PAIN

MANAGEMENT

Oleh:
Ema Pristi Yunita, M.Farm.Klin., Apt.
DEFINITION
Pain is an unpleasant sensation that
can negatively affect all areas of a
person's life, including comfort,
thought, sleep, emotion, and normal
daily activity
Pain is defined by the International
Association for the Study of Pain
(IASP) as an unpleasant sensory &
emotional experience associated with
actual or potential tissue damage or
described in terms of such damage
 TYPES OF PAIN
The IASP classification system describes pain according to
five categories: (1) duration and severity, (2) anatomical
location, (3) body system involved, (4) cause, and (5)
temporal characteristics (intermittent, constant, etc.)

Duration and severity :

1. Acute pain
2. Chronic Pain
a. Inflammatory pain
b. Neuropathic pain
 PAIN PATHWAYS
Specialized receptors = free nerve endings
Stimulation
Mechanical damage
Extreme temperature
Chemical irritation
Two types of neurons
A-delta fibers: first pain, sharp
C-fibers: second pain, dull
Four distinct processes
Transduction, transmission, modulation, perception
Transduction
Process by which noxious stimuli are translated into electrical
signals at peripheral receptor sites. This begins when
nociceptors (free nerve endings located throughout the skin,
muscle, and viscera) are exposed to a sufficient quantity of
mechanical, chemical, or thermal noxious stimuli.
In addition, a variety of chemical compounds (e.g., histamine,
bradykinin, serotonin, prostaglandins and substance P) are
released serially from damaged tissues and can activate or
sensitize nociceptors.
Serotonin has the additional action of modulating the
peripheral release of primary afferent neuropeptides that are
responsible for neurogenic inflammation. These
neuropeptides include substance P, calcitonin gene-related
peptide, and neurokinin A.
Transmission
Transmission continued ...
Transmission involves the propagation of an electrical signal along neural
membranes.
Stimuli, such as prostaglandins and inflammatory mediators, change the
permeability of the membrane, producing an influx of sodium and an
efflux of potassium, thereby depolarizing neuronal membranes.
Electrical impulses are transmitted to the spinal cord via two primary
afferent nerve types: myelinated A-fibers and unmyelinated C-fibers.
The A-delta fiber is responsible for rapidly conducting electrical impulses
associated with thermal and mechanical stimuli to the dorsal horn of
the spinal cord. A-delta fibers release excitatory amino acids, such as
glutamate, which activate AMPA (-amino-3-hydroxy-5-methylisoxazole-
4-propionic acid ) receptors located on dorsal horn neurons.
Transmission of signals along these fibers results in sharp or stabbing
sensations that alert the subject to an injury or insult to tissue. CNS input
rapidly produces reflex signals, such as musculoskeletal withdrawal to
prevent further injury.
Modulation
Modulation of nociceptive information occurs quickly
between descending inhibitory pathways from the
thalamus and brainstem and interneurons in the dorsal
horn.
Neurons from the thalamus and brainstem release
inhibitory neurotransmitters, such as norepinephrine,
serotonin, -aminobutyric acid (GABA), glycine,
endorphins, and enkephalins, which block substance P
and other excitatory neurotransmitter activity on primary
afferent fibers.
Perception
The conscious awareness, or perception, of pain is the end
result of this complex cascade of actions. The perception of
pain involves not only nociceptive processes, but also
physiologic and emotional responses, which contribute
significantly to the sensation that is ultimately experienced by
the person. The perception of pain may be influenced by
abnormal generation or processing of electrical pain signals
and by the psychological framework created by the patient's
temporal affective state or from previous painful experiences.

