Prima Resort Kuningan
9 April 2010
Definisi Nyeri (Pain) dari IASP
(International Association for the Study of Pain)
Pain (Nyeri) adalah suatu
pengalaman sensorik dan
emosional yang berkaitan
dengan kerusakan
jaringan atau diduga ada
kerusakan jaringan
Nyeri adalah
pengalaman sensorik
yang berkaitan dengan
aktivasi nociceptor dan
lintasan nyeri
Nyeri adalah suatu
pengalaman emosional
Kerusakan jaringan
tidak mesti ada
JENIS NYERI
Neuropathic Pain
Pain initiated or caused by a
primary lesion or dysfunction
in the nervous system
(either peripheral or
central nervous system)1
Examples
Peripheral
• Post herpetic neuralgia
• Trigeminal neuralgia
• Diabetic peripheral neuropathy
• Postsurgical neuropathy
• Posttraumatic neuropathy
Central
• Posts troke pain
Common descriptors2
• Burning
• Tingling
• Hypersensitivity to touch or cold
Mixed Pain
Pain with
neuropathic and
nociceptive
components
Inflammatory Pain
Pain caused by injury to
body tissues
(musculoskeletal,
cutaneous or visceral)2
Examples
Examples
• Low back pain with
radiculopathy
• Cervical
radiculopathy
• Cancer pain
• Carpal tunnel
syndrome
1. International Association for the Study of Pain. IASP Pain Terminology.
2. Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999.;11-57
•
•
•
•
Pain due to inflammation
Limb pain after a fracture
Joint pain in osteoarthritis
Postoperative visceral pain
Common descriptors2
• Aching
• Sharp
• Throbbing
Neuropathic Pain
Muscle/skeletal Pain
Chronic pain (months/years)
Acute pain (hours or days)
Caused by injury or disease to
nerves
Caused by injury or inflammation that
affects both the muscles and joints
Mild to excruciating pain that can last
indefinitely
Moderate to severe pain that
disappears when the injury heals
Causes extreme sensitivity to touch –
simply wearing light clothing is
painful
Causes sore, achy muscles
Sufferers can become depressed or
socially withdrawn because they see
no relief in sight and may experience
sleep problems
Sufferers can become anxious and
distressed but optimistic about relief
from pain
Wall PD. Textbook of Pain. 4th ed; 1999; Jude EB. Clin in Pod Med and Surg.1999;16:81-97;
Price SA. Pathophysiology: Clinical Concepts of Disease Processes. 5th ed; 1997: Goldman L.
Cecil Textbook of Medicine. 21st ed; 2000
Symptoms of Neuropathic Pain
Characterized Differently
Neuropathic Pain
Muscle/Skeletal Pain
Price SA. Pathophysiology: Clinical Concepts of Disease Processes. 5th ed; 1997; Galer BS et
al. Diabetes Res Clin Pract. 2000;47:123-128
Neurophatic
pain
Nociceptive/
imflammatory/
musculoskletal
pain


Thick, myelinated, fast
conducting neurons
Mediate the feeling of initial
fast, sharp, highly localized
pain.
Rabaan
Tekanan


