Revista fop n 13

Braz J Oral Sci. July-September 2005 - Vol. 4 - Number 14 Analgesic choice in dentistry.
Part I: The mechanism of action

Filipe Polese Branco 1*
Marcos Luciano Pimenta Pinheiro 2**

Maria Cristina Volpato 3*
Analgesics are frequently used in dentistry for the management of Eduardo Dias de Andrade3*
dental pain. Dental clinicians should choose the medicine based on its mechanism of action and toxicity, to promote a successful analgesic effect as well as comfort to the patient. The purpose of this first article is to describe the pharmacological mechanisms of action of the *Science Physiological Department, Piracicaba three analgesics considered for the management of mild to moderate Dental School, Campinas State University, Piracicaba-SP, Brazil.
**Diamantina Dental School, Diamantina,
Key Words:
analgesics, mechanism of action, dentistry Correspondence to:
Eduardo Dias de Andrade
Department of Physiological Sciences
Piracicaba Dental School
Campinas State University
Av. Limeira, 901
13414-903 Piracicaba-SP, Brazil
E-mail: [email protected]
Braz J Oral Sci. 4(14):762-765 Analgesic choice in dentistry. Part I : The mechanism of action Introduction
synthesis of several mediators, including the prostaglandins Analgesics are commonly recommended for mild, moderate that protect the gastric mucosa and regule renal blood flow, or acute pain. About 16 million of these drugs are annually and the thromboxanes, which initiate platelet aggregation5.
prescribed by American dentists. In Brazil, analgesics are Tissue damage resulting from pulpits, periodontitis, or oral the most sold out class of medicine; dipyrone is the first in surgery will induce the production of COX-2, which, in turn, this list followed by acetaminophen (paracetamol) and leads to the synthesis of the prostaglandins that sensitize pain fibers and promote inflammation.
Although these drugs are safe, recent studies alert to Traditional NSAIDs, such as aspirin, act by blocking both intoxication risk and severe adverse effects, even at doses cyclooxygenase enzymes (COX-1 and COX-2). This non- or concentrations nearly the same as those used to relieve selective inhibition is responsible for many of the unwanted pain, increasing the need for either pharmacological effects of this drug6. Aspirin, like all the other NSAIDs, induce inhibition of thromboxane synthesis resulting in a decrease The clinician should employ a variety of effective and safe in the platelet aggregation. For most NSAIDs this effect is analgesic regimens based on estimates of anticipated pain reversible within 24 hours; however, aspirin is unique in intensity, mechanism of action and toxicity1.
that it irreversibly damages cyclooxygenase for the life of The purpose of this first article was to describe the the platelet5. Although an increase in the time of coagulation pharmacological mechanisms of action of three analgesics can be accepted in normal patients, aspirin might promote considered for the management of mild to moderate acute post-operative hemorrhage, mainly if the clot is not totally dental pain in dentistry as well as parameters to choose each formed. There are some reports of hemorrhage after aspirin ingestion in dentistry7-8.
Use of aspirin in children during or immediately after a viral infection has been associated with the increase in the Aspirin has been used in dentistry as an anti-inflammatory, incidence of Reye’s syndrome9. This syndrome is a rare acute analgesic and antipyretic drug prescribed for use within short encephalopathy associated with fatty degeneration of the periods2. The mechanism of action of aspirin, a nonsteroidal liver and its etiology remains uncertain. It is known to occur anti-inflammatory drug (NSAID), was established after viral infections such as chickenpox (varicella) and approximately 30 years ago3. Clinical trials have shown repeatedly that aspirin is effective in the management of Table 1 shows the clinical use of aspirin in dentistry.
dental pain4.