Therefore, treatment that includes drug therapy to

alter the nociceptive and physiologic responses, in
addition to cognitive-behavioral strategies (e.g.,
distraction, relaxation, and imagery) to alter the
psychological response, may be more effective
together than if either intervention is used alone
Tissue Damage
Release of chemical substances and enzymes
(mediators) that alter the activity and sensitivity
of sensory neurons
Prostaglandins, leukotriens: sensitization of receptors
Bradykinin and PGs: stimulate the neurons directly
Histamine: pain, itching
Result
Increase in nociceptor activity
Hyperalgesia
Neurogenic edema
 Injury stimulates peripheral
nociceptors, which synapse in
the dorsal root ganglion to
send signals of pain to the
brain inflammatory mediators
are released which again
stimulate the nociceptors,
which in turn release
substance P to create mast
cell degranulation and
peripheral vasodilation

calcitonin gene-related peptide (CGRP)

Dorsal Horn
Neurotransmittors causing
enhanced excitability and
sensitization of dorsal horn
cells
Persistent changes
Cause of allodynia (touch
becomes pain)
Prevented by pre-treatment
with e.g opioids
calcitonin gene-related peptide (CGRP)
 Excitation of the nociceptors in an
organ then triggers pain sensations
in those areas of the skin whose
afferents make connections in the
same spinal cord segment (referred
pain). In myocardial infarction, for
example, pain radiates into the left
shoulder and left arm (Heads
zones)
Projected pain is produced by
stimulation of a nerve (e.g., of the
ulnar nerve in the ulnar sulcus). The
perception of pain is projected to
the innervation area of the nerve
A special form of projected pain is
phantom pain of an amputated
limb or part thereof
Wong-Baker FACES Pain Rating Scale

Explain to the person that each face is for a person who feels happy because he has no
pain (hurt) or sad because he has some or a lot of pain. Face 0 is very happy because he
doesnt hurt at all. Face 1 hurts just a little bit. Face 2 hurts a little more. Face 3 hurts
even more. Face 4 hurts a whole lot. Face 5 hurts as much as you can image, although
you dont have to be crying to feel this bad. Ask the person to choose the face that best
describes how he is feeling.

Rating scale is recommended for persons age 3 years and older.

Point to each face using the words to describe the pain intensity. Ask the child to choose
face that best describes own pain and record the appropriate number.
010 Numeric Pain Rating Scale

Visual Analog Scale

Verbal Pain Intensity Scale
Pharmacological Treatment of
Pain
Periphery-along axons-CNS
Single treatment/polymodal
Continuosly/intermittently
1. Regional anesthesia
2. NSAIDs
3. Opioids
4. NMDA-receptor antagonists
5. Alpha-2-receptor agonists
6. Other agents
1. Regional Anesthesia
Lidocaine (lignocaine): Xylocain
Bupivacaine: Marcain
Tricaine: MS-222
Preoperatively and postoperatively
Underuse in small species
Na+channels inhibitor
2. NSAIDs
Non-steroidal anti-inflammatory drugs
Reduce synthesis of PGs
COX inhibitors (cyclooxygenase)
Diminish nociceptor activation
Block peripheral sensitization
Antipyretic
Anti-hyperalgesic
No sedation
2. NSAIDs continued ...
Salicylates (aspirin)
Ketoprofen: Romefen
Carprofen: Rimadyl
PO, SC, IM
Gastrointestinal ulceration
and renal function disturbances,
embryotoxic, prolong bleeding
3. Opioids
Spinal cord
Decreasing neurotransmitter release
Blocking postsynaptic receptors
Activating inhibitory pathways
Receptor subtypes
mu > delta > kappa
Supraspinal analgesia
Peripheral analgesia (prevent nociceptor
sensitization)
3. Opioids continued ...
Morphine
Fentanyl: Leptanal, Hypnorm
Sufentanil
Burprenorphine: Temgesic
Sedation
PO, SC, IM, IP
Side effects:
respiratory depression, severe
bradycardia, decreased gastric HCl secretion
4. NMDA-receptor antagonists
(N-methyl-D-aspartate)

Spinal cord receptors

Repetitive C-fiber activation
Central hyperalgesia
Not effective against acute inflammatory pain
Effective against prolonged inflammatory pain
Neuropathic and cancer pain
Abolish the wind-up phenomenon
Work in synergy with opioids
Contoh: ketamine, tiletamine
 5. Alpha-2-agonists
Xylaxine: Rompun
Medetomidine: Domitor
Receptors in the spinal cord and brain
Activated by descending noradrenergic pathways
Inhibit pre-synaptic calcium influx and neurotransmitter release
IM, SC, IP, IV
Sedation, analgesia, muscle relaxation and anxiolysis
Side effects
Initial hypertension
Hypotension
Bradycardia
Decreased cardiac output
Depress insulin release
Diuresis
Hypothermia
6. Other agents
Sedatives and tranquillizers
Diazepam, acepromazine, fluanisone
Relieve anxiety, decrease stress
Minimal respiratory and cardiovascular effects
Hypotension, hypothermia
GABA (enhancement), dopamine (blockade)
Antagonist benzodiazepine (flumazenil) to reserve
sedative effects of BZD
SC, IM, IV
Tricyclic antidepressants
Amitryptilline

