ANALGESIK

Chenny , dr.
Bagian Farmakologi
Fakultas Kedokteran
Universitas Wijaya Kusuma Surabaya
 Pain

• An unpleasant sensory and emotional

experience associated with actual or
potential tissue damage, or described
in terms of such damage
INTERNATIONAL ASSOCIATION FOR THE STUDY OF PAIN ( IASP )
LANGKAH – LANGKAH MENGHADAPI NYERI

1. TENTUKAN MACAM NYERI

2. DURASINYA ( AKUT / KRONIK )
3. INTENSITASNYA
4. PENYEBABNYA
 MACAM NYERI

NYERI

N. NOSISEPTIK N. PSIKOGENIK

N. NEUROPATIK
 INTENSITAS NYERI
MENGUKUR NYERI….?
1. NUMERIC PAIN INTENSITY SCALE (NPIS)
1-3 NYERI RINGAN
4-6 NYERI SEDANG
7 - 10 NYERI BERAT

2. PICTORIAN SCALE ANAK

( WAJAH YANG KESAKITAN )
 TERMINOLOGI
• AINS : Anti Inflamasi Non Steroid
• NSAID : Non Steroidal Anti Inflammation Drug
• SAARD : Slow Acting Anti Rheumatic Drug
• DMARD : Disease Modifying Anti Rheumatic Drug
• Analgesik : Obat utk mengurangi nyeri
• Antipiretik : Obat utk menurunkan demam
• Anti inflamasi : Obat utk menghambat keradangan
 ANALGESIK

Opioid Analgesik Non-Opioid Analgesik

Analgesik Antipiretik AINS Obat Pirai/Gout

Beberapa mediator inflamasi akut dan efeknya

Permeabilitas
Mediator Vasodilatasi Kemotaksis Nyeri
Vaskuler

Prostaglandin +++ +++ +

Bradikinin +++ - +++

Leukotrien - +++ -

Histamin ++ - -

Serotonin +/- - -
 Eicosanoid
• Klasifikasi
Prostaglandin, Prostasiklin, Tromboksan,
Leukotrien
• Mekanisme Kerja
Aktifasi reseptor Protein G  menghambat
Adenylyl Cyclase (c AMP) /
Phosphatidylinositol cascade ( IP3 & DAG)
 Schemes for prostaglandin biosynthesis

stimulus
disturbance of cell membrane phospholipids
phospholipase corticosteroid inhibit

arachidonic acid

lipoxygenase cyclooxigenase

NSAID & Aspirin inhibit

Hidroperoxides Endoperoxides

Leukotrien PG TA2 PROSTASIKLIN(PGI2)

 Prostaglandin
• Prostaglandin E2 (PGE2) * Eritema
• Prostasiklin (PGI2) * Vasodilatasi
• Prostaglandin E1 (PGE1) * Peningkatan aliran darah
lokal
• Prostaglandin H2 (PGH2)
* Demam
• Prostaglandin D2 (PGD2) * Nyeri
• Prostaglandin F (PGF)
• Prostaglandin G2 (PGG2)
 Penggunaan Klinis
• Obgyn
PGE2 (Dinoprostone), PGF2α,  mematangkan Cervix,
PGE1 (Misoprostol)  Kontraksi uterus
• Pediatry
PGE1  Patent Duktus Arteriosus
• Dialysis
PGI2 (Epoprostenol)  Hipertensi Pulmoner
• Ulkus Peptikum AINS
Misoprostol
• Urology
PGE1 (Alprostadil)  Impotensi
• Ophthalmology
PGE2α (Latanoprost)  Glaucoma, Unoprostone 
Meningkatkan out flow Humor Aqueous
 Antagonis Eicosanoid
• Kortiko steroid
• AINS
• Antagonis Leukotrien
Zileuton  Lypoxygenase inhibitor,
Leukotrien receptor antagonist 
Zafirlukast, Montelukast
 Steps in Pain Control
1. NSAID or acetaminophen
→ Ibuprofen, Aspirin, Paracetamol
2. Add adjuvant analgesic
→ Antikonvulsan, Antidepresi, Antipsikotik
3. Add opioid analgesic to above
→ Codeine, Hydrocodone, Oxycodone
4. Increase potency of opioid
→ Morphine, Fentanyl, Hydromorphone
 Medications used for chronic
pain management
• Acetaminophen
• NSAID’s
• Adjunct medications
– Tricyclic antidepressants
– Anticonvulsants
– Serotonin reuptake inhibitors
– Muscle relaxants
 ANALGESIK ANTIPIRETIK
dan
ANTI INFLAMASI NON STEROID
• Merupakan kelompok obat yang heterogen,
bahkan beberapa sangat berbeda secara
kimiawi
• Namun memiliki banyak persamaan dalam efek
terapi maupun efek samping
• Prototip : aspirin
• K.I : Kehamilan TM III SINTESA PG θ
( Inhibisi agregasi platelet,renal fetal failure,
persalinan mjd lambat )
Ibuprofen - Advil
Naproxen - Anaprox, Naprosyn
Diclofenac - Voltaren
Indomethacin – Indocin
Piroxicam - Feldene
Metamizole - Novalgin
Mefenamic Acid - Ponstan
Ketorolac Tromethamine – Toradol
Ketoprofen - Profenid
 Acetaminophen
• Sejak 1893  Paracetamol
• Dipakai sebagai analgesik & antipiretik
• Tidak mempunyai efek anti inflamasi
• Menghambat PG di sentral
• Tidak mengiritasi lambung
• Do. besar (200-250 mg/kgBB) hepatotoksik
• Aman untuk Ibu hamil + menyusui
• Do. max : anak 60 – 90 mg/KgBB/hr
dewasa 8 x 500 mg
Antidot : Acetylcysteine i.v dalam larutan D5
 AINS

