CORTICOTROPIN AND

ADRENAL
CORTICOSTEROIDS

Dr.dr. Asep Sukohar, M.Kes

Bagian Farmakologi dan Terapi FK Unila
 Introduction
ADRENAL PHYSIOLOGY :

Adrenal Cortex :
Homeostatic organ, regulating reactions to stress
Release :
 Controlled by CNS
 Stimuli : Trauma, chemicals, diurnal rhythms, emotion

Corticotropin-releasing factors (CRF)

Corticotropin (adrenocorticotropic hormone (ACTH)

Glucocorticoids
GLUCORTICOID MINERALOCORTICOID
- Metabolic effect Retension of Na-H2O
- Antiinflamatorry/
Immunosupresive
BP, Edema
 Emotional stress
Trauma Diurnal rhythms

Hypothalamus

CRF

Anterior pituitary glands

Negative ACTH
inhibition
Adrenal cortex

Adrenal steroids

The pathway of adrenocorticotropic hormone (ACTH) and adrenal

steroid secretion.
MOA Steroid
• INTRODUCTION

Inflammation ?
Causative trauma , MO, Cold, Organ
transplants

Symptomatic Cell
NSAID
CS 
 Inflammation : color, dolor, flame
Masking effect
• Introduction
1. CS  hormone

That effects almost every organ/systems

SE … (1)
2. Therapeutic Uses
- Endocrine  substitution therapy
- Non endocrine

AI & Immunosuppresive

Obat dewa …(2) Masking effect

3. (1) & (2)  Pedang bermata dua

Adrenal cortex releases a number of endogenous CS
• GLUCOCORTICOID
• Zona fasciculata
• Chiefly affect carbohydrate, protein metabolism
and resistance to stress
• Feedback inhibitor of corticotropin and
corticotropin-releasing factor (CRF) secretion
• Endogenous glucocorticoids :
• Cortisol (hydrocortisone)  major
endog.glucocort, secreted : 10-25 mg/daily
• Cortisone
• Corticosterone  0,5-2 mg /daily
• Diurnal rhythm :
• 4 AM & 8 AM, 4 PM
• Mineralocorticoids

• Zona glomerulosa
• Chiefly affect electrolyte and water metabolism
• Sodium & water retention  edema
BP
• Endogenous mineralocorticoids :

• Aldosterone  30-150
g/daily
• Desoxycorticosterone
 REGULATION
• Synthesis & secretion
Regulation  FBM
CS level   FBM (-)
CS level   FBM (-)
What happens to the patient who chronically
consume CS exogenous in large dosage ?
CS level  FBM (-)
Adrenal gland suppression

ATROPHY
ADRENOCORTICOTROPIC HORMONE (ACTH)
• Mechanism of action
• To stimulate specific protein receptor sites on
the adrenal cortical cell membrane

• ACTH is required for the synthesis of

mineralocorticoids & glucocorticoids
(stimulate the synthesis of gluco > mineralo.)
Therapeutic uses

• Diagnostic tool :
• Primary adrenal insufficiency (Addison’s disease)
• The adm. of ACTH  no effect
• Adrenal cortex dysfunction
• Secondary adrenal insufficiency
• The adm. of ACTH  effect (+)
• Anterior pituitary dysfunction
Administration :
• Parenterally (IM)
• T ½ : 15 minutes

Untoward effects :
• Rare
• Hypersensitivity reactions
• Toxicity is dose-related (corticosteroid
excess)
 ADRENAL CS ACTIONS
• Glucocorticoids
• Promote normal intermediary metabolism
• Gluconeogenesis
• Amino acid uptake by the liver and kidney
• Elevating activities of gluconeogenic enzymes
• Stimulate protein catabolism (except in the
the liver) and lipolysis
• Glucocorticoid insuff.  hypoglycemia
• Increase resistance to stress
• Plasma glucose levels 
 energy >< stress (trauma, fright, infection,
bleeding, debilitating disease)
• Blood pressure (vasoconstrictor action)

• Alter blood cell levels in plasma

• Eosinophils, basophils, monocytes, lymphocytes 
• Hb,erythrocytes, platelets , polymorphonuclear
leukocytes 
 Anti-inflammatory action
- Reduce the inflammatory response
- To suppress immunity