GABA: gamma-aminobutyric acid

Pain Management

Prevention: preemptive approach

Recognition of pain
Choice of substance
Drug dose and duration
TUJUAN TERAPI
1. Menghilangkan nyeri
2. Menghambat perkembangan nyeri akut
menjadi nyeri kronik
3. Meningkatkan kualitas hidup pasien

Non farmakologis
Cognitive behavioral therapy (CBT)
Transcutaneous electrical nerve
stimulation (TENS) HOLISTIK
Spinal cord stimulation (SCS)
Akupuntur dan pemijatan
Farmakologis
 Strong opioid +
non opioid


adjuvant

Weak opioid + non opioid 2

adjuvant
1
Non opioid adjuvant
Pain
This three-step approach of administering the right drug in
the right dose at the right time is inexpensive and 80-90%
effective
WHO has developed a three-step "ladder" for cancer pain relief (1986)
WHO National Cancer Control program, Policies and Managerial Guidelines (2002)
The Joint Commission of Health Care Organizations Declaration of the present decade as the
decade of pain control and research (2001)
 Time to peak Analgesic
Class Agent Efficacy concentration duration
(h) (h)

Para- Acetaminophen (Tylenol) Good 0.5-2 3-6

aminophenol

NSAID Salicylates Excellence 0.25-2 3-6

Asetylsalisylic acid (Aspirin) 1.5-2 4
Choline /Mg salicylate
(Arthropan) 2-3 8-12
Diflunisal (Dolobid)
Fenamates Excellence
Mefenamic acid (Ponstan) 2-4 4-6
Meclofenamate (Meclomen) 0.5-2 3-6
Pyranokarboxylic acid Excellence
Etodolac (Lodine) 1 6-8
Acetic acid Excellence
Diklofenak Na/K 1 6-8
(Voltaren/Cataflam)
 Time to peak Analgesic
Class Agent Efficacy concentration duration
(h) (h)

NSAID Propionic acid Excellence 4-6

Ibuprofen (Motrin) 1-2
Fenoprofen (Nalfon) 1-2 4-6
Ketoprofen (Orudis) 0.5-2 4-6
Naproxen (Aleve) 2-4 4-8

Pyrolizine carboxylate acid Excellence

Ketorolac (Toradol) 0.5-1 6

COX 2 inhibitor Excellence

Rofecoxib (Vioxx) 2-3 up to 24
3 12-24
Celecoxib (Celebrex)
 Time to peak Analgesic
Class Agent Efficacy concentration duration
(h) (h)

Opioid Morphine-like agonis Excellence 3-5

Morphine (MS Contin) 0.5-1
0.5-1 3-5
Hydromorphone (Dilaudid) 0.5-1 5-8
Levorphanol (Levo-dromoran) 0.5-1 4-6
Codein 0.5-1 4-6
Oxycodone (Oxy contin)
Meperidine-like agonis Excellence 0.5-1 2-5
Meperidine (Demerol) 0.1-0.5 1-2
Fentanyl (Duragesic)
Others Excellence
2-3 4-6
Tramadol (Tramal)
 GI CNS Hepatic Renal
Analgesik non-opioid
Irritation Effects Toxicity Toxicity
Acetaminophen + + ++ +
Aspirin ++++++ + ++ ++
Choline / Mg salicylate +++ - - -
Diflunisal ++ - - -
Mefenamic acid ++ + + ++
Meclofenamate ++ + + ++
Etodolac ++ + + ++
Diklofenak Na/K ++ + + ++
Ibuprofen ++ + + ++
Fenoprofen ++ ++ + ++
Ketoprofen ++ + + ++
Naproksen ++ + + ++
Ketorolac ++ + + +
Rofecoxib + + + +
Celecoxib + + + ++
 Analgesik Opioid Potency Sedation Nausea Constipa Respiratory
tion Depression
(po)* and
vomiting
Codeine 0.05 - + + +
Dihydrocodeine 0.1 - + + +
Tramadol 0.1 - +++ + +
Pethidine (Meperidine) 0.1 + + + +
Morphine 1.0 ++ ++ +++ ++
Diamorphine 1.0 ++ ++ +++ +
Oxycodone 2 - + + +
Phenazocine 5 + + + +
Levorvanol 5 + + + +
Hydromorphone 7.5 ++ + + ++
Buprenorphine 50 +++ + + +
(sublingual)
Fentanyl (transdermal) 150 + + - +
Neuropathic Pain
 Dosis Frek/
Kelompok Analgesik Mekanisme
(mg/hari) Rute
Antikonvulsan Carbamazepin 100-1000 bid to qid -Penghambat
Gabapentin 900-3600 tid neurotransmiter eksitatori
Lamotrigin 150-500 bid (asam amino glutamat)
Pregabalin 5 bid -Menghambat voltage
Baclofen gated cation channel

