[sent] nsaids for upn
DESCRIPTION
asdfghhlkjhTRANSCRIPT
![Page 1: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/1.jpg)
OBAT ANTI INFLAMASI NON STEROID
Alyya Siddiqa
![Page 2: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/2.jpg)
Analgetik
• Analgetik opioid• Analgetik non-opioid
– AINS– Analgetik-antipiretik
![Page 3: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/3.jpg)
INFLAMASI
TRAUMA FISIK, ZAT KIMIA, MIKROBA ATAU AKIBAT RESPON IMUNOLOGIK
MEDIATOR-MEDIATOR KIMIA(Histamin, Serotonin,
Prostaglandin, Bradikinin, Interleukin)
OAI
![Page 4: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/4.jpg)
PROSTAGLANDIN
• Salah satu mediator lokal pd inflamasi• Disintesis dlm jml << hampir di slrh jaringan• Mediator lokal, cepat diinaktivasi tidak
terdapat dlm sirkulasi
• Berasal dari asam arachidonat yg dipecah oleh cyclooxygenase-1 (Cox-1) atau Cox-2
• Cox-1 : reaksi normal• Cox-2 : diinduksi oleh inflamasi, fisiologis
![Page 5: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/5.jpg)
FOSFOLIPID MEMBRAN
Fosfolipase A2
ASAM ARACHIDONAT
siklooksigenaselipoksigenase
PGLeukotrien
(Cox)
PG(proteksi) (inflamasi)
Cox1 Cox2
OAINS
* PG = Prostaglandin
![Page 6: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/6.jpg)
![Page 7: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/7.jpg)
• Prostaglandin yang dihslkan oleh kerja Cox-1 bersifat sitoprotektif Contohnya : PGE2 & PGF2α : me↑ sekresi mukus gasterPGI2 : menghambat sekresi asam lambung
OAINS yg bekerja menghambat Cox-1 seluruhnya menyebabkan gangguan GIT (erosi, ulkus, perdarahan lambung dll)
![Page 8: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/8.jpg)
OAINS• ASPIRIN & SALISILAT LAIN• DERIVAT ASAM PROPIONAT• ASAM INDOL ASETAT• DERIVAT OKSIKAM • FENAMAT• FENILBUTAZON• OBAT LAINNYA ; DIKLOFENAK, KETOROLAK
& NOBUMETON SPECIFIC COX-2 INHIBITOR
![Page 9: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/9.jpg)
ASPIRIN & SALISILAT LAINNYA
ASPIRIN : Prototype OAINS standar OAINS lainnya
• Efek : - antiinflamasi - analgetik (nyeri ringan – sedang) - antipiretik
• Mekanisme Kerja : menghambat Cox 1-2
menghambat pelepasan prostaglandin
![Page 10: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/10.jpg)
Farmakokinetik
• All but one of the NSAIDs are weak organic acids as given; the exception, nabumetone, is a ketone prodrug that is metabolized to the acidic active drug.
• Most of these drugs are well absorbed, and food does not substantially change their bioavailability.
![Page 11: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/11.jpg)
• Most of the NSAIDs are highly metabolized, some by phase I followed by phase II mechanisms and others by direct glucuronidation (phase II) alone
• NSAID metabolism proceeds, in large part, by way of the CYP3A or CYP2C families
![Page 12: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/12.jpg)
• While renal excretion is the most important route for final elimination, nearly all undergo varying degrees of biliary excretion and reabsorption (enterohepatic circulation).
• The degree of lower gastrointestinal tract irritation correlates with the amount of enterohepatic circulation
![Page 13: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/13.jpg)
• Most of the NSAIDs are highly protein-bound (~ 98%), usually to albumin.
• Some of the NSAIDs (eg, ibuprofen) are racemic mixtures, while one, naproxen, is provided as a single enantiomer and a few have no chiral center (eg, diclofenac).
