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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. 2. 3. 4. TENTUKAN MACAM NYERI DURASINYA ( AKUT / KRONIK ) INTENSITASNYA 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
7 - 10

NYERI SEDANG
NYERI BERAT

2. PICTORIAN SCALE ANAK ( WAJAH YANG KESAKITAN )

TERMINOLOGI
AINS NSAID SAARD : Anti Inflamasi Non Steroid : Non Steroidal Anti Inflammation Drug : Slow Acting Anti Rheumatic Drug

DMARD
Analgesik Antipiretik

: Disease Modifying Anti Rheumatic Drug


: Obat utk mengurangi nyeri : 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


Mediator Prostaglandin Vasodilatasi +++ Permeabilitas Kemotaksis Vaskuler +++ Nyeri +

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 Leukotrien PG Endoperoxides TA2 PROSTASIKLIN(PGI2)

Prostaglandin
Prostaglandin E2 (PGE2) Prostasiklin (PGI2) Prostaglandin E1 (PGE1) Prostaglandin H2 (PGH2) Prostaglandin D2 (PGD2) Prostaglandin F (PGF) Prostaglandin G2 (PGG2)
* Eritema * Vasodilatasi * Peningkatan aliran darah lokal * Demam * Nyeri

Penggunaan Klinis
Obgyn PGE2 (Dinoprostone), PGF2, 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 PGE2 (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 NSAIDs 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 ( 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
Fenilbutazon Oksifenbutazon

Derivat Oksikam
Piroksikam Tenoksikam

Asam Asetat

Der.As.Salisilat
Aspirin Benorilat Diflunisal Salsalat

Der.As.Propionat
Fenbufen Ibuprofen Ketoprofen Naproksen

Der.As.Fenamat
Asam mefenamat Meklofenamat

Der. As. Fenilasetat


Diklofenak Fenklofenak

Der.As. Asetat Inden/Indol


Indometasin 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
Xanthine Oxydase

Allopurinol

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 Anti Inflammatory Drugs Prototype Colchicine Other Significant Agents NSAIDs : Indomethacine, Glucocorticoid Sulfinpyrazone

Uricosuric Agent

Probenecid

Xanthine Oxidase Inhibitor

Allopurinol

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 Methotrexate

Antimalarial Anticancer

Rash, GIT, ototoxicity, myopathy, neuropathy Nausea, Ulcers, teratogenic Nephrotoxicity, hypertension, Peripheral neuropathy Upper respiratory infection Injection site reaction

Cyclosporine

Tissue Transplantation

Infliximab Etanercept Penicillamine

Chrons Disease

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 , a mediator in chronic inflamation

Terima kasih ! Terima kasih !