Amitriptilin 10-200 qd -5HT release

Antidepresan Imipramin 10-200 qd to bid -Noradrenergic pathway
Venlafaxine 37.5-340 tid to bid
-Sodium channel
Anestetik Lidocain 0.25-2 Continuous
iv blocking effect
-Local anestetic

Mexiletine bid
Anti aritmia 50 -Noradrenergic pathway
Clonidin tid
50 -Menghambat sistem
eksitatori

NMDA
Ketamin IV or IM
Antagonis 0.25-0.5 - NMDA blocking
Memantin
Recommended first-line treatments for
patients with neuropathic pain
Algorithm for pain management in oncology
patients
Migrain dan
Headache Type Tension
The International Classification of
Headache Disorders
MIGRAIN
Sakit Kepala Migrain vs
Tegang Otot (tension headache)
DEFINISI & KLASIFIKASI MIGRAIN
Migrain = suatu kondisi kronis yang ditandai oleh
sakit kepala episodik dengan intensitas sedang
berat yang berakhir dalam waktu 4 72 jam
(International Headache Society)
Migrain diklasifikasikan menjadi :
a) Migrain dengan aura (disebut "classic"
migraine) 20%
b) Migrain tanpa aura (disebut "common"
migraine) 80%
c) Status migrain yang tidak sembuh sendiri,
bertahan > 72 jam
GEJALA MIGRAIN
Bervariasi antar individu maupun antara kejadian migrain pada
individu
Ada lima gejala yang dapat diidentifikasi:
a) Prodrome: suatu rangkaian peringatan sebelum terjadi
serangan meliputi perubahan mood, perubahan perasaan
atau sensasi (bau atau rasa), atau lelah dan ketegangan otot
b) Aura: gangguan visual yang mendahului serangan sakit
kepala
c) Sakit kepala: umumnya satu sisi, berdenyut-denyut, disertai
mual dan muntah, sensitif terhadap cahaya dan suara
terjadi antara 4 72 jam
d) Berhentinya sakit kepala: meskipun tidak diobati, nyeri
biasanya akan menghilang dengan tidur
e) Postdrome: tanda-tanda setelah serangan migrain seperti
tidak bisa makan, tidak bisa konsentrasi, kelelahan
 PATOFISIOLOGI MIGRAIN
Menurut teori/hipotesis vaskular : aura disebabkan oleh
vasokonstriksi intraserebral diikuti dengan vasodilatasi
ekstrakranial
Aura mungkin merupakan manifestasi penyebaran depresi,
suatu peristiwa neuronal yang ditandai oleh gelombang
penghambatan yang menyebabkan turunnya aliran darah otak
sebesar 25-35%
Nyeri disebabkan karena aktivitas sistem trigeminal yang
menyebabkan pelepasan neuropetida vasoaktif vasodilatasi,
plasma neurogenik ekstravasasi, dan nyeri
Aktivitas di dalam sistem trigeminal diregulasi oleh saraf
noradrenergik dan serotonergik
Reseptor 5-HT, terutama 5-HT1 dan 5-HT2 terlibat dalam
patofisiologi migrain
SARAF TRIGEMINAL

Nervus Trigeminus /saraf

trigeminal merupakan saraf
kranial terbesar
Nervus ini disebut nervus
trigeminus, karena
mempunyai tiga cabang yaitu
n.optalmikus, n. maksilaris,
dan n.mandibularis
Nervus trigeminus terdiri dari
serabut sensoris maupun
serabut motoris
 Lanjutan PATOFISIOLOGI MIGRAIN ..

