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8/13/2019 Kuliah Nyeri Icsada
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Dr Pramono Apriawan WijayantoSekolah Tinggi Ilmu Kesehatan
ICSADA Bojonegoro
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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.
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Pendahuluan
Nyeri adalah anugerah Sesungguhnya nyeri adalah anugerah yg besar dari maha
pencipta (Allah SWT)
Pain is alarm protection tell us that something wrong inour body.
Sulit dibayangkan seandainya tubuh kita tidakdilengkapi dgn reseptor nyeri, sehingga kita tidakpernah menyadari kalau tubuh kita telah terancamkerusakan.
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Pendahuluan
Pain can occur due to Potential tissue damage --- >
Physiological Pain
Actual tissue damage ----- > Nociceptivepain or Acute pain or inflammation pain
Described in term of such damage ----- >Chronic Pain
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1. PHYSIOLOGICAL PAIN
Pain that occur to stimulate withdrawalsreflex
To prevent tissue damage
To prevent our body from harmfulthings.
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REFLEK
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2. Acute or Nociceptive Pain
Acute Pain or Nociceptive Pain is pain thatelicited by activation of nociceptors
There are 4 distinct process involved:
1. Transduction
2. Transmission
3. Modulation and
4. Perception
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The Pain Pathway Pain PerceptionBrainDorsal Root
Ganglion
Dorsal Horn
Nociceptor
Spinal Cord
Gottschalk A et al. Am Fam Physic ian. 2001;63:1979-84.
Fields HL et al. Harrisons Principles of Internal Medicine. 1998:53-8.
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Stage of Nociception
1. Transduction Conversion of noxious stimuli
(mechanical, thermal, chemical intoelectrical activation
2 Transmission Communication of the nerve impulsefrom the periphery to the spinal cord,
up to spinothalamic track to thethalamus and cerebral cortex
3 Modulation Process by which impulse travel fromthe brain back down to the spinal cordto selectiveley inhibit (or sometimesamlpify) pain impulse
4 Perception Net result of three events thesubjective experience of pain
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4. Pain Perception
Pain perception much depend onmodulation ---- > 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)
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The Somatosensory System
Somatosensory
cortex
Thalamus
Hypothalamus
Ascending tracts
Midbrain
Medulla
Spinal
cord
Frontal
cortex
Descending
pathway
Periaqueductalgray matter
Dorsal horn area
Noxious stimuli activate receptors in periphery
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Activation of the Central
Nervous System
at the Spinal Cord Level
Tissue DamageActivation of the
Peripheral Nervous
System
Transmission of the Pain
Signal to the Brain
Pain
The Pain Response
Samad TA et al. Nature.2001;410:471-5.
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Nyeri dibedakan atas:Nyeri Neuropatik: Nyeri yang disebabkan oleh lesi
(kerusakan) sistem saraf.
Nyeri Nosiseptif: Nyeri yang disebabkan oleh proses
inflamasi dan kerusakan jaringan
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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
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PendahuluanReseptor 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
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Sensasi Nyeri
Nyeri berperan melindungi tubuh
Nosiseptor adalah suatu reseptor nyeri pada ujung sarafbebas yg ditemukan pada jaringan tubuh, kecuali otak.
Rangsangan termal, kimia dan mekanik akanmengaktifkan nosiseptor, dengan jalan melepaskanprostaglandin, kinin dan ion kalium
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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
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Jenis Nyeri:
Impuls nyeri lambat terjadi disepanjang
saraf tipe C tdk bermielin
- nyeri sangat menyiksa, dan menjadi khronik spt; rasaterbakar, 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
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Jenis Nyeri:
- nyeri viseral; akibat rangsangan nosiseptor organ pd
viseral spt distensi abdomen dan iskhemia organinternal.
- zat kimia yg merangsang nyeri adalah bradikinin,serotonin, ion kalium, asetil kholine dan enzim
proteolitik
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Jaras rangkap penjalaran sinyal nyeriDua jaras penyaluran sinyal nyeri ke sistem
saraf pusatNyeri cepat dan tajam dirangsang oleh
mekanik dan suhu.- disalurkan ke medula spinalis oleh serabut
tipe A- kecepatan 6-10 m/detik.
