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OBATOBAT--OBAT SISTEM IMMUNOBAT SISTEM IMMUNOBATOBAT--OBAT SISTEM IMMUNOBAT SISTEM IMMUN
FathiyahFathiyah SafithriSafithriLaboratoriumLaboratorium FarmakologiFarmakologi
FakultasFakultas KedokteranKedokteran UMMUMM20112011
FathiyahFathiyah SafithriSafithriLaboratoriumLaboratorium FarmakologiFarmakologi
FakultasFakultas KedokteranKedokteran UMMUMM20112011
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The immune system protect individualsagainst pathogenic viruses, microorganism and
parasites. Immune responses depend on theability of the system to recognize foreignmolecules (antigens) then to amount anappropriate reaction to eliminate the source of
the antigen.
DEFINITION
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IMMUNE SYSTEM
Innate immunity Adaptive immunity
(immune system nonspesific) (spesific system)The defenses against pathogenic Respond specifically to substancesmicroorganism that are present in and organismshost who has not been previouslyexposed to the pathogen
Complement Immunoglobulins
Natural Killer Cells T Lymphocytes
Phagocytic cells
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ImmunofarmakologiImmunofarmakologi : ilmu yang mempelajri: ilmu yang mempelajritentang bagaimana mengontrol (menekan /tentang bagaimana mengontrol (menekan /meningkatkan ) respon imun denganmeningkatkan ) respon imun dengan
mediator biologis ataupun khemismediator biologis ataupun khemisObat ImmunosupressanObat Immunosupressan : mempelajari obat: mempelajari obatyg digunakan pd keadaan overaktivasi sistemyg digunakan pd keadaan overaktivasi sistemimun (penyakit autoimun, post transplantasi)imun (penyakit autoimun, post transplantasi)Obat ImmunostimulanObat Immunostimulan : mempelajari obat: mempelajari obatyang dapat meningkatkan status imun padayang dapat meningkatkan status imun padakeadaan immunodefisiensi, HIVkeadaan immunodefisiensi, HIV- -AIDS, kanker AIDS, kanker
ImmunofarmakologiImmunofarmakologi : ilmu yang mempelajri: ilmu yang mempelajritentang bagaimana mengontrol (menekan /tentang bagaimana mengontrol (menekan /meningkatkan ) respon imun denganmeningkatkan ) respon imun dengan
mediator biologis ataupun khemismediator biologis ataupun khemisObat ImmunosupressanObat Immunosupressan : mempelajari obat: mempelajari obatyg digunakan pd keadaan overaktivasi sistemyg digunakan pd keadaan overaktivasi sistemimun (penyakit autoimun, post transplantasi)imun (penyakit autoimun, post transplantasi)Obat ImmunostimulanObat Immunostimulan : mempelajari obat: mempelajari obatyang dapat meningkatkan status imun padayang dapat meningkatkan status imun padakeadaan immunodefisiensi, HIVkeadaan immunodefisiensi, HIV- -AIDS, kanker AIDS, kanker
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Obat Sistem ImunObat Sistem ImunObat Sistem ImunObat Sistem Imun
Obat utk Penyakit AllergiObat utk Penyakit Autoimmun &Keganasan (Immunosupressan)Immunostimulan
Obat utk Penyakit AllergiObat utk Penyakit Autoimmun &Keganasan (Immunosupressan)Immunostimulan
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OBAT UNTUK PENYAKITOBAT UNTUK PENYAKIT ALLERGI ALLERGI
OBAT UNTUK PENYAKITOBAT UNTUK PENYAKIT ALLERGI ALLERGI
H1 reseptor antagonisGlukokortikoid (Kortikosteroid)
Cystenyl-Leukotrien Recept Antagonis
5-Lipoxygenase inhibitorsKromolin sodium
Epinefrin
H1 reseptor antagonisGlukokortikoid (Kortikosteroid)
Cystenyl-Leukotrien Recept Antagonis
5-Lipoxygenase inhibitorsKromolin sodium
Epinefrin
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MekanismeMekanismeAllergiAllergi
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Target Terapi Anti AllergiTarget Terapi Anti Allergi1. Me IgE berikatan dg sel mast (anti-IgE antibody)
2. Mencegah degranulasi sel mast
(kromolin, simpatomimetik)
3. Menghambat kerja mediator yg dilepaskan sel mast
(anti H1, antagonis leukotrien reseptor)
