This document discusses dental pain medications. It begins by explaining the physiology of pain and the mechanisms of different classes of analgesics. It then reviews several commonly used non-opioid analgesics for dental pain, including acetaminophen, ibuprofen, naproxen, and ketoprofen. For each drug, it covers absorption, metabolism, dosing, efficacy, and potential side effects. It also discusses the use of corticosteroids as an adjunctive analgesic and provides protocols for their short-term use.

1. 牙科常用止痛藥
義大醫院
口腔外科
陳文惠
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2. Pain
Cellular& Emo/onal&
Damage Experience
Tissue&Injury,&
Infec/on
Unpleasant&
Sensa/on
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3. Cerebral Cortex : Interpretation
Limbic System (emotional Center)
CNS
Spinal Cord
Nerve Fiber
PNS
Nociceptor or Pain Receptor
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4. Cerebral Cortex : Interpretation
X
Limbic System (emotional Center)
CNS
Spinal Cord
X
Analgesics
X
Nerve Fiber
PNS
Nociceptor or Pain Receptor
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5. Physiology
Pain of Inflammatory Origin
Cyclooxygenase
Prostaglandins
Induce pain perception
Influence inflammation
Stimulate elevated B.T,
Affect the tone & permeability of B.V.
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6. Physiology
Pain of Inflammatory Origin
Cyclooxygenase
Aspirin
COX inhibitors ✘
Prostaglandins
Induce pain perception
Influence inflammation
Stimulate elevated body temperature,
Affect the tone & permeability of
B.V.
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7. Found in brain, kidney
Found in most tissue, PLTs
Not in PLTs
Protect gastric mucosa
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8. Analgesics For Dental Pain
Non$
Opioid Adjunc7ve
Opioid
APAP Morphine Steroid3
NSAID Meperidine
Codeine3
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9. Non-Opioid Analgesics
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10. Non-Opioid Analgesics
First-line drug
Lack of the unwanted side effect of opioid
Constipation, respiratory depression and
physical dependence
Not change the perception of sensory
modalities other than pain
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11. Classification
Centrally acting : APAP
Highly effective inhibitor of COX-1 variant(CNS)
Weak inhibitor of peripheral PG
Peripheral acting: NSAIDs
Non-selective COX inhibitor
COX-2 inhibitor
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12. Absorption
Rapidly absorbed from
Stomach and the upper small intestine
Effective plasma concentrations
30 to 60 minutes
Peak concentrations
About 2 to 3 hours.
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13. Rate of Absorption
The product formulation
pKa of the drug
The pH in the stomach
Vascularity of the absorptive surface
Gastric emptying time
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14. Rate of Absorption
The product formulation
pKa of the drug Antacid
The pH in the stomach
Vascularity of the absorptive surface
Gastric emptying time
Food
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15. Liver : Metabolism
Metabolize
Kidney :
Excretion
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16. Common Rx
Acetaminophen
Ibuprofen
Naproxen
Ketoprofen
COX-2 inhibitor
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17. Acetaminophen
Weak anti-inflammatory agent
More effective against COX effects in
the CNS
Ability to reduce fever and relieve
pain, with minimal effect on peripheral
inflammation
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18. Indication
A suitable substitute in patients
with peptic ulcer disease,
hemophilia, or other bleeding
disorders, and for those individuals
taking anticoagulants
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19. Dosage
The Single dose
Adult : 650 mg every 4 hours.
Children : 80-120mg , age & weight
Ceiling dose of 1000 mg
The daily dose < 4000 mg for adults and
1200 mg for children
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20. Toxicity of APAP
Occurs when a toxic, highly
reactive metabolite of APAP
accumulates in the liver
➡Serious, irreversible and
occasionally fatal liver damage
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21. Side Effect
Usually well tolerated in recommended
therapeutic dosages
Erythematous or urticarial skin rash may
occur occasionally, sometimes accompanied
by fever and mucosal lesions
The mechanism of intolerance to APAP is
unknown
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22. Ibuprofen
Ibuprofen : between 400 and 800 mg
Longer duration of action
Dose-dependent increase in its analgesic
and anti-inflammatory efficacy
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23. Ibuprofen
The current gold standard for surgical dental pain
Control pain at lower dosages (200-400mg q6h)
Anti-inflammatory activity at higher dosages
(600-800mg q6h)
Ibuprofen 600mg q6h : controls most dental
pain
The max. adult daily dose : 2400 mg.
