1. Antiinflammatory Agents and Nonsteroidal Antiinflammatory Drugs (NSAIDs)

2. glucocorticosteroids
Groups of anti-inflammatory agents and mechanism of action:
1) nonsteroidal anti-inflammatory drugs - NSAI
2) glucocorticosteroids (GCS) + -
Phospholipids
Arachidonic
acid
Cyclic
endoperoxydases
glucocorticosteroids LK
Phospholipase А2 -
Cyclooxygenases
(COG-1, COG-2, COG-3)
NSAID
Prostaglandins Thromboxan
Inflammation Pain Fever Vasoconstriction
Increasing of platelets aggregation
- depressing effect
- stimulating effect - +

3. NSAIDs
Large and chemically diverse group of drugs with the following properties:
Analgesic
Antiinflammatory
Antipyretic

4. NSAIDs: Mechanism of Action
Activation of the arachidonic acid pathway causes:
pain
headache
fever
inflammation

5. Arachidonic Acid Pathway

6. NSAIDs: Mechanism of Action
Analgesia—treatment of headaches and pain
Block the undesirable effects of prostaglandins, which cause headaches

7. NSAIDs: Mechanism of Action
Antipyretic: reduce fever
Inhibit prostaglandin E2 within the area of the brain that controls temperature

8. NSAIDs: Mechanism of Action
Relief of inflammation
Inhibit the leukotriene pathway, the prostaglandin pathway, or both

9. NSAIDs Six structurally related groups: Acetic acids Carboxylic acids
Propionic acids
Enolic acids
Fenamic acids
Nonacidic compounds

10. NSAIDs: Acetic Acid diclofenac sodium (Voltaren)
diclofenac potassium (Cataflam)
etodolac (Lodine)
indomethacin (Indocin)
sulindac (Clinoril)
tolmetin (Tolectin)

11. NSAIDs: Carboxylic Acids
Acetylated
aspirin (ASA)
choline magnesium salicylate (Trilisate)
diflunisal (Dolobid)
Nonacetylated
salicylamide
salsalate (Disalcid)
sodium salicylate

12. NSAIDs: Propionic Acids
fenoprofen (Nalfon)
flurbiprofen (Ansaid)
ibuprofen (Motrin, others)
ketoprofen (Orudis)
ketorolac (Toradol)
naproxen (Naprosyn)
oxaprozin (Daypro)

13. NSAIDs: Other Agents Enolic acids Fenamic acids Nonacidic compounds
phenylbutazone (Butazolidin)
piroxicam (Feldene)
Fenamic acids
meclofenamic acid (Meclomen)
mefenamic acid (Ponstel)
Nonacidic compounds
nabumetone (Relafen)

14. NSAIDs: Other Agents COX-2 Inhibitors celecoxib (Celebrex)
rofecoxib (Vioxx)

15. Acetylsalicylic acid

16. Aspirin С

17. Aspirin

18. Butadion

19. Indometacin (methyndol)

20. Ibuprofen (brufen)

21. Piroxicam

22. Sodium diclofenac

23. Voltaren

24. NSAIDs: Drug Effects Analgesic (mild to moderate) Antigout
Antiinflammatory
Antipyretic
Relief of vascular headaches
Platelet inhibition (ASA)

25. NSAIDs: Therapeutic Uses
Relief of mild to moderate pain
Acute gout
Various bone, joint, and muscle pain
Osteoarthritis
Rheumatoid arthritis
Juvenile rheumatoid arthritis
Dysmenorrhea
Fever

26. NSAIDs: Specific Agents
salicylates (aspirin)
More potent effect on platelet aggregation and thermal regulatory center in the brain
analgesic
antipyretic
antiinflammatory
Antithrombotic effect: used in the treatment of MI and other thromboembolic disorders

27. NSAIDs: Specific Agents
phenylbutazone (Butazolidin)
Greater effects on uric acid production and excretion, in addition to antiinflammatory effects
More commonly used for treatment of gout

28. NSAIDs: Side Effects Gastrointestinal
dyspepsia, heartburn, epigastric distress, nausea
**GI bleeding
**mucosal lesions (erosions or ulcerations)
Misoprostol (Cytotec) can be used to reduce these dangerous effects.

29. NSAIDs: Side Effects Renal reductions in creatinine clearance
acute tubular necrosis with renal failure

30. NSAIDs: Side Effects
Cardiovascular
noncardiogenic pulmonary edema

31. NSAIDs: Salicylate Toxicity
Adults: tinnitus and hearing loss
Children: hyperventilation and CNS effects
Effects arise when serum levels exceed 300g/mL.
Metabolic acidosis and respiratory alkalosis may be present.

32. NSAIDs: Nursing Implications
Before beginning therapy, assess for conditions that may be contraindications to therapy, especially:
GI lesions or peptic ulcer disease
Bleeding disorders
Assess also for conditions that require cautious use.
Perform lab studies as indicated (cardiac, renal, liver studies, CDC, platelet count).

33. NSAIDs: Nursing Implications
Perform a medication history to assess for potential drug interactions.
Several serious drug interactions exist:
alcohol
heparin
phenytoin
oral anticoagulants
steroids
sulfonamides

34. NSAIDs: Nursing Implications
Salicylates are NOT to be given to children under age 12 because of the risk of Reye’s syndrome.
Because these agents generally cause GI distress, they are often better tolerated if taken with food, milk or an antacid to avoid GI irritation.
Explain to patients that therapeutic effects may not be seen for 3 to 4 weeks.

