CORTICOSTEROID DRUGS

TRULY SITORUS Depart.Of Pharmacology Medical Faculty-Padjadjaran University

INTRODUCTION
1.

Cs

hormone
That effects almost every organ/systems S.E . . . . . . . (1)

2. Therapeutic uses
* endocrine * non endocrine substitution th/.

AI & IMMUNOSUPPRESIVE

OBAT DEWA . . . . . . .(2)

masking effect

3. (1) & (2)

PEDANG BERMATA DUA

Adrenal cortex
Glucocorticoids

CS (CORTISOL)

* antiinflammatory immunosuppressive * metabolic potency MINERALOCORTICOIDS (Aldosteron) * Sod water retention edema BT androgen

REGULATION
Synthesis & secretion

regulation CS level CS level

FBM FBM (+) FBM (-)

What happens to the patient who chrocicaly consum CS exogen in large dosage ?

CS level

FBH (-)

adrenal gland suppresium

ATROPHY

DIURNAL CYCLE
Concentrion in plasma 8 am : 16 mg/100 ml 4 pm : 4 mg/100 ml What does this clinically mean ?

CORTISOL
Natural glucocorticoid

Potency : * antiinflammation : 1 * Na+ retention :1 * metabolic : 20

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

D : 80 90% is bound to globulin 5 10% albumin The free fraction is 3 10%

CS is widely distribution M : liver : Rifampicin Phenobarbital Phenytoin Met cs

Apa akibat interaksi ?

E : Kidney

MECHANISM OF ACTION
1. AFFECTS THE RNA TRANSCRIPTION RNA

2. INHIBITION OF PHOSPHOLIPID ENZYM

3. STABILITIZING MEMBRAN (?)

CS EFFECTS
I. METABOLIC EFFECTS
Cs dose related effect on CM, protein and fat metabolism 1. Carbohydrate gluconeogenesis HYPERGLYCAEMIA or GLUCOCA 2. Proteins Catabolic effect in lymphoid connective tissue muscle ATROPHY fat skin

3. Fat

Redistribution of fat

moon face buffalo hump supraclav deposit

atrophy

II. ANTIIMFLAMMATORY AND IMMUNOSUPRESION

1. On vascular events Reduced vasodilatation Decreased fluid exudation

2. On cellular events Indication * in area of acute inflammation : decreased ( ) number and activity of leucosit

* 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 cytokine secreting T cells.

3. On inflammatory and immune mediators decreased : cytokines (IL) eicosanoid PAF complement histamin 4. Histamin release from basophil

(2) (3) INDICATION : ALLERGIC AUTOIMMUNE DISEASE TRANSPLANTION LLA ADR : IMMUNOSUPRESSIV poor wound healing, vurnable to infection

CI : VIRAL, BACT, FUNGI INFECTION

III. BONE

Long term CS treatment OSTEOPOROSIS High risk : children post menopausal IV. CNS euphoria treatment

with bawl effect depression, sleep disturbances, psychotic

V. STOMATCH

gastric acid protective (mucopolysaccharidas)

VI. ELECTROLYTE AND WATER BALANCE Retention : sodium & water edema BPT

VII. SCELETAL MUSCLE

steroid myopathy VIII. EYE Long term therapy

weakness & fatigue

subcapsular caturaces intraocular pressure glaucoma blind

IX. GROWTH

Long term therapy

growth retardation

X. REPRODUCTIVE synthesis & secretion of gonadotropins : hypogonadism : anovulation, oligomenorrhea, uterine bleeding

ADVERSE EFFECT
I. LARGE DOSE LONG TERM CS THERAPI

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

CS SYNTHESIS
Compound Anti Inflammatory Potency 1 0,8 4 4 5 5 25 25 Na+ retaining Metabolic DOA Pot Pot Equivalent Dose

Cortisol Cortone Prednisone Prednisolone Methylprednisolone Triamcinolone Betamethasone Dexamethasone

1 0,8 0,8 0,8 minimal 0 0 0

20 5 5 4 1 1-1,5

S S I I I I L L

20 5 5 4 4 0,75 0,6

S : 8-12 h

I : 12-36 h

L : 36-72 h

SELECTION OF DRUG
1. REPLACEMENT THERAPY 2. LONG TERM ANTIINFLAMMATORY

3. THERAPY ACUTELY

DEXAMETHASONE
Synthetic CS

AI T (20)
Na water retaining potency 0 Metabolic potency (0)

DOA : 36-72 h (long

) Indication : * patient with HT, DM * acute therapy (septic shockbrain edema)

KORTIKOSTEROID TOPIKAL
Untuk kelainan kulit. Klasifikasi KS Topikal
Golongan 1 Potensi Sangat Lemah Nama KST Hidrokortison m-prednisolon Deksametason Aklometason dipropionat Betametason valerat Triamsinolon asetonid Hidrokortison butirat Flutikason propionat Desoksimetason Flusinolon asetonid Hidrokortison valerat Mometason fluroat Flusinolon asetonid Bentuk krim 0,25 2,5% krim 0,25 & 1,0% krim 0,1% krim 0,05% krim 0,01% krim 0,025% krim 0,1% krim 0,05% krim 0,05% krim 0,25% krim 0,2% krim 0,1% salep 0,02%

Lemah

Sedang

Kuat/poten

Betamason dipropionat Flutikason propionat Flusinolon asetonid Desoksimetason Mometason fluroat

krim 0,05% salep 0,005% salep 0,2% krim 0,05% salep 0,1% dalam vehikulum yang dioptimalkan 0,05% krim 0,05% krim 0,05%

Sangat poten

Batametason dipropinat Klobetasol propionat Diflorasone diacetat

EFEK KS TOPIKAL
1. Vasokontraksi vasokontriksi kapiler-kapiler di lap. dermis superficial eritema berkurang (pada : sunburn) 2. Antiproliferasi mengurangi mitosis dan proliferasi (pada : Psoriasis)

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

ABSORPSI (PENETRASI)
* Pada kulit normal hanya sedikit diabsorpsi, pada kulit terinflomasi absorpsi meningkat.

* Pada bayi anak, absorpsi lebih tinggi

* Penetrasi KS bervariasi berdasarkan regional tubuh.

PEMILIHAN KS
1. KS lemah regio : skrotum, kelopak mata bayi kelainan luas kelainan kulit responsit Penggunaan : 4 6 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.

INDICATION
1. Allergic drug reaction 2. Allergic rhinitis 3. Atopic dermatitis, exzema 4. Rheumatoid arthritis 5. Bronchial asthma 6. LLA 7. Organ transplants 8. Cerebral deem 9. Septicemia 10. Nephritic syndrome 11. Lupus erythematic