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Rpcendo.comAn Update on Local Anesthetics in Dentistry
• Daniel A. Haas, BSc, DDS, BScD, PhD, FRCD(C) •
Local anesthetics are the most commonly used drugs in dentistry. This article provides a brief update on thepharmacology, adverse effects and clinical applications of these drugs, as well as the role of vasoconstrictors. MeSH Key Words: anesthesia, dental; anesthetics, local/adverse effects; pharmacology; vasoconstrictor agents
J Can Dent Assoc 2002; 68(9):546-51 This article has been peer reviewed. Intraoperative pain control by means of local anesthesia which is no longer available in dental cartridge form. The is an intrinsic part of clinical practice in dentistry.
topical anesthetic benzocaine is an ester.
Each dentist in Canada injects approximately 1,800 The onset and duration of action of local anesthetics are cartridges of local anesthetic yearly,1 and it has been esti- influenced by several factors, as summarized in Table 1.
mated that more than 300 million cartridges are adminis- The most important factors affecting onset are pH of the tered by dentists in the United States every year.2 Therefore, tissue and pKa of the drug. The pH may drop in sites of all dentists should have expertise in local anesthesia. This infection, which causes onset to be delayed or even article provides a brief overview of local anesthetics to rein- prevented. Clinically, there are no significant differences in force dentists’ knowledge of these agents.
pKa among the amides, with the exception of bupivacaine,which has a slightly higher pKa and hence a slower onset of Pharmacology
action. Proximity of the deposition of local anesthetic to the What follows here is a brief synopsis of the pharmacol- nerve can also be a factor, which is why infiltration is asso- ogy of local anesthetics. Dentists should be familiar with ciated with rapid onset whereas the Gow-Gates block is sources that provide more detailed information on this relatively slow. Nerve morphology is a factor, in that the relatively thin pain fibres are usually anesthetized readily.
Local anesthesia is induced when propagation of action Within limits, higher concentration and greater lipid solu- potentials is prevented, such that sensation cannot be trans- bility improve onset to a small degree.
mitted from the source of stimulation, such as a tooth or The duration of action depends on the length of time that the drug can stay in the nerve to block the sodium the periodontium, to the brain. Local anesthetics work by channels. Local anesthetics cause vasodilatation, which blocking the entry of sodium ions into their channels, leads to rapid diffusion away from the site of action and thereby preventing the transient increase in permeability of results in a very short duration of action intraorally when the nerve membrane to sodium that is required for an these drugs are administered alone. This diffusion can be reduced by the addition of a vasoconstrictor, usually Structurally, local anesthetics have specific fundamental epinephrine. Bupivacaine is unique in that it provides long- features in common. These include a lipophilic group, duration anesthesia for soft tissue in both the arches and joined by an amide or ester linkage to a carbon chain pulp of mandibular teeth. The duration of action of local which, in turn, is joined to a hydrophilic group. Local anes- anesthetics is summarized in Table 2.3,4,6 In general, blocks
thetics are classified by these amide or ester linkages. All last longer than infiltrations, and soft-tissue anesthesia lasts local anesthetics available in dental cartridges in Canada today, namely articaine, bupivacaine, lidocaine, mepiva- Biotransformation of amides occurs primarily in the liver.
caine and prilocaine, belong to the amide class. The proto- Prilocaine is also metabolized in the plasma and kidney, and type for the ester group is procaine (Novocain, Abbot), one of its metabolites may lead to methemoglobinemia, as Journal of the Canadian Dental Association An Update on Local Anesthetics in Dentistry discussed below. Esters are biotransformed by plasma Psychogenic Reactions
cholinesterase, also known as pseudocholinesterase. Patients Anxiety-induced events are by far the most common with the genetic disorder pseudocholinesterase deficiency can adverse reaction associated with local anesthetics in be expected to metabolize procaine at a much slower rate.
