ANALGETIKA

Hendra Wana Nuramin

Departemen Farmakologi
Fakultas Kedokteran Universitas
Lambung Mangkurat
Pain unpleasant
sensory and
emotional
experience.
Analgetic any
member of the
group of drugs used
to
achieve analgesia
relief from pain
Analgetic
Non Steroid Anti-inflamatory Drugs (NSAIDs)
Opioid

NON STEROID ANTIINFLAMATORY DRUGS
(NSAIDs)
Indikasi
Common Pharmacological Effects
Analgesic (CNS and peripheral effect) may
involve non-PG related effects
Antipyretic (CNS effect)
Anti-inflammatory (except acetaminophen) due
mainly to PG inhibition
Steroids work
here
Steroids work
here
NSAIDs work
here
5/13/2014 10
COX-1
COX-2
COX-3
COX-1 membentuk prostaglandin (proses normal tubuh)
proteksi mukosa lambung
COX-2 berperan dalam peradangan
COX-3 varian dari COX-1, yang terdistribusi di sistem
saraf pusat.
Tidak mempengaruhi lambung paracetamol
Efek samping AINS terhadap asma
Penghambatan COX mengarahkan
metabolisme asam arakidonat ke arah
jalur lipoksigenase leukotrien
bronkokonstriksi
COX 2 Selektif celecoxib, rofecoxib,
valdecoxib.
Penghambatan secara selektif terhadap
COX-2 mengkatalisis pembentukan
tromboksan A2 (pembekuan darah dan
bersifat vasokonstriktor blood clots
Untuk mengatasi efek obat NSAID terhadap lambung:
digunakan setelah makan
dalam bentuk bersalut selaput jangan digerus atau
dikunyah
Gangguan lambung sebelumnya, bisa diiringi
penggunaannya dengan obat-obat yang menjaga
lambung seperti antasid, golongan H2 bloker
seperti simetidin atau ranitidin, golongan penghambat
pompa proton
seperti omeprazol atau lansoprazol, atau
dengan sukralfat.
FARMAKODINAMIK
SALISILAT
Indikasi : analgetik & antipiretik, pada sakit
kepala, nyeri sendi ringan-sedang, nyeri otot
& saraf
Sistemik, enteral: Aspirin, Na-salisilat,
diflunisal, salsalat
ES: iritasi saluran cerna salut enterik
Aspirin : pencegahan infark miokard anti
agregasi platelet
ASAM FENILPROPIONAT
Indikasi: analgetik, antipiretik, antiinflamasi
Ibuprofen > aspirin: efektif untuk dismenor
Naproxen, fenoprofen, keteoprofen, flurbiprofen
antiinflamasi penyakit sendi
DERIVAT ASAM ASETAT
Indometasin: antiinflamasi penyakit sendi, dan PDA
pada neonatus
Toksik sebagai antipiretik dan analgetik
Tolmetin pengganti indometasin
Sulindak



