Post on 02-Mar-2018
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Dermatoterapi Topical
Anggelia Puspasari, dr
Bagian Farmakologi dan TerapiFakultas Kedokteran dan Ilmu
Kesehatan
Universitas Jambi
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Pendahuluan
Terapi topikal didenisikansebagai aplikasiobat dengan !ormulasi tertentu pada kulit"ang bertu#uan mengobati pen"akit kulit
atau pen"akit sistemik "ang bermani!estasipada kulit$
Terapi topikal merupakan metode "angn"aman, namun keberhasilann"abergantung pada pemahaman kitamengenai !ungsi sa%ar kulit$
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Pendahuluan
Keuntungan
&emintas rst'pass
metabolism$ &enghindari resikodanketidakn"amananpemberian obat I(
maupun oral )!ek samping dan I*#arang ter#ad Absorbsi tidak
dipengaruhi kondisi
saluran cerna
Kelemahan
Dapat menimbulkan
dermatitis kontak Beberapa obatmemilikipermeabilitas kulit"ang rendah
Denaturasi olehen+im kulit
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truktur kulit-apisan kulit.Epidermis :
lapisan terluar dari kulit,ketebalann"a /$/0 mmpada kelopak mata sampai1$0 mm pada telapak kaki$
Terdapat 0 lapis pen"usunepidermis$ Tiap lapis
mengekspresikan keratin"ang berbeda$
Proses akhir di!erensiasikeratinosit menghasilkanst$korneum "ang ber!ungsimencegah ter#adin"a
kehilangan air danpen"erapan +at "gberbaha"a bagi tubuh$
Diba%ah st$korneumterdapat lapisan granular"ang mempun"ai granulakerato hialin, granula
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truktur kulit
-apisan kulit.Dermis: Ber!ungsi untuk
men"okong dermis$
Ketebalan bervariasi$ Padalapisan tersebut
terdapat pembuluh darah,sara! dan struktur lain,"aitu !olikel rambut,kelen#ar keringat, dan
kelen#ar sebum "ang #ugaberperan penting dalamproses pen"erapan obatmelalui kulit$
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Farmakokinetik sediaan kulit
Perubahan konsentrasi obatsetelah aplikasin"a padapermukaan kulit$
Per#alanann"a menembussa%ar kulit dan #aringan di
ba%ahn"a$ Distribusin"a ke dalam sirkulasi
sistemik$ &asuk ke dalam kulit mengikuti
suatu gradien konsentrasi2di!usi pasi!3
Tiga kompartemen "ang dilaluiobat akti!, "aitu vehikulumsebagai pemba%a obat akti!,stratum korneum, dan lapisanepidermis serta dermis
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Farmakokinetik sediaan kulit Pelepasan4 disolusi bahan akti!
dari vehikulumn"a ditentukanoleh koesien partisin"a$ &akin besar nilai koesien
partisi, maka bahan akti! makinmudah terlepas dari vehikulum$
Di!usi bahan akti! terutama
berlangsung melalui !olikelrambut 2#alur trans!olikular3$
etelah tercapai keseimbangan2steady state3, di!usi melaluistratum korneum men#adi lebihdominan
Di!usi bahan4obat akti!mencapai lapisan epidermishingga kemudian dermissetelah mele%ati transkornealdan trans !olikuler
Pembuluh darah didermis
memungkin absorbsi obatsistemik$
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Faktor "ang memepengaruhipen"erapan obat melalui kulit
Fisikokimia%i obat 2kosentrasi obat,koesien partisi dan ukuran molekulobat3
Penetrasi enhancer
*klusi dan lokasi aplikasi obat
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(ehiculum
(ehikulum adalah +at inakti!4inert"ang digunakan pada sediaan topikalsebagai obat4+at akti! agar dapat
berkontak dengan kulit
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(ehiculum
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-uas area lesi (s #umlah obat "ang
dibutuhkan
5ambar di lippincot
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Prinsip pemilihan sediaan
2vehiculum based3
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T*PI6A- A7TII7F)6TI()
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A7TIBI*TIK T*PI6A-
Patogen utama pada in!eksi kulitmeliputi streptococcus beta hemoliticgrup A, staphylococcus aureus,
streptococcus pyogenes maupunkombinasi diantaran"a$