4. Me respon inflamasi (glukokortikosteroid)
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Target Terapi Anti AllergiTarget Terapi Anti AllergiTarget Terapi Anti AllergiTarget Terapi Anti Allergi
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ANTI ANTI--Ig E MONOCLONALIg E MONOCLONAL
ANTIBODY (Omalizumab) ANTIBODY (Omalizumab)
ANTI ANTI--Ig E MONOCLONALIg E MONOCLONAL
ANTIBODY (Omalizumab) ANTIBODY (Omalizumab)merup immunoglobulin G yang bekerja
sebagai antihuman Ig dg cara menghambatikatan IgE dengan mast sel
Dapat menurunkan frekuensi daneksaserbasi berulang penyakit allergi
Half life sangat panjang diberikan 1X /bulan
Diberikan melalui injeksi subkutaneus
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KROMOLIN &KROMOLIN &NEDOKROMILNEDOKROMIL
Per inhalasi Absorbsi per oral
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dibentuk dr asam amino histidin & disimpan dlmkonsentrasi tinggi di sel mast jaringan dan basofil darah.Lokasi paru, kulit, GIT
Histamin diproduksi & disekresi oleh granula mast sel.Me pd reaksi allergi yg diperantarai Ig-E (immediate),mis : seasonal rhinitis (hay fever), urticaria, andangioneurotic edema.
HISTAMINN N
N H2
H
1
2
3
45
Histamine
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Manifestasi pd allergic reactions H1 receptorMekanisme kerja : release IP3 & DAG Ca2+ intake
Kontraksi otot polos (bronkhokonstriksi, peristaltik ) Arteri vasodilatasi (H1 & H2), akibat dr pe release
endothelium-derived relaxing factor (EDRF) & PGI2.,Permeabilitas vaskuler edema, angioedema
Kontraksi jantung , aliran koroner
Sekresi kelenj eksokrin hidung & bronkus Headache, kewaspadaan Release katekolamin oleh adrenal Gatal, eritema eczema, urtica
Efek Aktivasi Reseptor Histamin-1
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Mek kerja AH1 : kompetitif inhibitor pd reseptor H1
Struktur sgt mirip dg muscarinic blockers & alphaadrenoceptor blockers (anti H1 sedatif) efekantikolinergik & antagonis adrenergikBbrp bisa memblok resept serotonin (cetirizine).efek pd resept H2 (-)
Mekanisme Kerja AH1
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AntihistaminAntihistamin- - HH11
Sedative (Sedative ( 11 stst Generation)Generation)difenhydramindifenhydraminchlorpheniraminechlorpheniramine
embraminembraminprometazinprometazincyproheptadincyproheptadinbisulepinbisulepindimetindendimetindenazatadinazatadinklemastinklemastin
Sedative (Sedative ( 11 stst Generation)Generation)difenhydramindifenhydraminchlorpheniraminechlorpheniramine
embraminembraminprometazinprometazincyproheptadincyproheptadinbisulepinbisulepindimetindendimetindenazatadinazatadinklemastinklemastin
Non sedative (Non sedative ( 22ndnd Generation)Generation)terfenadineterfenadineastemizolastemizol
cetirizincetirizinloratadinloratadin
Non sedative (Non sedative ( 22ndnd Generation)Generation)terfenadineterfenadineastemizolastemizol
cetirizincetirizinloratadinloratadin
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1. Antiallergi ( Blok pd H 1receptors perifer) u/
reaksi allergi ringan (insectbite, urtica, dll)
2. Sedasi ( blok resep H 1 & Mdi SSP)
3. Anti emetik u/ motionsickness (Dimenhidrinate)
EFEK AH1
4. Antikolinergik (retensi4. Antikolinergik (retensiurine, pand kabur,urine, pand kabur,konstipasi,mulutkonstipasi,mulutkering)kering)
5. Blok5. Blok --adrenergikadrenergik(hipotensi ortosttik)(hipotensi ortosttik)
6. Anesthesi lokal6. Anesthesi lokal
4. Antikolinergik (retensi4. Antikolinergik (retensiurine, pand kabur,urine, pand kabur,konstipasi,mulutkonstipasi,mulutkering)kering)
5. Blok5. Blok --adrenergikadrenergik(hipotensi ortosttik)(hipotensi ortosttik)
6. Anesthesi lokal6. Anesthesi lokal
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Toksisitas:Sedasi (t.u AH1 sedatif)
Antimuscarinic effects (dry mouth, blurred vision etc.) -blocking actions (orthostatic hypotension).
