Corticosteroids have both mineralocorticoid and glucocorticoid actions. Mineralocorticoid action increases sodium reabsorption leading to fluid retention and hypokalemia. Glucocorticoid actions include increased blood glucose through gluconeogenesis and breakdown of proteins and fats. Short acting corticosteroids include hydrocortisone and prednisolone while dexamethasone and betamethasone are long acting. Adverse effects include fluid retention, skin thinning, infections, and bone loss. Corticosteroids are used to treat inflammation, autoimmune diseases, and cancers. Contraindications include peptic ulcer and infections. In dentistry, corticosteroids can treat oral

1. Corticosteroids
Dr.Deepak Daniel

2. Outline for today’s session
Introduction
Actions of corticosteroids
Pharmacokinetics
Distinctive features
Adverse effects
Uses
Contraindications
Dental implications

3. Introduction
‘Corticosteroid’ or ‘corticoid’ includes natural gluco- and mineralocorticoids and
their synthetic analogues.
21 carbon compounds having a cyclopentanoperhydro-phenanthrene (steroid)
nucleus.
Synthesized in the adrenal cortical cells from cholesterol.
Adrenal steroidogenesis takes place under the influence of ACTH which is under
negative feed back regulation by circulating cortisol level .
The normal rate of secretion of the two principal corticoids in man is—
Hydrocortisone (cortisol) — 1 0 - 2 0 m g d a i l y (nearly half of this in the few
morning hours). Aldosterone — 0.125 mg daily

5. Actions of corticosteroids
Glucocorticoid
action
Mineralocorticoid
action

6. Mineralocorticoid Action
Aldosterone is the natural mineralocorticoid.
Increased Na+ reabsorption DCT  associated with increased
K+ and H+ excretion is the principal mineralocorticoid action.
Excess of this action leads to Na+ and water retention, edema,
progressive rise in BP, hypokalaemia and alkalosis.
Mineralocorticoid deficiency results in progressive Na+ loss →
dilutional hyponatraemia → cellular hydration → decreased
blood volume. Hyperkalaemia and acidosis accompany.

7. Glucocorticoid actions
1.Carbohydrate
and protein
metabolism
Glucocorticoids
promote glycogen
deposition in liver
by inducing hepatic
glycogen
synthetase and
promoting
gluconeogenesis.
They inhibit
glucose utilization
by peripheral
tissues. This along
with increased
glucose release
from liver results in
hyperglycaemia,
resistance to
insulin and a
diabetes-like state.

8. • Glucocorticoids also promote protein breakdown
and amino acid mobilization from peripheral
tissues which is responsible for side effects like
muscle wasting, lympholysis, loss of osteoid from
bone and thinning of skin.
• The amino acids so mobilized funnel into liver and
are used up in gluconeogenesis, excess urea is
produced resulting in negative nitrogen balance.
• Glucocorticoids are thus catabolic.
• Their function appears to be oriented to
maintaining blood glucose levels during starvation—
so that brain continues to get its nutrient.
• Corticosteroids increase uric acid excretion.
Protein
metabo
lism

9. 2. Fat metabolism
• Corticoids promote lipolysis.
• Redistribution of body fat occurs.
• Subcutaneous tissue over
extremities loses fat which is
deposited over face, neck and
shoulder.
• characteristic ‘moon face’, ‘fish
mouth’, ‘buffalo hump’.
3. Calcium
metabolism
• Cortisol inhibits intestinal
absorption and enhances renal
excretion of Ca2+.
• Loss of osteoid indirectly
contributes to loss of Ca2+ from
bone producing osteoporosis.
• Spongy bones (vertebrae, pelvis,
ribs, etc.) are more sensitive.

