1. Obat anti inflamasi non steroid
Nurina H, dr

2. 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

3. 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

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

5. 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

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

8. 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

9. Origin
& Effects
of Prostaglandin

10. 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

11. 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

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

13. 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)

14. NSAIDs: group-specific adverse effects

15. 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

16. 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

17. 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

18. 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

19. 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

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