Articaine - Cloudfront.net
Transcription
Articaine - Cloudfront.net
ARTICAINE June 2014 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 1 Today’s Menu Part 2: Articaine HCl: Just the Facts © 2014 Dr. Stanley F. Malamed! All Rights Reserved 2 Articaine HCl © 2014 Dr. Stanley F. Malamed! All Rights Reserved 3 Articaine HCl Availability Mg /cartridge MRTD 4%! epi 1:100k epi 1:200k 72 3.2 mg/lb! 7.0 mg/kg! Absolute max = n/a (USA) © 2014 Dr. Stanley F. Malamed! All Rights Reserved 4 Articaine HCl Onset 2 - 3 min (textbook) Duration! 60 min (pulpal) Duration! 3 - 5 hrs (soft tissue) © 2014 Dr. Stanley F. Malamed! All Rights Reserved 5 Articaine HCl 1976 Germany! 1985 Canada! 2000 USA! 2005 Australia © 2014 Dr. Stanley F. Malamed! All Rights Reserved 6 Articaine HCl Germany (2012) . . . 97% of ALL LAs used in dentistry*! USA (2009) . . . 41% of ALL LAs used in dentistry Australia (2012) . . . 70% of dentists use articaine** * Daublander. Personnal communication February 2012 ** Yapp, Hopcraft, Parashos. Australian Dent J 2012 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 7 Why do doctors LIKE articaine? Anecdotal comments from dentists:! “It works faster”! “It works better”! “I don’t miss as often”! “Hard to get ‘numb’ patients are easier to numb with articaine” © 2014 Dr. Stanley F. Malamed! All Rights Reserved 8 The SCIENCE of Articaine HCl Since 1973 there have been more than 200 papers published in the dental / medical literature on articaine HCl © 2014 Dr. Stanley F. Malamed! All Rights Reserved 9 The SCIENCE of Articaine HCl Articaine has been compared to lidocaine, mepivacaine and prilocaine! Virtually ALL studies have demonstrated that articaine is AS SAFE and AS EFFECTIVE as the drug it which it was compared. © 2014 Dr. Stanley F. Malamed! All Rights Reserved 10 The SCIENCE of Articaine HCl 1999 - Three identical randomized, double-blind, parallel group, active controlled, multicenter Phase 3 clinical trials! Safety & efficacy of articaine HCl for USA Food & Drug Administration (FDA) approval ! Patients aged 4 - 79 years! JADA 2000 . . . Efficacy of articaine HCl! JADA 2001 . . . Safety of articaine HCl! Pediatric Dentistry 2001 . . . Safety & efficacy in pediatric dentistry © 2014 Dr. Stanley F. Malamed! All Rights Reserved 11 The SCIENCE of Articaine HCl 1999 - Three identical randomized, double-blind, parallel group, active controlled, multicenter Phase 3 clinical trials Safety & efficacy of articaine HCl for USA Food & Drug Administration (FDA) approval Because of the Haas 1995 paper we were asked to actively pursue possible post-operative complications (e.g. paresthesia). All patients were contacted 24-hours and 7-days following their treatment and presented with a list of potential signs & symptoms © 2014 Dr. Stanley F. Malamed! All Rights Reserved 12 29 sites ! in the ! USA & UK Malamed SF, Gagnon S, Leblanc D 13 © 2014 Dr. Stanley F. Malamed! All Rights Reserved Efficacy of articaine: a new amide local anesthetic CONCLUSIONS! ! Four percent articaine with epinephrine 1:100,000 is a safe and effective local anesthetic for use in clinical dentistry. In this investigation consisting of three randomized, double-blind trials, we found articaine to be well tolerated in 882 subjects, and that it provided clinically effective pain relief during most dental procedures. Furthermore, we observed no significant difference in pain relief between subjects in the 4 percent articaine with epinephrine 1:100,000 group and those in the 2 percent lidocaine with epinephrine 1:100,000 group.! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 14 Efficacy of articaine: a new amide local anesthetic CONCLUSIONS! ! For 4 percent articaine with epinephrine 1:100,000, time to onset of anesthesia and duration of anesthesia are appropriate for clinical use and are comparable to those observed for other commercially available local anesthetics.! Articaine can be used effectively in both adults and children.! ! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 15 Malamed SF, Gagnon S, Leblanc D 16 © 2014 Dr. Stanley F. Malamed! All Rights Reserved Safety of articaine: a new amide local anesthetic CONCLUSIONS:! ! The incidence of complications (including paresthesia) was equal for both of the tested local anesthetics, lidocaine & articaine.! