2. CONTENTS
Introduction
Analgesic definition
Classification of analgesics
- Non opioid analgesics
-Opioid analgesics
Commonly used opioids
Opioid –nsaid combination
Adverse effects of opioids
Management of endodontic pain
Conclusion
References
3. INTRODUCTION
Pain that leads a patient to seek dental advice or treatment
may be a result of many different diseases or conditions of the
dental, oral, facial or nearby structures.
Dentists must be able to diagnose the source and nature of the
pain and they must be familiar with strategies for the
management of dental, oral, facial and post-operative pain.
4. DEFINITION
Algesia (pain) is an ill defined , unpleasant sensation ,usually evoked by an
external or internal noxious stimuli.
PAIN-“An unpleasant sensory and emotional experience associated with
actual or potential tissue damage, or described in terms of such damage.”
Analgesic : A drug that selectively relieves pain by acting in the CNS or on
peripheral pain mechanisms without significantly altering conscious.
IASP
6. NON STEROIDAL ANTI INFLAMMATORY
DRUGS
All drugs grouped in this class have analgesic, antipyretic and
antiinflammatory actions in different measures.
In contrast to morphine they do not depress CNS, do not
produce physical dependence, have no abuse liability and are
weaker analgesics (except for inflammatory pain).
They are also called nonnarcotic, nonopioid or aspirinlike
analgesics.
10. ASPIRIN
It has been a standard drug for dental pain for many years and is still useful.
It, however, prolongs bleeding, and for this reason is a poor presurgical drug.
The anticoagulant effect comes from interference with platelet formation.
Aspirin irreversibly binds the enzyme cyclooxygenase.
Platelets in circulation do not have enough protein synthesis reserves to
replace the bound cyclooxygenase and are thus unable to participate in
clotting for the remainder of their cell life — around 7days.
Many patients are on routine, low dosage aspirin therapy for prophylaxis
against stroke or heart attack. Prior to endodontic surgery, consultation with
their physician may be required. 10
11. PHARMACOKINETICS
Aspirin is absorbed from the stomach and small intestines. Its poor water
solubility is the limiting factor in absorption: microfining the drug-
particles and inclusion of an alkali (solubility is more at higher pH)
enhances absorption.
The plasma t½ of aspirin as such is 15–20 min, but taken together with
that of released salicylic acid, it is 3–5 hours.
However, metabolic processes get saturated over the therapeutic range;
t½ of antiinflammatory doses may be 8–12 hours while that during
poisoning may be as high as 30 hours. Thus, elimination is dose dependent
12. ADVERSE EFFECTS
Side effects that occur at analgesic dose (0.3–1.5 g/day) are nausea, vomiting,
epigastric distress.
Hypersensitivity and idiosyncrasy Though infrequent, these can be serious.
Reactions include rashes, fixed drug eruption, urticaria, rhinorrhoea,
angioedema, asthma and anaphylactoid reaction.
acute salicylate poisoning It is more common in children. Fatal dose in adults is
estimated to be 15–30 g, but is considerably lower in children. Serious toxicity is
seen at serum salicylate levels > 50 mg/dl.
Manifestations are: Vomiting, dehydration, electrolyte imbalance, acidotic
breathing, hyper/hypoglycaemia, petechial haemorrhages, restlessness,
delirium, hallucinations, hyperpyrexia, convulsions, coma and death due to
respiratory failure + cardiovascular collapse.
13. Treatment for Acute Salicylate Intoxication
• Gastric lavage
• IV fluids to correct acid-base imbalance and dehydration.
• Temperature is brought down by external cooling with alcohol or cold
water sponges
• Hemorrhagic complications - blood transfusion and vitamin K are needed
• IV fluids should contain Na+, K+, HCO3– and glucose (hypokalemia and
acidosis)
• Severe cases, forced alkaline diuresis with sodium bicarbonate and a
diuretic like frusemide is given along with IV fluids.
14. CONTRAINDICATIONS
Contraindicated in peptic ulcer patients, bleeding tendencies
Should be stopped one week prior to elective surgery.
Avoided in pregnancy since it may be responsible for low birth
weight babies.
