INTR-CORTI-dr.Truly.ppt

7/28/2019 INTR-CORTI-dr.Truly.ppt

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CORTICOSTEROID DRUGS

TRULY SITORUS

Depart.Of Pharmacology

Medical Faculty-Padjadjaran University


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INTRODUCTION1. Cs hormone

That effects almost every organ/systems

S.E . . . . . . . (1)

2. Therapeutic uses* endocrine substitution th/.

* non endocrine

AI & IMMUNOSUPPRESIVE

OBAT DEWA . . . . . . .(2) masking effect

3. (1) & (2) PEDANG BERMATA DUA


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Adrenal cortex

Glucocorticoids ~ CS (CORTISOL)* antiinflammatoryimmunosuppressive

* metabolic potency

MINERALOCORTICOIDS (Aldosteron)

* Sod water retention edema

BT

androgen


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REGULATION

Synthesis & secretion

regulation FBM

CS level FBM (+)

CS level FBM (-)


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Whathappens to the patient who

chrocicaly consum CS exogen in largedosage ?


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CS level FBH (-)

adrenal gland suppresium

ATROPHY


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DIURNAL CYCLE

Concentrion in plasma

8 am : 16 mg/100 ml

4 pm : 4 mg/100 ml

What does this clinically mean ?


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CORTISOL

Natural glucocorticoid

Potency :

* antiinflammation : 1

* Na+ retention : 1* metabolic : 20


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PHARMACOKINETICS

A : CS is a lipophylic drug

* Good : intestinal (p.o)

Conjunctival space (topical)

Synovial (p.e)Nasal (spray)

* Slowly : skin

Good penetration : mucosa,conjunctiva, sirotum - face


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D : 8090% is bound to globulin510% albumin

The free fraction is 3 10%

CS is widely distribution

M : liver: Rifampicin

Phenobarbital Met cs

Phenytoin

Apa akibat interaksi ?

E : Kidney


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MECHANISM OF ACTION

1. AFFECTS THE RNA TRANSCRIPTION RNA


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2. INHIBITION OF PHOSPHOLIPID ENZYM

3. STABILITIZING MEMBRAN (?)


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CS EFFECTS

I. METABOLIC EFFECTSCs dose related effect on CM, protein

and fat metabolism

1. Carbohydrate

gluconeogenesis HYPERGLYCAEMIAor GLUCOCA

2. Proteins

Catabolic effect

in lymphoid

connective tissue

muscle ATROPHY

fat

skin


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3. Fat

Redistribution of fat

moon facebuffalo hump

supraclav deposit

atrophy


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II. ANTIIMFLAMMATORY AND

IMMUNOSUPRESION

1. On vascular events

Reduced vasodilatation

Decreased fluid exudation

2. On cellular eventsIndication

* in area of acute inflammation :

decreased ( ) number and activity of leucosit


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* in area of chronic inflammation :

decreased activity of mononuclear cells.Decreased fibroblast function

* in lymphoid areas :decreased clonal expansion of T and B cells.

decreased action of cytokinesecreting T cells.


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3. On inflammatory and immune mediators

decreased : cytokines (IL)eicosanoid

PAF

complementhistamin

4. Histamin release from basophil


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(2) (3) INDICATION : ALLERGIC

AUTOIMMUNE DISEASE

TRANSPLANTIONLLA

ADR : IMMUNOSUPRESSIV

poor wound healing,

vurnable to infection

CI : VIRAL, BACT, FUNGI INFECTION


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III. BONE

Long term CS treatment OSTEOPOROSIS

High risk : children

post menopausal

IV. CNS

euphoria with bawl effect

treatment depression, sleepdisturbances, psychotic


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V. STOMATCH

gastric acid

protective (mucopolysaccharidas)

VI. ELECTROLYTE AND WATERBALANCE

Retention : sodium & water

edemaBPT


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VII. SCELETAL MUSCLE

steroid myopathy weakness & fatigue

VIII. EYE

Long term therapy subcapsular caturacesintraocular pressure

glaucoma

blind


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IX. GROWTH

Long term therapy growth retardation

X. REPRODUCTIVE

synthesis & secretion of gonadotropins : hypogonadism

: anovulation, oligomenorrhea, uterine

bleeding


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ADVERSE EFFECTI. LARGE DOSELONG TERM CS