10. • Glucocorticoids, but not
aldosterone, maintain g.f.r. and
help excreting excess water
load.
4. Water
excretion
• Glucocorticoids restrict capillary
permeability.
• Maintain tone of arterioles and
myocardial contractility.
• Permissive role in the
development of hypertension.
5. CVS

11. • Weakness occurs in both hypo- and hypercorticism,
but the causes are different.
• Hypocorticism: diminished work capacity and
weakness are primarily due to hypodynamic
circulation.
• Hypercorticism: excess mineralocorticoid action →
hypokalaemia → weakness; Excess glucocorticoid
action → muscle wasting and myopathy → weakness.
6. Skeletal
muscles
• Mild euphoria is quite common with
supraphysiological doses of glucocorticoids.
• This sometimes progresses to cause insomnia,
anxiety or depression as side effect of
corticosteroid therapy.
7. CNS

12. • Secretion of gastric acid and
pepsin is increased—may
aggravate peptic ulcer.
8.
Stomach
• Glucocorticoids enhance the rate of
destruction of lymphoid cells (T cells
are more sensitive than B cells).
• A marked lytic response is shown by
malignant lymphatic cells.
• Corticosteroids are palliative in
lymphomas.
9.
Lymphoid
tissue

13. 10. Inflammatory responses
This is the basis of most of their clinical uses.
The action is direct and can be restricted to a site by local application. The cardinal signs
of inflammation—redness, heat, swelling and pain are suppressed.
Most important overall mechanism appears to be limitation of recruitment of
inflammatory cells at the local site.
Production of PGs and several other mediators of inflammation like LTs, PAF, TNFα and
cytokines is interfered.
Glucocorticoids induce formation of anti-inflammatory protein called annexins.
Corticoids are only palliative, do not remove the cause of inflammation.
They favour spread of infections because capacity of defensive cells to kill microorganisms
is impaired.
They also interfere with healing and scar formation: peptic ulcer may perforate
asymptomatically

14. 11. Immunological and allergic responses
Glucocorticoids impair immunological competence.
Suppress all types of hypersensitization and allergic phenomena.
Suppression of recruitment of leukocytes at the site of contact
with the antigen, and of inflammatory response to immunological
injury.
Greater suppression of cell mediated immunity (CMI) in which T
cells are primarily involved, e.g. delayed hypersensitivity and
graft rejection.
This is the basis of use in autoimmune diseases and organ
transplantation.

15. Mechanism of action at cellular level
Corticosteroids penetrate cells and bind to a high affinity cytoplasmic receptor protein
→ a structural change occurs in the steroid-receptor complex that allows its migration
into the nucleus and binding to the glucocorticoid response elements (GRE) on the
chromatin → transcription of specific m-RNA → regulation of protein synthesis.
This process takes at least 30-60 min. Therefore, effects of corticosteroid are not
immediate, and once the appropriate proteins are synthesized—effects persist much
longer than the steroid itself.
In many tissues, the overall effect is catabolic, i.e. inhibition of protein synthesis. This
may be a consequence of steroid directed synthesis of an inhibitory protein.
The glucocorticoid receptor (GR) is very widely distributed (in practically all cells of
the body). Therefore, effects of corticosteroids are widespread.

17. Pharmacokinetics
All natural and synthetic corticoids are absorbed by the oral route. Hydrocortisone
undergoes high first pass metabolism. Therefore, it has low oral: parenteral activity ratio.
Oral bioavailability of synthetic corticoids is high. Hydrocortisone is 90% bound to plasma
protein, mostly to a specific cortisol-binding globulin (CBG or transcortin) as well as to
albumin.
The steroids are metabolized primarily by hepatic microsomal enzymes. The metabolites are excreted in
urine. The plasma t½ of hydrocortisone is 1.5 hours. However, biological effect t½ is longer because of
action through intracellular receptors and regulation of protein synthesis—effects that persist long after
the steroid is removed from plasma.
The synthetic corticosteroids are more resistant to metabolism and are longer acting.
Phenobarbitone and phenytoin induce metabolism of hydrocortisone, prednisolone and dexamethasone,
etc. to decrease their therapeutic effect

