This document discusses pain management through pharmacological therapies. It defines pain and describes the physiological mechanisms of pain. It discusses the types and causes of pain such as nociceptive, neuropathic, acute, and chronic pain. The pathways of pain transmission and modulation are explained. Various classes of pain medications are described including non-opioid analgesics like NSAIDs, opioids, and adjuvant analgesics. The mechanisms of action, effects, and side effects of different analgesic drugs are provided. Multimodal analgesia combining different classes of analgesics to improve pain relief and reduce side effects is also mentioned.

1. Farmakoterapi
OBAT ANTI NYERI
M Fadhol Romdhoni
Laboratorium Farmakologi
Fakultas Kedokteran Univ. Muhammadiyah Purwokerto

2. DEFINISI NYERI
= Pengalaman sensorik dan emosional yang tidak
menyenangkan akibat kerusakan jaringan,
MEKANISME PROTEKSI TUBUH
(berfungsi melindungi & memberi tanda bahaya)

3. JENIS NYERI : SUMBER NYERI
• adanya kerusakan / inflamasi
jaringan  ujung saraf
menerima rangsang nyeri
NYERI
NOSISEPTIF /
INFLAMASI
• berhub dg lesi sist syaraf
perifer / sentral
• mis. Neuropatik DM,
kompresi serabut saraf,
neuroma
NYERI
NEUROPATIK
NYERI
NOSISEPTIF-
NEUROPATIK

4. JENIS NYERI : LAMA NYERI
• terjadi segera setelah
trauma, operasi, atau lesi
saraf
NYERI AKUT
• terjadi kontinu (minimal 3
bulan)
NYERI KRONIK

5. FISIOLOGI NYERI
STIMULUS
KERUSAKAN JARINGAN
MEDIATOR NYERI
(HISTAMIN, PG, BRADIKININ, LEOKOTRIEN, SEROTONIN DLL)
RESEPTOR NYERI (nociceptor)
SARAF SENSORIS
MEDULA SPINAL
THALAMUS / KORTEKS PUSAT NYERI
Transmisi
Modulasi
Persepsi
Transduksi

6. JALUR TRANSMISI NYERI

7. (Golan et al., 2008)

8. JALUR TRANSMISI NYERI

9. Stimuli : panas, bhn kimia, mekanik
Tujuan tubuh menimbulkan reaksi radang :
1. Menetralkan dan menghancurkan bahan
berbahaya
2. Mencegah penyebaran bahan berbahaya
3. Memperbaiki kondisi yang rusak
Proses yang terjadi :
 kerusakan mikrovaskular
 peningkt permeabilitas kapiler
 migrasi lekosit ke jar radang.
Mediator kimiawi yang dilepas secara lokal
histamin, 5 HT, bradikinin,PAF, substance P,
tromboksan, proton, radikal bebas, leukotrien,
prostaglandin
INFLAMASI / RADANG
Tanda radang 
cardinal signs :
 rubor
 calor
 tumor,
 dolor
 functiolaesa

10. Suhu tubuh diatur oleh keseimbangan produksi dan hilangnya panas
oleh hipotalamus (normal termostat mengatur pd setpoint 37o C )
termoregulator
Demam : Ada gangguan keseimbangan pengaturan panas akibat
pelepasan zat pirogen (sitokin IL-1 , memicu peningkatan PG di
hipotalamus)
DEMAM / PANAS

11. FEBRIS

12. PENATALAKSANAAN NYERI
Tx Non-Farmakologis
Tx Farmakologis/
Ox antinyeri
Non-Opioid
NSAID
Specific
COX2-inh
Non specific
/Konvension
alParacertamol,
Tramadol, dll
Opioid
Morfin,
Pethidin, dll

13. Terapi Nyeri : Non-farmakologik
Cognitive-Behavioral
• Relaxation
• Preparatory information
• Hypnosis
Physical Agents
• Application of superficial heat and cold
• Massage
• Exercise
• Immobilization
• Electroanalgesia (eg, TENS= transcutaneous electrical nerve
stimulation )
• Acupuncture
Carr DB, et al. AHCPR Pub. No. 92-0032. 1992.

