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Pendahuluan
Nyeri adalah pengalaman sensorik dan emosional yang tidak menyenangkan terkait kerusakan jaringan, baik aktual maupun potensial atau yang digambarkan dalam bentuk kerusakan tersebut.
Pendahuluan
Nyeri adalah anugerah Sesungguhnya nyeri adalah anugerah yg besar dari maha pencipta (Allah SWT)
Pain is alarm protection tell us that something wrong in
our body.
Sulit dibayangkan seandainya tubuh kita tidak
dilengkapi dgn reseptor nyeri, sehingga kita tidak pernah menyadari kalau tubuh kita telah terancam kerusakan.
Pendahuluan
Pain can occur due to
1. PHYSIOLOGICAL PAIN
Pain that occur to stimulate withdrawals reflex To prevent tissue damage To prevent our body from harmful things.
REFLEK
Pain Perception
Stage of Nociception
1.
Transduction
Conversion of noxious stimuli (mechanical, thermal, chemical into electrical activation Communication of the nerve impulse from the periphery to the spinal cord, up to spinothalamic track to the thalamus and cerebral cortex Process by which impulse travel from the brain back down to the spinal cord to selectiveley inhibit (or sometimes amlpify) pain impulse Net result of three events the subjective experience of pain
Transmission
Modulation
Perception
4. Pain Perception
Pain perception much depend on modulation ---- > 3 possibilities
1. Nociception without pain (ada nosisepsi tanpa nyeri) 2. Nociception with pain (ada nosisepsi dengan nyeri). 3. Pain without Nociception (ada nyeri tanpa nosisepsi)
Frontal cortex
Descending pathway Periaqueductal gray matter
Medulla
Spinal cord
Pain
Samad TA et al. Nature. 2001;410:471-5.
Nyeri dibedakan atas: Nyeri Neuropatik: Nyeri yang disebabkan oleh lesi (kerusakan) sistem saraf. Nyeri Nosiseptif: Nyeri yang disebabkan oleh proses inflamasi dan kerusakan jaringan
Pd keadaan sakit, tubuh merasakan nyeri Nyeri merupakan mekanisme pertahanan tubuh sehingga individu memindahkan stimulus nyeri Ada 2 jenis rasa nyeri: Nyeri cepat: tajam, menusuk, rasa kesetrum dan akut. Nyeri lambat: rasa terbakar, pegal, berdenyut, nyeri mual dan khronik
Peripheral Activation
VR1
Extern al Stimuli
Ca2+
Action Potentials
Pendahuluan
Reseptor nyeri dan rangsangannya: Semua reseptor adalah ujung saraf bebas. Tersebar dipermukaan kulit dan jaringan seperti: - periosteum - dinding dalam arteri - permukaan sendi - falks / tentorium serebri Ada 3 macam stimulus: - mekanik - suhu - kimiawi
Peripheral Modulation
External Stimulus HEAT Sensitizing Stimulus
PGE
2
VR1
EP Recept or
PK A
SNS/PN3
PKCeTTX-Resistant
Sodium Channel
Bradykinin
BK Recept or
EP = prostaglandin E; BK = bradykinin.
Sensasi Nyeri
Nyeri berperan melindungi tubuh Nosiseptor adalah suatu reseptor nyeri pada ujung saraf bebas yg ditemukan pada jaringan tubuh, kecuali otak. Rangsangan termal, kimia dan mekanik akan mengaktifkan nosiseptor, dengan jalan melepaskan prostaglandin, kinin dan ion kalium
Jenis Nyeri:
Impuls nyeri cepat - berlangsung cepat (0,1 dtk pasca rangsangan - disepanjang saraf tipe A bermielin - nyeri bersifat akut, tajam atau menusuk - tdk dijumpai pd struktur dalam
Jenis Nyeri:
Impuls nyeri lambat terjadi disepanjang saraf tipe C tdk bermielin - nyeri sangat menyiksa, dan menjadi khronik spt; rasa terbakar, tumpul dan berdenyut. spt sakit gigi dan infeksi kuku, - nyeri pd rangsangan reseptor kulit disebut dgn; superficial somatic pain - pd rangsangan otot skeletal, sendi, tendon disebut; deep somatic pain
Jenis Nyeri:
- nyeri viseral; akibat rangsangan nosiseptor organ pd viseral spt distensi abdomen dan iskhemia organ internal. - zat kimia yg merangsang nyeri adalah bradikinin, serotonin, ion kalium, asetil kholine dan enzim proteolitik
Large A fibers
Dorsal Horn
Physiological Pain
NOXIOUS STIMULUS INNOCUOUS STIMULUS
C fiber
DHN
DHN
INNOCUOUS SENSATION
- utk nyeri lambat dan khronik melalui saraf tipe C dan sebgn saraf tipe A - berakhir di lamina II dan III subs. Gelatinosa dan lamina V dan VII kornu dorsalis - Neurotransmiternya Subst. P dan Glutamat - Berakhir di tiga tempat Nc. Retikularis medula, pons dan mesensefalon Area tekt. mesensefalon dan kol. Sup dan Inf Subst. grisea peri akuadukt
Substance P AMPA
P
NMD A
(-)
Ca2+
(+) PKC
(+)
DHN
ACTION SYSTEM
akuadukt dan raphe magnus. menghambat pd pre dan post sinaps serabut nyeri tipe C dan A
Serotonin oleh radiks dorsalis MS menghambat pd pre-
Diagnosis
Acute and chronic pain
Drug Treatment
NSAIDS (al Meloxicam/ Movi-cox), Opioids, Paracetamol
Analgesics (Movi-cox), tricyclics, centrally-acting muscle relaxants, glucocorticoids Carbamazepine, phenytoin, baclofen, tricyclics, gabapentin, others?
Acetaminofen
Electrical Stimulation
Transcutaneous electrical nerve stimulation (TENS) Percutaneous electrical nerve stimulation (PENS)
Alternative methods
(NSAID)
Gottschalk et al., 2001
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
l biological response to injury or
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
LTB4
Renal function
[salicylates, meclofenamate, diflunisal] l Indoleacetic acids [indomethacin, sulindac] l Propionic acids [ibuprofen, fenoprofen, ketoprofen, flurbiprofen] l Naphthalene acetic acids [naproxen]
COX - 2 Inhibitors
l Celecoxib l Rofecoxib l Valdecoxib l Meloxicam (Movi-cox)*
Golongan Coxib
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.
COXIBS
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
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
TOXICITY OF NSAIDs
Ototoxic Color blindness
Bronchospam
CHF
Hepatotoxic
Bleeding
Allergy
Tocolytic
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
mengatasi masalah efek samping terhadap lambung. Dapat diberikan bersama golongan PPI, Misoprostol
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.