![Page 14: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/14.jpg)
Karena Cox-1 & 2 dihambat :
o Efek thd trombosit : hambatan agregasi trombosit akibat penurunan TXA2
o Efek thd GIT : penurunan PGI2 (prostasiklin) : sekresi asam ↑penurunan PGE2, PGF2α : sintesis mukus ↓
![Page 15: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/15.jpg)
EFEK SAMPING OBAT
GIT : distress epigastrium, gastritis, ulkus
Darah : Waktu perdarahan memanjang akibat agregrasi trombosit dihambat (hati hati penggunaan sblm operasi & bumil trimester 3)
Reye Syndrome ; penggunaan pd infeksi virus
SSP : salisilism : tinitus, pendengaran <<, vertigo
![Page 16: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/16.jpg)
Efek pada kehamilan
• Pada trimester ketiga :– Prolonged gestation– Menghambat persalinan– Risiko perdarahan– Penutupan duktus arteriosus
![Page 17: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/17.jpg)
Efek Samping NSAID
• GI : nyeri abdominal, mual, anoreksia, erosi gaster/ulkus, anemia, perdarahan GI, perforasi, diare
• Renal : retensi air dan garam, edema (memperburuk fungsi ginjal pada pasien renal/cardiac cirrhtotic), menurunkan efektivitas antihipertensi, menurunkan efektivitas terapi diuretik, menurunkan ekskresi urat (terutama aspirin)
![Page 18: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/18.jpg)
ESO (2)
• CNS : sakit kepala, vertigo, pusing (dizziness), confusion, depresi, menurunkan ambang kejang, hiperventilasi (salisilat)
• Platelet : menghambat aktivasi platelet, cenderung timbul memar, peningkatan risiko perdarahan
• Uterus : memperpanjang masa gestasi, menghambat persalinan
![Page 19: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/19.jpg)
ESO (3)
• Hipersensitivitas : vasomotor rhinitis, angioneurotic edema, asthma, urticaria, flushing, hipotensi, syok
• Vaskuler : penutupan ductus arteriosus
![Page 20: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/20.jpg)
INDIKASI
• Analgetik – antipiretik (Headache, artrhalgia, myalgia)• Antiinflamasi (RA, OA, gout dll)
• Efek lainnya : anti agregasi trombosit (profilaksis angina pectoris, TIA)
• Sedang diteliti : profilaksis terhadap ca-colon
![Page 21: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/21.jpg)
SALISILAT LAINNYA• SODIUM SALISILAT, CHOLINE SALISILAT
analgetik, antipiretik, antiinflamasi• ASAM SALISILAT, METIL SALISILAT
topikal : kalus; sangat iritatif, hanya sebagai obat luar• SALISILAMID
analgetik-antiiretik lbh lemah dari salisilat• DIFLUNISAL
efek analgetik-antiinflamasi lebih kuat daripada aspirin, 4-5 kaliefek antipiretik (-)efek samping GI dan platelet <<
![Page 22: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/22.jpg)
Salisilat
antasid
probenesidsulfinpirazon
FenitoinTiopentalTiroksin dll
Heparinantikoagulan
Menghambat absorpsi aspirin
me↓
ekskresi asam
urat
Hem
orrh
age
me↑ kons plasma aspirinProlonged half life, th/ effects and toxicity
Interaksi obat dgn aspirin
![Page 23: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/23.jpg)
Interaksi (2)
• NSAID + aspirin dosis rendah meningkatkan terjadinya efek samping gastrointestinal
• NSAID + ACEI menurunkan efektivitas ACEI akibat NSAID menghambat produksi vasodilator dan natriuretic prostaglandin
• NSAID + ACEI hiperkalemi : bradikardi yang dapat menyebabkan sinkop terutama pada lansia, penderita hipertensi, diabetes melitus dan ischemic heart disease
![Page 24: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/24.jpg)
Klasifikasi NSAID berdasarkan selektivitasnya
• Non-selective : aspirin, indometasin, piroksikam, ibuprofen, naproksen, asam mefenamat
• Preferentially COX – 2 : diclofenac, meloxicam, nimesulide, nabumeton, etodolac
• Selective COX – 2 : the coxibs generasi pertama dan kedua
![Page 25: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/25.jpg)
ANALGETIK ANTIPIRETIK
ASETAMINOFEN (parasetamol)Efek : analgetik-antipiretik (nyeri ringan - sedang)
antiinflamasi << atau (-)
Mekanisme kerja : menghambat sintesis prostaglandin di SSPEfek thd cox << atau (-) Efek antiinflamasi (-)
cox-3 Tdk mempengaruhi agregasi trombosit
![Page 26: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/26.jpg)
Parasetamol
• Diduga menghambat isoenzim cox-3 di otak• Kemampuan menghambat enzim cox diatur oleh
adanya peroxides• Hambatan biosintesis PG oleh parasetamol hanya
terjadi bila kadar peroksid rendah, yaitu di hipotalamus
• Pada lokasi terjadinya inflamasi, kadar peroksid yang dihasilkan lekosit tinggi efek antiinflamasi parasetamol tidak ada
![Page 27: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/27.jpg)
Indikasi :
Analgetik antipiretik pd :- Pasien dgn ggn lambung- Bila pemanjangan wkt perdarahan merupakan hal yg tdk menguntungkan- Anak-anak dengan infeksi virus- Ibu hamil dan menyusui
![Page 28: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/28.jpg)
FarmakokinetikA : cepat dari sal cernaD : luasM : hati, konjugasi dgn glukoronat & sulfatE : ginjal
ESO : MinimalToksisitas : nekrosis hati (dosis tinggi)
![Page 29: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/29.jpg)
Patogenesis gastropati NSAID
• Sistemik : Cox-1 dihambat sintesis mucosal cytoprotective prostaglandins tertutama PGI2 dan PGE2 menurun
• Eicosanoids tersebut menghambat sekresi asam oleh lambung, meningkatkan aliran darah mukosa dan mensekresikan mukus sitoprotektif di usus
![Page 30: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/30.jpg)
