penatalaksanaan nyeri ringkas

39
Kuningan, 9 April 2010

Upload: meviraf-benny

Post on 30-Oct-2014

105 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Penatalaksanaan Nyeri Ringkas

Kuningan, 9 April 2010

Page 2: Penatalaksanaan Nyeri Ringkas

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)

Page 3: Penatalaksanaan Nyeri Ringkas

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

Page 4: Penatalaksanaan Nyeri Ringkas

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?

 

Page 5: Penatalaksanaan Nyeri Ringkas

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).

Page 6: Penatalaksanaan Nyeri Ringkas

Descending Pain Modulation Pathway

Descending pain pathway (Purves, 2001).

The Descending Pain Pathway – The Periaqueductal Grey (PAG) is the major convergence point.

Page 7: Penatalaksanaan Nyeri Ringkas

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)

Page 8: Penatalaksanaan Nyeri Ringkas

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

Page 9: Penatalaksanaan Nyeri Ringkas

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

Page 10: Penatalaksanaan Nyeri Ringkas

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.

Page 11: Penatalaksanaan Nyeri Ringkas

Inflammation biological response to injury or

foreign substances acute and chronic

inflammation components:

cellular responsebiochemical mediators

Page 12: Penatalaksanaan Nyeri Ringkas

Mechanisms of InflammationCellular Mechanisms:

Acute inflammationPMN

Chronic inflammation lymphocytesmonocytes

Page 13: Penatalaksanaan Nyeri Ringkas

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

Page 14: Penatalaksanaan Nyeri Ringkas

Mediators of Inflammation

Arachidonic Acid Metabolites Prostaglandins Leukotrienes

Page 15: Penatalaksanaan Nyeri Ringkas

Generation of Eicosonoids

Phospholipids Phospholipase

Arachidonic Acid 5-lipoxygenase cyclooxygenase

5-HPTE PGG2 peroxidase

LTB4 LTC4 PGH2

TXA2 PGI2 PGE2 PGF2 PGD2

Page 16: Penatalaksanaan Nyeri Ringkas

Biological Effects of Prostaglandins

PGE2 Vasodilatation, pain sensitization,gastric cytoprotection

PGF2 Bronchoconstriction, uterinecontraction

PGI2 Inhibit platelet aggregation,gastric cytoprotection

TxA2 Platelet aggregation

Page 17: Penatalaksanaan Nyeri Ringkas

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

Page 18: Penatalaksanaan Nyeri Ringkas

Non-COX selective inhibitors of cyclooxygenase

Selective COX-2 inhibitors

Leukotriene inhibitors

Page 19: Penatalaksanaan Nyeri Ringkas

Non-COX Selective NSAIDs Carboxylic acids

[salicylates, meclofenamate, diflunisal] Indoleacetic acids

[indomethacin, sulindac] Propionic acids

[ibuprofen, fenoprofen, ketoprofen, flurbiprofen]

Naphthalene acetic acids [naproxen]

Page 20: Penatalaksanaan Nyeri Ringkas

Non-COX Selective NSAIDs[cont’d]

Diclofenac Etodolac Nabumetone Oxaprozin Ketorolac

Page 21: Penatalaksanaan Nyeri Ringkas

COX - 2 Inhibitors

Celecoxib Rofecoxib Valdecoxib Meloxicam (Movi-cox)*

*[less COX-2 selective]

Page 22: Penatalaksanaan Nyeri Ringkas

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.

Page 23: Penatalaksanaan Nyeri Ringkas

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

Page 24: Penatalaksanaan Nyeri Ringkas

COX-2 Selectivity:Molecular Basis

NSAID Binding Clefts COX-1 COX-2

Page 25: Penatalaksanaan Nyeri Ringkas

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

Page 26: Penatalaksanaan Nyeri Ringkas

COX-2 Selectivity

DRUG COX-2 IC50/COX-1 IC50

Rofecoxib .013Celecoxib .080Meloxicam .200Diclofenac .170Indomethacin 1.500

Page 27: Penatalaksanaan Nyeri Ringkas

Efficacy as an emerging concern of NSAID used

Potency (strong) Onset of action (rapid) Duration of action (long)

•Efek samping minimal•Harga terjangkau

Page 28: Penatalaksanaan Nyeri Ringkas

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)

Page 29: Penatalaksanaan Nyeri Ringkas

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

Page 30: Penatalaksanaan Nyeri Ringkas

Onset of action of NSAID

onset NSAID T-max (hr)Rapid Diclofenac 0.8

Nimesulide 1.2 – 2.7Slow Celecoxib 2 – 4

Meloxicam 6

Page 31: Penatalaksanaan Nyeri Ringkas

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

Page 32: Penatalaksanaan Nyeri Ringkas

Ototoxic

Bronchospam CHF

Hepatotoxic UGIB

Bleeding Nephrotoxic

TocolyticAllergy

Color blindness

TOXICITY OF NSAIDs

Mechanism of = Mechanism of therapeutic effects adverse effects

Perdarahan GI

Page 33: Penatalaksanaan Nyeri Ringkas

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]

Page 34: Penatalaksanaan Nyeri Ringkas

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

Page 35: Penatalaksanaan Nyeri Ringkas

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.

Page 36: Penatalaksanaan Nyeri Ringkas
Page 37: Penatalaksanaan Nyeri Ringkas

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.

Page 38: Penatalaksanaan Nyeri Ringkas

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

Page 39: Penatalaksanaan Nyeri Ringkas