14. TERAPI FARMAKOLOGIS
Bds target kerja obat :
1. Menghambat mediator nyeri
(transduksi):
 Analgetik non-opioid (NSAID, dll)
 Antiinflamasi steroid
2. Menghambat transmisi nyeri
 anestesi lokal
3. Blokade pusat nyeri di SSP (Persepsi)
 Analgesik opioid
 Paracetamol
 Anestesi umum

16. ANALGETIK OPIOID
• “opioid” is a natural or
synthetic drug that binds
to opioid receptors
producing agonist effects
• RESEPTOR OPIOID : Mu
(), Kappa () & Delta ()
• Resept delta : regulasi
aktifitas resept Mu
• Sangat efektif
• Efek samping sering
Response Mu-1 Mu-2 Kappa
Analgesia
Respiratory
Depression
Euphoria
Dysphoria
Decrease GI
motility
Physical
Dependenc
e

17. ANALGETIK OPIOID
Aktivasi Reseptor Opioid
menyebabkan :
- Me  konduktansi ion K
- Hiperpolarisasi
- Aksi potensial
terhambat
- Release
neurotransmitter
terhambat

18. Tx overdosis opioid

19. Efek Farmakologis Analgetik Opioid
• Sedation and anxiolysis
– Drowsiness and lethargy
– Apathy
– Cognitive impairment
– Sense of tranquility
• Depression of respiration
– Main cause of death from opioid overdose
– Combination of opioids and alcohol is especially
dangerous
• Cough suppression
– Opioids suppress the “cough center” in the brain
• Pupillary constriction
– pupillary constriction in the presence of analgesics is
characteristic of opioid use

20. Efek Farmakologis Analgetik Opioid
• Nausea and vomiting
– Stimulation of receptors in an area of the medulla called
the chemoreceptor trigger zone causes nausea and
vomiting
– Unpleasant side effect, but not life threatening
• Gastrointestinal symptoms (constipation)
– Opioids relieve diarrhea as a result of their direct actions
on the intestines
• Urine Retention
• Other effects
– Opioids can release histamines causing itching or more
severe allergic reactions including bronchoconstriction
– Opioids can affect white blood cell function and immune
function

21. Analgesic Non Opioid Drugs
– Acetaminophen
– NSAID
• Non selective COX inhibitor
–Salicylic acid (aspirin)
–Asetic acid (indomethacine, ketorolac,
diclofenac)
–Propionic acid (ketoprofen)
–Anthranic acid (mefenamat)
–Enolic acid (piroxicam)
• Selective COX – 2 Inhibitor
–Rofecoxib
–Celecoxib
–Etedolac

22. Analgesik Non-opioid
Acetaminophen Tramadol
Mekanisme kerja hamb sintesa PG  sintetik weak -opioid
hipotalamus,  inhibisi re-uptake
norepinephrine dan
serotonin (5-HT3)
Efek samping Hepatotoksik Opioid-like effects
Sisson CB. In: Benzon HT, et al, eds. Essentials of Pain Medicine and Regional Anesthesia;
1999:59–62.

23. 10/02/2010 Ngatidjan, NSAIDs - 23
(7-10%)
Acetaminophen
Memiliki efek Analgesic & antipyretic
Efek antiinflamasi?  hampir tidak ada / lemah
Efek samping  disebabkan o/ NABQI
- Hemolytic anemia
- Liver damage (large dose only)
Paracetamol
NABQI (N-asetyl benzoquinoneimine) conjugation
(sulfate or glucuronate)
conjugation
(sulfate or glucuronate)
excretion excretion
gluthation 
(90-93%)

24. NSAID
(NON STEROIDAL ANTI INFLAMMATORY DRUG)
 Mekanisme kerja : Menghambat sintesa PG melalui
penghambatan enzim COX 1 dan atau COX 2
– NSAID konvensional menghambat COX-1 dan COX-2
– Inhibisi COX-1 gastrotoksik,  agregasi platelet
– Obat baru hanya menghambat COX-2 pada dosis terapi
 Antiinflammatory, analgesics and antipyretics
(few of them have also antithrombus and uricosuria activity)
• Some of them have long half life
(naproxen, salicylate, piroxicam, and phenylbutazone)
• May induce gastropathy
(dyspapsia, gastrotoxicity, gastric mucosal erosion,
subepithelial damage and hemorrhage, frank ulceration, gastric
mucosal necrosis)