35. NSAIDs: Nursing Implications
Educate patients about the various side effects of NSAIDs, and to notify their physician if these effects become severe or if bleeding or GI pain occur.
Patients should watch closely for the occurrence of any unusual bleeding, such as in the stool.
Enteric-coated tablets should not be crushed or chewed.

36. NSAIDs: Nursing Implications
Monitor for therapeutic effects, which vary according to the condition being treated:
decrease in swelling, pain, stiffness, and tenderness of a joint or muscle area

37. GLUCOCORTICOIDS Reduce inflammation and immune responses
Simple, derivatives of cholesterol
Regulate nearly every organ system in the body
Maintain homeostasis; e.g. dampen immunoresponses, regulate glucose metabolism
Most prescribed class of drugs world wide (treatment of varioue inflammatory diseases)
Reduce inflammation and immune responses
In clinical practice since 1948
$10,000,000,000./year market size in US

38. Steroid Hormones: Derived from Cholesterol
Lipid Soluble: Able to cross plasma membrane by passive diffusion

39. PHYSIOLOGICAL EFFECTS OF GLUCOCORTICOIDS
 Regulation of carbohydrate, protein and lipid metabolism
 Maintenance of fluid and electrolyte balance
Preservation of normal function of the cardiovascular system, the immune system, the kidney, skeletal muscle, the endocrine system and the nervous system
Preservation of organismal homeostasis

40. GR GR

41. Effects of Glucocorticoids on Components of Inflammatory/Immune Responses
CELL TYPE FACTOR COMMENTS
Macrophages Prostaglandins, Inhibition of COX-2,
Monocytes Leukotrienes Phospholipase A2
IL-1, IL-6. TNF Inhib. Transcript., Release
Endothelial Cells ICAM-1. ELAM-1 Inhib. Transcript., Release
IL-1, Prostagl., Leuko. As above
Basophils Histamine, Leukotriene Inhib. IgE Release
Lymphocytes IL-1, IL-2, IL-3, etc As above

42. The anti-inflammatory and immunosuppressive actions of glucocorticoids play an important role in preventing potential damaging effects of an unopposed inflammatory response and can be exploited therapeutically

43. Glucocorticoids: Side Effects

44. The beneficial effects of systemic glucocorticoids to limit inflammation is counter-balanced by its many adverse side effects

45. The broad anti-inflammatory actions of glucocorticoids are due primarily to transcriptional repression of many pro-inflammatory genes in multiple cell types by the glucocorticoid receptor.

46. From Glass and Rosenfeld

48. Relative Potencies of Glucocorticoids
Compound Anti-Inflammatory Na+ -Retaining Duration
Potency Potency of Action
Cortisol S
Cortisone S
Prednisolone I
Triamcinolone I
Betamethasone L
Dexamethasone L
S, short (i.e., 8–12 hour biological half-life); I, intermediate (i.e., 12–36 hour biological half-life); L, long (i.e., 36–72 hour biological half-life)

49. IMPORTANT CONCEPT 7: Structural modifications of the natural glucocorticoid cortisol generate hormones with enhanced half-life and more potent and efficacious glucocorticoid activity

50. Antiseptics and Disinfectants

51. Antiseptics and Disinfectants
Most desirable quality is the ability to destroy microorganisms
They have 2 uses: disinfect instruments and treat infections in oral cavity and on body surfaces
2 different agents may have to be used to achieve adequate cleaning

52. Actions of Antiseptics and Disinfectants
Agent
Action
antiseptic
inhibits growth of microorganisms
disinfectant
chemical applied to objects
fungicide
destroys fungi
germicide
destroys bacteria
preservative
prevents decomposition
sanitizer
reduces the number of bacteria
sporicide
destroys spores

53. Antiseptics and Disinfectants
Drug List
Antiseptics and Disinfectants
alcohol, isopropyl
hexachlorophene (pHisoHex)
povidone-iodine (Betadine)
sodium hypochlorite (Clorox)

54. hexachlorophene (pHisoHex)
Surgical scrub and bacteriostatic skin cleanser
Especially effective against gram-positive bacteria
Do not leave on skin for an extended period of time

55. Antiseptics and Disinfectants Heavy Metal Compounds
Drug List
Antiseptics and Disinfectants Heavy Metal Compounds
silver nitrate
zinc oxide (Desitin Creamy)

56. Antiseptics and Disinfectants Orals
Drug List
Antiseptics and Disinfectants Orals
benzocaine (Hurricaine, Orabase-B)
carbamide peroxide (Gly-Oxide Oral)
cevimeline (Evoxac)
chlorhexidine gluconate (Hibiclens)
clove oil (Eugenol)

57. Antiseptics and Disinfectants Others
Drug List
Antiseptics and Disinfectants Others
benzalkonium chloride (Zephiran)
hydrogen peroxide
phenytoin (Dilantin)

58. What characteristics make an ideal antiseptic?
Answer: can inhibit all forms of microorganisms, nontoxic, does not induce sensitization, can penetrate tissues and body fluids, water soluble, noncorrosive, inexpensive