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OBAT AINS (ANALGESIK ANTIPIRETIK)
Oleh
Wiwik Kusumawati
TUJUAN
1. Menyebutkan tentang penggolongan obat AINS
2. Menjelaskan tentang mekanisme kerja (farmakodinamik) obat AINS (analgesik, antipiretik, antiinflamasi)
3. Menjelaskan farmakokinetik obat AINS (analgesik antipiretik)
4. Menjelaskan aspek EBM obat AINS (analgesik antipiretik)
5. Menentukan penggunaan klinis obat AINS (analgesik antipiretik)
OBAT AINS (NSAIDs)
Analgesik Antiinflamasi Nonsteroid
Nonsteroidal Anti-inflammatory Drugs
Efek analgesik
Efek antipiretik
Efek antiinflamasi
Penggolongan
SALISILAT (aspirin, asetosal, diflunisal, dll)
PARAAMINOFENOL (asetaminofen/parasetamol)
PIRAZOLON (dipiron/metampiron, aminopirin, fenilbutazon, dll)
ASAM ORGANIK LAIN (ibuprofen, asam mefenamat, indometasin, diklofenak, dll)
The evolution of NSAID chemistry for the control of
pain
1853
SalicylicAcidClass
Aspirin
1970-
PropionicAcidClass
Ibuprofenketoprofen
1980-
OxicamClass
PiroxicamMeloxicam
1990-
AceticAcidClass
DiclofenacEtodolac
2000-
CoxibClass
CelecoxibRofecoxibValdecoxibEtoricoxibParecoxib
Lumiracoxib
traditional, classic, non-COXIB NSAIDtraditional, classic, non-COXIB NSAID COXIBCOXIB
painpain
redness heat
swelling hoarseness
PROSTAGLANDIN
COX-2COX-1
COX inhibitor
ProstaglandinesPGE2, PGI2, TXA2
ProstaglandinesPGE2, PGI2, TXA2
Gastricmucosal
protection
InflammationPainFever
COX-1 COX-2
anti-inflammatory
Exposed issues in marketing of COX-2 inhibitors
COOH
Arachidonic acid
COX-2 specific inhibitor
causes GI damagebleeding
Non-specific COX-inhibitor COX-2 specific inhibitor
The role of COX in inflammatory pain
MEKANISME AKSI OBAT AINS
TRAUMA/LUKA
ASAM ARAKIDONAT
KORTIKOSTEROID
FOSFOLIPID
PROSTAGLANDIN
OBAT AINSCOX 1 / 2
SIKLOOKSIGENASE
1, 2, 3?
FOSFOLIPASE
Efek antipiretik
PIROGEN ENDOGEN
(INTERLEUKIN-1) PROSTAGLANDIN
OBAT AINS
HIPOTALAMUS
DEMAMPIROGEN EKSOGEN
(infeksi Virus, bakteri, dll)
SALISILAT
Aspirin, Asetosal, Diflunisal, dll.
Prototipe obat AINS
Efek analgesik, antipiretik, antiinflamasi
Efek antiinflamasi, urikosurik (dosis tinggi :2-4 gram)
Efek antiagregasi trombosit (dosis rendah)
Efek keratolitik, astringent
REYE Sindrome
SALISILAT
Absorbsi sempurna di lambung
Lama kerja 4 jam (4-6x/hari)
Ekskresi meningkat dengan alkalinisasi urin
Iritasi saluran cerna (ulkus, perdarahan)
Pseudoalergi (Bronkokonstriksi)
SALISILAT
Analgesik & antipiretik (300-600 mg 3x sehari)
Nyeri disertai inflamasi (penyakit inflamasi sendi/rheumatik), 3 – 6 gram/hari
Inflamasi sendi akut, 5 – 8 gram/hari
Pencegahan IMA
Topikal (metil salisilat)
PARASETAMOL
Derivat paraaminofenolAsetaminofen Efek sentral dan perifer (lebih dominan perifer)Efek analgesik & antipiretik Efek antiinflamasi lemahEfek iritasi lambung minimalHepatotoksis, NABQI (dosis tinggi : 10-12 gram)
PARASETAMOL
Absorbsi – pengosongan lambung
Efek 15-30 menit
Kadar puncak 30-60 menit
Lama kerja 3-4 jam
Frekuensi pemberian 4-6x/hari
Dosis 10 mg/kg BB/x
Dosis 500 -1000 mg/x
DIPIRON
Derivat pirazolon
Metamizole, Metampiron, Antalgin
Efek analgesik & antipiretik
Efek antiinflamasi lemah
Efek diskrasia darah (agranulositosis, anemia aplastik, trombositopenia)
Efek iritasi lambung
Efek hipersensitif
DIPIRON
Efek 30 menit
Kadar puncak 2 jam
Lama kerja 2-4 jam
Frekuensi pemberian 4-6x/hari
Dosis 500 -1000 mg/x
Analgesik tanpa disertai inflamasi
Kombinasi dg obat lain, INJEKSI
IBUPROFEN
Derivat asam propionatEfek analgesik sama dg aspirin Efek antiinflamasi lebih lemah dibandingkan aspirin (lebih dari 2400 mg/hari 600 mg 4x/hari)Metabolisme di liverWaktu paruh 2,5 jam, ikatan protein plasma 99 %
IBUPROFEN
Efek samping di lambung lebih jarang
Efek samping : retensi cairan dan alergi
Pada penderita asma bronkial dapat menimbulkan bronkokonstriksi
IBUPROFENIbuprofen for the treatment of feverThe most frequently used are ibuprofen and paracetamol. The effectiveness of ibuprofen in fever reduction, and the effectiveness compared to paracetamol and aspirin, has been investigated in a large number of clinical trials.