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 17 FDA-approved to age 4 years Malamed SF, Gagnon S, Leblanc D 18 © 2014 Dr. Stanley F. Malamed! All Rights Reserved The SCIENCE of Articaine HCl Virtually ALL studies have demonstrated that articaine is AS SAFE and AS EFFECTIVE as the drug it which it was compared.! WHY?! Because local anesthetics are VERY EFFECTIVE drugs © 2014 Dr. Stanley F. Malamed! All Rights Reserved 19 Before Articaine HCl! Pre-2005 (Australia)! Pre-2000 (USA) Lidocaine + epinephrine! Mepivacaine + epinephrine! Prilocaine + epinephrine! USA Prilocaine + felypressin Australia © 2014 Dr. Stanley F. Malamed! All Rights Reserved 20 Before Lidocaine HCl! Pre-1948 Procaine + epinephrine! Tetracaine + epinephrine! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 21 Procaine HCl ♥ Procaine HCl ♥ ♥ Remains the most well-known local anesthetic in the world by its proprietary name: NOVOCAIN. Procaine was the 1st local anesthetic to be marketed in glass dental cartridges (1922) © 2014 Dr. Stanley F. Malamed! All Rights Reserved 22 Procaine HCl Procaine 6-10 min Onset - 2-3 hrs Duration - 20-30 min Duration - Allergy YES, rare Overdose Rare from “too much” © 2014 Dr. Stanley F. Malamed! All Rights Reserved 23 Procaine HCl Lidocaine HCl Procaine Lidocaine 6-10 min 3-5 min 2-3 hrs 3-5 hrs 20-30 min 60 min Allergy YES, rare Exceedingly rare Overdose Rare from “too much” More likely from ‘too much’ Onset Duration Duration - © 2014 Dr. Stanley F. Malamed! All Rights Reserved 24 So, What, if any, are the clinical advantages of articaine HCl compared with the other amide LAs? © 2014 Dr. Stanley F. Malamed! All Rights Reserved 25 Articaine HCl Advantages 1. More lipid-soluble! Diffuses through soft & hard tissues better! Palatal anesthesia with buccal infiltration! Mandibular anesthesia in adults via infiltration! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 26 Maxillary Infiltration Articaine Articaine More lipid-soluble Flared palatal roots Palatal soft tissue © 2014 Dr. Stanley F. Malamed! All Rights Reserved 27 Articaine HCl by Mandibular Infiltration in Adults Mandibular infiltration John Meechan (UK)! Al Reader (USA) More lipid-soluble © 2014 Dr. Stanley F. Malamed! All Rights Reserved 28 Articaine HCl Advantages ! 2. Elimination half-life of 27 minutes (162 min = 2:42) Lidocaine, mepivacaine, prilocaine ~ 90 minutes (540 min = 9 hrs) © 2014 Dr. Stanley F. Malamed! All Rights Reserved 29 Articaine HCl Advantages 3. Pregnancy All other amide local anesthetics Elimination half-life Beta half-life ~90 minutes + of 27 minutes ARTICAINE Beta half-life 27 minutes © 2014 Dr. Stanley F. Malamed! All Rights Reserved 30 Articaine HCl Advantages 4. Nursing Elimination half-life All other local anesthetics of 27 minutes Pump & discard for 9 hours* USA FDA ARTICAINE USA FDA Pump & discard for 4 hours* © 2014 Dr. Stanley F. Malamed! All Rights Reserved 31 Articaine HCl Advantages ! 5. Pediatrics - preferred LA ! Elimination half-life !Decreased risk of overdose! of 27 minutes Elimination half-life of 27 minutes! ! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 32 Articaine HCl Advantages Articaine is the LEAST LIKELY anesthetic to induce an overdose caused by administration of too many cartridges © 2014 Dr. Stanley F. Malamed! All Rights Reserved 33 Articaine HCl Advantages 6. Endodontics (infected / inflammed teeth)! Greater lipid-solubility! Thiophene ring = articaine! Benzene ring = other LAs! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 34 Articaine HCl Advantages 7. ‘Hard to ‘numb’ patients (anecdotal) © 2014 Dr. Stanley F. Malamed! All Rights Reserved 35 Articaine HCl Advantages 1. More lipid-soluble! Diffuses through soft& hard tissues better! Palatal anesthesia with buccal infiltration! Mandibular anesthesia in adults via infiltration! 2. Elimination half-life of 27 minutes (162 min = 2:42) Lidocaine, mepivacaine, prilocaine ~ 90 minutes (540 min = 9 hrs)! 3. Pregnancy - preferred LA! 4. Nursing - ‘Pump & dump’ for 4 hours (FDA)! Lidocaine, mepivacaine, prilocaine P&D for 9 hours! ! 5. Pediatrics - Lesser risk of OD! 6. Endodontics (infected/inflammed teeth)! 7. ‘Hard to ‘numb’ patients (anecdotal) © 2014 Dr. Stanley F. Malamed! All Rights Reserved 36 Articaine 4% Epinephrine 1:100,000 or 200,000 • Should I use articaine 4% with 1:100,000 or 1:200,000 epineprine? 