corticosteroids
DESCRIPTION
CorticosteroidsTRANSCRIPT
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CORTICOTROPIN AND ADRENAL CORTICOSTEROIDS
Dwi Indria Anggraini
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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
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GLUCORTICOID- Metabolic effect
- Antiinflamatorry/ Immunosupresive
MINERALOCORTICOID
Retension of Na-H2O
BP, Edema
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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.
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INTRODUCTION
Inflammation ? Causative trauma , MO, Cold, Organ transplants Symptomatic Cell NSAID
CS Inflammation : color,
dolor, flame Masking effect
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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
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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
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Mineralocorticoids
▪ Zona glomerulosa▪ Chiefly affect electrolyte and water
metabolism▪ Sodium & water retention edema
BP▪ Endogenous mineralocorticoids :
▪ Aldosterone 30-150 g/daily
▪ Desoxycorticosterone
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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
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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.)
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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
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Administration :
• Parenterally (IM)• T ½ : 15 minutes
Untoward effects :
• Rare• Hypersensitivity reactions • Toxicity is dose-related (corticosteroid excess)
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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
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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
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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
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Mineralocorticoids Aldosterone - reabsorption of
sodium, bicarbonate and
water
- decreases reabsorption of
potassium
Alkalosis & hypokalemia Blood volume & Blood
Pressure
Hyperaldosteronism >< spironolactone
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THERAPEUTIC USES
Replacement therapy for primary adrenocortical insufficiency
(Addison’s disease) :
Hydrocortisone natural cortisol•Dosage : 2/3 morning + 1/3 afternoon
Fludrocortisone (synthetic mineralocorticoid with some
glucocr. activity)
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• An enzymes defect in the synthesis of one or more adrenal steroid hormone
Replacement therapy for congenital
adrenal hyperplasia
(CAH)
• Inflammation : (redness, swelling,heat, tenderness)• rheumatoid• osteoarthritic inflammations• inflammatory skin
Relief of inflammatory
symptoms
• Treatment of the symptoms of drug, serum, transfusion allergic reactions, bronchial asthma, allergic rhinitis
• Beclomethasone dipropionate, triamcinolone , etc topical/inhalation (SE )
Treatment of allergies
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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.
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If conc. > 20-30 µg/dL, CBG is saturated free cortisol
CBG is increased in :PregnancyAdministration of estrogen Synthesis by the liver Hyperthyroidism
CBG is decreased in :HypothyroidismGenetic defects in synthesisProtein deficiency states
Synthetic corticosteroid (dexamethason) bound to albumin
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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
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Classification of Glucocorticoids and Mineralocorticoids
Group Drugs Anti-inflammatory effect
Salt-retaining effect
-Short-acting (8-12 hours) -Intermediate- acting (18-36 hours)
-Long-acting (1-3 days)
-Mineralocorticoids
-Hydrocortisone-Cortisone
-Prednison-Prednisolone-Methylprednisolone-Triamcinolone
-Betamethasone-Dexamethasone-Paramethasone
-Fludrocortisone-Deoxycorticosterone
10,8
4555
353010
100
10,8
0,30,80,50
000
12520
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DOSAGE
•Glucocorticoids vs mineralocorticoids activity•Duration of action•Type of preparation •The time of day that steroid is administered
Consideration :
•Suppresion of HPA axis •To prevent : regimen of alternate-day administration
Long Time Period &
large doses (> 2 weeks):
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Adverse Effects of Corticosteroids
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EFFECT-SIDE EFFECT OF CORTICOSTEROIDTruncal
obesity
Moon face
Buffalo hump
Atrophi
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Inhibitors of adrenocorticoid biosynthesis
Metyrapone
Aminoglutethimide
KetoconazoleMifepristone
Spironolactone
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Glucocorticoids: principal and adverse effect
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