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

Mixed Pain

Pain initiated or caused by a

primary lesion or dysfunction
in the nervous system
(either peripheral or
central nervous system)1

Pain with
neuropathic and
nociceptive
components

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

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

Diagnosis

Drug Treatment

Acute and chronic pain

NSAIDS (al Meloxicam/

Movi-cox), Opioids,
Paracetamol

Myofascial pain
dysfunction

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

Neuropathic pain,
neuralgias

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)

Electrical Stimulation

Acetaminofen

Transcutaneous electrical nerve

stimulation (TENS)
Percutaneous electrical nerve
stimulation (PENS)

Alternative methods
(NSAID)
Gottschalketal.,2001

Acupuncture
Physical Therapy
Chiropractics
Surgery

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

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
acute and chronic
inflammation
components:
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

PGG2
peroxidase

LTB4

LTC4

PGH2

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-1and COX-2

Arachidonic acid
COX-1
Constitutive

COX-2

PGs
PGs

GI cytoprotection
Platelet activity
Renal function

Inducible

Inflammation
Pain
Fever

Constitutive

Renal function

Non-COX selective inhibitors of cyclooxygenase

Selective COX-2 inhibitors

Leukotriene inhibitors

Non-COX Selective
NSAIDs

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

Non-COX Selective NSAIDs

[contd]

Diclofenac
Etodolac
Nabumetone
Oxaprozin
Ketorolac

COX - 2 Inhibitors

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 Selectivity:
Molecular Basis
NSAID Binding Clefts
COX-1
COX-2

Chemical
Structures
of
Oxicams
and
OXICAMS
COXIBS
Coxibs
Linear, enolic acid
Y-shaped, Tricyclic
CH3

Meloxicam

OH

S
O

N
O

S
N
H

NH2
O

Celecoxib

S
O

N N

CF3

CH3

H3C
O

CH3

Piroxicam

OH

Rofecoxib

CH3
O

N
O

S N

N
H

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

strong Meloxicam
Piroxicam
Diclofenac

mg/formula
7.5, 15
10, 20
25, 50, 75

moderate Celecoxib
Nimesulide

100, 200
100

Ketorpofen

100, 200

weak Mefenamic acid

Naproxen
Nabumetone

500
500
500

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

Bronchospam

Color blindness

CHF

Hepatotoxic

UGIB
Perdarahan
GI

Bleeding

Nephrotoxic

Allergy

Tocolytic

Mechanism of = Mechanism of
therapeutic effects
adverse effects

Table IV. Incidence of gastrointestinal (GI) adverse events

No. of
patients

Drug
exposure
(days)

Patients/
byear

No. of GI
adverse
events

Percentage
per 100
patients/year

736

56

113

Meloxicam
7.5mg

10158

33

918

0.3

Meloxicam
15mg

2960

179

1451

0.6

Meloxicam
22.5mg

910

241

600

Diclofenac

5464

35

524

1.7

Naproxen

243

117

78

1.3

Treatment
Placebo

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

Kombinasi OAINS dan

Analgetik:
Masih dapat
dipertanggungjawabkan

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)
Anti-depressants /
psychotropics

Cognitive therapies
Functional restoration

Pain Behaviors
Suffering

Opioid

Relaxation
Spiritual

Pain
Perception

Adjuvants
NSAIDs?
Acetaminophene
Neural augmentation
Ablative surgery

Nociception

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.

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