'''Lidocaine''' ([[International Nonproprietary Name|INN]], [[British Approved Name|BAN]]) {{IPAc-en|ˈ|l|aɪ|d|ɵ|k|eɪ|n}}, '''xylocaine''', or '''lignocaine''' ([[Australian Approved Name|AAN]], former [[British Approved Name|BAN]]) {{IPAc-en|ˈ|l|ɪ|ɡ|n|ɵ|k|eɪ|n}} is a common [[local anesthetic]] and class 1b [[antiarrhythmic agent|antiarrhythmic]] drug. Lidocaine is used [[topical]]ly to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.
<!-- Society and culture -->
It is on the [[World Health Organization's List of Essential Medicines]], a list of the most important medications needed in a basic [[healthcare system]].<ref>{{cite web|title=WHO Model List of EssentialMedicines|url=http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1|work=World Health Organization|accessdate=22 April 2014|date=October 2013}}</ref>
== Medical Uses ==
The efficacy profile of lidocaine as a local anesthetic is characterized by a rapid onset of action and intermediate duration of efficacy. Therefore, lidocaine is suitable for infiltration, block and surface anesthesia. Longer-acting substances such as [[bupivacaine]] are sometimes given preference for subdural and epidural anesthesias; lidocaine, on the other hand, has the advantage of a rapid onset of action. Epinephrine (aka [[adrenaline]]) vasoconstricts arteries reducing bleeding and also delays the resorption of lidocaine, almost doubling the duration of anaesthesia. For surface anesthesia several formulations are available that can be used e.g. for endoscopies, before intubations etc. Buffering the [[pH]] of lidocaine makes local freezing less painful.<ref name="pmid21154371">{{cite journal | author = Cepeda MS, Tzortzopoulou A, Thackrey M, Hudcova J, Arora Gandhi P, Schumann R | title = Adjusting the pH of lidocaine for reducing pain on injection | journal = Cochrane Database Syst Rev | volume = | issue = 12 | pages = CD006581 | year = 2010 | pmid = 21154371 | doi = 10.1002/14651858.CD006581.pub2 }}</ref> Lidocaine drops can be used on the eyes for short ophthalmic procedures.
[[Topical]] lidocaine has been shown in some patients to relieve the pain of [[postherpetic neuralgia]] (a complication of [[Herpes zoster|shingles]]), though there is not enough study evidence to recommend it as a [[first-line treatment]].<ref name="pmid17443559">{{cite journal | author = Khaliq W, Alam S, Puri N | title = Topical lidocaine for the treatment of postherpetic neuralgia | journal = Cochrane Database Syst Rev | volume = | issue = 2 | pages = CD004846 | year = 2007 | pmid = 17443559 | doi = 10.1002/14651858.CD004846.pub2 }}</ref> [[Intravenous therapy|IV]] lidocaine also has uses as a temporary fix for [[tinnitus]]. Although not completely curing the disorder, it has been shown to reduce the effects by around two thirds.<ref>{{cite news |url=http://newsvote.bbc.co.uk/2/hi/health/7175306.stm |title=New hope for tinnitus sufferers |date=9 January 2008 |publisher=BBC News}}</ref><ref>{{cite journal | author = Kalcioglu MT, Bayindir T, Erdem T, Ozturan O. | title = Objective evaluation of the effects of intravenous lidocaine on tinnitus. | journal = Hearing Research | year = 2005 | url = http://www.ncbi.nlm.nih.gov/pubmed/15574302}}</ref>
Lidocaine is also the most important [[Antiarrhythmic agent#Class I agents|class 1B antiarrhythmic drug]]: it is used intravenously for the treatment of [[ventricular arrhythmia]]s (for [[acute myocardial infarction]], [[digoxin]] poisoning, [[cardioversion]] or [[cardiac catheterization]]) if [[amiodarone]] is not available or contraindicated. Lidocaine should be given for this indication after defibrillation, CPR, and vasopressors have been initiated.
{{Lidocaine}}
A routine prophylactic administration is no longer recommended for acute cardiac infarction; the overall benefit of this measure is not convincing.
{{CMG}}; {{AE}} {{AZ}}
Inhaled lidocaine can be used as an [[antitussive]] (cough suppressor) acting peripherally to reduce the cough reflex. This application can be implemented as a safety and comfort measure for patients that have to be intubated as it reduces the incidence of coughing and any tracheal damage it might cause when emerging from anesthesia.<ref name="pmid12569065">{{cite journal | author = Adcock JJ, Douglas GJ, Garabette M, Gascoigne M, Beatch G, Walker M, Page CP | title = RSD931, a novel anti-tussive agent acting on airway sensory nerves | journal = Br. J. Pharmacol. | volume = 138 | issue = 3 | pages = 407–16 | date = February 2003 | pmid = 12569065 | pmc = 1573683 | doi = 10.1038/sj.bjp.0705056 }}</ref><ref name="isbn0-7817-9595-8">{{cite book | editor = Berger AM, Shuster JL, Von Roenn JH | title = Principles and practice of palliative care and supportive oncology | publisher = Lippincott Williams & Wilkins | location = Hagerstwon, MD |year=2007 | isbn = 978-0-7817-9595-1 | author = Biller JA | chapter = Airway obstruction, bronchospasm, and cough | chapterurl = http://books.google.com/books?id=LngD6RFXY_AC&pg=PA297 | pages = 297–307 | quote = Inhaled lidocaine is used to suppress cough during bronchoscopy. Animal studies and a few human studies suggest that lidocaine has an antitussive effect…}}</ref><ref>{{cite journal | author = Minogue SC, Ralph J, Lampa MJ | title = Laryngotracheal topicalization with lidocaine before intubation decreases the incidence of coughing on emergence from general anesthesia. | journal = Anesthesia and analgesia | volume = 99 | issue = 4 | pages = 1253–7, table of contents | date = Oct 2004 | pmid = 15385385 }}</ref>
'''''For patient information about Lidocaine Transdermal Patch, click <u>[[Lidocaine (patient information)|here]]'''''</u>.
