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

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 descriptors2 Burning Tingling Hypersensitivity to touch or cold

Examples

Examples

Low back pain with

radiculopathy Cervical radiculopathy Cancer pain Carpal tunnel syndrome

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

Common descriptors2 Aching Sharp Throbbing

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

Diagnosis
Acute and chronic pain

Drug Treatment
NSAIDS (al Meloxicam/ Movi-cox), Opioids, Paracetamol

Myofascial pain dysfunction

Neuropathic pain, neuralgias

Analgesics (Movi-cox), tricyclics, centrally-acting muscle relaxants, glucocorticoids Carbamazepine, phenytoin, baclofen, tricyclics, gabapentin, others?

Ascending Pain Transmission Pathway

The ascending neural pain pathway is only a 3 neuron relay The major convergence point is the ventral posterior lateral nucleus of the thalamus, which relays the signal to limbic and cortical areas

Ascending Pain Pathway (Purves, 2001).

Descending Pain Modulation Pathway

The Descending Pain Pathway The Periaqueductal Grey (PAG) is the major convergence point.

Descending pain pathway (Purves, 2001).

Targets of Pain Therapies

Pharmacotherapy
Non-opioid analgesics Opioid analgesics Nerve Blocks Adjuvant analgesics (neuropathic, musculoskeletal)

Acetaminofen

Electrical Stimulation
Transcutaneous electrical nerve stimulation (TENS) Percutaneous electrical nerve stimulation (PENS)

Alternative methods
(NSAID)
Gottschalk et al., 2001

Acupuncture Physical Therapy Chiropractics Surgery

Thick, myelinated, fast conducting neurons Mediate the feeling of initial fast, sharp, highly localized pain.

Very thin, unmyelinated, slowconducting 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

Chemical mediators are released from damaged tissue and inflammatory cells. Some inflammatory mediators directly activate nociceptors, while others act together to sensitize the pain pathway.

Inflammation
biological response to injury or foreign substances l acute and chronic inflammation l components:
l
cellular response biochemical mediators

Mechanisms of Inflammation Cellular Mechanisms:

Acute inflammation PMN Chronic inflammation lymphocytes monocytes

Mechanisms of Inflammation
Biochemical Mediators

vasoactive amines plasma proteases (complement, kinins) arachidonic acid metabolites (PG, LT) lysosomal constituents oxygen derived free radicals cytokines growth factors

Mediators of Inflammation
Arachidonic Acid Metabolites
Prostaglandins Leukotrienes

Generation of Eicosonoids
Phospholipids
Phospholipase

Arachidonic Acid
5-lipoxygenase cyclooxygenase

5-HPTE
peroxidase

PGG2 LTC4 PGH2

LTB4

TXA2 PGI2 PGE2 PGF2 PGD2

Biological Effects of Prostaglandins

PGE2 Vasodilatation, pain sensitization, gastric cytoprotection PGF2 Bronchoconstriction, uterine contraction PGI2 Inhibit platelet aggregation, gastric cytoprotection TxA2 Platelet aggregation

Roles of COX-1 and COX-2

Arachidonic acid COX-1 Constitutive COX-2

PGs PGs Inducible Constitutive

GI cytoprotection Platelet activity Renal function

Inflammation Pain Fever

Renal function

Non-COX selective inhibitors of cyclooxygenase

Selective COX-2 inhibitors

Leukotriene inhibitors

Non-COX Selective NSAIDs

Carboxylic acids [salicylates, meclofenamate, diflunisal] l Indoleacetic acids [indomethacin, sulindac] l Propionic acids [ibuprofen, fenoprofen, ketoprofen, flurbiprofen] l Naphthalene acetic acids [naproxen]
l

Non-COX Selective NSAIDs [contd]

Diclofenac l Etodolac l Nabumetone l Oxaprozin l Ketorolac
l

COX - 2 Inhibitors
l l l l

Celecoxib Rofecoxib Valdecoxib Meloxicam (Movi-cox)* *[less COX-2 selective]

Golongan Coxib stroke

resiko kardiovaskuler +

Physicians prescribing celecoxib or valdecoxib should consider the emerging cautionary data "when weighing the benefits against risks for individual patients." The most appropriate candidates for coxib therapy are patients at a high risk of GI bleeding or who have a history of intolerance to "or are not doing well on" nonselective NSAIDs. "Individual patient risk for cardiovascular events and other risks commonly associated with NSAIDs should be taken into account for each prescribing situation." Consumers should use all over-the-counter analgesics, "including NSAIDs," strictly according to the label instructions and consult a physician if using them for longer than 10 days.