Nyeri lambat dirangsang secara kimia,mekanik dan suhu
- disalurkan melalui saraf tipe C- kecepatan 0,5-2 m/dtk
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Dorsal Horn
Dorsal root
ganglion
Peripheral sensory
Nerve fibers
A
A
C
Largefibers
Small
fibers
There are Two Sensory Afferent Neurons1. Large myelinated Afibers, very fast conduction velocity. Respond to
innocuous stimuli
2. Small myelinated A& C unmyelinated fibers, have slow conductionvelocity. Respond to noxious stimuli
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DHN
PAININNOCUOUS SENSATION
NOXIOUS
STIMULUSINNOCUOUS
STIMULUS
DHN
Touch
Tactile
Pressure
Physiological Pain
A C fiber A
First Pain
Second Pain
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Jaras nyeri di MS dan batang otak
Dari kornu dorsalis menuju otak, sinyal nyeri
disalurkan di MS melalui:
Tr. Neo-spinotalamikus
- untuk nyeri cepat berakhir di lamina I
(lamina marginalis) kolumna anterolat.- sebgn berakhir di kompleks ventrobasal
dan sebgn lagi di korteks somatosensorik
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Jaras nyeri di MS dan batang otak
Tr. Paleo-spinotalamikus
- utk nyeri lambat dan khronik melalui saraf tipe Cdan sebgn saraf tipe A
- berakhir di lamina II dan III subs. Gelatinosa danlamina V dan VII kornu dorsalis
- Neurotransmiternya Subst. P dan Glutamat- Berakhir di tiga tempatNc. Retikularis medula, pons dan mesensefalon
Area tekt. mesensefalon dan kol. Sup dan InfSubst. grisea peri akuadukt
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Activation of Central Neurons
Dorsal Horn Neuron
C-Fiber Terminal
AMPA
NMD
A
Ca2+
Glutamate
PKC
P
P
(+)
(+)
(-)
Woolf CJ et al. Science. 2000;288:1765-8.
Schwartzman RJ et al. Arch Neuro l.2001;58:1547-50.
Substance P
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DHN
GATE CONTROL SYSTEM
+
+
ACTION
SYSTEM
Brain
SG
+
-
-
-
A
C
1965 MELZACK and WALL
Introduce Hypothesis of
GATE CONTROL THEORY
The beginning of MODULATION
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Sistim Inhibisi Sensasi Nyeri
Sistim Opium Otak, Endorfin dan Enkefalin
Morphin like subst. bekerja pd sebagian sistemanalgesia.
Ada 12 macam opium like substdi-otak
Berasal dari pemecahan 3 mol. Protein, y.i pro-opiomelanokortin, pro-enkefalin dan pro-dinorfin.
Bhn yg penting adalah -endorfin, met-enkefalin danleu-endorfin.
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Proses Sensasi Nyeri
Pd reseptor sensasi diseleksi dan di-olah jadi
4 tahap
1. Rangsangan reseptor sensorik
- Hrs tepat dan adekuat hingga terjadi
respons.
2. Transduksi stimulus.
- terjadi pd kornu dorsalis MS (dikonversi)
menjadi energi rangsangan (gradasi pottergantung kuat rangsangan dan ampl
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Proses Sensasi Nyeri
3. Membangkitkan impuls saraf.
- Pd grad. potensial mencapai ambang
tercetus 1 impuls atau lebih, kmdian
menyebar ke pusat.
4. Integrasi input sensorik.Daerah tertentu di-otak akan menerima
dan meng-integrasikan impuls sensorik
dan diterima pd area tertentu di korteks
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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 nervestimulation (PENS)
Acetaminofen
(NSAID)
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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
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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.