Interaksi :Obat dg efek sedatif ( benzodiazepin, alcohol).Obat yg menghambat metab di hepar (ketakonazol)kdr AH 1 lethal arrhythmia (terfenadin).
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ANTI LEUKOTRIEN
1.1. LTLT--11 reseptor reseptor antagonisantagonis ((ZafirlukastZafirlukast, ,montelukastmontelukast, , pranlukastpranlukast) )
efektif efektif hambhamb Ag / exercise Ag / exercise- -induced asthmainduced asthmap.op.o 11--2 x2 x seharisehari
2.2. 55--lipoxygenase inhibitorlipoxygenase inhibitor ((ZileutonZileuton))HambHamb produksiproduksi leukotrienleukotrienInteraksiInteraksi obatobat : me: me konsentr konsentr teofilinteofilin &&walfarinwalfarin did i serumserum
1.1. LTLT--11 reseptor reseptor antagonisantagonis ((ZafirlukastZafirlukast, ,montelukastmontelukast, , pranlukastpranlukast) )
efektif efektif hambhamb Ag / exercise Ag / exercise- -induced asthmainduced asthmap.op.o 11--2 x2 x seharisehari
2.2. 55--lipoxygenase inhibitorlipoxygenase inhibitor ((ZileutonZileuton))HambHamb produksiproduksi leukotrienleukotrienInteraksiInteraksi obatobat : me: me konsentr konsentr teofilinteofilin &&walfarinwalfarin did i serumserum
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GLUKOKORTI KOSTEROI D
Newton, Thorax2000; 55: 603-613
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Hypothalamic-Pituitary Adrenal (HPA) AxisHypothalamic-Pituitary Adrenal (HPA) Axis
Adrenal cortexAdrenal cortex
Produces 30 steroid hormones
Major divisions include:Glucocorticoids
MineralocorticoidsAdrenal Sex steroids
Negative Feedback controlof ACTH Production.Suppression of HPA
STRESS : Overrides theneg. feedback mechanism.
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Disorders of the Adrenal CortexDisorders of the Adrenal CortexDisorders of the Adrenal CortexDisorders of the Adrenal CortexPrimary Adrenocortical Insufficiency (Addisons Disease)
Destruction of the adrenal cortex leads to inadequate production of
cortisol and aldosterone.Tuberculosis, cancer, hemorrhage Atrophy of the adrenal cortex
Autoimmune diseaseProlonged corticosteroid treatment (Long-term admin)Surgical excision of the adrenal glands
Secondary Adrenocortical Insufficiency; inadequate secretion ofcorticosteroid. Mainly a GC deficiency
Prolonged treatment with cortocosteroids (early effects) Mineralocorticoid secretion is not altered.
Congenital Adrenogenital Syndromes and Adrenal Hyperplasia Synthetic enzyme deficiency Abnormally low cortisol levels results in excessive ACTH secretion,
excessive adrenal secretion of androgens and hyperplasia.
Adrenocortical Hyperfunction (Cushings Disease: Moonface) Excessive ACTH secretion Adrenal tumor (benign or malignant)
Abnormally high corticosteroid levels
Primary Adrenocortical Insufficiency (Addisons Disease) Destruction of the adrenal cortex leads to inadequate production of
cortisol and aldosterone.Tuberculosis, cancer, hemorrhage Atrophy of the adrenal cortex
Autoimmune diseaseProlonged corticosteroid treatment (Long-term admin)Surgical excision of the adrenal glands
Secondary Adrenocortical Insufficiency; inadequate secretion ofcorticosteroid. Mainly a GC deficiency
Prolonged treatment with cortocosteroids (early effects) Mineralocorticoid secretion is not altered.
Congenital Adrenogenital Syndromes and Adrenal Hyperplasia Synthetic enzyme deficiency Abnormally low cortisol levels results in excessive ACTH secretion,
excessive adrenal secretion of androgens and hyperplasia.
