16/07/2018

Dr Lina Elsalem
BDS, MSc, PhD
Assistant Professor (Pharmacology)

Adrenal glands
• Adrenal glands are
endocrine glands

• Located above the

kidneys

• Each gland consists of

an outer cortex and
adrenal medulla

• Each one responsible of

secreting certain hormones

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Mineralocorticoids

Glucocorticoids
Catecholamines

Adrenal androgens

Adrenal
Mineralocorticoids Glucocorticoids
androgens

Aldosterone Dehydro-
epiandrosterone

Sexual characteristics

salt & water

metabolism

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Secretion of corticosteroids is
controlled by pituitary(ACTH)
and hypothalamus(CRH)
hormones.

Glucocorticoids serve as
feedback inhibitors of ACTH
and CRH secretion.

Factors such as stress and

levels of the circulating steroid
influence secretion.

The Adrenocorticoids

Mineralocorticoids Glucocorticoids
 The main endogenous  The main hormone is
hormone is Hydrocortisone (Cortisol)
Aldosterone.
 Regulated by Renin-  Actions:
Ang System.
 Actions:-  CHO, fat , blood vessels
Helps to control the & protein metabolism.
body's water and  Immune response.
electrolyte balance
(sodium & potassium).

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Conn’s Cushing’s
syndrome. syndrome.
Excess Excess
in Aldosterone in
production. Glucocorticoids
production.
Addison’s
disease.
Deficiency
in
Adrenocorticoids
production.

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Mineralocorticoids
(MCs)

Mineralocorticoids (MCs)
Control the body's WATER volume and concentration
of ELECTROLYTES (K, NA)
Aldosterone:
Acts on kidney tubules and collecting ducts:

 Reabsorption of sodium, bicarbonate, and water

 Execration of K, H+ in the urine

Water and Na Increased Blood

retention volume pressure

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Excess
Mineralocorticoids (MCs)
Conn's syndrome :
High secretion of aldosterone
Causes: Tumor or enlargement of the adrenal
gland
Signs and symptoms:
• Hypertension Increased Na & water.
• Hypokalemia ‘’Decreased K ‘’.
Treatment:
• Surgery
• Spironolactone???

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Deficiency of
adrenocorticoids

No enough aldosterone
secretion and cortisol.

Mineralocorticoids as
Replacement therapy in:
Addison’s disease (primary
adrenal insufficiency)

Fludrocortisone

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Activities are all

relative to
hydrocortisone =1

Glucocorticoids (GCs)

The major regulator of the negative

feedback mechanism …….
Suppress the HPA axis!

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Immunosuppression
 The exact mechanism for the
immunosuppression ???
 Prevent production of
cytokines including IL–1, IL-2,
IL-6, tumor necrosis factor-α,
chemokines, prostaglandins,
major histocompatibility class
II, and proteases.
 They are able to rapidly
reduce lymphocyte
populations by lysis or
redistribution

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Cushing's
syndrome

Hyper- secretion
of
Glucocorticoids
OR
Excess
corticosteroid
treatment

Pharmacological applications
and indications

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Activities are all

relative to
hydrocortisone =1

• Cortisone (prodrug) Hydrocortisone

Short Acting

•Prednisone (prodrug) Prednisolone

•Methylprednisolone
Intermediate
Acting

•Betamethasone
•Dexamethasone
Long Acting

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• Prednisone and cortisone are prodrug, which

also needs the hepatic microsomal enzymes to
be activated into prednisolone and
hydrocortisone respectively.

• It is not preferable to give cortisone or

prednisone to patients with improper liver
function or liver diseases.

• The advantages of GCs :

There are several routes of
administration.

• Epidural steroid injections

(ESIs)
A common treatment option
for many forms of low back
pain and leg pain.