Cautious use in chronic liver disease: cases of hepatic
necrosis have been reported.
DOSAGE
300-600mg/6-8 hourly. 14
15. PROPRIONIC ACID DERIVATIVES
Ibuprofen was the first member of this class to be introduced in 1969 as a
better tolerated alternative to Aspirin. Many others have followed. All have
similar pharmacodynamic properties but differ considerably in potency and
to some extent in duration of action.
Well absorbed orally, highly bound to plasma protien. Largely metabolized
in liver by glucuronide conjugation. 15
16. Pharmacokinetics
All are well absorbed orally, highly bound to plasma proteins
(90–99%)
All propionic acid derivatives enter brain, synovial fluid and
cross placenta. They are largely metabolized in liver by
hydroxylation and glucuronide conjugation and excreted in
urine as well as bile.
17. Adverse effects
Side effects are milder and their incidence is lower. Gastric discomfort, nausea
and vomiting, though less than aspirin or indomethacin, are still the most
common side effects. Gastric erosion and occult blood loss are rare.
CNS side effects include headache, dizziness, blurring of vision, tinnitus and
depression. Rashes, itching and other hypersensitivity phenomenon are
infrequent.
However, these drugs precipitate aspirin-induced asthma. Fluid retention is
less marked. They are not to be prescribed to pregnant women and should be
avoided in peptic ulcer patient.
18. FENAMATE
An analgesic antipyretic and anti-inflammatory drug, Known from
1950s but has not gained popularity because of lower efficacy . It
inhibits PG synthesis.
Mefanimic acid exerts peripheral as well as central analgesic action.
Dose
250-500mg/TDS (Meftal, Medol.)
18
19. PHARMACOKINETICS
Oral absorption is slow but almost complete.
It is highly bound to plasma proteins; partly metabolized and
excreted in urine as well as bile. Plasma t½ is 2–4 hours.
20. ADVERSE EFFECTS
Diarrhoea is the most important dose-related side effect.
Epigastric distress is complained, but gut bleeding is not
significant. Skin rashes, dizzines and other CNS manifestations
have occurred.
Haemolytic anaemia is a rare but serious complication.
21. DICLOFENAC SODIUM
Newer Analgesic, Antipyretic and Anti-inflammatory similar to
Ibuprofen in efficacy. It inhibits Prostaglandin synthesis and
has short lasting antiplatelet action. Neutrophil chemotaxis
and superoxide production is reduced at inflammatory site.
Dosage
50mg twice a day ( Voveran, Diclonac, Inac)
21
22. Excreted both in urine and bile. Plasma t1/2 2hrs.
Adverse effects
Generally mild ,Epigastric pain, nausea, headache,
dizziness, rashes
22
23. PIROXICAM
It is a novel long acting potent NSAID with
anti-inflammatory potency similar to indomethacin and good antipyretic
analgesic action. It is a reversible inhibitor of Cycloxygenase ; lowers
PG concentration in synovial fluid and inhibits platelet aggregation;
prolonging bleeding time.
Dosage
20mg BD followed by 20 mg OD. (Pyrox, Dolonex)
Adverse effects
common- nausea and anorexia 23
24. KETOROLAC
Acetic acid derivative, has potent analgesic and modest
antiinflammatory action.
In postoperative pain it has equalled the efficacy of morphine, but
does not interact with opioid receptors.
It inhibits PG synthesis and relieves pain primarily by a peripheral
mechanism.
Plasma half life-5-7hrs. Mainly excreted by glucuronide conjugation.
24
25. Adverse effects-
nausea, dizziness, headache , ulceration, abdominal pain
Orally it is used in a dose of 10-20mg 6hourly for short term
management of pain.
Ketorolac has been rated superior to aspirin(650mg) and
paracetamol(600mg).
25
26. NIMESULIDE
This newer NSAID is relatively weak inhibitor of Prostaglandin
synthesis some what selective for COX2.
The Analgesic, Antipyretic and Anti-inflammatory activity of
Nimesulide has been rated comparable to other NSAIDs . It has
been used primarily for short lasting painful inflammatory
conditions.
