basic,eucosanoids, nsaid

ANALGESIC AND NSAIDS

Dr. Budhi Setiawan, M.Kes

Pharmacology

OBJECTIVES

• List the major effects of prostaglandin and leucotriene

• List important sites of synthesis and the effects of thromboxane and prostacyclin in the vascular system

• List the currently available antagonists of leucotrienes and prostaglandins and their targets

• Explain the different effects of aspirin on prostaglandin synthesis and on leucotriene synthesis

OBJECTIVES

• Contrast the functions of COX-1 & COX-2

• Describe the effects of Aspirin on prostaglandin synthesis

• Contrast the action and toxicity of Aspirin, the older non selective NSAIDs & COX-2 selective drugs

• List the toxic effect of Aspirin

• Describe the effects and the major toxicity of Acetaminophen

TERMINOLOGY

• 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 sedang-

ringan• Antipiretik Obat utk menurunkan demam• Anti inflamasi Obat utk menghambat keradangan

Pain

An unpleasant sensory and emotional experience associated with actual or

potential tissue damage, or described in terms of such damage.

Eicosanoid

• Klasifikasi : Prostaglandin, Prostasiklin, Tromboksan, Leukotrien

• Mekanisme Kerja : Aktifasi reseptor : protein G Adenylyl Cyclase (c AMP) / Phosphatidylinositol cascade ( IP3 & DAG)

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, Naprosyn, Tylenol)

2. Add adjuvant analgesic(TCA, Anticonvulsant, Tramadol)

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– Anitconvulsants– Serotonin reuptake inhibitors– Muscle relaxants

Psychotropic Drugs

• Tricyclic Antidepressants– Amitryptiline, Nortryptiline

• Serotonin Reuptake Inhibitors– Prozac, Zoloft

• Anticonvulsant– Tegretol, Dilantin, Gabapentin

• Effective for chronic nerve-related pain

Ibuprofen - Advil Naproxen - Anaprox, NaprosynDiclofenac - VoltarenIndomethacin – IndocinPiroxicam - FeldeneMetamizole - NovalginMefenamic Acid - PonstanKetorolac Tromethamine – ToradolKetoprofen - Profenid

AINS Selective COX-2

• Celecoxib

• Rofecoxib

• Nimesulide

• Meloxicam

TOKSISITAS

• Gastritis

• Tinnitus

• Prolonged Bleeding Time

• Allergy

• Reyes syndrome Aspirin

Analgesik Lainnya : Acetaminophen

• Sejak 1893 Paracetamol• Dipakai sebagai analgesik &

antipiretik• Tidak mempunyai efek anti inflamasi• Menghambat PG di sentral• Tidak mengiritasi lambung• Dosis besar hepatotoksik