• Intra-articular – joint
(arthritis)

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Glucocorticoids forms

Anti-inflammatory and
immunosuppression actions
 Inhibit phospholipase A2 .
 They interfere in mast cell degranulation
results in decreased histamine and capillary
permeability.
They inhibit all components & stages of
inflammation
Depress inflammatory immune response by
decreasing: production of cytokines,
complement components in the blood, T&B
lymphocyte activity, inhibiting PLA2

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Immunosuppression
 The exact mechanism for the
immunosuppression ???
 Prevent production of
cytokines including IL–1, IL-2,
IL-6, tumor necrosis factor-α,
chemokines, prostaglandins,
major histocompatibility class
II, and proteases.
 They are able to rapidly
reduce lymphocyte
populations by lysis or
redistribution

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Indications
 Autoimmune& inflamatory diseases:
1. Rheumatoid arthritis.
2. Osteoarthritis.
3. Inflammatory bowel disease: ulcerative colitis

 Prevent graft rejection

 Dermatology
Topically as (Creams, eye drops) in various
inflammatory conditions of eczema, dermatitis, allergic,
conjunctivitis, nappy rash.

 Treatment of Asthma (beclomethasone and

fluticasone inhalation)

 Life threating emergencies:

ex: Anaphylaxis & angioedema

Indications
in Oral ulcerations

Ex: Triamcinolone

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Indications
Replacement therapy

Primary adrenocortical insufficiency

Adrenal glands do not produce

enough hormones

Signs and symptoms:

Actions and indications

 Increases surfactant production.

Prevents respiratory distress syndrome.

Acceleration of lung maturation: Betamethasone
or dexamethasone

Given IM to the mother 48 hours before delivery,

followed by a second dose 24 hours before
delivery.

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Actions and indications

 Increased uric acid excretion:

Gout

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Before and After treatment

with glucocorticoids

Oral candidiasis may result

with use of steroid inhalers.

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Not
necessary

Growth retardation

Hirsutism

Cataract. (With long term )

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Glucocorticoids actions Adverse effects

1- Stimulate gluconeogenesis (Inc
hepatic glc production) inhibit glucose
uptake and utilization
2- Lipid profile: Increase cholesterol and
triglycerides
3- Stimulate protein catabolism
Chronic Uses of
corticosteroids
• Cause hyperglycemia
Blood glucose should be
monitored in DM patients.
This leads to increase fat
deposition in face, shoulder,
abdomen and back .
This lead to Muscle weakness
and slow growth in children)

4- CNS Euphoria. behavioral changes.

5- Reduction of WBCs Delay wound healing
infections

Glucocorticoids actions Chronic Uses of

corticosteroids
6- Stimulate gastric acid and pepsin
production. Peptic ulcer

7- On blood vessels :
Decreased Vasodilatation.
Increased sensitivity of Blood
Vessels to Vasoconstrictors of
catecholamine
8- Decrease calcium absorption
from GIT and increase renal
excretion.
One of the complication is
(hypertension)
Increased blood pressure
Chronic glucocorticoid therapy can
cause severe bone loss. This lead to
Osteoporosis
Advice the patient to take Ca and
vit D

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“Iatrogenic Cushing’s Syndrome”
1. Osteoporosis :
Patients are advised to take
calcium and vitamin D
supplements.
2. Increased appetite.
3. Increased risk of infection.
4. Hypertension.
5. Diabetes mellitus.
6. Edema and hypokalemia.
7. Peptic ulcer.
8. Euphoria and psychosis.
9. Cataract. (With long term )
16/07/2018
10. Increased convulsion.
11. Menstrual disturbances.
12. Growth retardation in
children.
13. Easy bruising.
14. Poor wound healing
15. Thinning of the skin, arms
,legs and muscle wasting.
16. Moon face, red cheeks and
buffalo hump
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Withdrawal
Chronic use (more than 2 weeks) and large doses will
cause will: Suppress of the hypothalamic-pituitary-
adrenal (HPA) axis
Abrupt removal of the corticosteroids will Cause an
acute adrenal insufficiency
(atrophy)
syndrome that can be lethal

Dose must be tapered down slowly

Alternate-day administration of
the hormones allows the HPA axis to
recover/function on the days the hormone is not taken

Stress dose
Increasing (doubled) the dose of
glucocorticoids
Ex: Before surgery for patient with
Addison disease????

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Adrenal Insufficiency
Crisis

Adrenal insufficiency
 Collapse in a patients with adrenal suppression
 Often occurs in response to stress

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 Management:
• Lay patient flat
• Give high flow oxygen
• Call for ambulance
• Cardiac arrest, start CPR

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IV saline solution with IV hydrocortisone Fludrocortisone

5% glucose
2/3 morning
1/3 afternoon

Treat the precipitating factors, e.g: infection

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