K29 - Farmakologi Adrenal

8/10/2019 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

Documents

K29 - Farmakologi Adrenal