Very thin, unmyelinated, slowconducting
Mediate slow, dull, more
diffuse, often burning pain.
Nerve Fibers
Class
Velocity
Function
A-
A-
Fast
Fast
Motor
A-
A-
Intermediate
Intermediate
B
C
Small
Small
Touch,
pressure
Muscle tone
Pain,
temperature
Motor
Pain
Targets of Pain Therapies
Pharmacotherapy
Non-opioid analgesics
Opioid analgesics
Nerve Blocks
Adjuvant analgesics (neuropathic,
musculoskeletal)
tramadol
Electrical Stimulation
Acetaminofen
Transcutaneous electrical nerve
stimulation (TENS)
Percutaneous electrical nerve
stimulation (PENS)
Alternative methods
(NSAID)
Gottschalk et al., 2001
Acupuncture
Physical Therapy
Chiropractics
Surgery
Anamnesa nyeri secara sistematik dan
teratur
Berpikiran positif (percaya) terhadap
keluhan pasien atau keluarga
Carilah metode kontrol nyeri yang nyaman
untuk pasien dan keluarga
Dilakukan intervensi yang tepat
waktunya, logis dan terkoordinasi
Edukasi pasien dan keluarga untuk
mengatasi nyeri sekuat mungkin
Analgesics
Non-opioid analgesics (non-opioids):
paracetamol, acetylsalicylic acid, metamizole* and
nonsteroidal anti-inflammatory drugs (NSAIDs).
Opioid analgesics (opioids):
weak opioids (codeine, dihydrocodeine,
tramadol) and strong opioids (i.e., morphine).
Papaver somniferum
Co-analgesics: a diverse group of drugs, with primary
indications for conditions other than pain, with analgesic
properties relevant to some conditions. Commonly used
adjuvant analgesics include antiepileptic drugs (AEDs), tricyclic
antidepressants (TCAs) and local anaesthetics (LAs).
Diagnosis
Drug Treatment
Acute and chronic pain
NSAIDS , Opioids (al tramadol),
Paracetamol
Myofascial pain
dysfunction
Analgesics , tricyclics,
centrally-acting muscle
relaxants, glucocorticoids
Neuropathic pain,
neuralgias
Carbamazepine, phenytoin,
baclofen, tricyclics,
gabapentin, others?
Acetaminophen
 May inhibit COX selectively in central nervous
system
 Only weak inhibitor of peripheral COX (peroxide
effects?)
 Inhibits effects of substance P in CNS?
 Inhibits effects of glutamate in CNS?
Paracetamol
1.
2.
3.
4.
Paracetamol is an effective analgesic for acute pain
(Level I*).
Paracetamol is an effective adjunct to opioids (Level I).
NSAIDs given in addition to paracetamol improve
analgesia (Level I).
IV paracetamol is an effective analgesic after surgery
(Level II), is as effective as ketorolac (Level II) and
equivalent to morphine after dental surgery with better
tolerance (Level II).
Mekanisme Kerja Tramadol
Dua mekanisme kerja yang saling melengkapi:
1. Kerja di opioid:
- Agonis reseptor µ
- Metabolit aktif
(O-desmethyl-tramadol/M1)
2. Kerja di monoaminergic:
Menghambat re-uptake
serotonin/noradrenalin
Mekanisme Kerja Tramadol
Tramadol
Menuju Otak
Descending pathway
Neuron dari saluran spinothalamic
Serotonin/Noradrenalin
µ-Receptor
2-Receptor
Tramadol
Transmiter nyeri
Spinal neuron
Rangsang Nyeri
Enkephalin
Choose drugs based on:
– mechanism of pain
– safety and pharmacology of aging
– match pain severity with drug potency
– use combined drug and non-drug strategies
Use adequate dose; appropriate route
Anticipate, prevent and manage side effects
Rationale for a fixed-dose
combination analgesic
• Enhanced analgesia
•
• Reduced doses of components - fewer side effects
• Rapid onset of action and lasting duration
• Broad spectrum of efficacy in terms of indications
and pain intensity
• Higher patient compliance and ease of
administration
Fixed drug combinations ( ZALDIAR)
Fixed combinations are appropriate for on-demand treatment typically
used in acute pain conditions and situations of non-stable pain or
intermittent pain in chronic conditions.
A fixed analgesic combination simplifies drug delivery without the
need for complicated dose-escalating regimens and, therefore,
improves compliance.
Free drug combinations
Free drug combinations are particularly appropriate for the
management of stable chronic pain syndromes.
The main advantage of free drug combinations is that they allow the
dose regimen to be tailored to individual requirements. On the other
hand, this may be time-consuming because it involves a gradual and
dose-escalating strategy.
Kombinasi NSAID
Kombinasi 2 NSAID:



Tidak dianjurkan
Efek samping meningkat
Tidak menambah efikasi
Kombinasi NSAID
dengan Pelindung
Lambung:

Kombinasi NSAID dan
Analgetik (paracetamol)
Masih dapat
dipertanggungjawabkan

Ditujukan untuk sedikit
mengatasi masalah efek
samping terhadap
lambung.
Dapat diberikan bersama
golongan PPI,
Misoprostol
(37,5 MG TRAMADOL PLUS 325 MG PARASETAMOL)
PHAROS INDONESIA

Komposisi
:
37.5 mg Tramadol plus 325 mg Taracetamol

Indikasi
:
Mengurangi nyeri sedang sampai berat

Sediaan:
Tablet salut film

Kemasan
:
Box isi 10 tablet
Harga 1 box : Rp 65.000
Harga 1 tablet Rp 6.500
INDIKASI ZALDIAR
Nyeri sedang sampai berat seperti :
Nyeri Pasca Operasi
Trauma karena
kecelakaan
Low-back pain
Bedah minor
Rehabilitasi pasca
cedera olahraga
Nyeri Osteoarthritis
Tambahan pengobatan
pada OA/RA yang telah
diberi NSAID/COX-2
Dosis Untuk Dewasa (>12 Tahun)
 Dosis
ZALDIAR fleksibel tergantung dari
intensitas nyeri.
 Untuk
nyeri yang berat dosis awal bisa
2 tablet kemudian diberikan setiap 6 jam
 Rata-rata
dosis per hari 3-4 tablet
 Maksimal 8 tablet per hari
(Sama dengan 300 mg tramadol/2600 mg parasetamol)
ZALDIAR: Onset cepat durasi lama
Pain relief probabilities
4
3
Tramadol/paracetamol
2
Paracetamol
1
Tramadol
0
0
2
4
6
8
10
Waktu (jam)
Kerja analgesik yang saling melengkapi:
Onset cepat dari parasetamol dikombinasi dengan durasi lama dari tramadol
Perhatian pada kelompok pasien
berikut :
ZALDIAR® jangan diberikan pada:

Anak-anak <12 tahun

Selama hamil

Selama menyusui

Kategori ZALDIAR C
Kontraindikasi
 Hipersensitif
terhadap tramadol dan parasetamol
 Acute
intoxication alkohol, hypnotic, analgesik
sentral, opioids atau obat psychotropic
 Pemberian
bersamaan dengan MAO inhibitor or
within two weeks of withdrawal
 Gangguan
 Epilepsi
fungsi hati berat
yang tidak sedang dalam pengobatan
Peringatan
 Dosis
maksimal 8 tablet per hari
 No
concurrent use of any other products containing
paracetamol or tramadol
 Tidak
direkomendasikan pada pasien dengan
gangguan ginjal (creatinin clearance <10ml/mm)
 Jangan
diberikan pada pasien dengan gangguan
hati berat
 Tidak
direkomendasikan pada pasien dengan
gangguan pernafasan berat
Interaksi
Kontra indikasi / tidak direkomendasikan
digunakan bersamaan dengan:
MAO inhibitors, Alcohol,
Carbamazepine, Opioid agonistsantagonists
STUDI KLINIS
Nyeri setelah bedah mulut (gigi)
Medve RA et al. Anesthesi Prog, 2001
Tujuan:
Membandingkan efikasi dan keamanan dari
tramadol/parasetamol (ZALDIAR) dengan tramadol atau
parasetamol monoterapi
Dosis:
 Tramadol 75 mg/parasetamol 650 mg
 75 mg tramadol
 650 mg parasetamol
 400 mg ibuprofen
 Plasebo
Desain penelitian:
 1200 pasien dengan nyeri sedang sampai berat
setelah bedah (cabut) gigi geraham paling belakang
(geraham bungsu) yang di random menjadi 3, double
blind, paralel group, studi dosis tunggal yang
diobservasi selama 8 jam.
 Tiga pusat penelitian terdiri dari 400 pasien; yang
terdistribusi merata dalam pengobatan
Medve RA et al. Anesth Prog, 2001
Hasil penelitian: efikasi
Nilai Rata-rata
20
15
ZALDIAR
Tramadol
Paracetamol
Ibuprofen
Placebo
13.6
12.1
8.6*
10
6.7*
3.3‡
5
5.8
4.7
2.7†
0.9*
0
-1.6‡
-5
TOTPAR8
SPID8
*P  .0001 vs Tramadol/paracetamol; †P = .0004 vs Tramadol/paracetamol;
‡P  .0001 vs all active treatments
TOTPAR 8 = Total pengurangan nyeri dalam 8 jam
SPID = Jumlah perbedaan intensitas nyeri dalam 8 jam
Kesimpulan penelitian ZALDIAR pada
pasien bedah gigi
 Pengurangan
/ penurunan intensitas nyeri dengan
ZALDIAR lebih superior dibanding tramadol atau
parasetamol sendiri atau plasebo
 Mula
kerja ZALDIAR lebih cepat dan durasi kerja lebih
lama dibanding tramadol atau parasetamol sendiri.
 Masing-masing
komponen dari ZALDIAR berkontribusi
terhadap efikasi analgesik

ZALDIAR adalah analgesik kuat dengan
onset cepat, durasi panjang yang efektif
dalam pengobatan nyeri akut
Efek samping setelah pemberian
ZALDIAR ( 5%)
Tramadol/
paracetamol
(n=240)
Tramadol
(n=238)
Paracetamol
(n=240)
Ibuprofen
(n=240)
Placebo
(n=239)
Nausea
(mual)
56 (23%)
56 (24%)
22 (9%)
23 (10%)
38 (16%)
Vomiting
(muntah)
51 (21%)
49 (21%)
17 (7%)
16 (7%)
23 (10%)
Dizzines
(pusing)
11 (5%)
12 (5%)
10 (4%)
7 (3%)
9 (4%)
Hasil penelitian: onset (mula kerja)
70
66
ZALDIAR
Tramadol
Paracetamol
Ibuprofen
Placebo
60
Waktu (menit)
51
50
40
34
30
20
17
18
10
0
Waktu mula kerja
Hasil penelitian: durasi kerja
6
5.42
ZALDIAR
Tramadol
Paracetamol
Ibuprofen
Placebo
5.03
Waktu (Jam)
5
4
3.05
3
2.03
2
2.00
1
0
Durasi kerja (lama kerja)
Pain: A conceptual approach to treatment
(Biopsycosocial approach)
Anti-depressants /
psychotropics
Cognitive therapies
Functional restoration
Pain Behaviors
Suffering
Opioid
Relaxation
Spiritual
Pain
Perception
Adjuvants
NSAIDs?
Acetaminophene
Neural augmentation
Ablative surgery
Local block
Nociception
NSAIDs (Movicox ®)
Surgery
Physical modalities
1. Looser JD, Cousins MJ. Med J aust 1990;216: 153-208; 2. van den Hout JH, et al. Clin J Pain. 2003;19:87-96.; 3.
Mynors-Wallis L, et al. Br J Psychiatry. 1997;170:113-119.; 4. Morley S, et al. Pain. 1999;80:1-13.