Adrenocortical Hyperfunction (Cushings Disease: Moonface) Excessive ACTH secretion Adrenal tumor (benign or malignant)
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Aktivasi Reseptor SteroidAktivasi Reseptor SteroidAktivasi Rese ptor SteroidAktivasi Reseptor Steroid
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Aktivasi Reseptor Steroid Aktivasi Reseptor Steroid Aktivasi Reseptor Steroid Aktivasi Reseptor Steroid
S mengikat resept S(R) di sitoplasma, R sec normal berhubS mengikat resept S(R) di sitoplasma, R sec normal berhubdg 2 molekul hsp90. kompleks Sdg 2 molekul hsp90. kompleks S- -R translokasi ke nukleusR translokasi ke nukleusdan berinteraksi dg GRE (glucocort icos teroid responsedan berinteraksi dg GRE (glucocort icos teroid responseelement) pd rantai promotor sel targetelement) pd rantai promotor sel target mempengaruhimempengaruhi
proses transkripsi & sintesa proteinproses transkripsi & sintesa protein
Antara lain menyebabkan : Antara lain menyebabkan :Induksi sintesa polipeptida (lipocortin-1) yg menghambat enzimfosfolipase A2 menurunkan produksi mediator inflamasi (PG,leukotrien, platelet-activating factor /PAF)Netralisasi peran transcription factor (mis. AP1) dlm sintesa sitokin(IL5, TNF ) sintesa sitokin me inflamasi
S mengikat resept S(R) di sitoplasma, R sec normal berhubS mengikat resept S(R) di sitoplasma, R sec normal berhubdg 2 molekul hsp90. kompleks Sdg 2 molekul hsp90. kompleks S- -R translokasi ke nukleusR translokasi ke nukleusdan berinteraksi dg GRE (glucocort icos teroid responsedan berinteraksi dg GRE (glucocort icos teroid responseelement) pd rantai promotor sel targetelement) pd rantai promotor sel target mempengaruhimempengaruhi
proses transkripsi & sintesa proteinproses transkripsi & sintesa protein
Antara lain menyebabkan : Antara lain menyebabkan :Induksi sintesa polipeptida (lipocortin-1) yg menghambat enzimfosfolipase A2 menurunkan produksi mediator inflamasi (PG,leukotrien, platelet-activating factor /PAF)Netralisasi peran transcription factor (mis. AP1) dlm sintesa sitokin(IL5, TNF ) sintesa sitokin me inflamasi
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FISIOLOGI KORTISOL
Metabolic Effect Anti-inflammatory effect Antiproliferative effectImmunosuppressive effect
Metabolic Effect Anti-inflammatory effect Antiproliferative effectImmunosuppressive effect
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A. Metabolisme Glukosa, Lemak dan Protein A. Metabolisme Glukosa, Lemak dan Protein
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B. Mekanisme KerjaSteroid sbg Anti-Inflammasi
B. Mekanisme KerjaSteroid sbg Anti-Inflammasi
Menghambat aktivasi T-cell dan produksi sitokin.
Menghambat degranulasi mast cell.
Menurunkan permeabilitas kapiler secara tidak langsung akibathambatan pada mast cells dan basophils.
Menurunkan ekspresi cyclooxygenase II (COX2) dan sintesa
prostaglandin.
Induksi sintesa lipocortin1 hamb enz fosfolipase A2 mekadar prostaglandin, leukotriene and platelet activating factor(PAF)
Menghambat aktivasi T-cell dan produksi sitokin.
Menghambat degranulasi mast cell.
Menurunkan permeabilitas kapiler secara tidak langsung akibathambatan pada mast cells dan basophils.
Menurunkan ekspresi cyclooxygenase II (COX2) dan sintesa
prostaglandin.
