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  1. 1. Analgesics and pain control inDentistry Iyad Abou Rabii DDS. OMFS. MRes. PhD
  2. 2. Analgesics Central Analgesics Peripheral Analgesics (NSAID)
  3. 3. Central Analgesics
  4. 4. Central Analgesics Centrally acting analgesics are thought to affect the opiate receptors in the brain and perhaps also those in the spinal cord. (Receptors are specialized sites with which a drug interacts to produce its effects.) The most widely used and effective of these narcotic analgesics are derived from opium alkaloids. Morphine is one typical example
  5. 5. Central Analgesics Opiums (Morphine, Heroine, Codeine, Fentanyl, Meperidine, Tramadol, Alfetanil) Increase pain threshold and decrease reaction movements Decreasing Respiratory Center`s sensibility for CO2 Some of them cause addiction
  6. 6. Central Analgesics Non-opiums Nevopame Not anti-inflamatory Don`t causes sleep Pain is reduced on the CNS level
  7. 7. Central Analgesics - opiums Morphine
  8. 8. Morphine receptors Morphine is attached to special cellular receptors in order to perform its effects Three kind of receprors are been identified Mu µ Kappa κ Delta δ
  9. 9. Morphine receptors
  10. 10. Morphine receptors Mechanism of action Morphine is linked to theses receptors Activating receptor activated Potassium channels causing rapid burst of K outside the neuron cell (hyperpolarization) Decrease the voltage-gated calcium chanels activity preventing calcium ions entrance (More hyperpolarization) Hyperplorisation prevent propagation of the action potential (electrical signals) along the axon.
  11. 11. MorphinesFor sever and mild pain, two types Opium derived from opium plant Opium agonists Natural (Endomorphine) Synthetic (Methadon, meperidine, Alfantenyl))
  12. 12. Morphine Agonists Classified to1. Strong Agonists 1. Morphine 4 h 2. Meperidine 2 h 3. Methadone 24h 4. Heroine 2 h 5. Alfentanyl‫ 5 ا‬to 45 min2. Mild Agonists (Hydropoxyphene, Codeine)
  13. 13. Morphine3. mixed agonists and antagonists 1. Pentazocaine: Agonist on κ and weak antagonist on µ and δ 2. Nalbuphine : same as Pentozocaine but stronger afonist to µ 3. Buprenorphine : 0.4 mg from it is equal to 10 mg of Morphene it is partial agonist to µ and antagonist to κ
  14. 14. Morphines4. Antagonists 1. Naloxon : Rapidly emove opiums linked to the receptors µ ، κ and δ (30 sec after inhection) 2. Naltrixone its effects are longer than naloxon (one oral administration can block heroine effects for more than 48 h)
  15. 15. Morphines
  16. 16. Pharmaceutical effects Opium can affect CNS, Digestive tube, pupil, and cardio vascular system. CNS 1. Prevent pain reception with a dose related effect 2. Sedation but with high doses convulsion may occur 3. Euphoria (False feeling of happiness) 4. 10 mg (IV) for mild pain 15-20 mg (IV) for severe pain (respiratory depression is possible at this dose)
  17. 17. Pharmaceutical effects CNS (suite) 6. Decrease the RC (Respiratory Center) sensibility to CO2 blood level. In that case no benefit of giving pure Oxygen (apnea may develop) 7. Nausea and vomiting (Phenothiazine is administrated to overcome these effects) 8. cough suppressant (specially Codeine)
  18. 18. Pharmaceutical effects Digestive system 1. Spasm of sphincters 2. Constipation 3. These effects can be reversed by the administration of atropine (Acetylcholine receptors antagonists)
  19. 19. Pharmaceutical effects Other 1. Morphine pin point pupils 2. Hypotension 3. Bronchospasme 4. ischuria (urinary retention)
  20. 20. Pharmacodynamic Can be used orally, mostly used by injection Analgesic for the treatment of pain (except spasmodic origin , why?) Its effect starts IV : 7 min IM : 20 min SC (subcutaneous) : 40 min
  21. 21. Pharmacodynamic Metabolized in the liver (not to be used with hepatic pathology) Eliminated by kidneys as inactive metabolites Also eliminated by sweat, bile, and maternal milk (not to be administrated to breast feeding woman)
  22. 22. Opium in Dentistry1. Low to mild pain (codeine ,hydrocodone oxycodone Propoxyphene, and tramadol)2. For severe pain :Morphine, Pentazocaine Butorfanol, Meperidine, and Fentanyl
  23. 23. Opium in Dentistry In most cases dental pain is accompanied or caused by an inflammation process, so NSAIDs is the first choice. Anyhow it is not uncommon to use a combination of opium with Aspirin or other NSAID, thus two pain control mechanisms are combined.