Stimulasi pd saraf trigeminal

Melepas substansi-P, CGRP, neurokinin-A dari sensory C-

fiber

Substansi-substansi tsb menyebabkan inflamasi

neurogenik

Berinteraksi dgn dinding pembuluh darah shg terjadi

dilatasi, ekstravasasi plasma, inflamasi

Ekstravasasi neurogenik plasma dpt dihambat oleh 5-HT1

agonis, neurosteroid, prostaglandin inhibitor, antagonis
substansi-P, antagonis endotelin
 FAKTOR PEMICU MIGRAIN
Faktor psikologis Obat-obatan
Stress, depresi Simetidin
Faktor lingkungan Kokain
Rokok Fluoksetin
Bau menyengat Indometasin
Perubahan cuaca Nikotin
Cahaya atau suara Nifedipin, dll
Faktor hormonal
Faktor makanan
Menstruasi
Yg mengandung tiramin
Hamil, menopause
Food additive (MSG, aspartam)
Gaya hidup
Coklat, kopi
Kurang atau kebanyakan tidur
Jeruk Terlambat makan, dll
 TUJUAN TERAPI

Mengurangi frekuensi dan

keparahan serangan
Terapi bertujuan Mengurangi patient disability
menghilangkan selama serangan
gejala/nyeri pada saat Memperbaiki kualitas hidup
pasien
serangan (terapi Mencegah serangan
abortif) atau berikutnya
mencegah serangan Menghindarkan penggunaan
(terapi profilaksis) obat yang makin bertambah
Dan mengedukasi pasien utk
dapat menatalaksana
penyakitnya
STRATEGI TERAPI

Terapi profilaksis dimulai jika

Menghindari Terapi abortif serangan terjadi > 2-3 x/bln,
atau dimulai pada serangan berat dan
menyebabkan gangguan fungsi,
menghilangkan saat terjadinya terapi simptomatik gagal atau
pemicu serangan menyebabkan efek samping yang
serius
 Algoritma
Terapi pada
Migrain

Midrin: kombinasi PCT,

isometheptene mucate
(simpatomimetik amin) &
dikloralfenazon (turunan
kloralhidrat)
 TERAPI ABORTIF VS PROFILAKSIS

Pembeda Terapi Abortif Terapi Profilaksis

Melibatkan analgesik Ya Tidak
Waktu Saat serangan Setelah serangan
Tujuan Meredakan rasa Memperbaiki pengaturan
nyeri ketika serangan proses fisiologis yang
terjadi mengkontrol aliran darah
dan aktivitas sistem saraf
TERAPI ABORTIF
Analgesik
& NSAID

Golongan
Antiemetik
Triptan

Alkaloid
ergot &
turunannya
 Analgesik ringan : aspirin (drug of choice),
parasetamol
NSAIDs: menghambat sintesis prostaglandin,
Analgesik antiagregasi platelet, dan pelepasan 5-HT;
Naproksen terbukti lebih baik dari
ergotamin; Pilihan lain: ibuprofen, ketorolak
Analgesik opiat

Agonis reseptor 5-HT1D menyebabkan

vasokonstriksi di kranial vasodilatasi pembuluh
darah di kranial dapat dihambat inflamasi
neurogenik terhambat
Gol. Triptan Contoh: sumatriptan, zolmitriptan, naratriptan, dll
Efikasinya setara dengan dihidroergotamin, tetapi
onsetnya lebih cepat
Sumatriptan per oral lebih efektif dibandingkan
ergotamin per oral
 Menstimulasi reseptor 5-HT1 presinaptik
Alkaloid vasokonstriksi di vaskular intrakranial vasodilatasi
dapat dicegah blokade inflamasi neurogenik
ergot & Pemberian IV dapat dilakukan untuk serangan yang
berat
turunannya Contoh: ergotamin tartrat & dihidroergotamin