19. Distinctive features
• In addition to primary glucocorticoid, it has
significant mineralocorticoid activity with
rapid and short lasting action.
1.
Hydrocortisone
(cortisol)
• 4 times more potent than hydrocortisone.
• More selective glucocorticoid, but fluid retention
does occur with high doses.
• Intermediate duration of action
• Less pituitary-adrenal suppression when a single
morning dose or alternate day treatment is given.
• It is used for allergic, inflammatory, autoimmune
diseases and in malignancies.
2. Prednisolone

20. • Slightly more potent and more selective than
prednisolone.
• Pulse therapy with high dose methylprednisolone
(1 g infused i.v. every 6–8 weeks) has been tried
in nonresponsive active rheumatoid arthritis,
renal transplant, pemphigus, etc.
3.
Methylprednisol
one
• Slightly more potent than prednisolone but
highly selective glucocorticoid
4.
Triamcinolone

21. •Very potent and highly selective glucocorticoid.
•Long acting, causes marked pituitary-adrenal suppression,
but fluid retention and hypertension are not a problem.
•It is used for inflammatory and allergic conditions, shock,
cerebral edema, etc.
5.
Dexamethasone
• Similar to dexamethasone.
• Dexamethasone or betamethasone are preferred in
cerebral edema and other states in which fluid
retention must be avoided.
6.
Betamethasone
•It is a highly selective glucocorticoid, dose-to-dose slightly
less potent than prednisolone, but lacks mineralocorticoid
activity.
•It is claimed to produce fewer adverse effects and less
growth retardation in children.
7. Deflazacort

22. Adverse effects
• Sodium and water retention, edema,
hypokalaemic alkalosis and a progressive rise in
BP is a consequence of mineralocorticoid action.
• This is infrequent now, because more selective
glucocorticoids are generally used.
• Gradual rise in BP occurs due to excess
glucocorticoid action as well.
Minera
locorti
coid

23. B. Glucocorticoid
1.Cushing’s habitus characteristic appearance with rounded face, narrow
mouth, supraclavicular hump, obesity of trunk with relatively thin limbs.
2.Fragile skin, purple striae—easy bruising, telengiectasis, hirsutism.
Cutaneous atrophy occurs with topical application of the steroid as well.
3.Hyperglycaemia, precipitation of diabetes.
4.Muscular weakness, especially of proximal limb muscles; myopathy occurs
occasionally.
5.Susceptibility to infection; opportunistic infections with low-grade
pathogens (Candida, etc.).

24. 6. Delayed healing of wounds.
7. Peptic ulceration.
8. Osteoporosis Specially involving vertebrae and other flat spongy
bones.
9. Growth retardation in children occurs even with small doses if given
for long periods.
10. Foetal abnormalities cleft palate and other defects are produced in
animals, but have not been encountered in pregnant women.
11. Psychiatric disturbances.

26. 12. Suppression of hypothalamo-pituitary adrenal (HPA) axis
occurs depending both on dose and duration of therapy. In time, adrenal cortex atrophies and stoppage
of exogenous steroid precipitates a withdrawal syndrome producing malaise, anorexia, nausea, postural
hypotension, weakness, etc. and reactivation of the disease.
Subjected to stress, these patients may go into acute adrenal insufficiency.
Any patient who has received > 20– 25 mg/ day hydrocortisone or equivalent such as ≥ 5 mg
prednisolone/day for longer than 2–3 weeks should be put on a scheme of gradual withdrawal.
Such patients may need protection with steroids if a stressful situation develops up to one year after
withdrawal.
If a patient on corticosteroid therapy develops an infection—the steroid should not be discontinued
despite its propensity to weaken host defence. Rather, the dose may have to be increased to meet the
stress of the infection

27. • Use shorter acting steroids (hydrocortisone,
prednisolone) at the lowest possible dose.
• Use steroids for the shortest period of time
possible
• Give the entire daily dose at one time in the
morning.
• Switch to alternate-day therapy if the
condition does not deteriorate on the ‘off’ day.
• If appropriate, use local (dermal, inhaled,
ocular, nasal, buccal, rectal, intrasynovial)
preparations
Measures
that
minimise
HPA axis

28. Uses
Systemic as well as topical corticosteroids have one of the
widest spectrum of medical uses for their anti-inflammatory
and immunosuppressive properties. They are powerful drugs.
Potential to cause dramatic improvement in many severe
diseases, but can produce equally serious adverse effects.

