kuningan, 9 april 2010. definisi nyeri (pain) dari iasp pain (nyeri) adalah suatu pengalaman...
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Kuningan, 9 April 2010
DefiniDefinissi i Nyeri (Nyeri (PainPain) dari ) dari IASPIASP
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 nyeriNyeri adalah suatu pengalaman emosionalKerusakan jaringan tidak mesti ada
(International Association for the Study of Pain)
ExamplesPeripheral• Post herpetic neuralgia• Trigeminal neuralgia• Diabetic peripheral neuropathy• Postsurgical neuropathy• Posttraumatic neuropathyCentral• Posts troke painCommon descriptors2
• Burning• Tingling• Hypersensitivity to touch or cold
Examples • Pain due to inflammation• Limb pain after a fracture• Joint pain in osteoarthritis• Postoperative visceral pain Common descriptors2
• Aching• Sharp• Throbbing
Examples • Low back pain with
radiculopathy• Cervical
radiculopathy• Cancer pain• Carpal tunnel
syndrome
Mixed PainPain with
neuropathic and nociceptive components
Neuropathic PainPain initiated or caused by a
primary lesion or dysfunction in the nervous system (either peripheral or
central nervous system)1
Inflammatory PainInflammatory PainPain caused by injury to Pain caused by injury to
body tissues body tissues (musculoskeletal, (musculoskeletal,
cutaneous or visceral)cutaneous or visceral)22
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
JENIS NYERI JENIS NYERI
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
Neuropathic pain, neuralgias
Carbamazepine, phenytoin, baclofen, tricyclics, gabapentin, others?
Ascending PainTransmission 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
Descending pain pathway (Purves, 2001).
The Descending Pain Pathway – The Periaqueductal Grey (PAG) is the major convergence point.
Targets of Pain Therapies
Gottschalk et al., 2001
Alternative methodsAcupuncture
Physical Therapy
Chiropractics
Surgery
PharmacotherapyNon-opioid analgesics
Opioid analgesics
Nerve Blocks
Adjuvant analgesics (neuropathic, musculoskeletal)
Electrical StimulationTranscutaneous electrical nerve stimulation (TENS)
Percutaneous electrical nerve stimulation (PENS)
Acetaminofen
(NSAID)
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.
RabaanTekanan
Nerve FibersClass 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 biological response to injury or
foreign substances acute and chronic
inflammation components:
cellular responsebiochemical mediators
Mechanisms of InflammationCellular Mechanisms:
Acute inflammationPMN
Chronic inflammation lymphocytesmonocytes
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, uterinecontraction
PGI2 Inhibit platelet aggregation,gastric cytoprotection
TxA2 Platelet aggregation
Roles of COX-1 and COX-2
Arachidonic acidArachidonic acid
COX-2COX-2
PGsPGs
Inducible ConstitutiveInducible Constitutive
InflammationInflammation PainPain FeverFever
COX-1COX-1“Constitutive”“Constitutive”
PGsPGs
GI cytoprotectionGI cytoprotection Platelet activityPlatelet activity Renal functionRenal function
Renal functionRenal 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[cont’d]
Diclofenac Etodolac Nabumetone Oxaprozin Ketorolac
COX - 2 Inhibitors
Celecoxib Rofecoxib Valdecoxib 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.
COX-2: A New Anti-inflammatory Drug Target
Glucocorticoids
Arachidonic acid
COX-1(Constitutive)
COX-2(Inducible)
Stomach Intestine Kidney Platelet
Inflammatory site: Macrophages Synoviocytes Endothelial cells
(–)
(–)
NSAIDsXX
TARGET FOR ASPECIFIC COX-2
INHIBITOR
Justification for the Development of
COX-2 Selective Inhibitors
COX-2 Selectivity:Molecular Basis
NSAID Binding Clefts COX-1 COX-2
OHOH OO
OOOO
NNSS
NNHH
CHCH33
NN
PiroxicamPiroxicam
CHCH33
OHOH OO
OOOO
NNSS
NNHH
NN
SS
CHCH33
MeloxicamMeloxicamCelecoxibCelecoxib
NH2
SO
O
N NCF3
H3C
OXICAMS COXIBS
Chemical Structures of Oxicams and Coxibs
RofecoxibRofecoxib
Linear, enolic acid Y-shaped, Tricyclic
O
O
OO
CH3
S
OO
COX-2 Selectivity
DRUG COX-2 IC50/COX-1 IC50
Rofecoxib .013Celecoxib .080Meloxicam .200Diclofenac .170Indomethacin 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/formulastrong Meloxicam
Piroxicam
7.5, 15
10, 20
Diclofenac 25, 50, 75
moderate Celecoxib
Nimesulide
100, 200
100
Ketorpofen 100, 200
weak Mefenamic acid
Naproxen
500
500
Nabumetone 500
Onset of action of NSAID
onset NSAID T-max (hr)Rapid Diclofenac 0.8
Nimesulide 1.2 – 2.7Slow Celecoxib 2 – 4
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
Ototoxic
Bronchospam CHF
Hepatotoxic UGIB
Bleeding Nephrotoxic
TocolyticAllergy
Color blindness
TOXICITY OF NSAIDs
Mechanism of = Mechanism of therapeutic effects adverse effects
Perdarahan GI
TreatmentNo. of
patients
Drug exposure
(days)Patients/
byear
No. of GIadverse events
Percentage per 100
patients/year
Placebo 736 56 113 0 0Meloxicam 7.5mg
10158 33 918 3 0.3
Meloxicam 15mg
2960 179 1451 9 0.6
Meloxicam 22.5mg
910 241 600 6 1
Diclofenac 5464 35 524 9 1.7Naproxen 243 117 78 1 1.3
Table IV. Incidence of gastrointestinal (GI) adverse events
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 OAINSKombinasi OAINS
Kombinasi 2 OAINS: Tidak dianjurkan Efek samping meningkat Tidak menambah efikasi
Kombinasi OAINS dan Analgetik:Masih dapat dipertanggungjawabkan
Kombinasi OAINS dengan Pelindung Lambung:
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)
Pain Behaviors
Suffering
PainPerception
NociceptionLocal block
NSAIDs (Movicox ®)SurgeryPhysical modalities
Opioid
Adjuvants
NSAIDs?
Acetaminophene
Neural augmentation
Ablative surgery
Anti-depressants / psychotropics
Relaxation
Spiritual
Cognitive therapies
Functional restoration
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