dentistry. These may manifest in numerous ways, the most However, little clinical effect would be expected unless the common of which is syncope. In addition, they may present with a wide variety of symptoms, including hyperventila- From a practical viewpoint, the dentist should be tion, nausea, vomiting and alterations in heart rate or blood concerned about alterations in biotransformation only in pressure. Psychogenic reactions are often misdiagnosed as patients with severe liver dysfunction. Reduced hepatic allergic reactions and may also mimic them, with signs such function predisposes the patient to toxic effects but, unlike as urticaria, edema and bronchospasm.
the situation for systemically administered drugs, shouldnot significantly increase the duration of action of locally Allergic Reactions
administered anesthetics. In this context, it must be remem- Patient reports of allergic reactions to local anesthetics bered that hepatic function does not affect the duration of are fairly common, but investigation shows that most of action of local anesthesia, which is determined by redistrib- these are of psychogenic origin.11,12 True allergy to an amide ution and not biotransformation. Therefore, a patient with is exceedingly rare, whereas the ester procaine is somewhat liver disease needs the standard amount of local anesthetic more allergenic. An allergy to one ester rules out use of at each site. However, the total dose is a concern. Therefore, another ester, as the allergenic component is the breakdown when treating a patient with significant liver disease, it is product para-aminobenzoic acid, and metabolism of all prudent to treat one quadrant at a time, thereby minimiz- esters yields this compound. In contrast, an allergy to one ing total dose. Use of an ester may not offer any advantage, amide does not rule out use of another amide. Allergy to because pseudocholinesterase is also synthesized in the liver.
With regard to efficacy, no studies have shown any A patient may be allergic to other compounds in the significant differences among the agents. Therefore it is anesthetic cartridge. For example, methylparabens are appropriate to assume that each of the 5 amides is equally preservatives necessary for multidose vials and were present in dental cartridges in the past. They are no longer Adverse Reactions
included as dental cartridges are single-use items. Allergy to para-aminobenzoic acid would rule out use of esters and Local anesthetics should be considered relatively safe, methylparabens. It may be best to avoid a vasoconstrictor if but with the high number of injections given yearly, adverse there is a true documented allergy to sulfites, as metabisul- reactions are seen (Table 3).
fite is added as an antioxidant whenever vasoconstrictor is Table 1 Factors affecting onset and duration
present. Vasoconstrictor can be used in patients with an of action of local anesthetics
allergy to the sulfonamide antibacterials, commonly calledsulfa, as there is no cross-allergenicity with sulfites.
Time of diffusion from needle tip to nerve The toxicity of local anesthetics is a function of systemic Time of diffusion away from nerveNerve morphology absorption. High blood levels of the drug may be due to repeated injections or could result from a single inadvertant intravascular administration. This is one reason why Table 2 Expected duration of action of local anestheticsa
Duration of action (min)
Inferior alveolar block
Articaine 4% with epinephrine 1:100,000 or 1:200,000 Bupivacaine 0.5% with epinephrine 1:200,000 Lidocaine 2% with epinephrine 1:50,000 or 1:100,000 Mepivacaine 2% with levonordefrin 1:20,000 aApproximations only. Adapted primarily from Yagiela3,4 and Haas.6 Journal of the Canadian Dental Association Table 3 Adverse reactions of commonly used
Table 4 Recommended maximum doses of
local anesthetics with vasoconstrictor
Alterations in heart rate or blood pressureMimicking of an allergic reaction Allergic (potential allergens)
Metabisulﬁte (present with epinephrine and with levonordefrin) Methylparaben (no longer added to dental cartridges) Toxic effects
a3% solution without vasoconstrictor Primarily neurologic signsMay initially manifest as sedation, lightheadedness, slurred speech, mood alteration, diplopia, sensory disturbances,disorientation, muscle twitching aspiration before every injection is so important. The signs Higher blood levels may result in tremors, respiratory and symptoms of toxicity are summarized in Table 3.