Optimal use of this drug is based on the understanding of its Paracetamol
action on the arachidonic acid metabolism pathways. Aspirin Paracetamol has become increasingly popular as a safe and blocks the cyclooxygenase enzymes, which exist in at least mild aspirin substitute, either alone or in associations, without two known isoforms: cyclooxygenase 1 (COX-1) and decreasing in the platelet aggregation. It is currently found cyclooxygenase 2 (COX-2). COX-1 is responsible for the in more than 200 formulations, most of which are available Table 1. Clinical use of aspirin, paracetamol and dipyrone in dentistry.
Recommended doses
Precautions or contraindications
- Coagulation defects- Chickenpox or influenza* - Glucose-6-phosphate dehydrogenase deficiency * Aspirin has being associated with Reye’s syndrome in children, although no causal relationship has been demonstrated31.
** In Brazil, paracetamol drops solution includes sodium metabissulfite.
Braz J Oral Sci. 4(14):762-765 Analgesic choice in dentistry. Part I : The mechanism of action over the counter. It is often categorized as a NSAID even (COX-2b) that is particularly sensitive to paracetamol. Then though it provides little anti-inflammatory activity in clinical the presumable site of action of paracetamol might be both in the locally acting “COX-2b” and COX-3 in the centrally The exact site and mechanism of action of paracetamol remain acting, but these points still need to be proved.
unclear. Flower et al.12 reported that paracetamol might The potential for adverse effects from paracetamol seems to produce analgesia by increasing pain threshold. Björkman be singularly confined to the situation in which there is an et al.13 suggested that the potential mechanism of action acute overdose, and herein lies its main therapeutic might involve the inhibition of the nitric oxide pathway and advantage over aspirin. The most serious manifestation of is mediated by several neurotransmitters, including the N- paracetamol overdose is hepatotoxicity. The degree of liver metil-D-aspartate and the P substance. Actually, this damage is directly related to the amount of drug ingested, discussion focuses on the relation between paracetamol and and people with preexisting liver disease are most Flower and Vane14 showed that paracetamol inhibited COX The clinical use of paracetamol in dentistry is shown in Table 1.
activity in dog brain homogenates more than in homogenatesfrom spleen, suggesting the existence of different isoforms Dipyrone
Dipyrone, a drug of the pyrazolone group, exhibits analgesic The great step forward in our understanding of the NSAIDs and antipyretic activity and its action may be central as well came in the early 1990s whem the existence of two isoforms as peripheral22. In dentistry, dipyrone, like aspirin and of COX was proved on a molecular basis, COX-1, paracetamol, is indicated to produce low or moderate constitutively expressed, and COX-2, inducible by pro- inflammatory stimuli15. However, not all questions were An important point to understand the mechanism of answered by the characterization of two COX enzymes inflammation and pain is to understand the hyperalgesia, originating from different genes. One such question is the which results from excitatory actions of endogenous effect of paracetamol, which, unlike NSAIDs, produce mediators released by inflamed or damaged tissues23. The analgesia and antipyresis but has little effect on inflammation.
biochemical mechanism of up-regulation (hyperalgesia) is The existence of additional COX enzymes was therefore through the increase of cAMP and Ca2+. Prostaglandins and dopamine are the most potent stimulators of neuronal tissue Investigations of the relative sensitivity of the 2 enzymes to adenylate cyclase and are the most active up-regulators of paracetamol found that although the drug was a weak inhibitor nociceptors. It has been shown that inhibitors of cAMP of both enzymes, COX-1 was marginally more sensitive than inactivation potentiate the up-regulation of the nociceptors24.
COX-216. In view of the low sensitivity to paracetamol of both When the nociceptor is up regulated, drugs that block the COX-1 and COX-2, the existence of a new, so far unknown release of prostaglandin or sympathomimetic amines are not isoform of COX provisionally named COX-3 has been effective as analgesic agents. Ferreira et al.24 described that repeated administration of nociceptor up-regulatory stimuli Chandrasekharan et al.17 discovered the enzyme COX-3, an induces a state of persistent hyperalgesia, which cannot be enzyme derived from the same COX-1 gene, observing its treated with standard COX inhibitors (NSAIDs). Dipyrone highest levels of message in the cerebral cortex and heart.
can be considered an analgesic that directly down-regulates Common analgesic/antipyretic drugs and NSAIDs were the nociceptor, because it reduces the state of persistent tested for their ability to inhibit of COX-1, -2, and -3 activities.