Induksi sintesa lipocortin1 hamb enz fosfolipase A2 mekadar prostaglandin, leukotriene and platelet activating factor(PAF)
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B. Mechanism of Action for Anti-Inflammatory SteroidsB. Mechanism of Action for Anti-Inflammatory Steroids
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Penggunaan GlukokortikoidPenggunaan GlukokortikoidPenggunaan GlukokortikoidPenggunaan Glukokortikoid
IInsufisiensi AdrenalSupresi HPA-axis overaktif Supresi penyakit autoimmunMencegah rejeksi organ transplantasiTerapi limfosit-derived tumor Terapi penyakit allergi (asma, penyakit kulitallergi)
IInsufisiensi AdrenalSupresi HPA-axis overaktif Supresi penyakit autoimmunMencegah rejeksi organ transplantasiTerapi limfosit-derived tumor Terapi penyakit allergi (asma, penyakit kulitallergi)
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NONENDOCRINE DISORDERS TREATED WITHGLUCOCORTICOIDS
NONENDOCRINE DISORDERS TREATED WITHGLUCOCORTICOIDS
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Routes of Administration for GCRoutes of Administration for GC
Local (Preferred)(Preferred)Intra-articular, IAIntrabursal, IBIntralesional, IL
Intrasynovial, ISSoft tissue, STIntrarectal, IRTopicalNasalInhaled
SystemicOral, POIntramuscular, IMIntravenous, IV
Local (Preferred)(Preferred)Intra-articular, IAIntrabursal, IBIntralesional, IL
Intrasynovial, ISSoft tissue, STIntrarectal, IRTopicalNasalInhaled
SystemicOral, POIntramuscular, IMIntravenous, IV
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Farmakokinetik GCFarmakokinetik GCFarmakokinetik GCFarmakokinetik GC
Pemberian corticosteroids pd konsentrasi fisiologisselama minimal 2 minggu akan menekan HPA axis,shg terjadi penurunan endogenous hormones.Recovery setelah 9-12 bulan.
Metabolisme Hepar :Hepar : tempat inaktivasi / metabolisme utama GC. GCdimetabolisme oleh enzim cytochrome P450 3A425% GC diekskresi bersama empedu & feces .
Renal Clearance75 % metabolit GC diekskresi bersama urine ..
Pemberian corticosteroids pd konsentrasi fisiologisselama minimal 2 minggu akan menekan HPA axis,shg terjadi penurunan endogenous hormones.Recovery setelah 9-12 bulan.
Metabolisme He par :Hepar : tempat inaktivasi / metabolisme utama GC. GCdimetabolisme oleh enzim cytochrome P450 3A425% GC diekskresi bersama empedu & feces .
Renal Clearance75 % metabolit GC diekskresi bersama urine ..
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Dampak Pemberian Kortikosteroid padaCortisol Release
Dampak Pemberian Kortikosteroid padaCortisol Release
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Corticosteroids control symptoms and DO NOT stop progression (cure) of the disease
Mineralocorticoid actvity
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AntiAnti--inflammatory Drugsinflammatory DrugsGlucocorticoidsGlucocorticoids
InhaledInhaledBeclomethasoneBeclomethasoneBudesonideBudesonideFlunisolideFlunisolideFluticasone propionateFluticasone propionateTriamcinolone acetonideTriamcinolone acetonide
Oral (Quick relief of asthmatic symptoms)PrednisonePrednisolone* Unresponsive to 2 agonists
AntiAnti--inflammatory Drugsinflammatory DrugsGlucocorticoidsGlucocorticoids
InhaledInhaledBeclomethasoneBeclomethasoneBudesonideBudesonideFlunisolideFlunisolideFluticasone propionateFluticasone propionateTriamcinolone acetonideTriamcinolone acetonide
Oral (Quick relief of asthmatic symptoms)PrednisonePrednisolone* Unresponsive to 2 agonists
Metered Dose
Inhaler Al so, Dry-powder inhalersand Nebulizers
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Kortikosteroid SistemikKortikosteroid SistemikKortikosteroid SistemikKortikosteroid Sistemik
Triamcinolone 5 0 18-36 3,0
Betamethasone 25 0 18-36 4,0
