Obat anti inflamasi non steroid Nurina H, dr

inflammatory response Inflammation injurious stimulus inflammatory process Calor Dolor Rubor Tumor Functiolesa noxious agents : Infection Antibodies Physical injuries Phase : acute subacute chronic proliferative Essential for survival in the face of environmental pathogens and injury inflammatory response may be exaggerated & sustained without apparent benefit & w/ severe adverse consequences

Slowing or-in theory-arrest of the tissue damaging process Inflammation Therapeutic Strategies Relief of pain Slowing or-in theory-arrest of the tissue damaging process

NSAIDS: NONSTEROIDAL ANTIINFLAMMATORY DRUGS Chemistry & Pharmacokinetics Grouped in several chemical classes Varied pharmacokinetic characteristics But NSAIDs have some general properties in common

NSAIDS: NONSTEROIDAL ANTIINFLAMMATORY DRUGS Chemistry & Pharmacokinetics Weak organic acids except nabumetone Most are well absorbed Food doesn’t substantially change bioavalability Most are highly metabolized : phase I & II ; phase II alone Elimination : most important route – renal excretion nearly all undergo enterohepatic circulation Most are highly protein bound, usually to albumin

NSAIDS: NONSTEROIDAL ANTIINFLAMMATORY DRUGS PHARMACODYNAMICS antiinflammatory analgesic antipyretic Except paracetamol w/ very low anti inflammatory effect Inhibition of Prostaglandin Biosynthesis

Cyclooxygenase (COX) 2 forms : cyclooxygenase-1 (COX-1) cyclooxygenase-2 (COX-2) COX-1 : primarily constitutive isoform found in most normal cells and tissues – kidney, GIT, platelet homeostasis COX-2 : induced during inflammation; facilitate the inflammatory response

Origin & Effects of Prostaglandin

Classification of NSAIDs NON SELECTIVE COX INHIBITORS 1. SALICYLIC ACID DERIVATIVES - ASPIRIN, SODIUM SALICYLATE, SALSALATE, 2. PARA – AMINOPHENOL DERIVATIVES - ACETAMINOPHEN ( PARACETAMOL ) 3. INDOLE & INDENE ACETIC ACIDS - INDOMETHACIN, SULINDAC 4. HETEROARYL ACETIC ACIDS - TOL METIN, DICLOFENAC, KETOROLAC

Classification of NSAIDs - cont 5. ARYL PROPIONIC ACIDS -IBUPROFEN, NAPROXEN, FLURBIPROFEN, KETOPROFEN, FENOPROFEN, OXAPROZIN 6. ANTHRANILIC ACIDS ( FENAMATES ) - MEFENAMIC ACID, MECLOFENAMIC ACID 7. ENOLIC ACIDS - OXICAM ( PIROXICAM, MELOXICAM ) 8. ALKANONES - NABUMETONE

Classification of NSAIDs - cont II SELECTIVE COX – 2 INHIBITOR DIARYL – SUBTITUTED FURANONES - ROFECOXIB DIARYL – SUBTITUTED PYRAZOLES - CELECOXIB INDOLE ACETIC ACIDS - ETODOLAC SULFONANILIDES - NIMESULIDE

Clinical uses of NSAIDs For analgesia (e.g. headache, dysmenorrhoea, backache, bony metastases, postoperative pain) For anti-inflammatory effects (e.g. rheumatoid arthritis and related connective tissue disorders, gout and soft tissue disorders) To lower temperature (antipyretic)

NSAIDs: group-specific adverse effects

Adverse Effects of NSAID Therapy Gastrointestinal : anorexia, nausea, dyspepsia, abdominal pain, diarrhea → gastric or intestinal ulcers (↓ with COX-2-selective drugs) Cardiovascular : COX-2-selective- ↑ risk of heart attack and stroke Analgesic Nephropathy

Adverse Effects of NSAID Therapy Pregnancy : Prolongation of gestation, postpartum hemorrhage, closure of the ductus arteriosus and impaired fetal circulation in utero Hypersensitivity: bronchial asthma, urticaria, shock Platelets: ↑risk of hemorrhage Cox -2 selective- ↑risk of thrombosis

Aspirin (acetylsalicylic acid) the oldest NSAID Is given orally and is rapidly absorbed; 75% is metabolised in the liver Also inhibits platelet aggregation → ↓ CHD Unwanted effects : gastric bleeding; dizziness, deafness and tinnitus ('salicylism‘); postviral encephalitis (Reye's syndrome) in children; respiratory alkalosis followed by metabolic acidosis

Paracetamol/Acetaminophen potent analgesic and antipyretic actions but rather weaker anti-inflammatory effects administered orally mild to moderate pain: headache, myalgia, postpartum pain preferred to aspirin in children with viral infections

Paracetamol/Acetaminophen Adverse Effects therapeutic doses→a mild increase in hepatic enzymes larger doses→dizziness, excitement, disorientation 15 g→ severe hepatotoxicity; acute renal tubular necrosis

DIPIRON analgesic +, antipyretic +, anti inflammatory – (weak) Administered orally; parenteral Adverse Effects : agranulositosis, anemia aplastik, trombositopeni, hemolisis