100,000 200,000 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 37 Articaine 4% Epinephrine 1:100,000 or 200,000 • 100,000 Less epinephrine is, of course, better for the patient, therefore MY RECOMMENDATION is the use of articaine 4% with 1:200,000 epinephrine for optimal depth and duration of pain control 200,000 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 38 So, Malamed, you think articaine’s a great drug, but . . . © 2014 Dr. Stanley F. Malamed! All Rights Reserved 39 Are there any concerns, out there in the community, regarding articaine HCl? YES Prolonged anesthesia! (paresthesia) 40 © 2014 Dr. Stanley F. Malamed! All Rights Reserved A basic truism regarding ANATOMY: Everybody is different ! We teach ‘normal’ anatomy: Insert the needle here Advance 25 mms Aspirate Deposit the drug We HOPE the nerve is in the area © 2014 Dr. Stanley F. Malamed! All Rights Reserved 41 A basic truism regarding INJECTIONS: Once a needle penetrates the skin or mucous membrane, every injection is BLIND © 2014 Dr. Stanley F. Malamed! All Rights Reserved 42 A basic truism regarding LOCAL ANESTHETICS: LAs are chemicals that interrupt nerve conduction (producing anesthesia) transiently (hopefully) © 2014 Dr. Stanley F. Malamed! All Rights Reserved 43 Another truism regarding LOCAL ANESTHETICS ! ALL LAs are neurotoxic (they can damage nerves) © 2014 Dr. Stanley F. Malamed! All Rights Reserved 44 A basic truism regarding PARESTHESIA: ! Paresthesia has existed ever since injections were first administered © 2014 Dr. Stanley F. Malamed! All Rights Reserved 45 Articaine ! and ! Paresthesia © 2014 Dr. Stanley F. Malamed! All Rights Reserved 46 Canada Articaine introduced in Canada in 1983 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 47 Haas, D A. Lennon, D.! ! A 21 year retrospective study of reports of paresthesia following local anesthetic administration.! ! J. Canadian Dental Association 61(4):319-20, 323-6, 329-30, 1995 Apr © 2014 Dr. Stanley F. Malamed! All Rights Reserved 48 Haas, D A. Lennon, D.! A 21 year retrospective study of reports of paresthesia following local anesthetic administration.! J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995 Overall incidence of paresthesia (all LAs) = 1:785,000! 2% and 3% LAs = 1:1,250,000! 4% prilocaine = 1:588,235! 4% articaine = 1:440,529 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 49 Haas, D A. Lennon, D.! A 21 year retrospective study of reports of paresthesia following local anesthetic administration.! J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995 70.6% involve! LINGUAL nerve © 2014 Dr. Stanley F. Malamed! All Rights Reserved 50 Haas, D A. Lennon, D.! A 21 year retrospective study of reports of paresthesia following local anesthetic administration.! J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995 Apr This was NOT a scientific study:! 1. Duration of paresthesia was NOT documented! 2. In > 30% of incidents the LA used was not identified! 3. The reports of paresthesia did not include cases where the LA might have been used for surgical procedures! **** Surgery is THE most common cause of paresthesia © 2014 Dr. Stanley F. Malamed! All Rights Reserved 51 Haas, D A. Lennon, D.! A 21 year retrospective study of reports of paresthesia following local anesthetic administration.! J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995 Apr 4. The gauge and length of the needle used was documented in only 26% of the reviewed cases (n = 143) ! 5. The injection technique used during each incident was not identified! 6. It was a review of voluntary reports reviewed by the Provincial Insurance Commission.! 7. Conclusions are quite subjective.! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 52 Haas, D A. Lennon, D.! A 21 year retrospective study of reports of paresthesia following local anesthetic administration.! J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995 Apr Yet this paper has taken on a life of its own . . . has become THE most cited paper purporting to demonstrate that 4% LAs are associated with a higher risk of paresthesia! Virtually all papers reporting increased risk of paresthesia from articaine ultimately use this paper as their initial source.! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 53 The DANISH experience Articaine introduced in Denmark in 2001 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 54 The DANISH experience Articaine introduced in Denmark in 2001! Prof. S. Hillerup 2006 IJOMS © 2014 Dr. Stanley F. Malamed! All Rights Reserved 55 77%! Lingual N. 77% (42/54) cases involved LINGUAL nerve 56 © 2014 Dr. Stanley F. Malamed! All Rights Reserved © 2014 Dr. Stanley F. Malamed! All Rights Reserved 57 The DANISH experience 2004 . . . Danish Dental Association recommended that articaine not be used by inferior alveolar nerve block! Sales of articaine declined significantly © 2014 Dr. Dr. Stanley F. Malamed! © 2013 Stanley F. Malamed! All All Rights Reserved Rights Reserved 58 Pharmacovigilance Working Party of the European Union EU equivalent to Canada’s TGA! Australia’s TGA and the USA’s FDA © 2014 Dr. Stanley F. Malamed! All Rights Reserved 59 Forside > Bivirkninger > Meddelelser