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Kortikosteroid TopikalKortikosteroid TopikalKortikosteroid TopikalKortikosteroid Topikal
Level of PotencyLevel of Potency CorticosteroidCorticosteroid Commercial ProductsCommercial Products
UltraUltra--highhigh Halobetasol propionateHalobetasol pro pionateClobetasol pro pionateClobetasol pro pionateBetamethasone diprop ionateBetamethasone diprop ionate
Diflorasone d iacetateDiflorasone d iacetate
Ultravate crm/ointUltravate crm/ointTemovate crm/ointTemovate crm/ointDiprolene ointDiprolene oint
Psorcon ointPsorcon oint
HighHigh HalcinonideHalcinonide Amcinonide AmcinonideBetamethasone diprop ionateBetamethasone diprop ionateMometasone fu roateMometasone fu roateDiflorasone d iacetateDiflorasone d iacetateFluocinonideFluocinonideDesoximetasoneDesoximetasone
Halog c rmHalog c rmCylocort ointCylocort ointDiprolene AF crmDiprolene AF crmElocon ointElocon ointFlorone ointFlorone ointLidex crm,gel,ointLidex crm,gel,ointTopicort crm,oint,gelTopicort crm,oint,gel
Mild to highMild to high HalcinonideHalcinonideTriamcinolone acetonideTriamcinolone acetonideBetamethasone diprop ionateBetamethasone diprop ionateFluocinonideFluocinonide
Halog oint,crm,solnHalog oint,crm,soln Aristoc ort A o in t Aristoc ort A o in tDiprosone crmDiprosone crmLidexLidex--E crmE crm
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Kortikosteroid TopikalKortikosteroid TopikalKortikosteroid TopikalKortikosteroid Topikal
Level of PotencyLevel of Potency CorticosteroidCorticosteroid Commercial ProductsCommercial Products
MildMild Hydrocortisone valerateHydrocortison e valerateTriamcinolone acetonideTriamcinolone acetonideFlurandrenolideFlurandrenolide
Mometasone fu roateMometasone fu roateFluocinolone acetonideFluocinolone acetonide
WestcortWestcortKenalog crm and ointKenalog crm and ointCordran ointCordran oint
Elocon crmElocon crmSynalar oin tSynalar oin t
Low to mildLow to mild Hydrocortisone valerateHydrocortison e valerateTriamcinolone acetonideTriamcinolone acetonideFlurandrenolideFlurandrenolideBetamethasone dipropionateBetamethasone dipropionateHydrocortisone butyrateHydrocortisone butyrateFlucolone acetonideFlucolone acetonide
Westcort c rmWestcort c rmKenalog crm and ointKenalog crm and ointCordran crmCordran crmDiprosone lotionDiprosone lotionLocoid crmLocoid crmSynalar crmSynalar crm
LowLow Alclometasone dipropionate Alc lometasone diprop ionateBetamethasone valerateBetamethasone valerateFluocinolone acetonideFluocinolone acetonideHydrocortison e, dexamethasone,Hydrocortison e, dexamethasone,prednisolone, methylprednisoloneprednisolone, methylprednisolone
Aclovate crm and o int Aclovate crm and o intValisone lo tionValisone lo tionSynalar soln and crmSynalar soln and crm
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Efek Samping Pemakaian KortikoSteroid jangka panjang
Efek Samping Pemakaian KortikoSteroid jangka panjang
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Efek SampingEfek SampingEfek SampingEfek Samping
Adrenocortical insufficiency: Suppression of HPA
Adrenocortical excess (Cushings disease): Moon face, buffalohump Diabetes Mellitus
CNS effects: psychological and behavioral changes; aggravationof pre-existing psychiatric disorders.
Impaired wound healing
Musculoskeletal effects: osteoporosis (brittle bones), muscleweakness and atrophy
Cardiovascular effects: fluid retention, edema, hypertension.
Adrenocortical insufficiency: Suppression of HPA
Adrenocortical excess (Cushings disease): Moon face, buffalohump Diabetes Mellitus
CNS effects: psychological and behavioral changes; aggravationof pre-existing psychiatric disorders.
Impaired wound healing
Musculoskeletal effects: osteoporosis (brittle bones), muscleweakness and atrophy
Cardiovascular effects: fluid retention, edema, hypertension.