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24. Side Effect
GI side effects : 5-15%
Been used with some success in p’ts with a
history of GI intolerance to other NSAIDs
Less frequency
Thrombocytopenia, rashes, headache, dizziness,
blurred vision, fluid retention, edema, and toxic
amblyopia
When ocular disturbance (+): discontinued
immediately
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25. Side Effect
Cross the placenta in animal studies
Evidence(+) of fetal risk : outweighs any
analgesic benefits when ibuprofen is taken
during the third trimester of pregnancy
No known controlled studies examining the
effects on the fetus during the 1st and 2nd
trimesters
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26. Drug Interaction
Immediate-release aspirin 81mg daily
≥ 400mg ibuprofen :interfere with aspirin’s
antiplatelet effects, with its greatest
effect occurring if its is administered less
than 8hrs prior to aspirin
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27. Drug Interaction
The proper timing of ibuprofen dosing
in relationship to aspirin therapy
Routine or long-term administration:
At least 8 hrs before taking aspirin
or 30-120 mins after taking aspirin
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28. Naproxen
Well absorbed
Food delays the rate but not the extent
of absorption
Peak plasma concentration : 2-4 hours ,
Concomitant administration of sodium
bicarbonate : accelerate the rate of
absorption
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29. Naproxen
Plasma half-life is variable
Ranges from 14 hours in the young
Approximately twice this in the elderly
because of decreased renal function
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30. Dosage
Naproxen (250,375,500mg tablets; 125 mg/5ml
suspension)
500mg initially, followed by 500mg q12h or
250mg q6-8h
Total daily dose on D1 < 1250mg
Thereafter the totally daily dose <1000mg
Greater analgesic : 1500mg/d for limited
period
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31. Side Effect
Cross the placenta and approximately 1%
is found in breast milk
GI side effect : the same frequency as
indomethacin but less severity
Drowsiness, headache, dizziness,
sweating, fatigue, depression and
ototoxicity have been observed
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32. Side Effect
Pruritus and other dermatologic problem :
less often
Rarely : jaundice, impairment of renal
function, angioedema, thrombocytopenia
and agranulocytosis
All => seemly associated with prolonged
treatment
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33. Ketoprofen
Plasma half-life : approximately 2 hours,
except in the elderly (longer half-life)
>75y/o, initial dose decreased even with
normal BUN levels
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34. Dosage
1st day dosage : 75mg q8H or 50mg q6h
Followed by 25 to 50mg q6-8h
Total daily dose of regular formulations <300mg
Mildly impaired renal function <150mg
More severe renal impairment(GFR <25ml/min) or end-
stage renal impairment <100mg
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35. Side Effect
30% : GI side effects
Reduced if taken with food or antacids
Increase plasma Cr, especially in the
elderly and/or those taking diuretics
Renal function studies : routinely on p’t
requiring long-term therapy
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36. Ketorolac
Adult: PO
Moderate to severe pain 10 mg 4-6 hrly.
Max: 40 mg/day.
Max duration: 7 days.
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37. Other Common Side
Effect for COX inhibitor
Intolerance to COX inhibitors
history of asthma, nasal polyps and
chronic urticaria
Immunoglobulin E (IgE)-dependent
hypersensitivity reactions leading to
hypotension and respiratory collapse
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38. GI Side Effect
GI distress, nausea and vomiting
Exacerbate the symptoms of peptic
ulcer disease and with chronic use,
GI bleeding, ulceration and
perforation can occur
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39. Ibuprofen
Aspirin
Diclofenac
Naproxen
Ketoprofen
Ketorolac
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40. Bleeding Tendency
COX-1 inhibitor
Impair platelet adhesion to tissue and
platelet aggregation
Platelet inhibition with ibuprofen and naproxen
Reversible
APAP : suitable substitute
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41. Renal Side Effect
COX inhibitors decrease the synthesis of renal
prostaglandins, decrease renal blood flow ➡
Fluid retention, precipitate renal failure
Risk factors include old age, chronic renal
insufficiency, congestive heart failure, hepatic
cirrhosis and concurrent use of diuretic drugs
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42. Pregnancy
APAP is a suitable substitute for ASA
and other COX-1 inhibitors in the
management of mild-to-moderate pain
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43. Alcohol Abuse
APAP : maximum dose of 2000 mg daily.
