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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
Coxib
Class
Acetic
Oxicam Acid Celecoxib
Class Class Rofecoxib
Propionic
Acid Valdecoxib
Salicylic Piroxicam Diclofenac Etoricoxib
Acid Class Etodolac
Meloxicam Parecoxib
Class Lumiracoxib
Ibuprofen
Aspirin ketoprofen

1853 1970- 1980- 1990- 2000-

traditional, classic, non-COXIB NSAID COXIB


pain
redness heat

swelling hoarseness
COX-1 COX-2
PROSTAGLANDIN

COX inhibitor
The role of COX in inflammatory pain
COOH

COX-1 COX-2
Arachidonic acid
Prostaglandines Prostaglandines
PGE2, PGI2, TXA2 PGE2, PGI2, TXA2

COX-2
Non-specific COX-inhibitor specific inhibitor

Gastric Inflammation
mucosal Pain
protection Fever

causes GI damage anti-inflammatory


bleeding

Exposed issues in marketing of COX-2 inhibitors


MEKANISME AKSI OBAT AINS

TRAUMA/LUKA

FOSFOLIPID KORTIKO
STEROID

FOSFOLI ASAM
PASE ARAKIDONAT OBAT AINS
COX 1 / 2
SIKLOOK
SIGENASE PROSTAGLANDIN
1, 2, 3?
Efek antipiretik
PIROGEN
EKSOGEN
(infeksi Virus, bakteri, dll)
DEMAM
HIPO
TALAMUS
PIROGEN
ENDOGEN
PROSTA
(INTERLEUKIN-1)
GLANDIN

OBAT AINS
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 paraaminofenol
Asetaminofen
Efek sentral dan perifer (lebih dominan
perifer)
Efek analgesik & antipiretik
Efek antiinflamasi lemah
Efek iritasi lambung minimal
Hepatotoksis, 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 propionat
Efek analgesik sama dg aspirin
Efek antiinflamasi lebih lemah
dibandingkan aspirin (lebih dari 2400
mg/hari 600 mg 4x/hari)
Metabolisme di liver
Waktu 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
IBUPROFEN
Ibuprofen for the treatment of fever
The 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 Fever
Infections 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.
IBUPROFEN
Ibuprofen 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°C
In 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
EBM
Intoksikasi 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.