Pharmacology Lecture Slides on Corticosteroids by Sanjaya Mani Dixit Assistant Professor of Pharmacology at Kathmandu Medical College

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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