In!eksi gram negati! pada kulit #arang
ter#adi$ Agent utama meliputi mupirocin,
bacitrasin, %alaupun sediaan lain
berupa neomisin, gentamisin
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A7TIBI*TIK T*PI6A- 2prinsip terapi3
Pilih obat "ang sesuai berdasarkan diagnosis dankultur kulit bila memungkinkan$
Antibiotik sistemik #uga diperlukan bila di#umpaiimpetigo di!usse, selulitis dan in!eksi "ang lebih
pro!unda dan luas$ Pengobatan harus dievaluasi, bila dalam 8'0 hari tidak
ada perubahan pertimbangkan mengganti terapi$
Penggunaan #angka pan#ang memerlukan pemantauan
khusus terkait dengan pertumbuhan berlebihanorganisme nonsuspectibel$
7eomisin topikal lebih sering menimbulkan dermatitiskontak$
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A7TIBI*TIK T*PI6A-
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A7TIBI*TIK T*PI6A- 2spesic drug .
mupirocin3
I . impetigo "ang disebabkan $ aureus 2termasukmetichillin resistan dan kuman "ang memproduksi beta'laktamase3, beta'hemolitic, streptococcus, $p"ogenes$
KI . alergi terhadap mupirocin, tidak boleh digunakan
pada mata$ P . &upirosin tidak di!ormulasikan untuk aplikasi
mukosa$ Komponen dasar sediaan biasan"a adalahpol"eth"len gl"col 2diabsorbsi sistemik terutama padakulit rusak,,,999penggunaan pada pasien renal !ailure3
Indeks keamanan kehamilan . B 2studi pada %anitahamil belum ada3
)kskresi pada AI belum diketahui$
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A7TIBI*TIK T*PI6A- 2spesic drug .
mupirocin3
Farmakokinetik . pen"erapansistemik tidak berarti
) . reaksi alergi lokal
Dosis dan cara pemberian . lihattabel 11'8
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A7TIBI*TIK T*PI6A- 2spesic drug .
bacitracin3
Antibiotic polipeptida
Inhibisi bakteri gram positi!
Absorbsi kulit angat sedikit :eaksi alergi #arang ter#adi$
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A7TIBI*TIK T*PI6A- 2spesic drug .neomisisn dan gentamisin3
5olongan aminoglikosida
)!ekti! memerangi bakteri gram negative
5entamisin lebih e!ektive daripada
neomisin dalam memerangi P$aureginosa,staph"lococcus, streptococcus beta'hemolitikus grup A$
Pada pasien dengan gagal gin#al, obat"ang terakumulasi dapat men"ebabkanne!rotoksik, neurotoksik dan ototoksik$
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A7TIBI*TIK T*PI6A- 2spesic drug .Polymyxin B sulfate3
ediaan topikal "ang paling e!ekti!terhadap organisme anaerob dangram negati! 2P$aureginosa, )$coli,
Klebsiella p, enterobacter3
Bakteri gram'positive dan strainproteus, serratia resisten$
:eaksi alergi #arang ter#adi$
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A7TIFU75A- T*PI6A- 2overvie%3
Pemilihan terapi sistemik atau topikalbergantung pada keparahan in!eksi, luasin!eksi dan ri%a"at terapi sebelumn"a$
Tinea berkaiatan dengan in!eksi olehdermatophyte, organisme "ang palingsering men"ebabkan tinea pada kulit, kukudan rambut$
In!eksi lainn"a disebabkan oleh candidasp$ ering men"erang daerah lipatan daninguinal$
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A7TIFU75A- T*PI6A- 2evidencebase recommendation3
Topikal all"lamines dan a+ole e!ekti!untuk athlete;s !oot
*ral itracona+ole dan terbinanee!ekti! untuk onikomikosis$
*ral
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A7TIFU75A- T*PI6A- 2prinsip
terapi3
*leskan dengan sedikit dipi#at pada area lesi dansekitarn"a
etelah ge#ala hilang terapi dilan#utkan sampai batasakhir %aktu turnover kulit$
ediaan gabungan anti!ungal dan steroid han"adigunakan untuk !ase in
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A7TIFU75A- T*PI6A- 2edukasi
pasien3
ebelum terapi cuci dengan sabundan air serta keringkan area lesi$
)dukasi kebersihan diri$
etelah ge#ala menghilang terapitetap dilan#utkan sesuai #ad%al danpenilaian klinis dokter$
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Tabel 11$?