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44. Adjunctive Drugs
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45. Enhance the efficacy of an analgesic or it
may have an analgesic activity of its own
Corticosteroids : anti-inflammatory
effects ➡ analgesia in some patients
with pain of inflammatory origin.
Some controversy
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46. Corticosteroid
Function
Decrease swelling and post-OP pain
Reduce local congestion
Diminish nerve damage, accelerate
recovery of normal sensory perception
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47. 13年2月2日星期六

48. Side Effect
Aggravate glycemic control in DM patients
Uncontrolled DM: Only in lift-threatening situations
Use steroid in DM patient : controversial
Controlled DM
Short time period at reduced dosage
Careful monitoring of blood glucose levels
Well-controlled type 1 DM : adjust daily insulin
doses based on their current blood glucose values
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49. Side Effect
Hypertension : unknown mechanism
Even with decreased sodium consumption
Monitor
Hyperglycemia, glycosuria and sodium
retention with edema or hypertension
Short-term therapy : no contraindication
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50. Side Effect with
Higher Dose
Behavioral change
Initial : insomnia and euphoria
Then : depression
Increased intracranial pressure
Peptic ulcer
Decreased Vit. D. and calcium absorption
Increase in PLT and RBC numbers
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51. Use with Caution
Active peptic ulcer Psychoses
Heart disease DM
Hypertension Osteoporosis
Congestive heart failure Glaucoma
Systemic infection Herpes simplex infection
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52. Rational for Use
Hypothalamic-pituitary-adranal(HPA)
axis suppression
Increased infection
Occurrence of inflammation and
swelling after steroids are cleared
from the body (approximately 2-3
days)
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53. Rational for Use
Short-term use
not induce HPA axis suppression
Nor higher incidence of infection
Antibody production : affected by large
dosages of steroid but not by moderate dosage
(20mg of prednisone/day)
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54. Rational for Use
Short-term use
not induce HPA axis suppression
Nor higher incidence of infection
Antibody production : affected by large
dosages of steroid but not by moderate dosage
(20mg of prednisone/day)
Long-Term Use Infection
Reactivate TB
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55. Suggested Protocol
Consideration
Age : very young or elder =>
adjustment of dosage
Weight
Surgical invasiveness
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56. Suggested Protocol
Injectable
Immediately prior to surgery
Dexamethasone sodium phosphate 4-8mg
IV or deep IM
After the procedure : long-acting IM
glucocorticoid, such as methylprednisolone
acetate suspension 20-60mg via deep IM
Not inject into small muscle
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57. Suggested Protocol
Oral form : Dexamethasone
Before surgery
Less than 5 days
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58. Caution
P’t take glucocorticoids routinely
Consult the physician : temporary dosage
increase
Abrupt cessation of glucocorticoids after
prolonged therapy : risk of adrenal
insufficiency due to suppression of the
HPA axis and may be fetal
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59. Efficacy
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60. Efficacy of Analgesics
ASA#650#mg = APAP#650#mg = Ibuprofen*200*mg = Naproxen)Sodium)
220)mg
>
Ceiling doses of APAP (1000mg)
60mm Codeine
Ibuprofen*400mg
650mg ASA+60mg Codeine
600mg APAP+60mg Codeine
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61. 3rd Molar Extraction
Diclofenac
Ibuprofen
The 95% confidence interval of the number needed to treat (NNT) for at ieast 50% pain
relief over 4 to 6 hours compared with placebo in third molar extraction trials." Adapted
with permission from Macmillan Publishers Ltd: British Dental Journal
(Barden J, et al. Br Dent J. 2004:197:407-411). Copyright 2004.
