vaccine more vigorously
189. MECHANISM OF ACTION OF
IMMUNOADJUVANTS
Translocation of antigens to the lymph nodes
Provide physical protection to antigens
Increase the capacity to cause local reactions
Induce the release of inflammatory cytokine
Increase the innate immune response to antigen
190. INORGANIC ADJUVANTS
ALUMINIUM SALTS
These augment the immunogenecity,
Aluminium phosphate
Aluminium hydroxide
MECHANISM OF ACTION
Trigger dendritic cells
Alum kills immune cells at the injection site.
191. ORGANIC ADJUVANTS
Squalene is an oil, made up of carbon and hydrogen
atoms, produced by plants and is present in many
foods.
MF59 is an oil-in-water emulsion of squalene adjuvant
used in some human vaccines.
Freund's complete adjuvant is a solution of
inactivated Mycobacterium tuberculosis in mineral oil
developed in 1930. A version without the bacteria,
that is only oil in water, is known as Freund's
incomplete adjuvant.
192. The plant extract QS21is a liposome made up of
plant saponins It is a part of the Shingrix vaccine
approved in 2017.
Monophosphoryl lipid A (MPL), a detoxified version
of Salmonella minnesota lipopolysaccharide, interacts
with TLR4 to enhance immune response.
204. Calcineurin inhibitors
Calcineurin (CN) is a protein phosphatase activates the
T cells of the immune system and can be blocked by
drugs.
CYCLOSPORIN
bind to the cytosolic protein cyclophilin (an
immunophilin) of immunocompetent lymphocytes,
especially T-lymphocytes. This complex of ciclosporin and
cyclophilin inhibits the phosphatase calcineurin, which
under normal circumstances induces the transcription of
interleukin-2.
The drug also inhibits lymphokine production and
interleukin release, leading to a reduced function of
effector T-cells.
208. TACROLIMUS
It binds to the immunophilin FKBP1A, followed by
the binding of the complex to calcineurin and the
inhibition of its phosphatase activity.
In this way, it prevents the cell from transitioning
from the G0 into G1 phase of the cell cycle.
209. USES
Prophylaxis of solid-organ allograft rejection
–Topical preparation available for use in atopic
dermatitis and psoriasis.
210. ADVRSE EFFECTS
Growth retardation
Avascular Necrosis of Bone
Risk of Infection
Poor wound healing
Cataract
Hyperglycemia
Hypertension
211. In Oral Medicine
RECURRENT APHTHOUS ULCERS
Topical cyclosporine 100mg/ml for moderate cases.
Systemic cyclosporine 3-6 mg/kg/day for chronic cases.
LICHEN PLANUS
Mouth rinse 5 ml of medication three times daily (500-1500mg
/day).
In a bioadhesive patch 100mg/ml added to alcohol phase of zilactin
to a final conentration of 0.5 mg/dl.
MUCOUS MEMBRANE PEMPHIGOID
100mg/ml is given once a day.
212.
213. SIROLIMUS
sirolimus affects the signal transduction and
lymphocyte clonal proliferation.
It binds to FKBP1A like tacrolimus, however the
complex does not inhibit calcineurin but another
protein, mTOR (mammalian target of rapamycin ).
214. It indirectly inhibits several T lymphocyte-specific
kinases and phosphatases, hence preventing their
transition from G1 to S phase of the cell cycle.
Sirolimus prevents B cell differentiation into plasma
cells, reducing production of IgM, IgG, and IgA
antibodies.
215.
216.
217. Uses
Prophylaxis of organ transplant rejection with other
drugs
Toxicity
Increase in serum cholesterol, Triglycerides
Anemia
Thrombocytopenia
Hypokalemia
Fever
GI effects
Risk of infection, tumors
218. AZATHIOPRINE
It is the main immunosuppressive cytotoxic substance. It is
nonenzymatically cleaved to mercaptopurine, that acts as a
purine analogue and an inhibitor of DNA synthesis.