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A7TI(I:A- T*PI6A- 2ac"clovir,
penciclovir3
Ac"clovir . managemen untuk herpes genitalis,pada pasien immunocompromised han"a untuklesi terabatas mukokutan "ang tidakmengancam n"a%a, active terhadap @(,varicella +oster, )B(, 6&(
Penciclovir. recurrent herpes labialis padade%asa, active terhadap @(
P. han"a untuk pemakaian luar, indekskeamanan kehamilan B, compatible for breastfeeding, keamanan dan ekasi untuk anakbelum diketahui
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A7TI(I:A- T*PI6A- 2ac"clovir,
penciclovir3
@an"a untuk penggunaan luar
Jangan diaplikasikan pada daerah sekitarmata
&ulai segera setelah adan"a bukti in!eksi D . Ac"clovir 0 oinment$ *leskan pada
tempat lesi =4hari selama C hari$
D . penciclovor 1 cream$ *leskansetiap > #am di%aktu bangun selama ?hari, gunakan han"a di bibir dan %a#ah$
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6ABI6ID)4P)DI6U-I6ID)2overvie%3
cabies disebabkan oleh arcoptes scabies 2%aktuhidup 8/ hari, 1 #am setelah mengin!eksi kulit,betina akan menggali tero%ongan di t$corneumdan meletakkan telur 8 butir4hari, telur akan
berkembang men#adi matang pada hari ke 1?'1C$ eorang penderita akan merasakan ge#ala setelah
1 bulan proses diatas belangsung$
Kutu men"ebabkan pedukulosis, ada 8 kutu badan
"aitu P$humanus var$capitis, P$@umanus var$corporisdan pthirus pubis$
Kutu makan 0= sehari, menggunakan mulut untukmelukai kulit, mengeluarkan saliva dan menghisapdarah, siklus hidup 1 bulan$
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6ABI6ID)4P)DI6U-I6ID)2evidence
based recommendation3
&alation dan permetrin e!ekti! untukkutu kepala
Permetrin e!ekti! untuk skabies,cromation kurang e!ekti!$
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6ABI6ID)4P)DI6U-I6ID)2prinsip
terapi3
Scabies
1stline . krim permetrin 0 diaplikasikankeseluruh tubuh 2leher keba%ah3 dan
dibasuh setelah '1? #am$ Pada in!ant >bulan atau lebih usapkan #uga pada garisrambut, leher, kulit kepala dan dahi$
Pediculosis-head1stline . permetrin 1 sd 0
>ndline . malathion
8rd
line . lindane
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6ABI6ID)4P)DI6U-I6ID)2prinsip
terapi3
Pediculosis-body
1stline . krim permetrin 1 dioleskanpada area terin!eksi dan bersihkan
setelah 1/ menit>ndline . lotio malathion /$0 dioleskanselama '1> #am
semua orang yang terinfeksi dalamkeluarga/yang tinggal satu rumah harus
diterapi bersamaan.