Inhibition of phospholipase A2

block the release of arachidonic acid

(precursor of PG & leukotriens)
Affects other components of the endocrine system
- Feedback inhibition
- Growth hormone production 
Effects on other systems
- Stimulate gastric acid & pepsin production (high doses)
 exacerbate ulcers
- Severe bone loss (chronic glucocorticoid therapy)
- Myopathy weakness
• Mineralocorticoids
• Aldosterone
- reabsorption of sodium,
bicarbonate and water
- decreases reabsorption of
potassium

Alkalosis & hypokalemia

Blood volume & Blood Pressure 

Hyperaldosteronism >< spironolactone

 THERAPEUTIC USES

Replacement therapy for Replacement therapy for

primary adrenocortical secondary or tertiary Diagnosis of Cushing’s
insufficiency (Addison’s adrenocortical syndrome :
disease) : insufficiency

Hydrocortisone  Hypersecretion of
natural cortisol glucocorticoids
• Dosage : 2/3 morning + 1/3 Hydrocortisone • Excessive release of
afternoon corticotropin
• Adrenal tumor

Fludrocortisone
(synthetic
mineralocorticoid
with some glucocr.
activity)
Replacement therapy
for congenital • An enzymes defect in the synthesis of one or more
adrenal hyperplasia adrenal steroid hormone

(CAH)

Relief of • Inflammation  : (redness, swelling,heat, tenderness)

• rheumatoid
inflammatory • osteoarthritic inflammations
symptoms • inflammatory skin

• Treatment of the symptoms of drug, serum, transfusion

Treatment of allergic reactions, bronchial asthma, allergic rhinitis
allergies • Beclomethasone dipropionate, triamcinolone , etc 
topical/inhalation (SE )
ADRENAL CORTICOSTEROIDS

Hydrocortisone (Cortisol)
• Pharmacokinetics :
• Synthesized from cholesterol
• Adrenal corticosteroids & their derivates are
readily absorbed from GIT
• Secretion in adult ( stress) : 10-25 mg/daily
• 90 % bound to plasma proteins (CBG=
corticosteroid-binding globulin), 5-10 % free
or bound to albumin.
• If conc. > 20-30 µg/dL, CBG is saturated free
cortisol 
CBG is increased in :
Pregnancy
Administration of estrogen 
Synthesis by the liver 
Hyperthyroidism
CBG is decreased in :
Hypothyroidism
Genetic defects in synthesis
Protein deficiency states

• Synthetic corticosteroid (dexamethason) bound to

albumin
 T1/2 : 60-90 minutes

Increase if :
- Large amounts adm.
- Stress
- Hypothyroidism
- Liver disease

 Metabolized by the liver microsomal oxidizing

enzymes
 conjugated to glucoronic acid or sulfate
 excreted by the kidney
 Classification of Glucocorticoids and Mineralocorticoids
Group Drugs Anti-inflammatory Salt-retaining
effect effect

-Short-acting -Hydrocortisone 1 1
(8-12 hours) -Cortisone 0,8 0,8

-Intermediate- -Prednison 4 0,3

acting -Prednisolone 5 0,8
(18-36 hours) -Methylprednisolone 5 0,5
-Triamcinolone 5 0

-Long-acting -Betamethasone 35 0
(1-3 days) -Dexamethasone 30 0
-Paramethasone 10 0

-Mineralocorticoids -Fludrocortisone 10 125

-Deoxycorticosterone 0 20
DOSAGE
• Glucocorticoids vs mineralocorticoids activity
• Duration of action
Consideration : • Type of preparation
• The time of day that steroid is administered

Long Time • Suppresion of HPA axis

• To prevent : regimen of alternate-day
Period & large administration
doses (> 2
weeks):
Adverse Effects of
Corticosteroids
Buffalo Moon EFFECT-SIDE
hump face
EFFECT OF
Truncal
CORTICOSTEROID
obesity

Atrophi
Inhibitors of adrenocorticoid biosynthesis

Metyrapone

Spironolactone Aminoglutethimide

Mifepristone Ketoconazole
Glucocorticoids: principal and adverse effect
Inhibitors of adrenocorticoid biosynthesis

• Metyrapone
• Aminoglutethimide
• Ketoconazole
• Mifepristone
• Spironolactone
HANUPIS