The maximum recommended doses of local anesthetics If severe, may result in coma, respiratory arrest, cardiovascular are shown in Table 4,4,6,13 although predisposition to toxic
effects in any given patient depends on several factors, such Methemoglobinemia
as site of administration, speed of injection and presence of Associated with prilocaine, articaine, benzocaine vasoconstrictor. Maximum doses are much more relevant in Paresthesia
the pediatric patient, and it is important to note how little Apparently more common with articaine and prilocaine anesthetic should be given to a child.14 Examples of dose
calculations for a young child are included in Table 5.
The high-concentration solutions, namely prilocaine and
articaine, will reach toxic levels with fewer injections than
is the case for the other drugs.
Table 5 Example calculations of maximum
local anesthetic doses for a
This uncommon adverse reaction is associated most 15-kg (33-lb) child
notably with prilocaine but may also occur with articaine or Articaine
the topical anesthetic benzocaine. Methemoglobinemia is induced by an excess of the metabolites of these drugs and manifests as a cyanotic appearance that does not respond to the administration of 100% oxygen. Cyanosis becomes 1 cartridge = 1.8 mLTherefore, 1 cartridge is the maximum.
apparent when methemoglobin levels are low, but symp-toms of nausea, sedation, seizures and even coma may result Lidocaine
when levels are very high.15 Prilocaine, articaine and benzo- 7 mg/kg × 15 kg = 105 mg2% lidocaine = 20 mg/mL caine are best avoided in patients with congenital methe- 1 cartridge = 1.8 mLTherefore, 2.9 cartridges is the maximum.
Prolonged anesthesia or paresthesia of the tongue or lip Mepivacaine
are known risks of surgical procedures such as extractions 6.6 mg/kg × 15 kg = 99 mg3% mepivacaine = 30 mg/mL but may also occur following nonsurgical dentistry. Most of these reactions are transient and resolve within 8 weeks, but they may become permanent. Articaine and prilocaine were Therefore, 1.8 cartridges is the maximum.
reported as more likely than other anesthetics to be associ- Prilocaine
ated with paresthesia, a difference that was statistically significant when their distribution of use was taken into 4% prilocaine = 40 mg/mL120 mg/(40 mg/mL) = 3 mL account.16 Such reactions have most commonly affected the lingual nerve. So far, the reasons for these findings are Therefore, 1.67 cartridges is the maximum.
Journal of the Canadian Dental Association An Update on Local Anesthetics in Dentistry Malignant Hyperthermia
Table 6 Drug interactions with epinephrine
Malignant hyperthermia can occur when patients with and levonordefrin
genetic susceptibility to this condition are exposed toinhalational general anesthetics or succinylcholine, but not Nonselective ß-blockers
to local anesthetics. Previous recommendations, now Examples: nadolol (Corgarda), oxprenolol (Trasicor), pindolol (Visken), propranolol (Inderal), sotalol (Sotacor), timolol known to be wrong, precluded the use of specific local anes- thetics in these patients. Today it is well accepted that all Interaction may result in increased blood pressure local anesthetics are safe for patients who are susceptible to Reduced use of vasconstrictor is warranted Tricyclic antidepressants
Examples: imipramine (Tofranil), amitriptyline (Elavil), desipramine (Norpramin), nortriptyline (Aventyl), doxepin (Sinequan), Unlike the vasoconstrictors in dental cartridges, local anesthetics have very few clinically significant interactions Interaction may result in increased blood pressure on their own.14,18 When they are combined with an opioid Levonordefrin is contraindicatedReduced dose of epinephrine is warranted and an antihistamine, there may be a predisposition toseizure activity, particularly in children. This concern can be General anesthetic (halothane [Fluothane])
minimized by use of low doses and careful monitoring, Interaction may result in serious cardiac dysrhythmia consistent with the standard of care for oral sedation.