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6ABI6ID)4P)DI6U-I6ID)2prinsip
terapi3
Pemakaian lindane dapat menimbulkanneurotoksisitastermasuk ke#ang demikian
#uga malathion$
Permetrin 0 lebih e!ekti! dibandingkan 1atau sen"a%a naturaln"a p"rethrins$ angataman bila digunakan sesuai petun#uk "angbenar$
&alathion adalah sen"a%a organopospat,paling cepat membasmi telur, kerugianpenggunaan meliputi bau dan bahan dasaralkohol, e!ekti! bagi "ang resisten terhadap
permetrin$
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6ABI6ID)4P)DI6U-I6ID)2prinsip
terapi3
-indan adalah pestisida slo%'killing, tersimpankedalam #aringan lemak dan sara!$
Ivermectin merupakan pilihan bila terapi kutukepala selainn"a gagal, bukan ovicidal sehinggadiperlukan tambahan$
:eevaluasi 1/ hari setelah terapi, pertimbangkanterapi ulang bila tidak ada perubahan ge#ala$
Pada scabies, gatal bertahan sampai denganbeberapa minggu setelah terapi, triamcinolone/$1 dapat membantu$
Pada pedikulosis, bila kutu hidup masih di#umpai1 minggu setelah terapi, ulangi terapi$
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6ABI6ID)4P)DI6U-I6ID)
Indeks keamanan kehamilan
6 2cromation, lindane, p"rethrins,ivermectin3
B 2malathion dan permetrin3
ekresi lindan pada air susu iburendah
ekresi malation, permetrin dancrotamiton pada AI tidak diketahui
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6ABI6ID)4P)DI6U-I6ID)
Kocok cairan dengan baik
Aplikasikan sesuai petun#uk
Terapi semua anggota rumah
6uci semua ba#u dan linen dengansabun dan air panas
Aplikasi obat ulang bila C'1/ harisetelahn"a di#umpai kutu hidup$
&in"ak akan mempercepat absorpsi$
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Pharmakokinetik pediculicides
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Kortikosteroidtopical
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Topical Kortikosteroid
Ehen prescribing topical steroids, it is
important to consider the diagnosis as%ell as steroid potenc", deliver"vehicle, !reuenc" o! administration,
duration o! treatment, and side eGects$ Topical corticosteroids are eGective !or
conditions that are characteri+ed b"
h"perproli!eration, in
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Kortikosteroid topical
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Steroid vehicles
*intmentsprovide more lubrication and occlusion than otherpreparations, and are the most use!ul !or treating dr" or thick,h"perkeratotic lesions$
*intments should not be used on hair" areas, and ma" causemaceration and !olliculitis i! used on intertriginous areas$
6reams are generall" less potent than ointments o! the samemedication$
Acute e=udative in
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Steroid potency
The antiin
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Steroid potency
-o%'potenc" steroids are the sa!est agents !orlongterm use, on large sur!ace areas, on the !aceor areas o! the bod" %ith thinner skin, and onchildren$
&ore potent agents are benecial !or severediseases and !or areas o! the bod" %here the skinis thicker, such as the palms and bottoms o! the!eet$
@igh' and ultra'highpotenc" steroids should not beused on the !ace, groin, a=illa, or under occlusion,e=cept in rare situations and !or short durations
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Steroid potency
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Steroid potency
F d d ti
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Frequency and durationtreatment
6hronic application o! topical steroids can inducetolerance and tach"ph"la=is$
Ultra'high'potenc" steroids should not be used!or more than three %eeks continuousl"$
I! a longer duration is needed, the steroid shouldbe graduall" tapered to avoid rebounds"mptoms, and treatment should be resumeda!ter a steroid'!ree period o! at least one %eek$
The amount o! steroid the patient should appl"to a particular area can be determined b" usingthe ngertip unit method
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Side efectTo reduce the risk, the least potent steroid should be used
!or the shortest time, %hile still maintaining eGectiveness$The most common side eGect o! topical corticosteroid use
is skin atroph"$
