1. N ON - STEROIDAL ANTI - INFLAMMATORY DRUGS

2. ANTI-INFLAMMATORY DRUGS A class of drugs that lower inflammation and that includes NSAIDs and DMARDs.NSAIDs

3. NSAID NON SELECTIVE COX INHIBITOR SELECTIVE COX 2 INHIBITOR Salicylates Others Propionic acid Derivatives Oxicams Aryl acetic Acid derivatives Indole derivatives Fenamates

4. P HARMACOKINETIC Oral administration Most NSAIDs are weak acid (absorbed well in stomach and intestinal mucosa) 95% bound to plasma-protein (high bioavailability) Most metabolized in liver (oxidation & conjugation)

5. MECHANISM OF ACTION OF NSAIDS

7. ASPIRIN IS IRREVERSIBLE INHIBITOR TO COX ENZYMES

8. NON- SLECTIVE -NON -STEROIDAL ANTI-INFLAMMATORY DRUGS Are group of drugs that share in common the capacity to induce: Analgesic effect. Antipyretic effect. Anti-inflammatory effect. Antiplatelet effect

9. M ECHANISM O F A CTION Analgesic Inhibition of COX enzymes in CNS Anti- Inflammatory action Antipyretic Centrally inhibiting Prostaglandins production Inhibit interleukin-1 release Peripheral vasodilation Anti-Inflam. Peripherally inhibiting Prostaglandins secretion Stabilization of lysosomes Inhibits phagocytosis Anti-oxidant

10. M ECHANISM O F A CTION ( CONTINUE ) Antiplatelet Inhibition of platelet COX1 enzyme & TXA2

11. ANALGESIC Drug that relieve pain.

12. ANTIPYRETIC Drug that lower the elevated body temperature to normal.

13.  C ONTINUE  Effect on GIT Inhibition of PGI 2 & PGE 2 & PGF 2 resulting in gastric upset up to gastric ulceration & bleeding

14. C ONTINUE  Kidney Inhibit PGE 2 & PGI 2 resulting in salt & water retention, edema, hyperkalemia & interstitial nephritis

15. C ONTINUE  Respiratory system With aspirin High dose act directly on respiratory center causing hyperventilation & respiratory alkalosis Toxic doses causing central respiratory paralysis& respiratory acidosis

16. THERAPEUTIC USES SHARED BY NS-NSAIDs

17. Fever. Analgesic (Type of pain?) Headache, Migraine, Dental pain Common cold.

18. C ONTINUE Rheumatic / Rheumatoid arthritis Dysmenorrhea Muscular pain

20. ADVERSE EFFECTS GIT upsets ( nausea, vomiting) GIT bleeding & ulceration Bleeding Hypersensitivity reaction Inhibition of uterine contraction Salt & water retention

22. C LINICAL USES Acute rheumatic fever Reducing the risk of myocardial infarction Prevention of pre-eclampsia

24. Adverse Effects Related to (A)Therapeutic Doses Of Aspirin Gastric irritation Hypersensitivity ( aspirin asthma) Acute Gouty arthritis Reye's syndrome

25. (B) TO HIGH DOSES & PROLONGED USE OF ASPIRIN Salicylism ( ringing of ears (tinnitus), vertiog) Hyperthermia Gastric ulceration & bleeding Metabolic acidosis

26. SIDE EFFECTS R ELATED TO H IGH DOSES

27. C ONTRAINDICATIONS Peptic ulcer Pregnancy Hemophilic patients Patients taking anticoagulants Children with viral infections Gout ( small doses )

28. PARACETAMOL A commonly used analgesic antipyretic instead of aspirin in cases of :

29. Peptic or gastric ulcers. Bleeding tendency. Allergy to aspirin. Viral infections in children. Pregnancy.

30. A DVERSE E FFECTS Mainly on liver due to its active metabolites Therapeutic doses elevate liver enzymes High doses cause liver & kidney necrosis Treatment toxicity of paracetamol: N- acetylcysteine to neutralize the toxic metabolites

31. P ROPIONIC ACID DERIVATIVES IBUPROFEN

32. C LINICAL USES Therapeutic uses shared by NS- NSAIDs Acute gouty arthritis Patent ductus arteriosus More potent as an anti-inflammatory than aspirin

33. P REPARATIONS OF I BUPROFEN Oral preparations. Topical cream for osteoarthritis. A liquid gel for rapid relief of postsurgical dental pain. Intravenous route as In patent ductus arteriosus

34. A DVERSE EFFECTS Adverse effects shared by NS-NSAIDs (Gastric upset less frequent than aspirin) Rare hematologic effects (agranulocytosis & aplastic anemia ). Ocular disturbance

35. C ONTRAINDICATIONS Peptic ulcer Allergic patients to aspirin Kidney impairment Liver diseases Pregnancy Haemophilic patients The concomitant administration of ibuprofen antagonizes the irrevesible platelet inhibition of aspirin( limit cardioprotective effect of aspirin ).

36. O XICAM DERIVATIVES Piroxicam Tenoxicam

37. P IROXICAM Half- Life 45 hours Given once daily

38. A DVERSE EFFECTS Less frequent gastric upset (20%). Dizziness Tinnitus Headache Allergy

39. A CETIC ACID DERIVATIVES Diclofenac

40. P REPARATIONS OF D ICLOFENAC Diclofenac with misoprostol decreases upper gastrointestinal ulceration,but result in diarrhea. Diclofenac with omeprazole to prevent recurrent bleeding..1% opthalmic preparation for postoperative opthalmic inflammation. A topical gel 3% for solar keratosis. Rectal suppository

41. C ONTINUE Oral mouth wash. Intramuscular preparations.

42. C LINICAL USES Clinical uses shared by Ns-NSAIDs Acute gouty arthritis Locally to prevent or treat post opthalmic inflammation A topical gel for solar keratosis

43. A DVERSE EFFECTS Adverse effects shared by NS-NSAIDs

44. S ELECTIVE COX-2 INHIBITORS General advantages : o Potent anti-inflammatory o Antipyretic & analgesic o Lower incidence of gastric upset o No effect on platelet aggregation ( COX-1)

45. G ENERAL ADVERSE EFFECTS Renal toxicity Dyspepsia & heartburn Allergy Cardiovascular ( do not offer the cardioprotective effects of non-selective group).

46. C LINICAL USES Postoperative patients undergoing bone repair Acute gouty arthritis Acute musculoskeletal pain Ankylosing spondylitis

47. C ELECOXIB Half-life 11 hours ( Given twicw daily) Food decrease its absorption Highly bound to plasma proteins Metabolized in liver to inactive metabolites

48. M ELOXICAM Relatively selective Cox2 inhibitors. Safer than piroxicam.

49. P HARMACOKINETICS Given orally,rectally, I.M.,I.V. Metabolized in liver to inactive metabolites. Excreted in urine 50% and in feces 50%. Half-life 20 hours. Given once daily.

50. C LINICAL USES Shared by selective COX-2 inhibitors

51. A DVERSE EFFECTS Shared by selective COX-2 inhibitors

52. D RUG INTERACTIONS Cholestyramine increases the clearance of the drug.

53. N ABUMETONE Relatively selective COX-2 inhibitor Well absorbed orally. Metabolized in liver to active metabolites. Half-life 26 hours. Taken once daily.

54. C LINICAL USES Shared by selective COX-2 inhibitors

55. A DVERSE EFFECTS Shared by selective COX-2 inhibitors Headache Tinnitus Photosensitivity