Anesthetist should be advised as to whether epinephrine is needed in local anesthetic; epinephrine should be limited to 1 µg/kgif thiopental is used and 2 µg/kg otherwise Vasoconstrictors
Vasoconstrictors are invaluable to local anesthesia in dentistry. There are clear indications for their use, of which Interaction may result in increased blood pressure and cardiac improving the depth and duration of anesthesia are themost important. Without them, local anesthetics have a aBrand names are included only as examples and not to promote any oneproduct. The manufacturers are as follows: Corgard, Squibb; Trasicor, very short duration of action intraorally. Vasoconstriction is Novartis Pharmaceuticals; Visken, Novartis Pharmaceuticals; Inderal, Wyeth- more important for infiltration techniques in vascular sites Ayerst; Sotacor, Bristol; Blocadren, MSD; Timoptic, Merck Frosst; Tofranil,Novartis Pharmaceuticals; Elavil, Merck Frosst; Norpramin, Aventis Pharma; than it is for mandibular blocks. The presence of a vaso- Aventyl, Lilly; Sinequan, Pﬁzer; Vivactil, Merck and Company; Fluothane, constrictor may also reduce systemic toxic effects and can provide hemostasis. The most common agent for thispurpose is epinephrine, which is available in formulationsof 1:50,000, 1:100,000 and 1:200,000.
It is beyond the scope of this article to cover the phar- Table 7 Treatment modifications to consider
macology of epinephrine, but the cardiovascular actions of if there are concerns regarding
this drug should be noted. Vasoconstriction is due to vasoconstrictors
epinephrine’s stimulation of α1 receptors in mucous Monitor blood pressure and heart rate preoperatively membranes. However, it also stimulates the ß1 receptor in Minimize administration of epinephrine or levonordefrin the heart, increasing heart rate, strength of contraction and Monitor blood pressure and heart rate 5 min after injection myocardial oxygen consumption, and the ß May re-administer epinephrine or levonordefrin if blood pressure vasodilating blood vessels in the skeletal muscle. These actions form the basis for potential interactions with other Consider limiting epinephrine to 0.04 mg, levonordefrin to 0.2 mg drugs that affect the same receptors (Table 6). Contrary to
the information in certain drug monographs, epinephrine Never use epinephrine-impregnated retraction cord can be given to patients receiving monoamine oxidaseinhibitors.19 A second vasoconstrictor is levonordefrin, which is avail- Table 8 Examples of calculations of doses of
able as a 1:20,000 solution and should be considered equiva-lent to 1:100,000 epinephrine. Levonordefrin is contraindi- vasoconstrictors
cated for patients receiving tricyclic antidepressants. Ratio concentrations represent grams per millilitre Epinephrine dosage should sometimes be minimized, for example, for patients with significant cardiovascular 1:200,000 = 0.005 mg/mL or 5 µg/mL1:50,000 = 0.02 mg/mL or 20 µg/mL disease, in particular ischemic heart disease. In these situa- 1 cartridge of epinephrine 1:200,000 = 9 µg tions, or when the patient is taking one of the drugs listed 1 cartridge of epinephrine 1:100,000 = 18 µg in Table 6, certain precautions, outlined in Table 7, should
1 cartridge of epinephrine 1:50,000 = 36 µg1 cartridge of levonordefrin 1:20,000 = 90 µg be followed. The recommendation to keep doses below Journal of the Canadian Dental Association Although high-dose vasoconstrictors used to manage Table 9 Use of local anesthetics during
significant hypotension may be a concern for pregnant pregnancy13,21
patients, the doses of epinephrine used in local anesthetic FDA category
formulations for dentistry are so low that they are unlikely to significantly affect uterine blood flow. The benefits of epinephrine or levonordefrin at the concentrations found in dental anesthetic cartridges justify their use.
The main concern in pediatrics is the relative ease of inducing an overdose. Before administering local anesthetic to a child, the dentist should determine the child’s weight and calculate the maximum dose, to help prevent inadver- tent overdose. The calculations shown in Table 5 indicate
the ease with which a young child can be overdosed. Given the concerns regarding toxicity, selection of a low- FDA = U.S. Food and Drug Administration concentration solution appears prudent. Thus, 2% lido-caine with epinephrine 1:100,000 may be the ideal localanesthetic for a child. Bupivacaine is best avoided in chil- 0.04 mg is arbitrary but can act as a guide (see Table 8).2,6
dren because of its long duration of soft-tissue anesthesia.
