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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 Mixed Pain Pain with neuropathic and nociceptive components Inflammatory Pain Pain caused by injury to body tissues (musculoskeletal, cutaneous or visceral) 2 Examples

• • • • •

Peripheral Post herpetic neuralgia

Trigeminal neuralgia

Diabetic peripheral neuropathy

Postsurgical neuropathy Posttraumatic neuropathy •

Central Posts troke pain

• • •

Common descriptors 2

Burning Tingling Hypersensitivity to touch or cold

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

Examples

• • • • Pain due to inflammation Limb pain after a fracture Joint pain in osteoarthritis Postoperative visceral pain • • •

Common descriptors 2

Aching Sharp Throbbing

Neuropathic Pain Muscle/skeletal Pain

Chronic pain (months/years) Acute pain (hours or days) Caused by injury or disease to nerves Mild to excruciating pain that can last indefinitely Caused by injury or inflammation that affects both the muscles and joints 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touch – simply wearing light clothing is painful Causes sore, achy muscles Sufferers can become depressed or socially withdrawn because they see no relief in sight and may experience sleep problems Sufferers can become anxious and distressed but optimistic about relief from pain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

Muscle/Skeletal Pain Neuropathic 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.   Very thin, unmyelinated, slow conducting Mediate slow, dull, more diffuse, often burning pain. Rabaan Tekanan

Nerve Fibers

Class A-



A-



A-



A-



B C Velocity Fast Fast Intermediate Intermediate Small Small Function Motor

Touch, pressure Muscle tone Pain, temperature

Motor Pain

Acetaminofen Gottschalk

et al.

, 2001

Targets of Pain Therapies

Pharmacotherapy tramadol Non-opioid analgesics Opioid analgesics Nerve Blocks Adjuvant analgesics (neuropathic, musculoskeletal) Electrical Stimulation Transcutaneous electrical nerve stimulation (TENS) Percutaneous electrical nerve stimulation (PENS) (NSAID) Alternative methods Acupuncture Physical Therapy Chiropractics Surgery

A

namnesa nyeri secara sistematik dan teratur

B

erpikiran positif (percaya) terhadap keluhan pasien atau keluarga

C

arilah metode kontrol nyeri yang nyaman untuk pasien dan keluarga

D

ilakukan intervensi yang tepat waktunya, logis dan terkoordinasi

E

dukasi 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

Acute and chronic pain Myofascial pain dysfunction Neuropathic pain, neuralgias

Drug Treatment

NSAIDS , Opioids (al tramadol), Paracetamol Analgesics , tricyclics, centrally-acting muscle relaxants, glucocorticoids 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

2. Kerja di monoaminergic:

- Metabolit aktif Menghambat re-uptake serotonin/noradrenalin (O-desmethyl-tramadol/M1)

Mekanisme Kerja Tramadol

Menuju Otak Tramadol Descending pathway Tramadol Neuron dari saluran spinothalamic µ-Receptor Serotonin/Noradrenalin



2 -Receptor 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 dan Analgetik (paracetamol)

Masih dapat dipertanggungjawabkan

Kombinasi NSAID dengan Pelindung Lambung:

  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 Nyeri Osteoarthritis Tambahan pengobatan pada OA/RA yang telah diberi NSAID/COX-2 Bedah minor Rehabilitasi pasca cedera olahraga

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

4 3

Tramadol/paracetamol

2

Paracetamol

1 0 0 2

Tramadol

4 6 Waktu (jam) 8 10 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 fungsi hati berat  Epilepsi 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 agonists antagonists

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

20 15 10 5 0

12.1

6.7* 8.6* 13.6

3.3

‡ ZALDIAR Tramadol Paracetamol Ibuprofen Placebo 4.7

0.9* 2.7

† 5.8

-5 TOTPAR8 SPID8

*

P

 ‡

P

 .0001 vs Tramadol/paracetamol; †

P

.0001 vs all active treatments = .0004 vs Tramadol/paracetamol; TOTPAR 8 = Total pengurangan nyeri dalam 8 jam SPID = Jumlah perbedaan intensitas nyeri dalam 8 jam -1.6

‡

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) 56 (23%)

Tramadol

(n=238) 56 (24%)

Paracetamol

(n=240)

Ibuprofen

(n=240)

Placebo

(n=239) 22 (9%) 23 (10%) 38 (16%)

Nausea

(mual)

Vomiting

(muntah)

Dizzines

(pusing) 51 (21%) 11 (5%) 49 (21%) 12 (5%) 17 (7%) 10 (4%) 16 (7%) 7 (3%) 23 (10%) 9 (4%)

Hasil penelitian: onset (mula kerja)

70 60 50 40 30 20 10 0

17 51 18 34 66 ZALDIAR Tramadol Paracetamol Ibuprofen Placebo

Waktu mula kerja

Hasil penelitian: durasi kerja

3 2 1 0 6 5 4

5.03

2.03

3.05

5.42

2.00

Durasi kerja (lama kerja)

ZALDIAR Tramadol Paracetamol Ibuprofen Placebo

Pain: A conceptual approach to treatment (Biopsycosocial approach) Cognitive therapies Functional restoration Opioid Adjuvants NSAIDs?

Acetaminophene

Neural augmentation Ablative surgery

Pain Behaviors Suffering Pain Perception Nociception

Anti-depressants / psychotropics Relaxation Spiritual Local block 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

.