Results of the clinical trials consistently show that a single dose of ibuprofen is more effective than paracetamol at reducing temperature over an 8 hour period. The onset of effect of ibuprofen starts within 30 minutes of dosing. Ibuprofen has been shown to be more effective than paracetamol in reducing high fevers, particularly above 39°C (102°F).
Symptoms of FeverInfections can disrupt the body temperature balance, and lead to temperatures higher than 37.4°C (a fever). Fevers can lead to increased loss of fluid from the body causing dehydration, discomfort for a child, and in a small proportion of children, febrile convulsions.A fever over 38°C or 100°F should be treated. The key to treating a fever is to reset the body's thermostat to bring the temperature back down to around 37°C or 98.5°F. Giving a child plenty to drink, to compensate for the fluid lost through sweating is important to avoid dehydration.
IBUPROFENIbuprofen and gastrointestinal bleeding
Serious gastrointestinal side effects associated with ibuprofen are dose-related: most occur with the high doses prescribed by doctors for the long term treatment of chronic disorders such as arthritis. This problem is extremely rare at the low doses recommended for short-term treatment with over-the-counter ibuprofen products and the risk is therefore negligible. In fact, the available evidence shows that the incidence of gastrointestinal side effects with over-the-counter doses of ibuprofen (up to 1200 mg/day) is comparable with that associated with paracetamol (acetaminophen). comparisons with other NSAIDs have consistently demonstrated that ibuprofen has the lowest risk of gastrointestinal side effects of any drug in its class.
Levels of Evidence
Level I - Evidence obtained from a systematic review of all relevant randomized controlled trials.
Level II - Evidence obtained from at least one properly designed randomized controlled trial.
Level III.1 - Evidence obtained from well designed controlled trials without randomization.
Level III.2 - Evidence obtained from well designed cohort or case control analytic studies preferably from more than one centre or research group.
Level III.3 - Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments.
Level IV - Opinion of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
Effect of Interventions on Fever
1. Paracetamol vs. Sponging
2. Paracetamol + Sponging vs. Sponging
3. Paracetamol + Sponging vs. Paracetamol
Effect of Interventions on Fever
Paracetamol vs. Sponging Paracetamol alone was found to be more effective in reducing the child's temperature when compared to sponging alone The mean reduction in temperature in the paracetamol group at one hour ranged from 0.8°C to 1.1°C. On the final measurement in these studies (1-4 hours) the mean reduction in temperature ranged from 0.9°C to 1.85°CIn the sponge only groups the mean reduction at both one hour and on final measurement ranged from 0.55°C to 0.75°C
Effect of Interventions on Fever
Paracetamol + Sponging vs. Sponging
The combination of paracetamol and sponging was found to be more effective than sponging alone.
A significant decrease in the mean reduction in temperature on final measurement between the group treated with paracetamol and sponging (range from 1.7°C to 1.3°C) when compared with the group who received sponging alone (range 0.55°C to 1.2°C).
Effect of Interventions on Fever
Paracetamol + Sponging vs. Paracetamol
The combination of paracetamol plus sponging was more effective in lowering temperature than paracetamol alone
The mean reduction in temperature in groups receiving medication plus sponging ranged from 1.3°C to 1.7°C.
In those groups receiving only paracetamol, the mean reductions on final measurement ranged from 0.9°C to 1.3°C
EBMIntoksikasi Parasetamol
48 % kasus intoksikasi dirujuk ke RS di UK disebabkan oleh overdosis parasetamol
100-200 kematian/tahun
Hepatotoksis - NABQI
Prinsip manajemen : monitoring kadar obat dalam plasma
Tx N-asetilsistein (metabolisme, oksidasi dan konjugasi)
Kasus 1
Seorang anak umur 5 tahun karena kecapaian main mendadak sorenya demam tinggi. Oleh ibunya anak tersebut segera dibawa berobat ke dokter praktek karena takut panyakitnya akan menjadi berat.
Kasus 2
Seorang laki-laki usia 60 tahun mengeluh nyeri pada lutut dan pinggang sudah beberapa hari. Sakit seperti ini sudah 1 tahun dan kumat-kumatan. Nyeri dirasakan lebih berat pada waktu bangun tidur pagi. Karena setelah minum obat yang dijual bebas tidak ada perubahan maka dia segera berobat ke rumah sakit.