26
28. PARACETAMOl
Introduced in 1950.
The central analgesic action of paracetamol is like
aspirin ,
i.e it raises pain threshold, but has weak peripheral anti-
inflammatory component.
Analgesic effect of aspirin and paracetamol is additive
28
29. Paracetamol is good and promptly acting antipyretic. It has less
anti-inflammatory action. It is a poor inhibitor of PG Synthesis in
peripheral tissues , but more active on COX in brain.
May be used in combination with an opioid such as codeine or
oxycodone.
Metabolism occurs mainly by conjugation with glucuronic acid.
Plasma t1/2 3-5hrs.
29
30. Dosage
300-600mg TDS( Crocin, Metacin)
Adverse effects
• when large doses are taken, Acute paracetamol poisoning.
• Children are more susceptible because their ability to conjugate by
glucuronidation is poor
• 10–15 grams in adults cause serious toxicity.
• Symptoms are—nausea, vomiting, anorexia and abdominal pain during
the first 24 hours
• Paracetamol is hepatotoxic and causes severe hepatic damage
30
31. TREATMENT
• Stomach wash is given
• Activated charcoal prevents further absorption.
• Antidote is N-acetylcysteine (150 mg/kg IV infusion over 15 min
repeated as required;
• Oral loading dose—140 mg/kg followed by 70 mg/kg every 4 hr–
17 doses)
32. SELECTIVE COX-2 INHIBITORS
Celecoxib and rofecoxib have the unique capability of limiting
prostaglandin synthesis from the pathways controlled by COX 2.
This spares the side effects of prostaglandin inhibition of the COX-
1 pathway that can harm the gut . The other NSAIDS have action
on both pathways.
32
33. Unfortunately, clinical use has shown them to have serious gut and
kidney side effects in some patients. The incidence of these side
effects is lower than with classic NSAIDS.
As with all new drugs, the practitioner should carefully weigh the
potential benefits with the higher costs always related to
development of new drugs, as well as the potential for yet
undiscovered side effects.
33
34. ADVERSE EFFECTS OF SELECTIVE
COX-2 INHIBITORS :
adminstration of rofecoxib was associated with a greater risk of
thrombotic cardiovascular event. Thus lead to withdrawl of
this drug.
34
35. Generic name Trade name Dosage Maximum daily
dose
Aspirin Dispirin 650-1000 mg qid 4000 mg
Acetaminophen Crocin 650-1000 mg qid 4000 mg
Ibuprofen Brufen 200-400 mg qid 1600 mg
Diclofenac Voveran 50 mg tid 150 mg
Ketorolac Ketorol 15-30mg iv or 10-20
mg orally at 6 hrs
60-120 mg im/iv
Rofecoxib Vioxx 50 mg od 50 mg
36. OPIOID ANALGESICS
• Opioid analgesics are one of the oldest remedies for relief of
pain.
• Opium is the dark brown exudate obtained from the poppy
capsule (Papaver somniferum).
• On incising the unripe seed capsule, a milky juice emerges
which turns brown on drying and this is crude opium
39. 1 Codeine has been a standard drug in dentistry for many years
because it is usually powerful enough to control dental pain. It is
irritating to the stomach in high doses.
Unfortunately, many patients with pain are troubled with this
gastrointestinal upset.
The degree of analgesia compared to aspirin i.e 60mg
codeine~600mg aspirin
39
40. 2 Hydrocodone a development of the 1980s, is less irritating to the
gut and has become very popular in dentistry.
It is synthetic derivative of codiene. Mainly give in combination with
paracetamol
40
41. 3 Morphine :- Because of rapid liver metabolism following oral
dosing, a larger dose is required than is of the parenteral
dose. Morphine pills are available in 10, 15, 30, 60, and 100 mg
amounts.
For severe dental pain, such as when the bony cortical plates
confine infection pressure, necessitating very strong drug
therapy, morphine remains a viable choice for the practitioner.
41
42. 4 Tramadol is a new, potent, synthetic pain reliever that has
similarities and differences with the classic opiates. Similarly, it
binds with the mu opioid receptor, decreases respiration, and
increases intracranial pressure.
