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Kuningan, 9 April 2010

Definisi Nyeri (Pain) dari IASP


(International Association for the Study of Pain)

Pain (Nyeri) adalah suatu Nyeri adalah


pengalaman sensorik dan pengalaman sensorik
emosional yang berkaitan yang berkaitan dengan
dengan kerusakan aktivasi nociceptor dan
jaringan atau diduga ada lintasan nyeri
kerusakan jaringan Nyeri adalah suatu
pengalaman emosional
Kerusakan jaringan
tidak mesti ada
JENIS NYERI

Neuropathic Pain Inflammatory Pain


Mixed Pain
Pain initiated or caused by a Pain with Pain caused by injury to
primary lesion or dysfunction neuropathic and body tissues
in the nervous system nociceptive (musculoskeletal,
(either peripheral or components
cutaneous or visceral)2
central nervous system)1

Examples Examples
Peripheral Examples
Post herpetic neuralgia Pain due to inflammation
Trigeminal neuralgia Low back pain with
Limb pain after a fracture
Diabetic peripheral neuropathy radiculopathy
Joint pain in osteoarthritis
Postsurgical neuropathy Cervical
Postoperative visceral pain
Posttraumatic neuropathy radiculopathy
Central Cancer pain
Common descriptors2
Posts troke pain Carpal tunnel
syndrome
Aching
Common descriptors2 Sharp
Burning Throbbing
Tingling
Hypersensitivity to touch or cold

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 Drug Treatment
Acute and chronic pain NSAIDS (al Meloxicam/
Movi-cox), Opioids,
Paracetamol
Myofascial pain Analgesics (Movi-cox),
dysfunction tricyclics, centrally-acting
muscle relaxants,
glucocorticoids
Neuropathic pain, Carbamazepine, phenytoin,
neuralgias 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
Acupuncture
(NSAID) Physical Therapy
Chiropractics
Gottschalk et al., 2001 Surgery
Thick, myelinated, fast
conducting neurons Very thin, unmyelinated, slow-
conducting
Mediate the feeling of initial
fast, sharp, highly localized Mediate slow, dull, more
pain. diffuse, often burning pain.

Rabaan
Tekanan
Nerve Fibers
Class Velocity Function
A- Fast Motor
A- Fast Touch,
pressure
A- Intermediate Muscle tone

A- Intermediate Pain,
temperature
B Small Motor
C Small 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
l biological response to injury or
foreign substances
l acute and chronic
inflammation
l 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-1 and COX-2

Arachidonic acid
COX-1
COX-2
Constitutive

PGs
PGs Inducible Constitutive

GI cytoprotection Inflammation Renal function


Platelet activity Pain
Renal function Fever
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]
l Diclofenac
l Etodolac
l Nabumetone
l Oxaprozin
l Ketorolac
COX - 2 Inhibitors

l Celecoxib
l Rofecoxib
l Valdecoxib
l Meloxicam (Movi-cox)*
*[less COX-2 selective]
Golongan Coxib resiko kardiovaskuler + stroke

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 COX-2
(Constitutive) (Inducible)
TARGET FOR A
() X SPECIFIC COX-2
INHIBITOR
NSAIDs
Stomach Inflammatory site:
Intestine Macrophages
Kidney Synoviocytes
Platelet Endothelial cells
COX-2 Selectivity:
Molecular Basis
NSAID Binding Clefts
COX-1 COX-2
Chemical Structures of Oxicams and Coxibs
OXICAMS COXIBS
Linear, enolic acid Y-shaped, Tricyclic

NH2
CH3
O S Celecoxib
Meloxicam OH O S O
N
N N N
H CF3
S N
CH3
O O
H3C

CH3 O

Piroxicam OH O S Rofecoxib
O
N N
H O
S N
CH3
O O O
COX-2 Selectivity

DRUG COX-2 IC50/COX-1 IC50

Rofecoxib .013
Celecoxib .080
Meloxicam .200
Diclofenac .170
Indomethacin 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


strong Meloxicam 7.5, 15
Piroxicam 10, 20
Diclofenac 25, 50, 75
moderate Celecoxib 100, 200
Nimesulide 100
Ketorpofen 100, 200
weak Mefenamic acid 500
Naproxen 500
Nabumetone 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 T-1/2 (hr)


short Diclofenac 1.1
Nimesulide 1.8 4.7
moderate Celecoxib 11
Naproxen 14
long Meloxicam 20
Piroxicam 57
TOXICITY OF NSAIDs
Ototoxic Color blindness

Bronchospam CHF

Hepatotoxic Perdarahan
UGIB GI

Bleeding Nephrotoxic

Allergy Tocolytic

Mechanism of = Mechanism of
therapeutic effects adverse effects
Table IV. Incidence of gastrointestinal (GI) adverse events

Drug No. of GI Percentage


No. of exposure Patients/ adverse per 100
Treatment patients (days) byear events patients/year
Placebo 736 56 113 0 0
Meloxicam 10158 33 918 3 0.3
7.5mg
Meloxicam 2960 179 1451 9 0.6
15mg
Meloxicam 910 241 600 6 1
22.5mg
Diclofenac 5464 35 524 9 1.7
Naproxen 243 117 78 1 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: Kombinasi OAINS
Tidak dianjurkan dengan Pelindung
Efek samping meningkat Lambung:
Tidak menambah efikasi
Ditujukan untuk sedikit
Kombinasi OAINS dan mengatasi masalah efek
Analgetik: samping terhadap
lambung.
Masih dapat Dapat diberikan bersama
dipertanggungjawabkan
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)
Anti-depressants /
Cognitive therapies psychotropics
Functional restoration Pain Behaviors Relaxation
Spiritual
Suffering

Pain
Opioid Perception
Adjuvants
NSAIDs? Local block
Nociception
Acetaminophene NSAIDs (Movicox )
Neural augmentation Surgery
Ablative 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