25. 1. Nonselective COX2-inhibitor
 antiinflamatory effects
 gastrointestinal, bronchial and renal side effects
 ibuprofen, ketoprofen, mefenamic acid, indomethacin
2. Selective COX2-inhibitor
 antiinflamatory effects
 minimal gastrointestinal, bronchial and renal side effects
 diflunisal, piroxicam, diclofenamate, diclofenac, meloxicam
NSAID

26.  Efek terapi atau efek samping NSAID tergantung pada
penghambatan biosintesis prostaglandin. Inhibisi PG
synthetase menurunkan inflamasi dan selanjutnya
mengurangi nyeri.
 PROSTAGLANDIN (PG) =Merup autakoid, terdapat di
semua jaringan dg spektrum aktivitas yg bervariasi
 Fungsi :
– Inflamasi  sebagai mediator  COX 2
– Homeostatic COX 1, terdapat di lambung, usus, platelet,
mucosa bronkus dan ginjal

29. Ibuprofen
Ketoprofen
Diclofenac
Meloxicam
Nimesulide
Celecoxib
Rofecoxib
Valdecoxib
Acetosal
Ketorolac
Indomethacin
Piroxicam
non-
selective
COX
inhibitor
preferentially
COX-2
selective
inhibitor
COX-2
selective
inhibitor
COX-1
selective
inhibitor
preferentially
COX-1
selective
inhibitor
COXIB
analgesic
anti-inflammatory
Less GI side effects
More GI side effects

30. (Finkel et al., 2009)

31. Salicylate derivatives
(Acetosal, diflunisal, Na-salicylate)
• Acetosal  inhibits COX1 and COX2 (nonselective)
 antiiflamatory effect in large dose
 g.i. side effects : gastric ulcer
• Diflunisal, Na-salicylate
 more COX2 selective inhibitors
 side effects ?  less than those of acetosal

32. Acetyl salicylic acid (ASA)
• Shows anti-thrombus activity  prevent
thromboembolism
a life threatening postoperative complication in patient who undergo
orthopedic procedure.
 small dose ASA  minimal side effects

33. 33
blocks
COX1-thrombocyte
• TX-A2 synthesis
(stimulate thrombocyte aggregation)
• COX1 can not be synthesized instantly
COX1-endothel
- prostacyclin synthesis
inhibit thrombocyte aggregation
(antithrombotic properties)
- new COX-1 can be synthesized
COX1
(cyclooxygenase-1)
ASA
low dose acetosal
effectively inhibit COX1 thrombocyte
thrombocyte aggregation
low dose acetosal
ineffective in COX1 endothel inhibition
Antithrombotic effect

34. (Finkel et al., 2009)
Side effects
1. Epigastric dyscomfort  pain
2. Gatric ulcer
3. Gastrointestinal bleeding
(melena)
4. Prolonged bleeding
5. Reye’s syndrome (in viral
infected infant)

35. Multimodal Analgesia
Kehlet H, Dahl JB. Anesth Analg. 1993;77:1048–1056.
• Pengurangan dosis
tiap analgesik
• Meningkatkan
antinociception karena
efek sinergistik
• Mengurangi efek
samping tiap obat
Morfin
NSAIDs,
acetaminophen,
blok saraf
Potensiasi

36. ANALGETIK ADJUVANt

37. = Obat yang dikombinasikan pada obat analgetik utama (non
opioid / opioid) untuk me  efek analgetik,
menyeimbangkan efek & efek samping
- Sering dipakai untuk terapi nyeri neuropatik
Yang termasuk adjuvant :
 Kortikosteroid
 Neuroleptik
 Benzodiazepin
 Antidepressan (TCA : amitriptilin, doxepin, imipramin,
desipramin, nortryptilin )
 Antikonvulsan (karbamazepin, Phenitoin, Sodium
valproate, Gabapentin)
 Klonidin