k29 - farmakologi adrenal
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THE HORMONES OFADRENAL CORTEX
Pharmacology DepartmentMedical School Jenderal Soedirman University
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GLUCOCORTICOID
Adrenal cortex produce anadrenocortical hormones, ie:
Mineralo-corticoid (Aldosterone) Gluco-corticoid (Cortisol)
Androgen
Corticosteroid + receptor to
control gene expression
(long time)
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Basal secretions
Group Hormone Daily
secretions
Glucocorticoids Cortisol
Corticosterone
5 30 mg
2 5 mg
Mineralocorticoids Aldosterone
11- deoxycorticosterone
5
150 mcgTrace
Sex Hormones
AndrogenProgestogen
Oestrogen
DHEAProgesterone
Oestradiol
15
30 mg0.4 0.8 mg
Trace
From Essential of Pharmacotherapeutics, ed. FSK Barar. P.351
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Adrenals
Kidney
PosteriorPituitary Gland
Hypothalamus
AnteriorPituitary Gland
ACTH
StressCircadian
rhythm
CRH
(-)
Glucocorticoids,Catecholamines, etc..
Glucocorticoids,Catec
holamines, etc..
Muscle:Net loss of amino
Acids (glucose)
Liver:
Deamination of
proteins into aminoacids,
gluconeogenesis(glucose)
Fat Cells:Free fatty
acid
mobilization
Heart rate:Increased
Immunesystem:altered
Hypothalamopituitary adrenal (HPA)
axis: Negative Feedback
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PHARMACODINAMIC
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Corticosteroids are Gene-Active
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The Model of steroid-receptor interaction
in The Target cells
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THE EFFECT OF GLUCOCORTICOID
Metabolic effect
Immunosuppressive effect
Anti-inflammatory effect Additional Effect
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Pharmacological Effect
Carbohydrate
Protein
Lipid Electrolyte &
water
CVS Sk. Muscle
CNS
Stomach
Blood
Anti-inflammatory Immunosuppressant
Respiratory system
Growth & CellDivision
Calcium metabolism
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EFFECT ON CARBOHYDRATE & PROTEIN
METABOLISM
Gluconeogenesis
Peripheral actions (mobilize AA & glucose andglycogen)
Hepatic actions
Peripheral utilization of glucose
Glycogen deposition in liver(activation of hepatic glycogen synthase)
Negative nitrogen balance & hyperglycemia
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Redistribution of Fat Buffalo hump
Moon face
Promote adipokinetic agents activity
(glucagon, growth hormone, adrenaline,
thyroxine)
EFFECT ON LIPID METABOLISM
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Aldosterone is more important
Act on kidney
Na+reabsorption
Urinary excretion of K+and H+
Addisons disease ??
EFFECT ON ELECTROLYTE AND WATER
BALANCE
Na+ loss
Reduction of ECF
Cellular hydration
Hypodynamic state of CVS
Circulatory collapse, renal failure, death
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Restrict capillary permeability
Maintain tone of arterioles
Myocardial contractility
EFFECT ON CV SYSTEM
Na+sensitize blood vessels
to the action ofcatecholamines &angiotensin
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Addison's disease: weakness & fatique is dueto inadequacy of circulatory system
Prolonged use: steroid myopathy
EFFECT ON SKELETAL MUSCLE
Needed for maintaining the normal function of Sk.muscle
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Direct:
Mood
Behaviour
Brain excitability
Indirect:
maintain glucose, circulation and
electrolyte balance
EFFECT ON CNS
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Pseudotumor cerebri(Intracranial hypertension)
Glucocorticoids
Mineralocorticoids
Amiodarone
Vitamin A
Oral contraceptives
Tetracyclines
From Harrison. 15thedition, volume 1, page 435
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Aggravate peptic ulcer. May be due to
Acid & pepsin secretion
immune response to H.Pylori
EFFECT ON STOMACH
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RBC: Hb & RBC content
(erythrophagocytosis )
WBC: Lymphocytes, eosinophils,monocytes, basophils
Polymorphonucleocytes
EFFECT ON BLOOD
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Recruitment of WBC & monocyte-macrophage into affected area & elaboration
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 & fibroblastic activity
Expression of cyclooxygenase II
EFFECT ON INFLAMATORY
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Phospholipids
Arachidonic acids
lipoxygenase Cycylooxygenase
LeukotrieneProstaglandins,ThromboxaneProstacyclins
Phospholipase A2
Lipocortin
Corticosteroids
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Anti-inflammatory actions of corticosteroids
Corticosteroid inhibitory effect
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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, delayrevascularization, sensitisation of Tlymphocytes etc.
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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 fromneutrophil & monocyte
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Inhibit cell division or synthesis of DNA Delay the process of healing
Retard the growth of children
Effect on Growth & Cell division
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Intestinal absorption
Renal excretion
Excessive loss of calcium from
spongy bones (e.g., vertebrae,ribs etc)
EFFECT ON CALCIUM METABOLISM
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Notbronchodilators
Most potent and most effective anti-inflammatory
Effects not seen immediately (delay 6 or
more hrs) Inhaled corticosteroids are used for long
term control
EFFECT ON RESPIRATORY SYSTEM
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Preparations
Drug Anti-inflam. Salt retaining Topical
Cortisol 1 1.0 1Cortisone 0.8 0.8 0
Prednisone 4 0.8 0
Prednisolone 5 0.3 4Methylpredni-
solone5 0 5
Intermediate acting
Triamcinolone 5 0 5
Paramethasone 10 0 -
Fluprednisolone 15 0 7
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Preparations
Drug Anti-inflam. Salt retaining Topical
Long acting
Betamethasone 25-40 0 10
Dexamethasone 30 0 10
Mineralocorticoids
Fludrocortisone 10 250 10
DOCA 0 20 0
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THE CLINICAL USE
Chronic adrenal cortical insufficiency Addisons disease
Acute adrenal insufficiency Shock, trauma, infection
Inflammatory reaction
Imunologic reaction
The others : Chemotherapy ofneoplasm, hyper-calcemia,mountain sickness
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MINERALOCORTICOID
Aldosterone (nature available)bebe regulated by ACTH and renin-angiostensin system (angiostensin
II) Has little glucocorticoid activity
The mechanism of action is the samewith glucocorticoid
Deoxycorticosterone Fludrocortisone
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THE CLINICAL USE
Addisons disease
Stress and The Adrenal Glands
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Stress and The Adrenal Glands
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To becontinued