Justification for the Development of COX-2 Selective Inhibitors

COX-2: A New Anti-inflammatory Drug Target
Arachidonic acid Glucocorticoids COX-1 (Constitutive) () NSAIDs Stomach Intestine Kidney Platelet Inflammatory site: Macrophages Synoviocytes Endothelial cells COX-2 (Inducible) ()

TARGET FOR A SPECIFIC COX-2 INHIBITOR

COX-2 Selectivity: Molecular Basis

NSAID Binding Clefts COX-1 COX-2

Chemical Structures of Oxicams and Coxibs OXICAMS COXIBS

Linear, enolic acid
CH3

Y-shaped, Tricyclic NH2 O O

N

Meloxicam

Celecoxib
N N

OH

O N H

S O

N CH3 O

CF3

H3C CH3 O S O
O
N H N

Piroxicam

OH

Rofecoxib

S N
O

CH3
O

COX-2 Selectivity
DRUG Rofecoxib Celecoxib Meloxicam Diclofenac Indomethacin COX-2 IC50/COX-1 IC50 .013 .080 .200 .170 1.500

Efficacy as an emerging concern of NSAID used

Potency (strong) Onset of action (rapid) Duration of action (long)

Efek samping minimal Harga terjangkau

Meloxicam (MOVI-COX) was approved recently by the FDA for use in osteoarthritis. The recommended dose for meloxicam is 7.5 to 15 mg once daily for osteoarthritis and 15 mg once daily for rheumatoid arthritis. Meloxicam demonstrates roughly tenfold COX-2 selectivity on average in ex vivo assays. However, this is quite variable, and a clinical advantage or hazard has yet to be established. There is significantly less gastric injury compared to piroxicam (20 mg/day) in subjects treated with 7.5 mg/day of meloxicam, but the advantage is lost with 15 mg/day
(Goodman & Gilman, 2006)

Potency of NSAID
milligram basis of active compound for each formula

potency

NSAID

mg/formula
7.5, 15 10, 20 25, 50, 75 100, 200 100 100, 200 500 500 500

strong Meloxicam Piroxicam Diclofenac moderate Celecoxib Nimesulide Ketorpofen weak Mefenamic acid Naproxen Nabumetone

Onset of action of NSAID

onset NSAID T-max (hr) Rapid Diclofenac 0.8 Nimesulide 1.2 2.7 Slow Celecoxib 24 Meloxicam 6

Duration of action of NSAID

duration NSAID short Diclofenac Nimesulide moderate Celecoxib Naproxen long Meloxicam Piroxicam T-1/2 (hr)
1.1 1.8 4.7 11 14 20 57

TOXICITY OF NSAIDs
Ototoxic Color blindness

Bronchospam

CHF

Hepatotoxic

UGIB Perdarahan GI Nephrotoxic

Bleeding

Allergy

Tocolytic

Mechanism of = Mechanism of therapeutic effects adverse effects

Table IV. Incidence of gastrointestinal (GI) adverse events

Drug exposure (days)
56 33

Treatment Placebo Meloxicam 7.5mg

No. of patients 736 10158

Patients/ byear 113 918

No. of GI adverse events

0 3

Percentage per 100 patients/year

0 0.3

Meloxicam 15mg
Meloxicam 22.5mg Diclofenac

2960
910 5464

179
241 35

1451
600 524

9
6 9

0.6
1 1.7

Naproxen

243

117

78

1.3

Efficacy and Tolerability of Meloxicam, a COX-2 Preferential Nonsteroidal Anti-Inflammatory Drug [Clin Drug Invest 22(12):799-818, 2002. 2002 Adis International Limited]

Kombinasi OAINS
Kombinasi 2 OAINS:

Tidak dianjurkan Efek samping meningkat Tidak menambah efikasi

Kombinasi OAINS dengan Pelindung Lambung:

Kombinasi OAINS dan Analgetik:

Masih dapat dipertanggungjawabkan

Ditujukan untuk sedikit mengatasi masalah efek samping terhadap lambung. Dapat diberikan bersama golongan PPI, Misoprostol

NSAID +Acetaminophen
Greater

analgesic effect than either

alone Avoids adverse effects of opioids Similar half lives for many NSAIDS and acetaminophen Over-the-counter Each has analgesic ceiling.

Pain: A conceptual approach to treatment

(Biopsycosocial approach)
Cognitive therapies Functional restoration
Pain Behaviors Suffering

Anti-depressants / psychotropics
Relaxation Spiritual

Opioid

Pain Perception

Adjuvants
NSAIDs? Acetaminophene Neural augmentation
Nociception

Local block

NSAIDs (Movicox )
Surgery Physical modalities

Ablative surgery

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.

Anamnesa nyeri secara sistematik dan

teratur Berprasangka baik (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