Systemic epinephrine has a brief duration of action There should be no concerns regarding prolonged duration (approximately 10 minutes), so if more is required, injec- of action due to vasoconstrictor, as it has been shown that tions can be repeated. If multiple quadrants are being soft-tissue anesthesia does not differ significantly between treated, the timing of the injections should be spread out.
2% lidocaine with epinephrine 1:100,000 and 3% mepiva- Minimizing the likelihood of systemic effects of vasocon- strictors is another reason why aspiration before every injec- Elderly Patients
There are no significant differences in the response to Topical Anesthetics
local anesthetics between younger and older adults.
Topical anesthetics may be indicated to minimize the Therefore, the doses required for each block are the same sensation of needle insertion or for very brief relief from regardless of patient age. Nonetheless, it is prudent to stay painful mucosal lesions. Their effectiveness in preventing well below the maximum recommended doses, as elderly pain due to injection is equivocal,20 but they may be of patients often have some compromise in liver function.
value for many patients. For this purpose benzocaine is Responses to vasoconstrictors should not be considered available in concentrations up to 20%, and lidocaine is significantly different in elderly patients, but some degree available as a solution or ointment in concentrations up to of cardiovascular compromise can be expected, even with- 5% or as a spray at a concentration of 10%. Dentists out an overt history of heart disease. Therefore, reducing should be aware that excessive doses may lead to toxic the dose of epinephrine may be prudent.
Special Patient Populations
All local anesthetics used in dentistry are efficacious. The decision regarding which drug to select should be based on Pregnant and Lactating Women
the estimated duration of action required, the patient’s The local anesthetics and vasoconstrictors used in medical history and potential drug interactions. Solutions dentistry can be safely administered to the pregnant or without vasoconstrictor, namely mepivacaine and prilo- nursing patient (Table 9).21 However, aspiration must
caine plain, may be selected for short procedures, particu- always be carried out to minimize the likelihood of larly those involving mandibular block, where vasoconstric- intravascular injection. Use of these agents enables defini- tion is less important. These drugs may also be used when tive treatment, which may in turn allow the avoidance of epinephrine must be avoided, as in patients with severe prolonged use of systemic analgesics and antibiotics.
ischemic heart disease or recent myocardial infarction.
Lidocaine and prilocaine have the best Food and Drug Bupivacaine can be selected when long duration of action Administration ranking (Table 9). Lidocaine may be
is desired, particularly in the mandible. Lidocaine with preferable because it has a low-concentration formulation, epinephrine may be preferred for treatment of children and which makes it easier to minimize the total dose. For topi- pregnant patients. Any one of articaine, lidocaine, mepiva- cal preparations, lidocaine also has the safest rating.
caine or prilocaine may be considered for routine dental Journal of the Canadian Dental Association An Update on Local Anesthetics in Dentistry procedures. Use of epinephrine can be justified for most (prilocaine HCl) in maxillary infiltration and mandibular nerve block.
dental procedures, but it may be necessary to minimize the J Can Dent Assoc 1987; 53(1):38-42.
8. Haas DA, Harper DG, Saso MA, Young E. Comparison of articaine dose for patients receiving specific medications and those and prilocaine anesthesia by infiltration in maxillary and mandibular arches. Anesth Prog 1990; 37(5):230-7.
9. Haas DA, Harper DG, Saso MA, Young ER. Lack of differential effectby Ultracaine (articaine) and Citanest (prilocaine) in infiltration anesthe- Dr. Haas is a professor and associate dean at the University of
sia. J Can Dent Assoc 1991; 57(3):217-23.