THERAPI


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II. REYBOND PHENOMENE (WITH DRAWL

EFFECT)

>= 7 days

Abrupt stopped

Reactivation (exacerbation) of the disease

Anorexia, nausea, vomiting, weigh loss,

lethargy, headache, fever, joint-muscle pain,

postural hipotension

Tapering off or alternate day


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CS SYNTHESIS

Compound Anti Na+ retaining Metabolic DOA Equivalent

Inflammatory Pot Pot Dose

Potency

Cortisol 1 1 20 S 20

Cortone 0,8 0,8 S

Prednisone 4 0,8 5 I 5

Prednisolone 4 0,8 5 I 5

Methylprednisolone 5 minimal I 4

Triamcinolone 5 0 4 I 4

Betamethasone 25 0 1 L 0,75

Dexamethasone 25 0 1-1,5 L 0,6

S : 8-12 h I : 12-36 h L : 36-72 h


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SELECTION OF DRUG

1. REPLACEMENT THERAPY

2. LONG TERM ANTIINFLAMMATORY

3. THERAPY ACUTELY


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DEXAMETHASONE

Synthetic CSAI T (20)

Nawater retaining potency 0

Metabolic potency (0)

DOA : 36-72 h (long )

Indication : * patient with HT, DM

* acute therapy (septic shock-

brain edema)


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KORTIKOSTEROID TOPIKAL

Untuk kelainan kulit.

Klasifikasi KS Topikal

Golongan Potensi Nama KST Bentuk

1 Sangat Hidrokortison krim 0,252,5%Lemah m-prednisolon krim 0,25 & 1,0%

Deksametason krim 0,1%

2 Lemah Aklometason dipropionat krim 0,05%

Betametason valerat krim 0,01%

Triamsinolon asetonid krim 0,025%

3 Sedang Hidrokortison butirat krim 0,1%Flutikason propionat krim 0,05%

Desoksimetason krim 0,05%

Flusinolon asetonid krim 0,25%

Hidrokortison valerat krim 0,2%

Mometason fluroat krim 0,1%

Flusinolon asetonid salep 0,02%


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4 Kuat/poten Betamason dipropionat krim 0,05%

Flutikason propionat salep 0,005%

Flusinolon asetonid salep 0,2%

Desoksimetason krim 0,05%

Mometason fluroat salep 0,1%

5 Sangat poten Batametason dipropinat dalam vehikulum yang

dioptimalkan 0,05%

Klobetasol propionat krim 0,05%

Diflorasone diacetat krim 0,05%


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EFEK KS TOPIKAL

1. Vasokontraksi

vasokontriksi kapiler-kapiler di lap. dermissuperficial eritema berkurang (pada :

sunburn)

2. Antiproliferasimengurangi mitosis dan proliferasi (pada :

Psoriasis)

3. Antiinflamasi(pada : eczema, sunburn, dll)


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ABSORPSI (PENETRASI)

* Pada kulit normal hanya sedikit

diabsorpsi, pada kulit terinflomasi absorpsi

meningkat.

* Pada bayianak, absorpsi lebih tinggi

* Penetrasi KS bervariasi berdasarkanregional tubuh.


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PEMILIHAN KS

1. KS lemah regio : skrotum, kelopak mata bayi kelainan luas kelainan kulit responsit

Penggunaan : 46 minggu

2. KS kuat regio : telapak tangan/kaki kelaianan kurang/tidak responsive

Penggunaan : 2 minggu

KS tidak boleh diberikan pada infeksi primer oleh bakteri,virus dan jamur serta daerah yang mengalami ulserasi.


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INDICATION

1. Allergic drug reaction2. Allergic rhinitis

3. Atopic dermatitis, exzema

4. Rheumatoid arthritis

5. Bronchial asthma6. LLA

7. Organ transplants

8. Cerebral deem

9. Septicemia

10. Nephritic syndrome

11. Lupus erythematic

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INTR-CORTI-dr.Truly.ppt