THE HORMONES OF

ADRENAL CORTEX
Pharmacology Department
Medical School Jenderal Soedirman University

GLUCOCORTICOID

Adrenal cortex produce an

adrenocortical hormones, ie:

Mineralo-corticoid (Aldosterone)
Gluco-corticoid (Cortisol)
Androgen

Corticosteroid + receptor
control gene expression
(long time)

to

Basal secretions
Group

Hormone

Daily
secretions

Glucocorticoids

Cortisol
Corticosterone

5 30 mg
2 5 mg

Mineralocorticoids Aldosterone
5 150 mcg
11- deoxycorticosterone 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

Immune
system:
altered

Stress
Circadian
rhythm

Hypothalamus

CRH
Anterior
Pituitary Gland

(-)

Posterior
Pituitary Gland

ACTH
Glucocorticoids,
Adrenals Catecholamines,
etc..

Kidney

Muscle:
Net loss of amino
Acids (glucose)
Liver:
Deamination of
proteins into amino
acids,
gluconeogenesis
(glucose)
Fat Cells:
Free fatty
acid
mobilization
Heart rate:
Increased

Hypothalamopituitary adrenal (HPA)

axis: Negative Feedback

PHARMACODINAMIC

Corticosteroids are Gene-Active

The Model of steroid-receptor interaction

in The Target cells

THE EFFECT OF GLUCOCORTICOID

Metabolic effect
Immunosuppressive effect
Anti-inflammatory effect
Additional Effect

Pharmacological Effect

Carbohydrate

Protein

Blood

Lipid

Anti-inflammatory

Immunosuppressant

Respiratory system

Electrolyte &
water

CVS

Sk. Muscle

CNS

Stomach

Growth & Cell

Division
Calcium metabolism

EFFECT ON CARBOHYDRATE & PROTEIN

METABOLISM

Gluconeogenesis

Peripheral actions (mobilize AA & glucose and

glycogen)

Hepatic actions

Peripheral utilization of glucose

Glycogen deposition in liver

(activation of hepatic glycogen synthase)

Negative nitrogen balance & hyperglycemia

EFFECT ON LIPID METABOLISM

Redistribution

of Fat

Buffalo hump
Moon face

Promote adipokinetic agents activity

(glucagon, growth hormone, adrenaline,
thyroxine)

EFFECT ON ELECTROLYTE AND WATER

BALANCE

Aldosterone is more important

Act on kidney

Na+ reabsorption
Urinary excretion of K+ and H+

Addisons disease ??

Na+ loss
Reduction of ECF
Cellular hydration
Hypodynamic state of CVS
Circulatory collapse, renal failure, death

EFFECT ON CV SYSTEM
Restrict

capillary permeability
Maintain tone of arterioles
Myocardial contractility
Na+ sensitize blood vessels
to the action of
catecholamines &
angiotensin

EFFECT ON SKELETAL MUSCLE

Needed for maintaining the normal function of Sk.
muscle

Addison's disease: weakness & fatique is due

to inadequacy of circulatory system
Prolonged use: steroid myopathy

EFFECT ON CNS

Direct:

Mood
Behaviour
Brain excitability

Indirect:

maintain glucose, circulation and

electrolyte balance

Pseudotumor cerebri
(Intracranial hypertension)

Glucocorticoids
Mineralocorticoids
Amiodarone
Vitamin A
Oral contraceptives
Tetracyclines

From Harrison. 15th edition, volume 1, page 435

EFFECT ON STOMACH

Aggravate peptic ulcer. May be due to

Acid & pepsin secretion

immune response to H.Pylori

EFFECT ON BLOOD

RBC:

Hb & RBC content

(erythrophagocytosis )
WBC: Lymphocytes, eosinophils,
monocytes, basophils
Polymorphonucleocytes

EFFECT ON INFLAMATORY

Recruitment of WBC & monocytemacrophage into affected area &

of chemotactic substances

Lipocortin

ELAM1 & ICAM-1 in endothelial cells

TNF from phagocytic cells

IL1 from monocyte-macrophage

Formation of Plasminogen Activator

Action of MIF &

Expression of cyclooxygenase II

fibroblastic activity

elaboration

Corticosteroids
Lipocortin
Phospholipids
Phospholipase A2
Arachidonic acids

lipoxygenase

Leukotriene

Cycylooxygenase

Prostaglandins,
Thromboxane
Prostacyclins

Anti-inflammatory actions of corticosteroids

Corticosteroid inhibitory effect

Immunosuppressive & anti-allergic Effect

Suppresses all types of hypersensitivity

& allergic phenomenon
At High dose: Interfere with all steps of
immunological response
hypersensitivity
Transplant rejection: antigen expression
from
grafted tissues, delay
revascularization, sensitisation of T
lymphocytes etc.

The Effect of Glucocoticoid to immune

System

To decrease eosinophil, basophil,

monocyte, and limfocyte in the circulation
To increase process of cell apoptosis
To decrease T-cell Proliferasi
To decrease synthesis of IL-2
To decrease the chemotactic process &
the secretion of the lysozim enzym from
neutrophil & monocyte

Effect on Growth & Cell division

Inhibit cell division or synthesis of DNA

Delay the process of healing
Retard the growth of children

EFFECT ON CALCIUM METABOLISM

Intestinal absorption

Renal excretion

Excessive loss of calcium from

spongy bones (e.g., vertebrae,
ribs etc)

EFFECT ON RESPIRATORY SYSTEM

Not bronchodilators
Most potent and most effective antiinflammatory
Effects not seen immediately (delay 6 or
more hrs)
Inhaled corticosteroids are used for long
term control

Preparations
Drug
Cortisol

Anti-inflam.

Salt retaining

Topical

1.0

0.8

0.8

Prednisone

0.8

Prednisolone

0.3

Methylprednisolone

Paramethasone

10

Fluprednisolone

15

Cortisone

Intermediate acting
Triamcinolone

Preparations
Drug

Anti-inflam.

Salt retaining

Topical

Long acting
Betamethasone

25-40
Dexamethasone
30
Mineralocorticoids
Fludrocortisone
10
DOCA
0

0
0

10
10

250
20

10
0

THE CLINICAL USE

Chronic adrenal cortical insufficiency

Acute adrenal insufficiency

Addisons disease
Shock, trauma, infection

Inflammatory reaction
Imunologic reaction
The others : Chemotherapy of
neoplasm, hyper-calcemia,
mountain sickness

MINERALOCORTICOID

Aldosterone (nature available) be

be regulated by ACTH and reninangiostensin system (angiostensin
II)

Has little glucocorticoid activity

The mechanism of action is the same
with glucocorticoid

Deoxycorticosterone
Fludrocortisone

THE CLINICAL EFFECTS

to increase re-absorption of Na and

excretion of K, H

Sodium retention
Hypocalemia
Alcalosis

THE CLINICAL USE

Addisons disease

Stress and The Adrenal Glands

To becontinued