Corticosteroids, predominantly glucocorticoids like cortisol, are steroid hormones crucial for various physiological processes, including inflammation regulation and metabolism, released by the adrenal cortex. They are synthesized on demand and exert effects by binding to glucocorticoid receptors, influencing gene transcription and protein synthesis. Therapies utilizing synthetic glucocorticoids aim to manage inflammatory conditions, suppress immune responses, and ensure appropriate hormonal replacement while considering potential side effects and withdrawal protocols.

1. CORTICOSTEROIDS
Sanjaya Mani Dixit
Assistant Prof of Pharmacology

2. Corticosteroids
• Corticosteroids are a class of steroidal
hormones released by the adrenal cortex,
which includes
– Glucocorticoids, &
– Mineralocorticoids.
• However, the term “corticosteroids” is
generally used to refer to glucocorticoids.

3. Glucocorticoids
• Glucocorticoids are primary stress hormones that regulate a
variety of physiologic processes and are essential for life.
• The actions of glucocorticoids are predominantly mediated
through glucocorticoid receptor (GR).
• A diverse collection of receptor isoforms have been identified.
• Glucocorticoids regulate diverse cellular functions:
– development,
– homeostasis,
– metabolism,
– cognition and
– Inflammation.

4. Glucocorticoids
• Glucocorticoids (cortisol in man and corticosterone in rodents)
are steroid hormones synthesized and released by the adrenal
glands in a circadian manner, in response to physiological cues
and stress.
* Cortisol when used as medication is k/a Hydrocortisone.
• Due to its lipophilic nature, glucocorticoids cannot be pre-
synthesized and stored in adrenal glands, but have to be rapidly
synthesized (using a number of enzymatic reactions) upon ACTH
stimulation.
• Biologically active glucocorticoids are synthesized from cholesterol
through a multienzyme process termed steroidogenesis.

5. Steroids
• Steroid: A group of compound, having a
common structure based on the steroid
nucleus.
• For examples:
– Sex hormones [androgen and estrogens],
– Hormones of the adrenal cortex [cortisone].

6. Corticosteroids
• ACTH is secreted by anterior pituitary under the
influence of CRH on hypothalamus
• The adrenal cortex secretes several hormones:
• Zona glomerulosa -Mineralocorticoids - Aldosterone
• Zona fasciculata -Glucocorticoids - Cortisol
• Zona reticularis -Androgens

7. Corticosteroid Synthesis

8. -Steroids-
Normal rates of secretion of
two principal corticoids in
man:
Cortisol
10-20 mg daily
(almost half in few morning
hours)
Aldosterone
0.125mg/day
• Corticosteroids
• Hydrocortisone
• Prednisolone
• Dexamethasone
• Beclomethasone
• Budesonide
• Fluticasone

9. Basal secretions
Group Hormone Daily
secretions
Glucocorticoids • Cortisol
• Corticosterone
5 – 30 mg
2 – 5 mg
Mineralocorticoid
s
• Aldosterone
• 11- Deoxycorticosterone
5 – 150 mcg
Trace
Sex Hormones
•Androgen
•Progestogen
•Oestrogen
• DHEA
• Progesterone
• Oestradiol
15 – 30 mg
0.4 – 0.8 mg
Trace
From Essential of Pharmacotherapeutics, ed. FSK Barar. P
.351

10. Steroids-MOA

11. Steroids-MOA
• Corticosteroids penetrate cells and bind to a high affinity cytoplasmic
receptor protein (large multi-protein complex ).
• On binding ligand GR undergoes a conformational change, resulting in
the dissociation of the multi-protein complex.
• The ligand bound GR is rapidly translocated into the nucleus through
nuclear pores.
• Then there is binding to glucocorticoid response elements (GRE)
on the chromatin.
• Transcription of specific m-RNA & Regulation of protein synthesis
• Onset of action takes at least 30-60 min: 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.

12. Effects of Corticosteroids

13. Pharmacological Actions
• The corticoids have widespread actions.
• They maintain fluid-electrolyte, cardiovascular
and energy substrate homeostasis and
functional status of skeletal muscles and nervous
system.
• They prepare the body to withstand effects of all
kinds of noxious stimuli and stress.