Glucocorticoid Withdrawal: Should be performed slowlyWithdrawal syndrome: hypotension, hypoglycemia, myalgia and fatigue
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Cushing Syndrome (Hypercorticism)Cushing Syndrome (Hypercorticism)Cushin g Syndrome (Hypercorticism)Cushing Syndrome (Hypercorticism)
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Strategi Mencegah ES Jangka PanjangStrategi Mencegah ES Jangka PanjangKortikosteroidKortikosteroid
Strategi Mencegah ES Jangka PanjangStrategi Mencegah ES Jangka PanjangKortikosteroidKortikosteroid
Pemberian dengan dosis intermit tenPemberian dengan dosis intermit ten(alternate(alternate- -day), mis. setiap 2hari sekaliday), mis. setiap 2hari sekaliPemberian yg berefek lokal : topikal atauPemberian yg berefek lokal : topikal atau
inhalasiinhalasi
Pemberian dengan dosis intermit tenPemberian dengan dosis intermit ten(alternate(alternate- -day), mis. setiap 2hari sekaliday), mis. setiap 2hari sekaliPemberian yg berefek lokal : topikal atauPemberian yg berefek lokal : topikal atau
inhalasiinhalasi
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Drug InteractionsDrug InteractionsDrug InteractionsDrug Interactions
Drugs that Enhance Corticosteroid EffectsEstrogensOral contraceptives
Antifungal agents
Antibiotics*all of these agents inhibit cytochrome P450 enyzymes
Drugs that Reduce Corticosteroid Effects AntacidsCholestyramine
*these drugs decrease the absorption of corticosteroidsPhenytoin: activate cytochrome P450 enyzymes
Drugs that Enhance Corticosteroid EffectsEstrogensOral contraceptives
Antifungal agents
Antibiotics*all of these agents inhibit cytochrome P450 enyzymes
Drugs that Reduce Corticosteroid Effects AntacidsCholestyramine
*these drugs decrease the absorption of corticosteroidsPhenytoin: activate cytochrome P450 enyzymes
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SYOK ANAFILAKTIKSYOK ANAFILAKTIKSYOK ANAFILAKTIKSYOK ANAFILAKTIK
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Clinical Features of AnaphylaxisClinical Features of Anaphylaxis
- Is there a predisposition? Latex and food allergies usuallyoccur against a background of atopy and other allergicdisorders e.g. asthma and eczema.
- Onset is rapid (5-10 minutes of exposure) peaking in 30minutes. Duration can be long especially if allergen persists(e.g. swallowed) or the response is biphasic (classical late-phase allergic response in the airways)
- May be heralded by impending sense of doom.Subsequent features reflect to some extent route of allergenexposure:
Systemic (IV drugs) - cardiovascular
(hypotension/syncope) Ingested (food allergens) - respiratory (laryngealoedema/bronchoconstriction) Percutaneous (insect stings) - respiratory orcardiovascular problems equally likely
All may be accompanied by cutaneous features
e.g. urticarial rash.
Urticarial Rash
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Features Suggesting Severe Anaphylactic Reaction
Wheeze Stridor
Cyanosis Skin Pallor* Prominent Tachycardia**
* 80% of fatal food-related anaphylactic reactions have no skin signs** Compared to bradycardia in vasovagal attack
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20052005GuidelinesGuidelinesof the UKof the UK
ResuscitatiResuscitation Councilon Council
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EPINEFRIN /ADRENALINEPINEFRIN /ADRENALINEPINEFRIN /ADRENALINEPINEFRIN /ADRENALIN
Bukan anti allergi, tp sering dipakai pd kasusallergi 1 st line drug syok anafilaktikMek kerja : agonis kuat resept &
adrenergikBerfungsi :
memberi efek antagonis thd efek mediatorinflamasi pada otot polos
Menghambat Ag-induced release mediatorinflamasi dari sel mast
Bukan anti allergi, tp sering dipakai pd kasusallergi 1 st line drug syok anafilaktikMek kerja : agonis kuat resept &
adrenergikBerfungsi :
memberi efek antagonis thd efek mediatorinflamasi pada otot polos
Menghambat Ag-induced release mediatorinflamasi dari sel mast
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The Use of Adrenaline in Anaphylaxis
The problems with its use :
Variable Absorpt ion - give IM AVOID SC Arrhythmogenic in high dose - NEVER give 1:1000 ADRENALINE IV
If using ADRENALINE as an IVI, it must be diluted and do not delayadministration of ADRENALINE to set up IVI and gain IV access.
Therefore:
1. Give ADRENALINE IM promptly (can repeat at 5-10 min intervals)
2. Gain IV access3. If patient remains shocked resort to IVI thus .
Dilute 0.5ml of 1:1000 ADRENALINE in 50ml of N/saline (1:100,000)4. Infuse at 0.1-2ml/min (1-20ug/min) until haemodynamically stable
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Other drugs used in Anaphylaxis
Nebul ised or IV 2 agonist (e.g. salbutamol) - useful wherebronchospasm is the major sign and fails to respond promptly to IMadrenaline.
IV Glucocorticoid (e.g. hydrocortisone 200-500mg) - probably oflimited efficacy (onset of action delayed 3-6 hrs) except where theresponse is biphasic or asthmatic features predominate.
IV Glucagon (1mg in 1L, infused at 5-15ml/min) - anecdotal reports of efficacy inrefractory hypotension. Releases catecholamines and +ve inotrope (raising cAMPindependent of cardiac -adrenoceptors).
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Tanya apa ya ???..