At a higher concentration of substrate, only COX-3 was concentrations25. Unlike aspirin and other NSAIDs dipyrone inhibited by paracetamol. These authors concluded that the has been suggested as a classic analgesic acting in the inhibition of COX-3 in the brain might be the long sought- prevention and elimination of dental pain6.
after mechanism of the action of paracetamol.
Recent research carried out at the Hospital das Clínicas de But pain is a difficult process to unravel. Prostanoids São Paulo showed that more than 50% of the patients produced at sites of inflammation can sensitize nerve endings reported dipyrone as the preferable analgesic26. In dentistry, and therefore promote the localized feelings of pain dipyrone is the most effective analgesic used in elective associated with inflammatory events and tissue injury18.
surgery and demonstrates the same potency as do These prostanoids can be produced by COX-2 induced by the local inflammatory processes. It remains unclear how Dipyrone use has been discussed because of its absolute paracetamol causes its analgesic effects, once it is not a risk of mortality caused by agranulocytosis, aplastic anemia, peripheral anti-inflammatory drug. Therefore, paracetamol anaphylaxis and upper gastrointestinal complications.
might act in an additional enzyme19. Simmons et al.20 have Andrade28 reported that this risk appears to be similar to that previously proposed the existence of an isoform of COX-2 caused by paracetamol and substantially lower than the risk Braz J Oral Sci. 4(14):762-765 Analgesic choice in dentistry. Part I : The mechanism of action associated with aspirin and diclofenac, drugs commonly used Gordon SM, Brahim JS, Rowan J, Kent A, Dionne RA.
for short-term pain relief. These considerations are well Peripheral prostanoid levels and nonsteroidal anti-inflammatory drug analgesia: replicate clinical trials in a tissue explained in the Boston Study29 and in the Painel injury model. Clin Pharmacol Ther 2002; 72: 175-83.
internacional de avaliação da segurança da dipirona30, Warner TD, Mitchell JA Cyclooxygenase-3 (COX-3): filling showing the safety of this drug, as will be discussed in the in the gaps toward a COX continuum? Proc Natl Acad Sci Simmons DL, Botting RM, Robertson PM, Madsen ML, Vane The clinical use of dipyrone in dentistry is presented in Table 1.
JR. Induction of an acetaminophen-sensitive cyclooxygenasewith reduced sensitivity to nonsteroid antiinflamatory drugs.
In conclusion, only dipyrone is a classic analgesic, acting Proc Natl Acad Sci USA 1999; 96: 3275-80.
effectively even after the hyperalgesia process sets out. It is Cooper AS, Desjardins PJ. Peripheral acting (nonopioid)analgesics. In: Neidle EA, Yagiela JÁ. Pharmacology and commonly prescribed in Brazil and seems to have the same therapeutics for dentistry. 3rded. Saint Louis: Mosby; 1989.
analgesic efficacy, as do paracetamol and aspirin.
Gladtke E. Use of antipyretic analgesics in the pediatric patient.
Phero JC, Becker D. Rational use of analgesic combinations.
Lynn B. Effect of neonatal treatment with capsaicin on the numbers and properties of cutaneous afferent units from the Ardekian L, Gaspar R, Peled M, Brener B, Laufer D. Does hairy skin of the rat. Brain Res 1984; 322: 255-60.
low-dose aspirin therapy complicate oral surgical procedures? Ferreira SH, Lorenzetti BB, De Campos DI. Induction, blockade and restoration of a persistent hypersensitive state.