14. Stress and The Adrenal Glands

15. Carbohydrate, protein & lipid metabolism
• Wasting of muscles
• Increased Gluconeogenesis
• Decreased Peripheral utilization of glucose
• Increased Glycogen deposition in liver
• Redistribution of Fat
• Buffalo hump
• Moon face
• Promote adipokinetic agents activity
(glucagon, growth hormone, adrenaline, thyroxine)
Negative nitrogen balance & hyper-
glycemia

16. Electrolyte and water balance
• Aldosterone is more important
• Act on D.T. & C.D. of kidney
– Increased Na+
re-absorption
– Increased Urinary excretion of K+
and H+
• Addison’s disease (Decreased Aldosterone Levels)
– Na+
loss
– Shrinkage of ECF
– Cellular hydration
– Hypodynamic state of CVS
– Circulatory collapse,
– Renal failure, death

17. Cushing’s Syndrome

18. • Decreased Recruitment of WBC & monocyte-
macrophage into affected area & increase of
chemotactic substances
• Decreased TNF from phagocytic cells
• Decreased IL1 from monocyte-macrophage
• Decreased Formation of Plasminogen Activator
• Decreased Action of MIF (Migration Inhibiting factor) &
decreased fibroblastic activity
• Decreased Expression of cyclooxygenase II
Actions: Anti-inflammatory

19. Immunosuppressive & anti-allergic actions
• Suppresses all types of hypersensitivity &
allergic phenomenon
• At High dose: Interfere with all steps of
immunological response
• Causes greater suppression of CMI (graft
rejection & delayed hypersensitivity)
• Transplant rejection: Decreased antigen expression
from grafted tissues, delay revascularization,
decreased sensitization of T lymphocytes etc.

20. • Inhibit cell division or synthesis of DNA
• Delay the process of healing
• Retard the growth of children
• Cause peptic ulcerations on prolonged exposure
Actions: Growth & Cell divi-
sion

21. Pharmacological Actions
• For most clinical purposes, synthetic
glucocorticoids are used because they have a
higher affinity for the receptor, are less
activated and have little or no salt-retaining
properties.
• Hydrocortisone orally for replacement
therapy, i.v. for shock and asthma, topically for
eczema (ointment) and enemas (ulcerative
colitis).
• Prednisolone the most widely used drug given
orally in inflammation and allergic diseases.

22. Pharmacological Actions
• Betamethasone and dexamethasone: very
potent, w/o salt-retaining properties; thus,
very useful for high-dose therapies (e.g.,
cerebral edemas).
• Beclometasone diproprionate, budesonide:
pass membranes poorly; more active when
applied topically (severe eczema for local anti-
inflammatory effects) than orally; used in
asthma, (aerosol).
• Triamcinolone: used for severe asthma and for
local joint inflammation (intra-articular inj.).

23. Uses
• Corticosteroids are used:
· To reduce inflammation (asthma, arthritis) and swelling
(cerebral oedema)
· To suppress the immune response SLE (systemic lupus
erythematosus)
· To reduce nausea and vomiting (as in cancer chemo-
therapy)
· To reduce terminal pain (associated with cancer)
· As replacement therapy (in Addison’s disease)

24. Unwanted Effects
Metabolic:
– growth suppression
– diabetes mellitus
– muscle wasting
– osteoporosis
– fat redistribution
– Hirsutism
– Acne
– hypertension
– hypokalaemia
– menstrual irregularities
Other:
– infection
– emotional disturbances
(psychosis, depression, mania)
– cataract, glaucoma
– GI bleeding, perforation
Withdrawal symptoms:
– Addisonian crisis
– raised ICP
– Arthralgia/myalgia
– Pustular rash

26. Avoiding unwanted effects
of corticosteroids
• Modification of dose/dose regimen
· Use short courses/low doses if possible
· Use steroid sparing drugs
· Withdraw chronic’ steroids slowly
· Give dose once daily and in morning
· Give on alternate days if possible
· Give prophylactics if possible
· Give product locally
· Remember contraindications

27. Giving products locally can
still cause problems!
• systemic dosing can occur
• local toxicity can develop -
–skin: infection, thinning, bruising.
–eye: viral infection, cataract, glaucoma.
–inhalation: fungal infection, hoarseness
–joints: infection, necrosis

28. Tapering of Corticosteroid Therapy
It is extremely important that these drugs not be
omitted or discontinued suddenly, the dose is slowly
reduced to a minimal dose and then it is stopped.

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