om bivirkninger > er om bivirkninger ning af bivirkninger hos er ning af bivirkninger hos dyr ning af bivirkninger ved orsøg indberetning gsrådet dsopdatering lance Konklusioner på vurdering af bivirkninger ved lokalbedøvelsesmidler brugt til tandbehandling Produktresumé for Septanest® EU´s Bivirkningskomité har på et møde d. 17. oktober 2006 igen vurderet forekomst af bivirkninger, især mistanke om nerveskader (paræstesier, føleforstyrrelser), ved brug af lokalbedøvelsesmidler anvendt i forbindelse med tandbehandling. Produktresumé for Septocaine® Vurderingen er en opfølgning på en undersøgelse, der indledtes i 2005. Undersøgelsen blev sat i værk, fordi der i Danmark var rejst mistanke om, at ét af lokalbedøvelsesmidlerne, articain, indebar øget risiko for nerveskader, set i forhold til risikoen ved anvendelse af andre lokalbedøvelsesmidler (mepivacain, prilocain, lidocain). Produktresumé for Ubistesin Forte® Undersøgelsen er foretaget i tæt samarbejde med indehaveren af markedsføringstilladelsen for lægemidlerne Septanest® og Septocain®. I undersøgelsen indgår de samlede internationale erfaringer indhentet fra 57 lande. Det anslås at ca. 100 millioner patienter årligt behandles med articain. Septanest® og Septocain® og risiko for føleforstyrrelser Undersøgelsen omfatter en gennemgang af eksperimentelle studier samt af kliniske forsøg med raske frivillige samt patienter. Gennemgangen omfatter de almindeligst anvendte lokalbedøvelsesmidler og altså ikke kun articain. Endvidere er samtlige bivirkningsrapporter indsamlet på verdensplan gennemgået. Produktresumé for Ubistesin® Undersøgelse af bivirkninger ved bedøvelsesmidler ved tandbehandling 20 October 2006 Med hensyn til articain er konklusionen, at der ikke er sket afgørende ændringer i dette lægemiddels sikkerhedsprofil siden tidspunktet for påbegyndelse af markedsføringen (1988). Der er således intet grundlag for at afvige fra at bruge articain efter de gældende retningslinier, som fremgår af produkt- resumeet. Konklusionen er endvidere at alle lokalbedøvelsesmidler kan forårsage nerveskade (er neurotoksiske). o Forekomsten af føleforstyrrelser forekommer tilsyneladende med lidt større hyppighed efter anvendelse af articain og prilocain. Set i forhold til antallet af behandlede patienter er føleforstyrrelserne imidlertid sjældent forekommende. Eksempelvis anslås forekomsten af føleforstyrrelser ved anvendelse af articain at være et tilfælde pr. 4.5 millioner behandlede patienter. nerveskader kan have flere årsager o mekanisk forårsaget skade ved nåleindstikket o direkte toksisk påvirkning af lægemidlet o utilstrækkelig ilttilførsel til nerven der er ikke umiddelbart behov for yderligere eksperimentelle undersøgelser eller kliniske forsøg der bør gøres en indsats for yderligere at mindske forekomsten af nerveskader o Indehaveren af markedsføringstilladelsen har fremsat forslag til, hvorledes risikoen for nerveskader kan nedsættes yderligere; forslaget indebærer bl.a. undervisningstilbud for tandlæger, forbedret information i produktresumeet samt øget rapportering i en periode til myndighederne. I Danmark er følgende lokalbedøvelsesmidler med indhold af articain markedsført: Septanest®, Septocaine®, Ubistesin® og Ubistesin Forte® (se link til produktresumeer for de fire lægemidler i faktaboksen øverst til højre på siden). Yderligere oplysninger kan fås ved henvendelse til overlæge Doris I. Stenver, Forbrugersikkerhed, tlf. 44 88 92 47, mobil 22 46 09 79. Lægemiddelstyrelsen, d. 23. oktober 2006 © 2014 Dr. Stanley F. Malamed! All Rights Reserved et d. 27.11.2006 60 Pharmacovigilance Committee of the European Union Regarding articaine, the conclusion is that safety profile of the drug has not significantly evolved since its initial launch (1998). Thus, no medical evidence exists to prohibit the use of articaine according to the current guidelines listed the summary of product characteristics. 20 October 2006 61 © 2014 Dr. Stanley F. Malamed! All Rights Reserved Pharmacovigilance Committee of the European Union All local anaesthetics may cause nerve injury (they are neurotoxic in nature).! The occurrence of sensory impairment is apparently slightly more frequent following the use of articaine and prilocaine. However, considering the number of patients treated, sensory impairments rarely occur. For example, the incidence of sensory impairment following the use of articaine is estimated to be 1 case in 4.8 million treated patients.! ! Nerve injuries may result from several incidents:! Mechanical injury due to needle insertion! Direct toxicity from the drug! Neural ischaemia! ! There is no need