DERIVAT PIRAZOLON
Metampiron, fenilbutazon & oksifenbutazon
ES: diskrasia darah (leukopenia, agranulositosis, anemia
aplastik)
Alternatif terapi dari kolkisin
Asetaminofen (Paracetamol)
Efek analgetik & antipiretik (+)
Efek antiinflamasi (-)
Bekerja pada COX-3
OBAT LAIN
Asam mefenamat & diklofenak, meklofenamat
Analgetik, antipiretik & antiinflamasi
Asam mefenamat: meredakan nyeri ringan
sampai sedang sehubungan dengansakit kepala,
sakit gigi, dismenore primer, termasuk nyeri
karena trauma, nyeri otot dan nyeri sesudah
operasi
EFEK SAMPING
SALISILAT
Iritasi GI (perdarahan, mual, muntah) 20%
Menurunkan ES :
buffered & enteric coated
diberi bersama makanan, dan
konsumsi air yang banyak
SSP salisilism (tinitus, penurunan
pendengaran, vertigo)
Aspirin menghambat agregasi platelet KI diberikan
bersama antikoagulan lain
Hipersensitif, asidosis respiratorik, asidosis metabolik
Gangguan hepar & ginjal
Asetaminofen
Dosis tinggi: hepatitis, nekrosis hepar
NSAIDs lain
Iritasi GI
Diatasi dengan H2 blockers, omeprazol & misoprostol
Interaksi: antihipertensi (diuretik, antagonis B-
adrenergik, ACE inhibitor)
Gangguan ginjal & hepar, SSP
PENGHAMBAT SELEKTIF COX-2
Celecoxib, Rofexocib
Aman terhadap saluran cerna cocok untuk penderita
dispepsia
Meningkatkan kejadian penyakit kardiovaskular
NSAIDs
COX-2 specific NSAIDs:
Rofecoxib (Vioxx)
Launched in 1999
Marketed in 86 countries: 2.5 bill.$ /year
Recent trial to test Rofecoxib for efficacy in colorectal polyps treatment revealed
an increased risk of heart disease (+ 50%) after 18 month continuous use
Sept. 2004: Merck voluntarily withdrew Vioxx from the market pending further
investigation.
Celecoxib (Celebrex)
April 2005: FDA required Pfizer to include a boxed warning indicating a
potential risk of cardiovascular side effects
Valdecoxib (Bextra)
April 2005: FDA required Pfizer to withdraw Bextra from the market due to
unfavorable risk vs. benefit profile (mostly already known adverse skin reactions)
FARMAKOKINETIK

Opioid Analgesics
Opiates:
Alkaloids derives from Papaver somniferum
Already used 4000 B.C. (opius greek: little juice)
1805: Morphine isolated (morpheus: Greek god of dreams)
1874: synthesis of heroin (introduced in 1898 by Bayer as a cough medicine)
Opium tincture heavily used during civil war
Opiates freely available in the US until 1914
1914: Harrison Act
Prevented physicians from maintaining addiction

Morphine was
first isolated by
Friedrich
Wilhelm
Serturner in
1805.
Sertrner named
his discovery
after Morpheus,
the Greek god of
dreams.
Morpheus is the
son of Hypnos,
the god of sleep.
RESEPTOR OPIOID
Reseptor : analgetik,
depresi napas, miosis,
euforia, penurunan
motilitas usus
1 : hanya di SSP
2 : di perifer
Reseptor : analgetik,
depresi napas, miosis,
sedasi < reseptor
Reseptor : depresi
napas
selektif untuk enkefalin
FARMAKODINAMIK
Analgetik & narkosis
Analgetik muncul sebelum penderita tidur
Pada pasien nyeri, sedih gelisah euforia
Pada orang normal disforia
Sedasi
Bila diberi bersama hipnotik & sedativa dan
antiemetik amnesia
Antitusif
Bekerja di reseptor opioid pusat batuk SSP
Kodein, hidrokodon (+)
Dekstrometorfan (+) bukan di reseptor opioid
Depresi pernapasan
Menurunkan respon batang otak terhadap CO2
Hati-hati jika diberikan bersama anestesi umum &
hipnotik-sedativa
Mual
Merangsang CTZ


Efek endokrin
aktivasi reseptor opioid
Menghambat pelepasan LRH (mens tidak teratur &
impotensi)
Menghambat diuresis
Aktivasi reseptor opioid
Menghambat ADH meningkatkan diuresis
Miosis
Efek pusat di nukleus Edinger Westphal nervus III
Efek kardiovaskular
Menurunkan TD
Bradikardi
Vasodilatasi, hipotensi & gatal lepasnya histamin
Imunosupresi
Efek sentral menekan sistem imun : NK sel