All topical steroids can induce atroph", but higher potenc"steroids, occlusion, thinner skin, and older patient age
increase the risk$
*ther side eGects !rom topical steroids include permanentdermal atroph", telangiectasia, and striae$
Topical steroids can also induce rosacea, contact
dermatitis, h"popigmentasi, %orsen in!ection$ @"pothalamic'pituitar"'adrenal suppression, glaucoma,
septic necrosis o! the !emoral head, h"pergl"cemia,h"pertension,and other s"stemic side eGects have beenreported$
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ntiacne topical
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Pathophysiolo!i cne vul!aris
Acne lesions arise !rom pilosebaceousunits, %hich consist o! sebaceous glandsand small hair !ollicles$
The pilosebaceous units atroph" duringchildhood but, under the in
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Pathophysiolo!y cne vul!aris
)=cess sebum production combined %ithincreased epithelial cell turnover leads to!ormation o! microcomedones$
The combination o! sebum and desuamatedcells provides an environment that is ripe !orthe gro%th o! Propionibacterium acnes, theprincipal organism in in
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tages o! acne$ (A)7ormal!ollicle (B)open comedo2blackhead3 ()closed comedo2%hitehead3(!)papule (")pustule$
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cne "ul!aris is related to # $actors:
Presence o! hormones 2androgens3
ebaceous gland activit" 2increased inpresence o! androgens3
P. acnes2bacteria3 in the hair !ollicle2lives on the oil and breaks it do%n to!ree !att" acids %hich cause
in
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cne vul!aris
6haracteri+ed b" open and closed comedones,papules, pustules, c"sts, nodulesand o!ten scars
*pen comedones are
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cne vul!aris
a$ 6omedonal b$Papule pustule c$nodular c"stic acne$
Acne classied as mild 2comedonalacne3, moderate 2papular and pustularacne3 and severe 2c"stic acne3
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%lassi&cation o$ cne vul!aris
6lassication o! acne is based on themorpholog"L5rade 1. open comedones
L5rade >. open and closed comedones andsome papulopustulesL5rade 8. pustular acneL5rade ?. noduloc"stic acneIt is euall" important to describe theseverit" 2each grade can be mild to severedepending on the amount o! acne3 and
note the presence o! scarring !or each
' di ti b $ di ti
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'edications: number o$ medications can cause or
(orsen acne includin!:
L-ithium
LPhen"toin
LIsonia+id
L"stemic corticosteroids
LAndrogens
LAnti'depressantsL6ertain chemotherap" medications
)mportant *istory )tems
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)mportant *istory )tems
Diet. Diets %ith high gl"cemic load ma" %orsenacne$ -o%ering the gl"cemic load o! the dietma" improve acne$ 6hocolate and oils in thediet are not causal e=cept through this
mechanism$
Eeight gain and supplements. Anabolicsteroids can cause and %orsen acne$Eeight'gaining and vitamin supplements ma" containlarge amounts o! iodine, %hich can %orsenacne$
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Epidemiolo!y cne vul!aris
T"picall" presents at ages '1> 2o!tenthe rst sign o! pubert"3, peaks at ages10'1, and resolves b" age >0
AGects M/ o! adolescents and aGectsraces euall"
Famil" histor" is o!ten positive
1> o! %omen and 8 o! men %ill haveacne until their ?/s
In %omen it is not uncommon to have arst outbreak at >/'80 "ears o! age
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"ehicles Treatments
6reamsare appropriate !or patients %ithsensitive or dr" skin %ho reuire a nonirritating,nondr"ing !ormulation$
Patients %ho have oil" skin ma" be more
com!ortable %ith gels, %hich have a dr"ingeGect$
-otions can be used %ith an" skin t"pe, and the"spread %ell over hair'bearing skin$
olutionsare mainl" used %ith topical antibiotics,%hich are o!ten dissolved in alcohol$ -ike gels,solutions %ork best in patients %ith oil" skin$
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+en,oyl peroide
This agent has bactericidal andcomedol"tic properties2increasingepithelial cell turnover %ith
desuamation3$ Ben+o"l pero=ide can be obtained in
