kuliah nyeri icsada

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.gif


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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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