Intranasal corticosteroids: patient administration angles ...
Corticosteroids
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Transcript of Corticosteroids
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
Corticotropin-releasing
factors (CRF)
Corticotropin (adrenocorticotropic hormone (ACTH)
Glucocorticoids
GLUCORTICOID- Metabolic effect
- Antiinflamatorry/ Immunosupresive
MINERALOCORTICOID
Retension of Na-H2O
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.
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 primary adrenocortical insufficiency
(Addison’s disease) :
Hydrocortisone natural cortisol•Dosage : 2/3 morning + 1/3 afternoon
Fludrocortisone (synthetic mineralocorticoid with some
glucocr. activity)
• 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
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 :PregnancyAdministration of estrogen Synthesis by the liver Hyperthyroidism
CBG is decreased in :HypothyroidismGenetic defects in synthesisProtein 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 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
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):
Adverse Effects of Corticosteroids
EFFECT-SIDE EFFECT OF CORTICOSTEROIDTruncal
obesity
Moon face
Buffalo hump
Atrophi
Inhibitors of adrenocorticoid biosynthesis
Metyrapone
Aminoglutethimide
KetoconazoleMifepristone
Spironolactone
Glucocorticoids: principal and adverse effect