It also causes dizziness, nausea, and constipation and potentiates
other CNS depressants. Tramadol is well absorbed orally, with t1/2
5-6hrs and the usual adult dose is 50 to 100 mg four times a day.
42
43. Analgesic Doses of Various Opioids (equivalent to codeine
60 mg)
a. Codeine: 60 mg.
b. Mepiridine: 90 mg
c. Hydrocodone: 10 mg
d. Dihydrocodeine: 60 mg
e. Propoxyphene hydrochloride: 102 mg
43
45. ADVERSE EFFECTS OF OPIOIDS:
1. Although opioids are effective as analgesics for moderate to
severe pain, their usage is generally limited by their adverse
side effect profile.
2. 0pioids induce numerous side effects like dizziness, nausea,
emesis, drowsiness.
3. They may have the potential for respiratory depression and
constipation.
4. Long-term use associated with tolerance and dependence.
45
46. Acute Morphine Poisoning
Acute morphine poisoning may be accidental, suicidal or
homicidal.
Lethal dose in non-addicts is about 250 mg.
Signs and symptoms include
respiratory depression with shallow breathing,
pin point pupils,
hypotension, shock,
cyanosis,
hypothermia,
coma and death due to respiratory failure and pulmonary
edema.
47. TREATMENT
Positive pressure respiration.
Maintenance of BP.
Gastric lavage with potassium permanganate to remove
unabsorbed drug
Specific antidote is naloxone—0.4–0.8 mg IV repeated every 10–
15 min.
48. Effective management of endodontic pain:
It starts with three D’s
1. Diagnosis
2. Definitive dental treatment
3. Drugs : pretreatment with NSAID’s
Use of flexible prescription plan
Use “by the clock” rather than as needed
48
49. Flexible analgesic strategy
200 to 400mg of ibuprofen or 650mg aspirin
inadequate relief
600 to 800 mg of ibuprofen
inadequate relief
49
Mild pain
Moderate pain
Aspirin like
drugs indicated
51. If aspirin like drugs are contraindicated then :
650-1000mg of acetaminophen
inadequate relief
650-1000mg acetaminophen + Opiate equivalent to 60mg codeine.
inadequate relief
1000mg acetaminophen + Opiate equivalent to 10mg oxycodone.
51
Mild pain
Moderate
severe
52. CONCLUSION
Pain represents a major stimulus for patients who seek endodontic treatment.
On the other hand, fear of pain represents a significant barrier that
discourages patients from seeking endodontic treatment.
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the clinician to manage different pain conditions effectively, thus
reducing dental phobia.
53. REFRENCES
1.Pharmacology and Pharmacotherapeutics. Sixteenth edition ;R S Satoskar
2. KDTripathi Essential of medical pharmacology- seventh edition
3. Clinical pharmacology in dentistry. Cawson AND Specter, 5th Edition.
4. Antibiotic use in dental practice. Newman and Kornmen.
5.Endodontic practice- 12th edition Grossman
John I Ingle, Leif K Bakland, J. Craig Ingle’s endodontics- 6th edition
Kenneth M. Hargreaves Louis H. Berman Cohen’s Pathways of pulp- 11th edition
53
These prostaglandins produce hyperalgesia.
Sensitize the nerve endings to pain caused by other mediators of
inflammation like bradykinin and histamine.
NSAIDs inhibit the PG synthesis by inhibiting the enzyme
cyclooxygenase.
Aspirin is an irreversible inhibitor of COX (by acetylation) while
the others are reversible competitive COX inhibitors.
Celecoxib t1/2 – 10hrs.
Morphine - By acting on specific opioid receptors, viz mu (m), kappa (k) and
delta (d).
All opioid receptors are G-protein-coupled receptors.
Stimulation of these receptors inhibits adenylyl cyclase resulting in decreased
intracellular cAMP formation.
Opening of K+ channels leading to hyperpolarization and inhibit the entry of
calcium into the cell.
They inhibit the opening of calcium channels.
Result in a decrease in the intracellular calcium which, in turn, decrease the
release of neurotransmitters.