29. 1.Collagen and autoimmune diseases, e.g. systemic lupus
erythematosus, polyarteritis nodosa, nephrotic syndrome,
glomerulonephritis, rheumatoid arthritis, rheumatic fever
2. Severe allergic reactions: anaphylaxis, angioneurotic edema, urticaria,
serum sickness.
3. Bronchial asthma: majority of cases are treated with inhaled
steroids. Other lung conditions  pulmonary edema, aspiration
pneumonia, allergic rhinitis. Dexamethasone/betamethasone given to
pregnant women before premature delivery, prevent respiratory
distress syndrome in the neonate.
4. Eye diseases: allergic conjunctivitis, iridocyclitis, keratitis, uveitis,
retinitis, optic neuritis, etc.

30. 5. Skin diseases: mostly topical use in dermatitis; systemic steroids are
needed in pemphigus vulgaris, exfoliative dermatitis, Stevens-Johnson
syndrome and other serious disorders
6. Inflammatory bowel disease: ulcerative colitis, Crohn’s disease.
7. Infective diseases: only in serious/life threatening infective diseases
under effective antimicrobial cover, e.g. in bacterial/tubercular
meningitis, miliary tuberculosis, severe lepra reaction, etc

31. 8. Neurological conditions: like cerebral edema due to tubercular meningitis/
cerebral tumours, Bells’ palsy, neurocysticercosis.
9. Malignancies: acute lymphatic leukaemia, Hodgkin’s disease, lymphomas, etc.
10. Nausea and vomiting: Dexamethasone injected i.v. is used to augment the
antiemetic effect of ondansetron against cancer chemotherapy induced vomiting.
11. Renal and other organ transplantation, skin allograft.
12. Substitution therapy in acute and chronic adrenal insufficiency and congenital
adrenal hyperplasia.

32. Contraindications
1.Peptic ulcer
2. Diabetes mellitus
3. Hypertension
4. Viral and fungal infections
5. Tuberculosis and other
infections
6. Osteoporosis
7. Herpes simplex keratitis
8. Psychosis
9. Epilepsy
10. CHF
11. Renal failure.

33. Implications In Dentistry
Application of corticosteroids in dental conditions is rather limited.
Recurrent oral ulceration may be treated with topical steroids, but maintaining
long enough contact between the steroid and the oral lesion is often difficult.
Severe oral lesions like pemphigus, erosive lichen planus, etc. need to be
treated with systemic corticosteroids.
Pain from exposed dental pulp is occasionally treated with locally applied steroids.
Intraarticular hydrocortisone may be injected in the temporomandibular joint to
relieve refractory pain and stiffness.
Only rarely a corticosteroid is needed to suppress pain and swelling due to dental surgery,
(e.g. impacted third molar extraction), for which NSAIDs are the first line drugs.

34. In the case of patients who are/have been in recent
past on long-term corticosteroid therapy, consideration
has to be given to the need for supplementary
prophylactic corticoid to cover a dental procedure.
In general, simple extractions and other mildly
traumatic surgeries do not warrant additional steroid
dose.
For traumatic procedures and those to be performed under general anaesthesia,
supplementary steroids may be needed, particularly if the dose and duration of
steroid therapy are such as to have caused significant adrenal suppression, or the
patient is excessively anxious. Monitoring of BP of such patients during surgery is
required. In case BP falls, hydrocortisone should be injected i.v. immediately.

35. Common oro-dental conditions
Aphthous ulcer
Pulp capping
Pulp pulpotomy
Post extraction of tooth
Temporomandibular arthritis
Desquamative gingivitis
Oral lichen planus
Oral Pemphigus
Oral submucosal fibrosis

36. Summarize
Actions of corticosteroids?
Mineralocorticoid action?
Glucocorticoid action?Short and long acting ?
Adverse effects ?
Uses?
Contraindications?
Dental implications?