for new experimental studies or clinical trials 20 October 2006 62 © 2014 Dr. Stanley F. Malamed! All Rights Reserved The DANISH experience Danish Medicines Agency (Laegemiddel Styrelsen) 25 October 2011! ! The Danish Medicines Agency's database of side effects contain 160 reports on adverse reactions from articaine that occurred from 2001-2005. The adverse reactions are mainly sensory impairment and nerve damage. © 2014 Dr. Stanley F. Malamed! All Rights Reserved 63 Danish Medicines Agency (Laegemiddel Styrelsen) 25 October 2011! ! Since 2005, we have seen a drop in the number of reports of new adverse reactions.! Up until 1 October 2011, we have received 2 reports on suspected adverse reactions from articaine which occurred in 2011. In both cases, the patients have experienced sensory impairment after treatment with articaine. © 2014 Dr. Stanley F. Malamed! All Rights Reserved 64 The DANISH experience t c e f f E Danish Medicines Agency (Laegemiddel Styrelsen) 25 October 2011! r e b e W e h T 2001 - 2005 . . . 160 reported cases! 2005 - 2011 . . . 2 reported cases © 2014 Dr. Stanley F. Malamed! All Rights Reserved 65 The AMERICAN experience Articaine introduced in USA in 2000 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 66 2010 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 67 FDA Adverse Event Reporting System (AERS)! Average number of adverse reports received by the FDA is currently over 400,000/year… ! “For the 159 of the 248 cases (of dental paresthesia) for which no procedure was listed, we assumed that they involved nonsurgical dentistry.” © 2014 Dr. Stanley F. Malamed! All Rights Reserved 68 Mepivacaine 1:623,112,900 Lidocaine 1:181,076,673 Bupivacaine 1:124,286,050 OVERALL 1:13,800,970 Articaine 1:4,159,848 Prilocaine 1:2,070,678 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 69 USA Ontario - 1993 Mepivacaine 1:623,112,900 1:1,125,000 Lidocaine 1:181,076,673 1:1,125,000 Bupivacaine 1:124,286,050 OVERALL 1: 13,800,970 Articaine 1: 4,159,848 Prilocaine 1: 2,070,678 70 1: 785,000 (2.27:1,000,000)! 1: 440,529 (1.7:1,000,000)! 1: 588,235 © 2014 Dr. Stanley F. Malamed! All Rights Reserved Annual risk of being struck by lightning (USA) = 1:750,000 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 71 Anaphylaxis to penicillin = 1:50,000 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 72 Risk of paresthesia following mandibular implant = 37%! Long term neuropathy = 13% © 2014 Dr. Stanley F. Malamed! All Rights Reserved 73 92.7%! involve! LINGUAL! nerve © 2014 Dr. Stanley F. Malamed! All Rights Reserved 74 FDA - AERS website © 2014 Dr. Stanley F. Malamed! All Rights Reserved 75 U.S. FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH OFFICE OF POST-MARKETING DRUG RISK ASSESSMENT revised 9 January 2009 AERS data do have limitations. ! First there is no certainty that the reported event was actually due to the product . . .! FDA does not require that a causal relationship between the product and event be proven . . .! Furthermore, FDA does not receive all adverse event reports that occur with a product.! Estimated ~10% of all ADRs are reported © 2014 Dr. Stanley F. Malamed! All Rights Reserved 76 U.S. FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH OFFICE OF POST-MARKETING DRUG RISK ASSESSMENT revised 9 January 2009 Many factors can influence whether or not an event will be reported, such as the time a product has been marketed (Weber Effect) and publicity about an event. © 2014 Dr. Stanley F. Malamed! All Rights Reserved 77 U.S. FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH OFFICE OF POST-MARKETING DRUG RISK ASSESSMENT revised 9 January 2009 Therefore, AERS cannot be used to calculate the incidence of an adverse event in the US population © 2014 Dr. Stanley F. Malamed! All Rights Reserved 78 the WEBER effect Dr JCP Weber! Epidemiology of adverse reactions to nonsteroidal antiinflammatory drugs. ! Rainsford KD, Velo GP, eds. Advances in inflammation research. Vol. 6. New York: Raven Press, 1984: 1-7. © 2014 Dr. Stanley F. Malamed! All Rights Reserved 79 the WEBER effect The Weber Effect is an epidemiologic phenomenon which states that the number of reported adverse reactions for a drug rises until about the middle to end of the 2nd year of marketing, peaks, and then steadily declines despite steadily increasing prescribing rates. © 2014 Dr. Stanley F. Malamed! All Rights Reserved 80 the WEBER effect Pharmacotherapy 24(6):743-749, 2004 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 81 Weber! Effect © 2014 Dr. Stanley F. Malamed! © 2014 Dr. Stanley F. Malamed! All Rights Reserved All Rights Reserved 82 Hillerup paper Publicity! ! EU report Negative! ! Positive © 2014 Dr. Stanley F. Malamed! © 2014 Dr. Stanley F. Malamed! All Rights Reserved All Rights Reserved 83 The Australian experience Articaine introduced in Australia in 2005 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 84 ARTICAINE HCL e n i a ic t r a e s u 0% >7 ARTICAINE HCL 85 ARTICAINE HCL ARTICAINE HCL © 2014 Dr. Stanley F. Malamed! All Rights Reserved Australian Dental Journal! 