various concentrations 2>$0 to 1/
percent3, although little evidence e=iststhat eNcac" is dependent on the dose$
kin irritation is the most common sideeGect o! ben+o"l pero=ide$
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+en,oyl peroide
Patients using ben+o"l pero=ide !ormulations!or the rst time should be instructed to test!or allergic dermatitis$
Because ben+o"l pero=ide is an o=idi+ingagent, patients should be %arned aboutpotential bleaching o! clothing and bed linens$
Ben+o"l pero=ide is not absorbed s"stemicall"$
imultaneous use %ith tretinoin ma" increasedskin irritation$
Transient skin discoloration ma" occure %ithPABA contain sunscreen$
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+en,oyl peroide
Patients using ben+o"l pero=ide !ormulations!or the rst time should be instructed to test!or allergic dermatitis$
Because ben+o"l pero=ide is an o=idi+ingagent, patients should be %arned aboutpotential bleaching o! clothing and bed linens$
Ben+o"l pero=ide is not absorbed s"stemicall"$
imultaneous use %ith tretinoin ma" increasedskin irritation$
Transient skin discoloration ma" occure %ithPABA contain sunscreen$
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Salicylic acid
This agent inhibits comedogenesis b"promoting the desuamation o! !ollicularepithelium$
It has been sho%n to be as eGective asben+o"l pero=ide in the treatment o!comedonal acne$
It is available at a concentration o! /$0 or
> percent in a number o! creams andlotions$
alic"lic acid is %ell tolerated and shouldbe applied once or t%ice dail"$
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Sul$ur preparation
Treatment o! in
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,elaic acid
In 1MM, the U$$ Food and Drug Administration 2FDA3labeled a+elaic acid !or the treatment o! mild tomoderate in/ percent cream
2A+ele=3, %hich is applied t%ice dail" to a clean, dr"aGected area$
The agent is !airl" %ell tolerated, because a+elaic aciddecreases pigmentation, it should be used %ith cautionin patients %ith darker comple=ions$
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Topical retinoids
:etinoids, %hich are derivatives o!vitamin A, !unction b" slo%ing thedesuamation process, thereb"
decreasing the number o! comedonesand microcomedones$
Until recentl", tretinoin %as the onl"
available topical retinoid$This agentis eGective as monotherap" inpatients %ith nonin
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Topical retinoids
Tretinoin is available as a cream, gelor liuid$ The cream has the lo%estpotenc", and the liuid has the
highest potenc"$Tretinoin should be applied in small
amounts to clean, dr" skin$
Because the irritation associated %ithtretinoin is compounded b" sune=posure, dose dependent anddecreased %ith continued therap"$
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Topical retinoids
&etaboli+ed b" skin
Appro=imatel" 0 o! the compoundis e=creted in urine and !eces$
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Topical retinoids
Patients should be %arned that the"ma" suGer a pustular
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Topical antibiotic
Topical antibiotics %ork directl" b"killing P. acnes$ Through theirbactericidal activit", the" also have a
mild indirect eGect oncomedogenesis$
Topical er"throm"cin and clindam"cin
26leocin T3 are the most commonl"used agents and have similareNcac" in patients %ith acne$
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Theraupeutic approach
#herapeutic approach to acne should begin $ith patienteducation. %t is important to dispel the many myths about thisdisorder.
Patients should be instructed to %ash their !ace t%ice a da" %ith amild soap and %ater$
Patients should be directed to use oil'!ree, noncomedogeniccosmetics$
*il !rom hair products and suntan lotions can also e=acerbate acne$
&echanical trauma can make acne %orse
!iet is not considered causati&e in acne, but the patient should
a&oid food that trigger an exacerbation #hey need to kno$ that treatment of their acne $ill re'uire time
and patience. o 'uick x* is a&ailable, and they may not seeimpro&ement for four to six $eeks.
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Terimakasih