Opioid Analgesics
Opiates:
Morphine:
CNS:
Sedation and drowsiness
Nausea (direct stimulation of the chemoreceptor trigger zone)
Cough suppressant (suppressive effect on medulla; independent of analgesic effect)
Eyes:
Pupillary constriction (stimulate parasympathetic portion of the oculomotor nucleus)
Respiratory system:
Strongly suppressive on all phases (frequency; volume)
GI:
Decreased peristaltic movements, increased sphincter tonus => constipation
Urinary tract:
Increased smooth muscle cell tone => urinary retention
Withdrawal symptoms:
Mostly autonomic hyperactivity: diarrhea, vomiting, chills, cramps, pain
Opioid Analgesics
Codeine (3-methoxy-morphine):
Better oral absorption than morphine
Only 20% of analgesic effect of morphine
(does not increase significanly by increasing the dose)
Little euphoria => rarely addictive
GI and respiratory effects similar to morphine
(=> codeine and dihydrocodeine are widely used as antitussive)
Dextromethorphane (DXM):
Synthetic morphine derivative
Equally antitussive as codeine
Does not act through opioid receptors
No analgesic or GI effects
Opioid Analgesics
Heroin (diamorphine):
Diacetylated morphine
Used in UK as analgesic
(~2x more potent than morphine)
Hydrocodone (Vicodin):
Often combined with NSAIDs
Meperidine (Pethidine):
Actions similar to morphine
Much shorter duration => used during labour
Methadone:
Actions similar to morphine
Significantly longer duration (t
1/2
= >24 h) => less psychological dependence
Used to treat morphine and heroin addiction
Fentanyl:
High potency (allows use in transdermal delivery systems)
Short lasting: used in anesthesia and in patient-controlled infusion systems

Opioid Analgesics
Opiate antagonists:
Naloxone:
Short acting
Rapidly reversed opoid-induced analgesia and
respiratory suppression
No effect if no opioids are present
Used to treat opiate overdoses and to improve breathing
in newborns whose mothers received opioids
Induces severe withdrawal symptoms in opioid addicts

Naltrexone:
Similar to naloxone, but much longer duration of action
Used to protect detoxified addicts by preventing any
opioid effect if the patient relapses
TOLERANSI
Perlu dosis lebih tinggi untuk menghasilkan efek
farmakologi
Diperantarai oleh reseptor opioid dan dilawan dengan
antagonis opioid
Perubahan selular masih belum jelas
Dapat terjadi toleransi silang
Morfin >< metadon; meperidin
KETERGANTUNGAN FISIK
Menyebabkan abstinence
atau withdrawal
syndrome
Menyebabkan gangguan
otonom, somatik,
endokrin, psikologis.
Nyeri dan tidak
menyenangkan tapi
TIDAK MENGANCAM
NYAWA


PENYALAHGUNAAN
Menyebabkan mood
positif EUFORIA
Tidak terjadi pada dosis
terapi
Opioid
Keracunan obat-obat
golongan opioid
banyak terjadi karena
kecanduan atau
penyalahgunaan.
Gejala-gejala:
mual, muntah
pusing
kulit dingin
pupil kecil
depresi nafas
koma
Opioid Poisoning
Opioid
Penatalaksanaan:
Bila ada depresi
nafas, berikan
nalokson HCl
Bila tidak ada depresi
nafas, simptomatik
saja.
References
Basic & Clinical Pharmacology by Bertram G. Katzung(11
th
Edition). The
McGraw-Hill Companies Inc, 2009
Goodman & Gilmans Manual of Pharmacology and Therapeutics (11
th
ed),
2008
Farmakologi dan Terapi FK UI (edisi 5). Jakarta: FK UI, 2007
DiPiro JT, et al. Pharmacotherapy: A Pathophysiologic Approach 6
th
Ed.
San Fransisco: McGraw Hill, 2005
Morgan GE. Clinical Anesthesiology, 4th Edition. McGraw-Hill Companies,
Inc, 2006
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5/13/2014 46 Contact: hendranuramin@gmail.com