56:348-351, 2011 5 case reports © 2014 Dr. Stanley F. Malamed! All Rights Reserved 86 Kingon A, Sambrook P, Goss A. Australian Dent J 56:348-351, 2011 Electric shock sensation Lingual nerve involvement 4% LA Restorative dentistry © 2014 Dr. Stanley F. Malamed! All Rights Reserved 87 Kingon A, Sambrook P, Goss A. Australian Dent J 56:348-351, 2011 Lingual nerve involvement 4% LA Restorative dentistry © 2014 Dr. Stanley F. Malamed! All Rights Reserved 88 Kingon A, Sambrook P, Goss A. Australian Dent J 56:348-351, 2011 Mental nerve involvement 4% LA Restorative dentistry © 2014 Dr. Stanley F. Malamed! All Rights Reserved 89 Kingon A, Sambrook P, Goss A. Australian Dent J 56:348-351, 2011 Electric shock sensation Lingual nerve involvement 4% LA Restorative dentistry © 2014 Dr. Stanley F. Malamed! All Rights Reserved 90 Kingon A, Sambrook P, Goss A. Australian Dent J 56:348-351, 2011 Lingual nerve involvement 3% LA Restorative dentistry © 2014 Dr. Stanley F. Malamed! All Rights Reserved 91 4 of 5 cases involve LINGUAL NERVE! 2 cases experienced ‘electric shock’ © 2014 Dr. Stanley F. Malamed! All Rights Reserved 92 Professor Dr. Stanley F. Malamed In my opinion . . .! If paresthesia involves the distribution of the inferior alveolar and/or mental nerves . . .! Possible etiologies:! Direct needle trauma! LA neurotoxicity! Edema! Hemorrhage! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 93 Professor Dr. Stanley F. Malamed However, IF it’s the lingual nerve . . .! ! It’s MECHANICAL! ! Not chemical © 2014 Dr. Stanley F. Malamed! All Rights Reserved 94 Paresthesia in dentistry > 95% of reported cases occur in the MANDIBLE! ! Of these the overwhelming percentage involve only the lingual nerve © 2014 Dr. Stanley F. Malamed! All Rights Reserved 95 Paresthesia in dentistry Is rarely observed in the maxilla! < 5%! Yet 1/2 of all dental care is in the upper arch! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 96 Paresthesia in dentistry Is rarely (no reported cases) observed following:! Gow-Gates mandibular nerve block! Vazirani-Akinosi mandibular nerve block! ! No lingual nerve in area Only occasionally following mental/incisive nerve block! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 97 Paresthesia and 4% Anesthetics Articaine is used in medicine:! Ophthalmology! Orthopedic surgery! Arthroscopic, hand, foot! Plastic and reconstructive surgery © 2014 Dr. Stanley F. Malamed! All Rights Reserved 98 Paresthesia and 4% Anesthetics Articaine is used in medicine:! NO reports of paresthesia from articaine following use in medicine © 2014 Dr. Stanley F. Malamed! All Rights Reserved 99 Paresthesia and 4% Anesthetics Question:! Is it possible that articaine is so specifically neurotoxic that it only affects nerves within the mouth and more specifically the lingual nerve? © 2014 Dr. Stanley F. Malamed! All Rights Reserved 100 M. Anthony Pogrel, DDS, MD 101 © 2014 Dr. Stanley F. Malamed! All Rights Reserved Pogrel MA, Thamby S. Permanent nerve involvement resulting from inferior alveolar nerve blocks JADA 2000;131:901-907 Prior to articaine’s introduction in the USA Estimates PERMANENT nerve damage at 1:26,762 ! Inferior Alveolar Nerve Block’s © 2014 Dr. Stanley F. Malamed! All Rights Reserved 102 Pogrel MA, Thamby S. Permanent nerve involvement resulting from inferior alveolar nerve blocks JADA 2000;131:901-907 Prior to articaine’s introduction in the USA “It is reasonable to suggest that during a career, each dentist may encounter at least one patient with an inferior alveolar nerve block resulting in permanent nerve involvement”! “The mechanisms are unknown and there is no known prevention or treatment” © 2014 Dr. Stanley F. Malamed! All Rights Reserved 103 Pogrel MA CDAJ 35(4):271-273, 2007 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 104 Pogrel MA! J. Calif Dent Assoc 35(4):271-273, 2007 Study covered 1 January 2003 through 31 December 2005 U. California San Francisco School of Dentistry n = 57! All NON-surgical ‘We were aware of the discussion in dental circles as to the use of articaine for inferior alveolar nerve blocks, and are aware of recommendations suggesting that