By preventing the clonal expansion of lymphocytes in the
induction phase of the immune response, it affects both the
cell and the humoral immunity.
Uses
Prevention of organ transplant rejection
Rheumatoid arthritis
219.
220. ADVERSE EFFECTS
Bone marrow suppression- leukopenia,
thrombocytopenia, anemia
Increased susceptibility to infection
Hepatotoxicity
Alopecia
GI toxicity
221. Use in Oral Medicine
RECURRENT APHTHOUS STOMATITIS
1 to 2 mg/kg/day
started with 50 mg/day and escalated till 150/day.
• LICHEN PLANUS
50 mg twice daily orally for a period of 3 to7 months.
PEMPHIGUS VULGARIS
0.5 mg -4 mg/kg depending on thiopurine metyltransferase
levels.
MUCOUS MEMBRANE PEMPHIGOID
1-2 mg/kg/day
SYSTEMIC LUPUS ERYTEMATOSUS
1-2 mg/kg/day
222. MYCOPHENOLATE MOFETIL
Prodrug Mycophenolic acid
Inhibits IMPDH – enzyme in guanine synthesis (Inosine
monophosphate dehydrogenase (IMPDH) is a major target for
both antitumor and immunosuppresive drug design.)
T, B cells are highly dependent on this pathway for cell
proliferation
Selectively inhibits lymphocyte proliferation, function ,
Antibody formation, cellular adhesion, migration
227. ANTITHYMOCYTE GLOBULIN
Purified gamma globulin from serum of rabbits
immunized with human thymocytes
Cytotoxic to lymphocytes & block lymphocyte
function
Uses
Induction of immunosuppression – transplantation
Treatment of acute transplant rejection
Toxicity
Hypersensitivity
Risk of infection, Malignancy
228. ANTI CD3 MONOCLONAL ANTIBODY
Binds to CD3, a component of T-cell receptor
complex involved in
◦ antigen recognition
◦ cell signaling & proliferation
229. USES
Treatment of acute organ transplant rejection
ADVERSE EFFECTS
“Cytokine release syndrome”
High fever, Chills, Headache, Tremor, myalgia,
arthralgia, weakness
Prevention: Steroids
230. ANTI IL-2 RECEPTOR ANTIBODIES
Daclizumab and Basiliximab )
Bind to IL-2 receptor on surface of activated T cells
Block IL-2 mediated T-cell activation
Uses
Prophylaxis of Acute organ rejection
Toxicity
Anaphylaxis, Opportunistic Infections
231. ANTI TNF ANTIBODIES
TNF – Cytokine at site of inflammation
Infliximab
Etanercept
Adalimumab
232.
233. LFA-1 INHIBITOR
Monoclonal Ab Targeting Lymphocyte Function
Associated Antigen
Blocks T-cell Adhesion, Activation, Trafficking
Uses
Organ transplantation
Psoriasis
234.
235.
236. CONCLUSION
Immunology plays a very important role in
homeostasis but it possesses two edge sword actions.
Either decrease or increase can cause systemic
diseases which will manifest in the oral cavity.
Immunomodulatory drugs are the agents which
modulate the body immunity according to the need.
There are natural and synthetic immunomodulatory
agents.
237. Immuno refers to immune response, immune system,
and modulation is the act of modifying or adjusting
according to due measure and proportion .
Immunomodulators modulate the immune reaction
and decrement inflammatory replication.
238. Immunology is probably one of the most rapidly
developing areas of medical research and has great
promises with regard to the prevention and
treatment of a wide range of disorders of the oral
cavity.
Immunomodulators are going to be a core part of the
next generation clinical medicine. Helping the body
help itself by optimizing the immune system is of
central importance in a society so stressed,
unhealthily nourished and exposed to toxins that
most of us are likely to have compromised immune
systems.
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Burkets ‘Oral Medicine, Diagnosis and
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Yagiela, Dowd , Neidle
240. Goodman and Gilman's –
”Pharmacological Basis Of Therapeutics-
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