• Lokal : Pemberian NSAID per oral menyebabkan adanya kontak dengan mukosa lambung terjadi back-diffusion asama lambung ke dalam mukosa gaster menginduksi kerusakan jaringan
• Kemungkinan juga akibat meningkatnya produk lipoksigenase yang bersifat ulcerogenicity
![Page 31: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/31.jpg)
The coxibs
• Celecoxib, valdecoxib, rofecoxib, lumiracoxib• Karena hanya menghambat cox-2, dihubungkan
dengan ES gastropati minimal pada penggunaan jangka pendek < 6 bulan
• Studi coxibs : CLASS, Celecoxib Long-term Arthritis Safety Study (2000), VIGOR (2000) dan TARGET (2004)
• Rofecoxib dan valdecoxib ditarik dari peredaran efek samping infark miokard dan kematian jantung mendadak
![Page 32: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/32.jpg)
• Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) study,2005
• Successive Celecoxib Efficacy and Safety Study-1 (SUCCESS-1), 2006
• Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR), 2010
![Page 33: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/33.jpg)
The coxibs • celecoxib, rofecoxib, valdecoxib, parecoxib,
etoricoxib, lumiracoxib
![Page 34: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/34.jpg)
• Tromboksan A2 yang disintesis trombosit oleh COX-1 agregasi trombosit, vasokonstriksi dan proliferasi otot polos
• Prostasiklin (PGI2) yang disintesis oleh COX-2 di endotel makrovaskuler menyebabkan penghambatan agregasi trombosit, vasodilatasi dan efek anti-proliferatif
![Page 35: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/35.jpg)
• Most of the coxibs are distributed widely throughout the body.
• Celecoxib is particularly lipophilic, so it accumulates in fat and is readily transported into the CNS.
• Lumiracoxib is more acidic than the others, which may favor its accumulation at sites of inflammation.
![Page 36: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/36.jpg)
• All are well absorbed, but peak concentrations are achieved with lumiracoxib and etoricoxib in approximately 1 hour compared to 2 to 4 hours with the other agents
• All of the coxibs are extensively protein-bound (etoricoxib and rofecoxib approximately 90%, the others approximately 97% to 99%).
![Page 37: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/37.jpg)
• Published estimates of the half-lives of these drugs vary (2 to 6 hours for lumiracoxib, 6 to 12 hours for celecoxib and valdecoxib, 15 to 18 hours for rofecoxib, and 20 to 26 hours for etoricoxib)
• However, peak plasma concentrations of lumiracoxib exceed considerably those necessary to inhibit COX-2, suggesting an extended pharmacodynamic half-life.
![Page 38: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/38.jpg)
• Penghambat cox-2 menggeser kesetimbangan hemostatik ke arah protrombotik, tromboksan meningkat disertai prostasiklin berkurang thrombotic cardiovascular
![Page 39: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/39.jpg)
Faktor yang dapat meningkatkan ESO NSAID
• Faktor obat : waktu paruh, selektivitas, dosis• Faktor penderita : lansia, riwayat tukak peptik,
penyakit penyerta, interaksi dengan obat lain ( antihipertensi, antikoagulan, sediaan hemat kalium, kortikosteroid)
![Page 40: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/40.jpg)
![Page 41: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/41.jpg)
![Page 42: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/42.jpg)
KEY POINTS
• Based upon efficacy, safety, and cost considerations, scheduled acetaminophen, up to 4 g/day, should be tried initially forpain relief in OA.
• If this fails, a nonsteroidal antiinflammatorydrug (NSAID) may be tried, if there are no contraindications
![Page 43: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/43.jpg)
• Strategies to reduce NSAID-induced GI toxicity include the use of nonacetylated salicylates, COX-2 selective inhibitors, or the additionof misoprostol or a proton pump inhibitor.
• COX-2 selective inhibitors vary in their ability to prevent GI toxicity, and concomitant use of aspirin largely negates their gastroprotective effects.
![Page 44: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/44.jpg)
• COX-2 selective inhibitors can increase the risk of cardiovascular events.
• This may be a class effect, but the extent of this risk varies among COX-2 selective inhibitors, and traditional NSAIDs may also pose risks.
![Page 45: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/45.jpg)
![Page 46: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/46.jpg)
• Proteksi lambung :Antagonis H2Proton Pump InhibitorMukoprotektan
![Page 47: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/47.jpg)
• This hazard, in addition to the GItoxicity possible with all NSAIDs, underscores the importance of using NSAIDs only as needed and after assessing the individual patient’s risk.
![Page 48: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/48.jpg)
• NSAIDs are associated with GI, renal, cardiovascular, liver, and central nervous system toxicity.
• Monitoring with complete blood count, serum creatinine, and hepatic transaminase levels can be valuable in detecting potential toxicity.
![Page 49: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/49.jpg)
![Page 50: [Sent] NSAIDs for UPN](https://reader036.vdocuments.net/reader036/viewer/2022062305/5695d1ba1a28ab9b0297b3cd/html5/thumbnails/50.jpg)
THANK YOU