it not be used for IANBs.! ! This was the predominant reason for submitting this paper at this time.” © 2014 Dr. Stanley F. Malamed! All Rights Reserved 105 Pogrel MA! J. Calif Dent Assoc 35(4):271-273, 2007 Study covered 1 January 2003 through 31 December 2005 U. California San Francisco School of Dentistry n = 57! All NON-surgical ALL patients evaluated! Dental records reviewed! Treating dentists consulted! Needle, type of injection(s), drug used and treatment known for ALL 57 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 106 If all LAs were equally neurotoxic the % of cases of paresthesia would be equal to the drugs % market share 50% of market share = 50% of cases of paresthesia 25% of market share = 25% of cases of paresthesia Ratio should be 1.0 % Cases of paresthesia % Market share © 2014 Dr. Stanley F. Malamed! All Rights Reserved 107 Pogrel MA J Calif Dent Assoc 35(4):271-273, 2007 Anesthetic # of cases (%) Approximate share of LA market in USA Lidocaine HCl 20 (35%) 54% 0.64 Prilocaine HCl 17 (29.8%) 6% 4.96 Articaine HCl 17 (29.8%) 25% 1.19 Articaine HCl + Lidocaine HCl Lidocaine HCl + Prilocaine HCl Ratio (1.0 = expected) 1 (1.75%) 1 (1.75%) Bupivacaine HCl 1 (1.75%) Mepivacaine HCl 0 (0%) 108 15% © 2014 Dr. Stanley F. Malamed! All Rights Reserved Pogrel MA J Calif Dent Assoc 35(4):271-273, 2007 “Therefore, using our previous assumption that approximately half of all local anesthetic used is for inferior alveolar nerve blocks, then on the figures we have generated from our clinic we do not see disproportionate nerve involvement from articaine” © 2014 Dr. Stanley F. Malamed! All Rights Reserved 109 Pogrel MA J. Calif Dent Assoc 40:795-797, 2012 (October) © 2014 Dr. Stanley F. Malamed! All Rights Reserved 110 Pogrel MA J. Calif Dent Assoc 40:795-797, 2012 (October) N = 38! January 2006 - December 2011 Articaine is still causing permanent inferior alveolar and lingual nerve damage (36%), which is proportionate to its market share (37%) Carbocaine: 11% of cases with a market share of 5% Prilocaine: However, by causing 26% of all cases seen since 2005 with a local market share of only 8% is somewhat disproportionate to its market share Lidocaine: The number of cases caused by lidocaine, on the other hand, appears to be only around 50% of its market share © 2014 Dr. Stanley F. Malamed! All Rights Reserved 111 Pogrel MA J. Calif Dent Assoc 40:795-797, 2012 (October) N = 38! January 2006 - December 2011 Ratio! (1.0 = expected) Lidocaine 0.5 Articaine 0.97 Mepivacaine 2.2 Prilocaine 3.25 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 112 2007 2011 Lidocaine 0.64 0.5 Articaine 1.19 0.97 Mepivacaine Prilocaine 2.2 4.96 3.25 M. Anthony Pogrel, DDS, MD © 2014 Dr. Stanley F. Malamed! All Rights Reserved 113 The German experience Articaine introduced in Germany in 1976 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 114 The German experience Synthesized articaine (carticaine) in 1973 - as a DENTAL LA ! Introduced into dentistry in 1976! 2010 . . . 97% of LA used in German dentistry is articaine! Deutscher Dentalmarkt Jahresbericht (DDM) 2010 (German Dental Market Annual Report 2010) GfK HealthCare, Nuremberg, Germany © 2014 Dr. Stanley F. Malamed! All Rights Reserved 115 The German experience Dr. Wolfgang Jakob! Dr. Monika Daublander! ! E-mail (1 February 2012):! “. . . the problem of neurosensory disturbances was never a big issue in the German speaking Countries.” © 2014 Dr. Stanley F. Malamed! All Rights Reserved 116 Dr. Wolfgang Jakob:! E-mail (1 February 2012):! Beside the ongoing about articaine in Dänemark the problem of neurosensory disturbances was never a big issue in the German speaking countries.! Hillerup reports 80 percent of all neurosensory after IANB with articaine in Europe. (Denmark = 5,6 million people; while the EU has a population of 501 million) © 2014 Dr. Stanley F. Malamed! All Rights Reserved 117 Dr. Wolfgang Jakob:! E-mail (1 February 2012):! ! ! ! ! ! ! ! Denmark . . . Population 5.6 million! EU . . . . . . Population 501 million! ! ! Denmark . . . 80% of all reports of neurosensory disturbance (Hillerup)! © 2014 Dr. Stanley F. Malamed! All Rights Reserved 118 Journal of Dentistry! April 2010! Volume 38, No. 4! 307-317 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 119 Journal of Dentistry! April 2010! Volume 38, No. 4! 