Glucocorticoids have physiological and pharmacological actions. Physiologically, they help the body respond to stress through metabolic effects like increasing blood sugar and breaking down proteins. Pharmacologically, high doses have anti-inflammatory, immunosuppressive, and antiproliferative effects. Glucocorticoid deficiency can cause respiratory distress syndrome in infants due to lack of surfactant in the lungs, while excess has side effects like Cushing's syndrome, osteoporosis, diabetes, and adrenal suppression. Long term glucocorticoid use requires slow withdrawal to avoid adrenal insufficiency.

2. Topic
Glucocorticoid
Presented by : Abdul Qahar buneri
AWKUM (Buner Campus)

3. Glucocorticoid action
physiological and pharmacological action
• Physiological action
Small doses correct the metabolic abnormalities
in part directly, in part by permitting other
reactions to occur :
Permissive action - the requirement for g.to be
present for catecholamines to exert their effects
(pressor response, bronchodilation)

4. Physiological action
• Intermediary metabolism:
Increased protein catabolism
Increased hepatic glycogenesis (glycogen
synthesis) and glyconeogenesis
decreased utilisation of glucose by muscle
• resistance to „Stress“

5. Physiological action
Hyperglycemia, catabolic and antianabolic
Hyperglycemia
effects
G.increase
serum glucose concentrations
(gluconeogenesis)
(and thus stimulates insulin release) and inhibits the
uptake
of glucose by muscle cells.
The increased insulin secretion stimulates lipogenesis.
All contributes to maintenance of an adequate supply to
the brain

6. Pharmacological action
At high doses:
Antiinflammatory (acute and chronic inflammation)
Immunosuppressive
Antiallergic
Antiproliferative

7. Antiinflammatory action
G.dramaticaly reduce the manifestation of inflammation due
to their profound effects on the concentration, distribution, and
function of peripheral leukocytes and to their suppressive effects
on the inflammatory cytokines and chemokines, and on the
mediators of inflammation.
The concentrations of neutrophils in the circulation increases
while the lymphocytes (T and B cells), monocytes, eosinophils
and basophils decrease. The changes are maximal in 6 hours
and are dissipitated in 24 h after a high (pharmacological) dose.
Function of tissue macrophages is inhibited.
G.cause vasoconstriction,and decrease capillary
permeability by reducing the amount of histamine released
by mast cells.

8. Doses physiological/pharmacological
• Cortisol secretion in a healthy human
Daily secretion at rest: 20-40 mg
secretion in stress: >100 mg
Cortisol 10-30 mg/day in two or three decreasing doses
15-10-5 mg (15-10 mg , 10-5 mg)
Synthetic corticosteroids that are long-acting and devoid of saltretaining activity should not be used.

9. IRDC and surfactant
• a lipid surface-tension-lowering agent
is a mixture of dipalmitoylphosphatidylcholine, other lipids, and
proteins the fluid lining the alveoli. If the surface tension is not
kept low when the alveoli become smaller during expiration,
they collapse - atelectasis. S. also helps to prevent
pulmonary edema.
S is produced by type II alveolar epithelial cells and is important
at birth.The lungs remain collapsed until birth.After birth, the
infant makes several movements and the lung expands. S.
keeps them from collapsing again.
S.deficiency is an important cause of
infant respiratory distress syndrome (IRDS) that develops
in infants born before their surfactant system is functional.

10. IRDC and surfactant
• Therapy:
Surfactant preparations derived from bovine lungs and
synthetic surfactant for use by inhalation
are used profylactically at birth to decrease the severity of IRDS
but not the incidence of chronic lung disease in suvivors.
Maturation of surfactant in the lungs is accelerated by
glucocorticoid hormones. The lungs are rich in
glucocorticoid receptors. Betamethasone 12 mg i.m
Patchy atelectasis is also associated with s. deficiency in
adults who have gone cardiac surgery involving use of a
pump oxygenator and interruption of the pulmonary
circulation. Abnormalities that develop following occlusion of a
main bronchus, occlusion of one pulmonary artery…..ARDS

11. Glucocorticoid excess (pharmacol.
•
•
•
•
•
•
•
therapy)-cont.
Cushing´s syndrome
Osteoporosis, mental disorders
Adrenal insufficiency
Diabetes resistant to insulin but rarely develops
ketoacidosis
Peptic ulcers (occasionaly observed even after
only a few days of treatment)
Wound healing is impaired
Bacterial and mycotic infections may be
masked

12. Glucocorticoid excess
Subcapsular posterior cataracta, increased intraocular
pressure, glaucoma
Growth retardation in children

13. Glucocorticoid excess
Cushing´s syndrome
Patients protein-depleted as a result of excess protein
catabolism. The skin and subcutaneous tissue are thin,
muscles are poorly developed. Wounds heal poorly, and minor
injuries are caused. Body fat is redistributed in a characteristic
way. The extremities are thin, but fat collects in the abdominal
wall, face and upper back („buffalo hump“). The subdermal
tissues rupture to form prominent reddish-purple striae. Moon
face.
Hyperglycemia (gluconeogenesis+decreased peripheral
utilization of glucose---insulin-resistant DM
About 85% of patients are hypertensive (deoxycorticosteron
secretion is increased ---- steroid diabetes

14. Glucocorticoid excess
Osteoporosis, mental disorders
• A loss of bone mass for decreasing bone
formation and increasing bone resorption leads
eventually to collapse of vertebral bodies and
other fractures.
• Mental aberrations ranging from increased
appetite, insomnia and euphoria to frank toxic
psychosis

15. Glucocorticoid excess
Adrenal suppression
Free glucocorticoid inhibits ACTH and the degree
of pituitary secretion inhibition is proportionate to
the circulating glucocorticoid concentration.
•
The dangers involved when prolonged treatment
with anti-inflammatory doses of G. is stopped
deserve emphasis. Not only is the adrenal atrophic
and unresponsive after such treatment but the
pituitary may be unable to secrete normal amount
of ACTH for as long as a month.The cause of the
deficiency is presumably diminished ACTH
synthesis.

16. Glucocorticoid excess
Adrenal suppression
When is this mechanism manifested during longterm therapy?
if dosing is suddenly withdrawn
What is the risk?
adrenal insufficiency
Prevention? Slow withdrawal of therapy with
antiinflammatory dosing,
At time of minor stress the patient should be given
supplementary therapy (twofold dose increases for 24-48
hours) or severe stress (up to 200 mg of cortisol or 50 mg of
Prednisone for 48-72 hours)- such accidental trauma or
major surgery.

17. Glucocorticoid excess
Therapy with steroids with mineralocorticoid effects in
addition to glucocorticoid effects:
sodium and fluid retention, loss of potassiumIn patients with normal cardiovascular and renal functions ,
this leads to a hypokalemic, hypochloremic alkalosis and
eventually a rise in blood pressure.
In patients with hypoproteinemia, renal disease, or liver
disease- edema may occur
In patients with heart disease: heart failure

18. Thank you