1. PAIN MANAGEMENT IN DENTISTRY 1

2. 2  Pain is defined as an unpleasant sensation that can be either acute or chronic and that is a consequence of complex neurochemical processes in the peripheral and central nervous system (CNS).

3. 3  Analgesics are the drugs (natural or synthetic origin) which relieve pain by acting on CNS or peripheral pain mechanism without causing loss of consciousness.  Analgesics can be divided into two main groups:  Opioid/narcotic/morphine like analgesics.  Nonopioid/nonnarcotic/aspirin like analgesics.

4. Pharmacological Action-NSAIDs  All NSAIDs act by inhibiting synthesis of prostaglandins  Chemical mediators that are released in allergic & inflammatory processes  Arachidonic acid (AA) present in phospholipids of cell membrane is released by action of phospholipase A2 under various stimuli.  Then AA is oxygenated by cyclooxygenase or lipooxygenase 4

5. Cyclooxygenase Pathway  Arachidonic acid is metabolized by cyclooxygenase COX into prostaglandins  COX exists in two isoforms: - COX-1 - COX-2 5

6. NSAIDS  NSAIDs are group of agents that differ in their antipyretic, analgesic & anti-inflammatory activities  All NSAIDs act by inhibiting synthesis of prostaglandins  They act by inhibiting cyclooxygenase enzymes, leading to decreased prostaglandine synthesis with both beneficial & unwanted effects 6

7. NSAIDS  NSAIDs are categorized according to their COX specificity:  Non-selective inhibitors (COX-1 & -2 inhibitors)  Selective inhibitors (COX-2 inhibitors) 7

8. Therapeutic uses of NSAIDs  Inflammation is a normal, protective response to tissue injury caused by physical trauma, chemicals & microbiological agents  Rheumatoid Arthritis  T-lymphocytes: Stimulate B-cell to attack the antigen Analgesia: - Effective for pain of mild to moderate intensity including headache, migraine, musculoskeletal, postoperative pain, osteo- & inflammatory arthritis - Unlike opioids, they do not cause dependence 8

9. Therapeutic uses of NSAIDs-2 Antipyretic:  Fever is caused by elevated levels of PGE2  PGE2 signals to the hypothalamus to increase the body's thermal set point. Antiplatelets function: - Aspirin is indicated for treatment & prevention myocardial infarction (MI), transient ischemic attacks (TIA) & embolic strokes - Thromboxane (TXA2) enhances platelets aggregation - Low doses of aspirin inhibits production TXA2 9

10. Patency of ductus arteriosus: - PGs maintain patency - Indonmetacin given to new-born child results in closure of ductus arteriosus - Primary dysmenorrhea : PGs cause uterine hypercontractility & pain. - PG are released during menstruation, due to the destruction of the endometrial cells, and the resultant release of their contents. 10 Therapeutic uses of NSAIDs-3

11. 11 Adverse effects: Renal effects:  CAUTION IS NEEDED! Renal failure in elderly, those with pre-existing renal disease or those with diuretic sufficient to reduce intravascular volume  Salt and fluid retention  Hypertension

12. Adverse effects-2 PG is Gastroprotective: by inhibiting acid secretion, promoting secretion of mucous - Inhibition of PG synthesis, removes this protection - Risk factors for the development of peptic ulcer disease include - Advanced age - History of previous ulcer - Concomitant use of corticosteriod or anticoagulants - Higher dosage of NSAID 12

13. NSAIDs Drugs  Propionic acid derivatives:  Ibuprofen, naproxen, ketoprofen  Inhibit COX (non-selectively) & thus inhibit synthesis of PG.  All possess anti-inflammatory (reduce inflammation), analgesic (reduce pain) & antipyretic (reduce fever) activities.  Chronic treatment of RA & osteoarthritis  Most common adverse effects: GI dyspepsia to bleeding  Ibuprofen has fewer side effects than other non-selective NSAIDs 13