307-317 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 120 Conclusion: The results suggest that articaine is not toxic to the nervous structure and further studies are necessary to explain the possible relation between articaine injection and paresthesia. © 2014 Dr. Stanley F. Malamed! All Rights Reserved 121 So, why is it that the lingual nerve is primarily involved in cases of paresthesia? © 2014 Dr. Stanley F. Malamed! All Rights Reserved 122 Dr. Anthony Pogrel E-mail 2 February 2012 Malamed to Pogrel:! Can you provide me with a summary of just why it appears that the lingual nerve is involved in this problem so much more so than others?! How much LA does a dentist deposit to anesthetize the lingual nerve when doing the IANB? ! Very little, if any. So why do 'they' cast blame on the drug? 123 © 2014 Dr. Stanley F. Malamed! All Rights Reserved Why LINGUAL nerve? Dr. Pogrel’s reply:! “I do think there is also a genuine difference in the incidence, and as you say,! It is not due to the local anesthetic itself since the vast majority (volume) is deposited close to the inferior alveolar nerve and not the lingual nerve. ! If it was a neurotoxic phenomenon, you would expect the inferior alveolar nerve to be affected much more.” © 2014 Dr. Stanley F. Malamed! All Rights Reserved 124 Why LINGUAL nerve? ! The fact that the lingual nerve is stretched when the mandible is open to an the inferior alveolar block probably does give it less opportunity to get out of the way and makes it much more likely that this phenomenon is traumatic. © 2014 Dr. Stanley F. Malamed! All Rights Reserved 125 “The Lingual Nerve is In the Way” © 2014 Dr. Stanley F. Malamed! All Rights Reserved 126 Perth Perth Sydney Adelaide Adelaide Sydney © 2014 Dr. Stanley F. Malamed! All Rights Reserved 127 Fascicle Fascicle Fascicle Fascicle Fascicle Fascicle © 2014 Dr. Stanley F. Malamed! All Rights Reserved 128 Pogrel, MA, Schmidt, BL, Sambajon, V, and Jordan, RCK ! Lingual Nerve Damage from Inferior Alveolar Nerve Blocks - A Possible Explanation, ! J Amer Dent Assoc 134, 195-199, 2003 The Inferior Alveolar Nerve usually had 5-7 fascicles whereas the Lingual Nerve in that area usually had around three but in the third of the cases was actually unifascicular in the area where the inferior alveolar nerve block was given. © 2014 Dr. Stanley F. Malamed! All Rights Reserved 129 Fascicle Normal Damaged © 2014 Dr. Stanley F. Malamed! All Rights Reserved 130 Professor Dr. Stanley F. Malamed IMO . . . IF it’s the distribution of the lingual nerve (loss of taste, paresthesia) . . .! ! It’s MECHANICAL! ! Not chemical 131 © 2014 Dr. Stanley F. Malamed! All Rights Reserved Haas, D A. Lennon, D.! A 21 year retrospective study of reports of paresthesia following local anesthetic administration.! J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995 Apr 70.6% involve! LINGUAL nerve © 2014 Dr. Stanley F. Malamed! All Rights Reserved 132 Hillerup, 2006 77% (42/54) cases involved LINGUAL nerve 133 © 2014 Dr. Stanley F. Malamed! All Rights Reserved Kingon, 2011 4 of 5 cases involve LINGUAL NERVE! 2 cases experienced ‘electric shock’ 80% © 2014 Dr. Stanley F. Malamed! All Rights Reserved 134 Garisto, 2010 92.7%! involve! LINGUAL! nerve © 2014 Dr. Stanley F. Malamed! All Rights Reserved 135 Author Country Year %! Lingual Haas, Lennon Canada 1995 70.6 Hillerup Denmark 2006 77 Kingon, Australia 2011 Sambrook 80 Garristo, Haas USA 2010 92.7 © 2014 Dr. Stanley F. Malamed! All Rights Reserved 136 So, what should YOU do? © 2014 Dr. Stanley F. Malamed! All Rights Reserved 137 Articaine has been claimed to be more effective, but there are reports of an increased risk of neurotoxicity, presenting as prolonged numbness in the areas of distribution, often with pain. This may be due to the high concentration of the solution rather than to the anesthetic itself.* Consequently, it is recommended that articaine should not be used for regional blocks (eg inferior alveolar). *Kingon A, Sambrook P, Goss A 138 © 2014 Dr. Stanley F. Malamed! All Rights Reserved Benefit v. Risk ! The doctor MUST always consider the BENEFIT to be gained from use of a procedure or drug versus the RISK involved in the procedure or drug.! ! ONLY when the benefit to be gained CLEARLY OUTWEIGHS the risk should the procedure be done or the drug administered © 2014 Dr. Stanley F. Malamed! All Rights Reserved 139 ALL reports claiming an increased risk of paresthesia with articaine are ANECDOTAL There is absolutely NO scientific evidence articaine has a greater risk of paresthesia than other LAs © 2014 Dr. Stanley F. Malamed! All Rights Reserved 140 [email protected] 141 © 2014 Dr. Stanley F. Malamed! All Rights Reserved www.elsevier.com OR 142 www.drmalamed.com © 2014 Dr. Stanley F. Malamed! All Rights Reserved [email protected] Thank you for listening . . . © 2014 Dr. Stanley F. Malamed! All Rights Reserved 143