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Inflammationl biological response to injury orforeign substances
l acute and chronic inflammation
l components: cellular response
biochemical mediators
Mec an sms o In ammat on
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Mec an sms o In ammat onCellular Mechanisms:
Acute inflammationPMN
Chronic inflammationlymphocytes
monocytes
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Mechanisms of Inflammation
Biochemical Mediatorsvasoactive amines
plasma proteases (complement, kinins)
arachidonic acid metabolites (PG, LT)
lysosomal constituents
oxygen derived free radicals
cytokines
growth factors
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Mediators of Inflammation
Arachidonic Acid MetabolitesProstaglandins
Leukotrienes
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Generation of EicosonoidsPhospholipidsPhospholipase
Arachidonic Acid
5-lipoxygenase cyclooxygenase
5-HPTE PGG2
peroxidase
LTB4 LTC4PGH2
TXA2 PGI2 PGE2 PGF2PGD2
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Biological Effects of ProstaglandinsPGE2 Vasodilatation ain sensitization
gastric cytoprotection
PGF2 Bronchoconstriction, uterine
contractionPGI2 Inhibit platelet aggregation,
gastric cytoprotection
TxA2 Platelet aggregation
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Roles of COX-1 and COX-2
Arachidonic acidArachidonic acid
COX-2COX-2
PGsPGs
Inducible ConstitutiveInducible Constitutive
InflammationInflammation PainPain
FeverFever
COX-1COX-1
ConstitutiveConstitutive
PGsPGs
GI cytoprotectionGI cytoprotection
Platelet activityPlatelet activity
Renal functionRenal function
Renal functionRenal function
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Non-COX selective inhibitors of cyclooxygenase
Selective COX-2 inhibitors
Leukotriene inhibitors
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Non-COX Selective NSAIDsl Carboxylic acids[salicylates, meclofenamate, dif lunisal]
l Indoleacetic acids
[indomethacin, sulindac]
l Propionic acids
[ibuprofen, fenoprofen, ketoprofen, flurbiprofen]
l Naphthalene acetic acids[naproxen]
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Non-COX Selective NSAIDs
[contd]l Diclofenac
l Etodolac
l Nabumetone
l Oxaprozin
l Ketorolac
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COX - 2 Inhibitorsl Celecoxib
l Rofecoxib
l Valdecoxib
l Meloxicam (Movi-cox)**[less COX-2 selective]
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Golongan Coxib resiko kardiovaskuler + stroke Physicians prescribing celecoxib or valdecoxib should consider the
emerging cautionary data "when weighing the benefits against risks forindividual patients." The most appropriate candidates for coxib therapyare 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 foreach prescribing situation."
Consumers should use all over-the-counter analgesics, "including
NSAIDs," strictly according to the label instructions and consult aphysician if using them for longer than 10 days.
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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
()
()
NSAIDs
XXTARGET FOR A
SPECIFIC COX-2
INHIBITOR
Justification for the Development of
COX-2 Selective Inhibitors
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COX-2 Selectivity:
Molecular BasisNSAID Binding Clefts COX-1 COX-2
Chemical Structures of Oxicams and Coxibs
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OH O
OO
NS
NH
CH3
N
Piroxicam
CH3
OH O
OO
NS
NH
N
S
CH3
MeloxicamCelecoxib
NH2
SO
O
NN
CF3
H3C
OXICAMS COXIBS
Rofecoxib
Linear, enolic acid Y-shaped, Tricyclic
O
O
O
CH3
S
O
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Efficacy as an emerging concern of
NSAID used Potency (strong)
Onset of action (rapid)
Duration of action (long)
Efek samping minimal
Harga terjangkau
http://edgewatertech.files.wordpress.com/2008/07/long-tail.png?w=400&h=300http://www.tasbaptists.org.au/assets/images/BUT%20images/Rapid-logo2.gif8/13/2019 Kuliah Nyeri Icsada
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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 vivoassays. However, this is quite
variable, and a clinical advantage or hazard has yet to be
established. There is significantly less gastric injurycompared 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)
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Potency of NSAIDmilligram basis of active compound for each formula
potency NSAID mg/formula
strong 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
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Onset of action of NSAID
onset NSAID T-max (hr)
Rapid Diclofenac 0.8
Nimesulide 1.2 2.7
Slow Celecoxib 2 4Meloxicam 6
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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
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Ototoxic
Bronchospam CHF
Hepatotoxic UGIB
Bleeding Nephrotoxic
TocolyticAllergy
Color blindness
TOXICITY OF NSAIDs
Mechanism of = Mechanism of
therapeutic effects adverse effects
Perdarahan GI
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Treatment
No. of
patients
Drug
exposure
(days)
Patients/
byear
No. of GI
adverse
events
Percentage
per 100
patients/year
Placebo 736 56 113 0 0
Meloxicam7.5mg
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 1.7
Naproxen 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]
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Anamnesa nyeri secara sistematik dan
teratur
Berprasangka baik (percaya) terhadap
keluhan pasien atau keluargaCarilah metode kontrol nyeri yang nyamanuntuk pasien dan keluarga
Dilakukan intervensi yang tepat
waktunya, logis dan terkoordinasi
Edukasi pasien dan keluarga untukmengatasi nyeri sekuat mungkin
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