14. Acetic acid derivatives  Indomethacin (Indocin), sulindac & etodolac  They are not used to lower fever  Toxicity of indomethacin limits its use to treat acute gout arthritis  Indomethacin side-effects: headache, dizziness & GI disturbances  useful in treatment of RA,OA 14

15. Acetic acid derivatives  Sulindac is a prodrug. Its active metabolite is, like diclofenac, an acetic acid derivative  Sulindac is useful in treatment of RA,OA  Less adverse effects than Indomethacin & other NSAIDs 15

16. Mefenamic Acid (Ponstan)  Used for pain and inflammation in RA and OA; postoperative pain; mild to moderate pain; dysmenorrhoea and menorrhagia.  Dose  ADULT over 18 years, 500 mg 3 times daily  CHILD 12–18 years, acute pain including dysmenorrhoea,  menorrhagia, 500 mg 3 times daily.  Has minor anti-inflammatory properties.  It has occasionally been associated with diarrhea and haemolytic anaemia which require discontinuation of treatment. 16

17. Oxicam derivatives  Piroxicam, meloxicam (Mobic), Tenoxicam  Are used to treat RA, OA, AS (ankylosing spondylitis)  They have long half-life (50hrs), once daily  Piroxicam has more GI side-effects than most other NSAIDs  Meloxicam selective COX-2 inhibitor  At high dose, Meloxicam is nonselective, inhibiting both COX-1 & COX-2 17

18. Diclofenac  Voltaren, Diclogesic  Is approved for long-term use in treatment of RA, OA, AS  It is more potent than indomethacin or naproxen  Diclofenac accumulates in synovial fluids 18

19. Selective COX-2 inhibitors Celecoxib,rofecoxib,..  COX-2 inhibitors shows a lower risk for development of peptic ulcer & GI bleeding  Have no effects on platelets  They are indicated for: - Patients who require chronic use of NSAIDs & are at high risk for NSAIDs-induced ulcer  COX-2 inhibitors should be avoided in patients with chronic renal insufficiency, severe heart disease & hepatic failure  Its half-life eleven hrs, is taken once daily 19

20. Acetaminophen (Paracetamol)  It inhibits prostaglandine synthesis in CNS, this explains its antipyretic & analgesic properties  Unlike NSAIDs, acetaminophen has little or no anti- inflammatory activity  Has less effect on cyclooxygenase in peripheral tissues, which accounts for its weak anti-inflammatory activity  Has no effects on platelets or increase blood clotting time  Half-life 2hrs  Oral dose: 0.5-1g every 4-6 hrs, maximum daily dose 4g 20

21. Therapeutic uses 1. It is effective in mild to moderate pain e.g. headache, dysmenorrhoea 2. Is a substitute for analgesic & antipyretic effects of aspirin (its analgesic efficacy is equal to that of aspirin) 3. Children with viral infections or chickenpox 4. In patients with gout who are taking probenecid 21

22. Aspirin (Acetylsalicylic acid)  Mechanism of action: - Irreversibly inhibits COX by acylating active site of enzyme, so preventing formation of thromboxane, prostacyline & other prostaglandins 22

23. Therapeutic uses of Aspirin 1. Antipyretic & analgesic: - PGE2 sensitizes nerve endings to chemical mediators released by inflammation - Aspirin decreases PGE2, thus repress sensation of pain - Are used in treatment of gout, rheumatic fever & RA - Headache, arthralgia & myalgia - Dose 300-900 mg every 4-6 hrs 23

24. Therapeutic uses of Aspirin 2. Cardiovascular effects: - Salicylates are used to inhibit platelets aggregation - Low dose of aspirin 75 mg daily are used to prophylactically to decrease incidence of transient ischemic attacks & stroke - A single dose of 300 mg is given as immediate treatment of MI 3. Aspirin facilitates closure of patent ductus arteriosus (PGE2 is responsible for keeping ductus open) 24