Asam karboksilat Asam Enolat

Derivat Pirazolon Derivat Oksikam

Fenilbutazon Piroksikam
Oksifenbutazon Tenoksikam

Der.As.Salisilat Der.As.Propionat Der.As.Fenamat

Asam Asetat Asam mefenamat
Aspirin Fenbufen
Benorilat Ibuprofen Meklofenamat
Diflunisal Ketoprofen
Salsalat Naproksen

Der. As. Fenilasetat Der.As. Asetat Inden/Indol

Diklofenak Indometasin
Fenklofenak Sulindak
Tolmetin
 AINS Selective COX-2

• Celecoxib
• Rofecoxib
• Nimesulide
• Meloxicam
 TOKSISITAS
• Gastritis
• Tinnitus
• Prolonged Bleeding Time
• Allergy
• Reyes syndrome  Aspirin
 Mekanisme terjadinya iritasi lambung :
• Iritasi yang bersifat lokal
☞ difusi kembali asam lambung ke mukosa dan
menimbulkan kerusakan jaringan.

• Iritasi / perdarahan lambung yang bersifat

sistemik
☞ inhibit PGI2, PGE2 dan PGF2a
( PG ini mempunyai fungsi menghambat
sekresi asam lambung dan merangsang
sekresi mukus lambung + usus halus yang
bersifat sitoprotektif ).
 DRUGS USED IN GOUT
• Pirai / Gout : Penyakit metabolisme familial yang
dikarakterisasi oleh episode berulang artritis
akut yang disebabkan endapan monosodium
urat pada sendi dan tulang rawan
• Pirai biasanya dikaitkan dengan kadar serum
asam urat yang tinggi
• Asam urat a zat sulit larut yang merupakan
hasil akhir utama metabolisme purin
 Purin

Hypoxanthine
Xanthine Oxydase
Xanthine Allopurinol
Xanthine Oxydase

Uric acid

GOUT
 Tujuan pengobatan

• Pengurangan intensitas serangan akut

• Mencegah kambuhnya episode pirai
• Mencegah timbulnya batu urat
 Terapi Keadaan Akut
• Menghentikan proses inflamasi
• Menghilangkan gejala

Terapi simptomatis
 Terapi Pirai Kronis
• Menurunkan kadar asam urat
• Memobilisasi asam urat
• Menghambat pembentukan tofi

Terapi kausatif
 OBAT PIRAI

Akut Kronis

AINS Uricosuric Agent

Xanthine Oxydase Inhibitor
 DRUGS USED IN GOUT
Subclass Prototype Other Significant
Agents

Anti Inflammatory Colchicine NSAIDs :

Drugs Indomethacine,
Glucocorticoid

Uricosuric Agent Probenecid Sulfinpyrazone

Xanthine Oxidase Allopurinol

Inhibitor
 Anti Inflammatory Drugs Used for Gout
• Mechanism
NSAIDs reduce prostaglandin formation, Colchicine
reduce leukocyte migration through microtubules
inhibition
• Clinical use
treatment of acute gouty arthritis
• Toxicity
Indomethasin  renal damage & bone narrow
depression
Glucocorticoid  behavioral & blood glucose,
Colchicine  liver & kidney damage
 Uricosuric Agent
• Mechanism
compete with uric acid reabsorbtion in S2
segment of proximal tubule
• Clinical Use
treatment of chronic gout (after 1-2 week)
• Toxicity
attack precipitation, allergenicity
 Xanthine Oxidase Inhibitor
• Mechanism
inhibit enzyme XO that converts hypoxanthine
to xanthine and uric acid
• Clinical Use
treatment of chronic gout (after 1-2 week)
• Toxicity
attack precipitation, GIT, neuritis & vasculitis
(rare)
 Disease Modifying Antirheumatic Drugs (DMARDS)
Drugs Other Clinical Uses Toxicity

Sulfasalazine Inflamatory Bowel Disease Rash, GIT, Dizziness,

Headache, Leukopenia

Hydroxy chloroquin Antimalarial Rash, GIT, ototoxicity,

myopathy, neuropathy
Methotrexate Anticancer Nausea, Ulcers,
teratogenic

Cyclosporine Tissue Transplantation Nephrotoxicity,

hypertension,
Peripheral neuropathy

Infliximab Chron’s Disease Upper respiratory infection

Etanercept Injection site reaction

Penicillamine Chelating Agent Many adverse effects

 DMARDs Mechanism of Action
• Methotrexate
– Reducing number of immune cells
• Sulfasalazine
– Unclear
• Hydroxychloroquin, Penicillamine
– Interfere T Lymphocyte activity
– Decrease leucocyte chemotaxis
– Stabilize lysosomal membrane
– Interfere DNA & RNA protein synthesis
– Trap free radical
 DMARDs Mechanism of Action
• Leflunomide
– Inhibit dihydroorotate dehydrogenase
• Decrease synthesis pirimidine in lymphocyte
• Cell cycle arrest in lymphocyte
• Infliximab, Etanercept
– Bind and prevent the action of TNF α, a
mediator in chronic inflamation
Terima kasih !
Terima kasih !