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62. Acute Post-OP Pain
Ibuprofen APAP
The 95% confidence interval of the number needed to treat (NNT) for at least 50% pain
relief over 4 to 6 hours compared with placebo in acute postoperative pain trials.'*^"
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63. Clinical Guideline
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64. Suggested Protocol
Mild'Pain
• ingle'Extrac.on,'Rou.ne'RCT,'SC/RP,'gingivectomy'
Moderate'Pain
• mplant,'Perio.'Flap'OP','Apical'Surgery
Severe'pain
• Impac.on,'Complex'implant'or'Perio.'OP'
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65. NSAIDs
Ibuprofen 200-400
Mild'Pain mg q4-6H
• ingle'Extrac.on,'Rou.ne'RCT,'SC/RP,'gingivectomy'
Moderate'Pain
• mplant,'Perio.'Flap'OP','Apical'Surgery
Severe'pain
• Impac.on,'Complex'implant'or'Perio.'OP'
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66. NSAIDs
Ibuprofen 200-400
Mild'Pain mg q4-6H
• ingle'Extrac.on,'Rou.ne'RCT,'SC/RP,'gingivectomy'
Ibuprofen 400-600 mg q4-6H
Moderate'Pain
x I then 400mg q4-6H or
Ibuprofen 400-600 mg + APAP
• mplant,'Perio.'Flap'OP','Apical'Surgery
500mg q6H x I then ibuprofen
Severe'pain 400mg q4-6H
• Impac.on,'Complex'implant'or'Perio.'OP'
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67. NSAIDs
Ibuprofen 200-400
Mild'Pain mg q4-6H
• ingle'Extrac.on,'Rou.ne'RCT,'SC/RP,'gingivectomy'
Ibuprofen 400-600 mg q4-6H
Moderate'Pain
x I then 400mg q4-6H or
Ibuprofen 400-600 mg + APAP
• mplant,'Perio.'Flap'OP','Apical'Surgery
500mg q6H x I then ibuprofen
Severe'pain Ibuprofen 400-600mg + APAP
400mg q4-6H
500mg + hydrocodone 10mg
• Impac.on,'Complex'implant'or'Perio.'OP'
q6H x II then ibuprofen 400mg
q4-6H
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68. non-NSAIDs
APAP 650-1000mg
q6H
Mild'Pain
• ingle'Extrac.on,'Rou.ne'RCT,'SC/RP,'gingivectomy'
Moderate'Pain
• mplant,'Perio.'Flap'OP','Apical'Surgery
Severe'pain
• Impac.on,'Complex'implant'or'Perio.'OP'
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69. non-NSAIDs
APAP 650-1000mg
q6H
Mild'Pain
• ingle'Extrac.on,'Rou.ne'RCT,'SC/RP,'gingivectomy'
APAP 650+ hydrocodone 10mg
q6H xI => APAP 650-1000mg
Moderate'Pain
Q6H
• mplant,'Perio.'Flap'OP','Apical'Surgery
Severe'pain
• Impac.on,'Complex'implant'or'Perio.'OP'
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70. non-NSAIDs
APAP 650-1000mg
q6H
Mild'Pain
• ingle'Extrac.on,'Rou.ne'RCT,'SC/RP,'gingivectomy'
APAP 650+ hydrocodone 10mg
q6H xI => APAP 650-1000mg
Moderate'Pain
Q6H
• mplant,'Perio.'Flap'OP','Apical'Surgery
APAP 650+ hydrocodone 10mg
Severe'pain
q6H xII => APAP 650-1000mg
Q6H
• Impac.on,'Complex'implant'or'Perio.'OP'
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71. Additional Consideration
Daily ibuprofen < 2400mg , APAP < 4000mg
NSAIDs contraindicated in
History of GI ulceration
Aspirin intolerance / Cross hypersensitivity
Receiving anticoagulant
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72. Periodontology 2000,
Vol. 46, 2008, 143–164
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