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CORTICOTROPIN

AND ADRENAL
CORTICOSTEROIDS

Dwi Indria Anggraini

Introduction
ADRENAL PHYSIOLOGY :
Adrenal Cortex :
Homeostatic organ, regulating reactions to stress

Release
:
Controlled by CNS
Stimuli :
Trauma, chemicals, diurnal rhythms,

emotion

factors (CRF)

hormone (ACTH)

Corticotropin-releasing

Corticotropin (adrenocorticotropic

Glucocorticoids

GLUCORTICOID

MINERALOCORTICOID

- Metabolic effect

Retension of Na-H2O

- Antiinflamatorry/
Immunosupresive

BP, Edema

Trauma
rhythms

Emotional stress

Diurnal

Hypothalamus
CRF
Anterior pituitary glands
Negative
inhibition

ACTH
Adrenal cortex
Adrenal steroids

The pathway of adrenocorticotropic hormone


(ACTH)
and adrenal steroid secretion.

INTRODUCTION

Inflammation ?
Causative trauma , MO, Cold, Organ
transplants

Symptomatic
NSAID

CS

Cell

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)


3. (1) & (2) Pedang bermata dua

Masking effect

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

Mineralocorticoids

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

Aldosterone
150 g/daily
Desoxycorticosterone

30-

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 (Addisons
disease)
The adm. of ACTH no effect
Adrenal cortex dysfunction
Secondary adrenal insufficiency
The adm. of ACTH effect (+)
Anterior pituitary dysfunction

Administration :

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

Pressure

Alkalosis & hypokalemia


Blood volume & Blood

THERAPEUTIC USES
Replacement therapy for primary

Replacement therapy for congenital adrenal hyperplasia (CAH)

ADRENAL
CORTICOSTEROIDS
Hydrocortisone (

If conc. > 20-30 g/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
-Cortisone

1
0,8

1
0,8

-Intermediateacting
(18-36 hours)

-Prednison
-Prednisolone
-Methylprednisolone
-Triamcinolone

4
5
5
5

0,3
0,8
0,5
0

-Long-acting
(1-3 days)

-Betamethasone
-Dexamethasone
-Paramethasone

35
30
10

0
0
0

-Mineralocorticoids

-Fludrocortisone
-Deoxycorticosterone

10
0

125
20

(8-12 hours)

DOSAGE
Consideration :

Adverse Effects of
Corticosteroids

Buffalo
hump

Moon
face
Truncal
obesity

Atrophi

EFFECT-SIDE
EFFECT OF
CORTICOSTEROID

Inhibitors of adrenocorticoid biosynthesis

Glucocorticoids: principal and adverse effect