Contoh: metoklopramid, klorpromazin,

proklorperazin
Antiemetik Digunakan untuk mencegah mual muntah
Diberikan 15-30 menit sebelum terapi antimigrain,
dapat diulang setelah 4-6 jam
Algoritma Terapi untuk
Pencegahan Migrain
 TERAPI PROFILAKSIS
Beta blocker
Merupakan drug of choice untuk prevensi migrain
Kemungkinan dpt meningkatkan ambang batas / treshold
dengan menurunkan transmisi saraf adrenergik atau
serotonergik di kortikal atau subkortikal
Contoh: propranolol, timolol, atenolol, metoprolol, nadolol

Antidepresan trisiklik
Kemungkinan menyebabkan downregulation dari 5-HT2 di sentral
aktivitas serotonergik di sentral menurun
Contoh: amitriptilin, doxepin, nortriptilin, protriptilin, dan imipramin
Sebaiknya digunakan pd malam hari ada ES sedasi (mengantuk)
Punya efek antikolinergik, tidak boleh digunakan untuk pasien
glaukoma atau hiperplasia prostat
 TERAPI PROFILAKSIS
Methysergide
Merupakan senyawa ergot semisintetik, antagonis 5-HT2 yang
poten menghambat aktivitas serotonergik pada saraf
trigeminal memblok inflamasi neurogenik
Kompetitif serotonin antagonis di perifer & serotonin agonis di
SSP

Asam-Valproat / Na-Valproat
Diduga meningkatkan aktivitas inhibisi melalui GABA,
memodulasi neurotransmiter eksitatori dan hambatan aktivitas
kanal ion natrium dan kalsium
Dapat menurunkan keparahan, frekuensi dan durasi pada 80%
penderita migrain
Sakit Kepala Tegang Otot
(Tension Headache)
 DEFINISI
Merupakan jenis yang paling banyak dijumpai, disebabkan
karena kontraksi otot di kepala
Rasa nyeri tumpul yang konstan, atau perasaan menekan
yang tidak enak pada leher, pelipis, dahi, atau di sekitar
kepala, leher terasa kaku
Umumnya terjadi secara bilateral (terjadi pada kedua belah
sisi pada waktu yang sama)
Episodic tension-type headaches frekuensi nyeri
sedikitnya 10 x sakit kepala yang lamanya berkisar 30 menit
7 hari, dan terjadi kurang dari 180 kali setahun
Chronic tension-type headache frekuensi rata-rata 15
hari dalam sebulan selama 6 bulan ( 180x setahun)
GEJALA
Rasa menekan/berat yang berlokasi di kedua
belah sisi kepala
Sakit dengan intensitas ringan sampai sedang
Tidak bertambah berat dengan aktivitas fisik
rutin
Tidak mual atau muntah
Mungkin sensitif terhadap cahaya atau suara,
tapi tidak keduanya
TERAPI NON-FARMAKOLOGI

Melakukan latihan peregangan leher atau otot bahu

sedikitnya 20 - 30 menit
Perubahan posisi tidur
Pernafasan dengan diafragma atau metode relaksasi otot
yang lain
Penyesuaian lingkungan kerja maupun rumah:
Pencahayaan yang tepat untuk membaca, bekerja,
menggunakan komputer, atau saat menonton televisi
Hindari paparan terus-menerus pada suara keras dan
bising
Hindari suhu rendah pada saat tidur pada malam hari
TERAPI FARMAKOLOGI
Menggunakan analgesik atau analgesik plus adjuvant sesuai
tingkat nyeri Contoh : obat-obat OTC seperti aspirin,
acetaminophen, ibuprofen atau naproxen sodium
Produk kombinasi dengan kafein dapat meningkatkan efek
analgesik
Untuk sakit kepala kronis, perlu assesment yang lebih teliti
mengenai penyebabnya, misalnya karena anxietas (cemas,
gelisah) atau depresi untuk antianxietas dpt digunakan
diazepam atau chlordiazepoxid
Pilihan obatnya adalah antidepresan, seperti amitriptilin,
trifluoroperazin atau antidepresan lainnya
Hindari penggunaan analgesik secara kronis memicu
rebound headache
SELAMAT BELAJAR