Moncada S, Ferreira SH, Vane JR. The blockade of the local generation of prostaglandins explains the analgesic action of Lorenzetti BB, Ferreira SH. Mode of analgesic action of aspirin. Pol J Pharmacol Pharm 1974; 26: 77-8.
dipyrone: direct antagonism of inflammatory hyperalgesia.
Hersh EV, Moore PA, Ross GL. Over-the-counter analgesics and antipyretics: a critical assessment. Clin Ther 2000; 22: Jardim C, Lotufo PA, Maluf EP, Benseñor IM. Painkiller usage for headache in Brazil. Cephalalgia 2001; 21: 469.
Haas, DA. An update on analgesics for the management of Maia LC, Valença MGV. Estudo comparativo do efeito da acute postoperative dental pain. J Can Dent Assoc 2002; 68: dipirona, paracetamol e ácido acetilsalicílico sobre o sistema cardiovascular, alívio da dor e sangramento em cirurgias Andrade ED. Terapêutica medicamentosa em odontologia.
odontológicas eletivas. Um estudo “in vivo”. Âmbito Odontol Foulke CN. Gingival hemorrhage related to aspirin ingestion.
Andrade SE. Comparative safety evaluation of non-narcotic A case report. J Periodontol 1976; 47: 355-7.
analgesics. J Clin Epidemiol. 1998; 51:1357-65.
Pawlak DF, Itkin AB, Lapeyrolerie FM, Zweig B. Clinical International Agranulocytosis and Aplastic Anemia Study (The effects of aspirin and acetaminophen on hemostasis after Boston Study) - Risks of agranulocytosis and aplastic anemia.
exodontics. J Oral Surg 1978; 36: 944-7.
A first report of their relation to drug use with reference to Sullivan-Bolyai JZ, Corey L. Epidemiology of Rey’s Syndrome.
analgesics. J Am Med Assoc 1986; 256: 1749-57.
Agência Nacional de Vigilância Sanitária. Painel internacional Hurwitz ES. Rey’s Syndrome. Epidemiol Rev 1989; 11: 249- de avaliação da segurança da dipirona; 2001 Jul 3-4. Brasília: Botting RM. Mechanism of action of Acetaminphen: Is there Holmes A, Davidson LE. Reye’s syndrome and analgesic a cyclooxygenase 3? Clin Infect Dis 2000; 31 Suppl 5: S202-10.
choice in dentistry. Br Dent J 1989; 167: 345-6.
Flower RJ, Moncada S, Vane JR. Analgesic-antipyretics andanti-inflammatory agents; drugs employed in the treatmentof gout. In: Gilman AG, Goodman LS, Gilman A. ThePharmacologic Basis of Therapeutics. 7thed. Elmsford:Pergamon Press; 1985. p.692-5.
Björkman R, Hallman KM, Hedner J, Hedner T, Henning M.
Acetaminophen blocks spinal hyperalgesia induced by NMDAand substance P. Pain 1994; 57: 259-64.
Flower RJ, Vane JR. Inhibition of prostaglandin synthetase inbrain explains the anti-pyretic activity of paracetamol (4-acetamidophenol). Nature 1974; 15: 410-1.
Vane JR. The fight against rheumatism: from willow bark toCOX-1 sparing drugs.J Physiol Pharmacol 2000; 51: 573-86.
Mitchell JA, Akarasereenont P, Thiemermann C, Flower RJ,Vane JR. Selectivity of nonsteroidal anti-inflammatory drugsas inhibitors of constitutive and inducible cyclooxygenase.
Proc Natl Acad Sci 1993; 90: 1693-7.
Chandrasekharan NV, Dai H, Roos LT, Evanson NK, TomsikJ, Elton TS et al.COX-3, a cyclooxygenase-1 variant inhibitedby acethaminophen and other analgesic/antipyretic drugs:cloning, structure and expression. Proc Natl Acad Sci USA2002; 99: 13926-31.


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