Toronto’s faculty of dentistry, where he holds the Chapman Chair inClinical Sciences, and is head of the discipline of dental anesthesia. He 10. Malamed SF, Gagnon S, Leblanc D. Efficacy of articaine: a new amide is also a professor with the department of pharmacology at the faculty local anesthetic. J Am Dent Assoc 2000; 131(5):635-42.
of medicine and active staff with the department of dentistry, 11. Gall H, Kaufmann R, Kalveram CM. Adverse reactions to local anes- Sunnybrook and Women’s College Health Sciences Centre, Toronto, thetics: analysis of 197 cases. J Allergy Clin Immunol 1996; 97(4):933-7.
12. Rood JP. Adverse reaction to dental local anaesthetic injection — Correspondence to: Dr. Daniel A. Haas, Faculty of Dentistry,
‘allergy’ is not the cause. Br Dent J 2000; 189(7):380-4.
University of Toronto, 124 Edward St., Toronto, ON M5G 1G6. 13. United States Pharmacopeial Drug Information Index. 22nd ed.
Greenwood Village (Colorado): Micromedex; 2002.
The author has no declared financial interests in any company manu- 14. Moore PA. Adverse drug reactions associated with local anesthesia. In: facturing the types of products mentioned in this article. Bennett JD, Rosenberg MB, editors. Medical emergencies in dentistry.
Philadelphia: Saunders; 2002. p. 447-59.
15. Wilburn-Goo D, Lloyd LM. When patients become cyanotic: References
acquired methemoglobinemia. J Am Dent Assoc 1999; 130(6):826-81.
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paresthesia following local anesthetic administration. J Can Dent Assoc 2. Malamed SF. Handbook of local anesthesia. 4th ed. St. Louis: Mosby; 17. Malignant Hyperthermia Association of the United States. Malignant 3. Yagiela JA. Local anesthetics. In: Yagiela JA, Neidle EA, Dowd FJ, hyperthermia: a concern in dentistry and oral & maxillofacial surgery.
editors. Pharmacology and therapeutics for dentistry. 4th ed. St. Louis: Available from: URL: http://www.mhaus.org/dentoral.html.
18. Moore PA. Adverse drug interactions in dental practice: interactions 4. Yagiela JA. Local anesthetics. In: Dionne RA, Phero JC, Becker DE, associated with local anesthetics, sedatives and anxiolytics. Part IV of a editors. Pain and anxiety control in dentistry. Philadelphia: W.B.
series. J Am Dent Assoc 1999; 130(4):541-54.
19. Yagiela JA. Adverse drug interactions in dental practice: interactions 5. Haas DA, Carmichael FJ. Local anesthetics. 6th ed. In: Roschlau associated with vasoconstrictors. J Am Dent Assoc 1999; 130(5):701-9.
WHE, Kalant H, editors. Principles of medical pharmacology. New York: 20. Meechan JG. Intra-oral topical anaesthetics: a review. J Dent 2000; 6. Haas DA. Drugs in dentistry. In: Compendium of pharmaceuticals 21. Haas DA, Pynn BR, Sands TD. Drug use for the pregnant or lactat- and specialties (CPS). 37th ed. Canadian Pharmaceutical Association; ing patient. Gen Dent 2000; 48(1):54-60.
22. Hersh EV, Hermann DG, Lamp CJ, Johnson PD, MacAfee KA.
7. Donaldson D, James-Perdok L, Craig BJ, Derkson GD, Richardson Assessing the duration of mandibular soft tissue anesthesia. J Am Dent AS. A comparison of Ultracaine DS (articaine HCl) and Citanest forte Journal of the Canadian Dental Association
NORMAS DE ORGANIZAÇÃO DO CALENDÁRIO DO ANO ACADÉMICO 2013 INTRODUÇÃO O calendário do ano académico é um dos instrumentos reguladores e estruturantes de todas actividades das Instituições de Ensino Superior (IES). O mesmo estabelece os períodos das acções de preparação do Ano Académico, a data de sua abertura, bem como define os períodos lectivos, as pausas e os p