  24. 24. Opium in Dentistry Oral way is the preferred way of opium administrations Most opiums have their effects appears after 2 hours, dose cant be repeated safely after 2 hours of the first administration if needed Injection forms of opium can not be administrated in dental clinics
  25. 25. Codeine 30 to 60 mg orally every 4-6 h With this dose side effects of Codeine is negligable In higher dose constipation and nausee may be noticed Used normally in combination with NAISD
  26. 26. Hydrocodone and oxycodone Used orally Hydrocodone 30 mg every 4-6 h oxycodone 5 mg every 4 to 6 h Pharmaceutical effects of 5 mg of Oxycodone equal to 30-60 mg of Codeine
  27. 27. ‫ا‬PropoxypheneSome false rumors about the addictioncapacity of Codeine led to the development ofPropoxypheneUsed for mild painIts sedative action is lower than CodeineNormally used in combination withParacetamol (60 to 100mg)
  28. 28. Morphine For severe pain The dose for 70 kg weight patient is 10 mg The best sedative effect between opium but also side effects (constipation, nausea, respiratory depression, addiction) are most obvious comparing to other opiums
  29. 29. Non Steroidal Anti-Inflammatory Drugs (NSAIDs)
  30. 30. NSAIDs Have analgesic, antipyretic V, and anti- inflammatory effects NSAIDs are Prostaglandin Antagonist Prostaglandin is important mediator of inflammation, pain and fever
  31. 31. Prostaglandin and Cyclooxygenases Prostaglandins are produced following the sequential oxidation of AA, DGLA or EPA by cyclooxygenases (COX-1 and COX-2) and terminal prostaglandin synthases: COX-1 is responsible for the baseline levels of prostaglandins. COX-2 produces prostaglandins through stimulation. (GLA) Gamma-linolenic acid (AA) Arachidonic acid (EPA) Eicosapentaenoic acid
  32. 32. NSAIDs COX-1 and COX-2 are both located in the blood vessels, stomach and the kidneys, Prostaglandin levels are increased by COX-2 in scenarios of inflammation. Inhibiting COX-1 is responsible of NSAIDs side effects A third form of COX, termed COX-3 is thought to exist in the brain and may be associated with relief of Headaches when on NSAID therapy.
  33. 33. NSAIDs COX-2 selective inhibitor is an anti-inflammatory drug (NSAID) that directly targets COX-2, with such NSAID pharmaceutical effect are maximal while side effects are minimal
  34. 34. NSAIDs-Pharmacodynamics Well absorbed in the digestive tube Metabolized in the liver Essentially eliminated by the Kidney
  35. 35. Paracetamol Most used NSAID especially when Aspirin is contraindicated Inhibit prostaglandin formation in the CNS level only (cox-3) Thais explains its maximal antipyretic and analgesic effects, and minimal anti-inflammatory effects (preferred with infection) 500 to 650 mg x4 daily Can be increased to 1000 mg X4 daily if needed
  36. 36. Paracetamol Side effects No side effects with therapeutic dose Allergy is rar Extensive use mais Excessive use of paracetamol can damage multiple organs, especially the liver and kidney. Non Tetragenic, can be administrated to pregnant and breast feeding woman.
  37. 37. Aspirin Aspirin also known as acetylsalicylic acid abbreviated ASA First choice in non-infection origin dental pain treatment (when there is no contraindication) Very effective in acute dental pain (650 mg of Aspirin is more effective than 60 mg of Codeine) The maximum effect of aspirin is not dose related (all or none), increasing the dose more than 650 mg is useless This dose is repeated four time daily.
  38. 38. Aspirin Aspirin use has been shown to increase the risk of gastrointestinal bleeding. Although some enteric coated formulations of aspirin are advertised as being "gentle to the stomach", in one study enteric coating did not seem to reduce this risk.
  39. 39. Aspirin Combining aspirin with other NSAIDs has also been shown to further increase this risk. Using aspirin in combination with clopidogrel or warfarin also increases the risk of upper gastrointestinal bleeding.
  40. 40. Aspirin Large doses of salicylate, a metabolite of aspirin, have been proposed to cause tinnitus Reyes syndrome, a severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given aspirin for a fever or other illnesses or infections Aspirin (or aspirin-containing products) should not be given to anyone under the age of 12 who has a fever
  41. 41. Propionic Acid derivatives Ibuprofen, fenoprofen, ketoprofen, and flurbuprofen. Effective for mild pain Used safely with children
  42. 42. Propionic Acid derivatives Ibuprofen 400 mg X4 daily May be administrated preoperatively to reduce postoperative pain Naproxen For mild pain 500 mg then 250 mg X3 daily
  43. 43. Propionic Acid derivatives Flurbuprofen More effctive than Ibuprofen 50-100 mg of it equal 400 mg of Ibuprofen in efficacity Daily dose is 300 mg divided on 2 to 3 administration. (150 X2 or 100 X 3)
  44. 44. Etodolac Etodolac Efective dose for dental pain is 200 – 400 X3 daily Analgesic effect with this dose starts after 30 min and last for 4-6 h Daily dose shouldn`t exceed 1200 mg
  45. 45. Diclofenac Diclofenac Its pharmaceutics and side effects are similar to Naproxen Dose is 25-50 mg X3 daily
  46. 46. Nimesulide Its side effects are minor, excellent analgesic and anti-inflammatory effects Analegesic effect are stronger than Ketoprofen (most effective propionic acid) Given orally 100 mg X2 daily
  47. 47. Possible analgesicscombinations Opiums + non-opiums Non-opiums + non-opiums NSAIDs + Caffeine NSAIDs + Sedative
  48. 48. Opiums + non-opiumsGood strategy (two pain controlmechanisms are involved)Most used non-opium used is Codeine(60 mg)Dextropropoxyphene (65 mg) mightalso be used but it is less effective thanCodeine
  49. 49. NSAIDs + SedativeNSAIDs can be combined with sedatives(Diphenhydramine hydrochloride)This help to release dental origin painnormally accompanied with insomniaBut increased possibility of Drug-druginteraction should be considered whenadministrated with other drugs
  50. 50. ‫ت‬ ‫د‬ ‫تا‬ ‫ا‬ ‫رة‬ ‫ور‬ ‫ا داع د‬ ‫أ ء ددة‬ ‫أدو‬ ‫و نا و‬ ‫و دواء‬ ‫ل‬