Lidocaine along with ethanol, ammonia, and acetic acid has also been proven to be effective in treating jellyfish stings, both numbing the affected area and preventing further [[nematocyst]] discharge.<ref name="pmid20116454">{{cite journal | author = Birsa LM, Verity PG, Lee RF | title = Evaluation of the effects of various chemicals on discharge of and pain caused by jellyfish nematocysts | journal = Comp. Biochem. Physiol. C Toxicol. Pharmacol. | volume = 151 | issue = 4 | pages = 426–30 | date = May 2010 | pmid = 20116454 | doi = 10.1016/j.cbpc.2010.01.007 }}</ref><ref>{{cite journal | author = Morabito R, Marino A, Dossena S, La Spada G | title = Nematocyst discharge in Pelagia noctiluca (Cnidaria, Scyphozoa) oral arms can be affected by lidocaine, ethanol, ammonia and acetic acid. | journal = Toxicon : official journal of the International Society on Toxinology | volume = 83 | pages = 52–8 | date = Jun 2014 | pmid = 24637105 }}</ref>
'''''For patient information about Lidocaine Viscous (lye' doe kane), click <u>[[Lidocaine (patient information)|here]]'''''</u>.
=== Insensitivity ===
Relative insensitivity to lidocaine is genetic. In [[hypokalemic sensory overstimulation]], relative insensitivity to lidocaine has been described in people who also have [[attention deficit hyperactivity disorder]].<ref>{{cite journal | author = Segal MM, Rogers GF, Needleman HL, Chapman CA | title = Hypokalemic sensory overstimulation. | journal = Journal of child neurology | volume = 22 | issue = 12 | pages = 1408–10 | date = Dec 2007 | pmid = 18174562 }}</ref> In dental anesthesia, a relative insensitivity to lidocaine can occur for anatomical reasons due to unexpected positions of nerves. Some people with [[Ehlers-Danlos syndrome]] are insensitive to lidocaine.<ref name="pmid15684369">{{cite journal | author = Hakim AJ, Grahame R, Norris P, Hopper C | title = Local anaesthetic failure in joint hypermobility syndrome | journal = J R Soc Med | volume = 98 | issue = 2 | pages = 84–5 | date = February 2005 | pmid = 15684369 | pmc = 1079398 | doi = 10.1258/jrsm.98.2.84 }}</ref>
{{SB}} XYLOCAINE
== Contraindications ==
==Overview==
Absolute contraindications for the use of lidocaine include:
'''Lidocaine''' '''xylocaine''', or '''lignocaine''' (former [[British Approved Name|BAN]] is a common [[local anesthetic]] and [[antiarrhythmic agent|antiarrhythmic]] drug. Lidocaine is used [[topical]]ly to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.
* [[Heart block]], second or third degree (without pacemaker)
* Severe [[sinoatrial block]] (without pacemaker)
* Serious [[adverse drug reaction]] to lidocaine or amide local anesthetics
* Hypersensitivity to corn and corn-related products (corn-derived dextrose is used in the premixed injections)
* Concurrent treatment with [[quinidine]], [[flecainide]], [[disopyramide]], [[procainamide]] (Class I [[antiarrhythmic agents]])
* Prior use of [[amiodarone hydrochloride]]
* [[Adams-Stokes syndrome]]<ref name="MedWatch_Lidocaine_HCl">{{cite web | url = http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm342035.htm | title = Lidocaine Hydrochloride and 5% Dextrose Injection | work = Safety Labeling Changes | publisher = FDA Center for Drug Evaluation and Research (CDER) | date = January 2014 }}</ref>
* Lidocaine viscous is not recommended by the FDA to treat tooth pain in children and infants.<ref name="MedWatch_Lidocaine_Viscous">{{cite web | url = http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm402790.htm | title = Lidocaine Viscous: Drug Safety Communication - Boxed Warning Required - Should Not Be Used to Treat Teething Pain | publisher = FDA Center for Drug Evaluation and Research (CDER) | date = June 2014 }}</ref>
Exercise caution in patients with any of the following
* [[Hypotension]] not due to [[arrhythmia]]
* [[Bradycardia]]
* [[Accelerated idioventricular rhythm]]
* Elderly patients
* Pseudocholinesterase deficiency
* Intra-articular infusion (this is not an approved indication and can cause [[chondrolysis]])
* [[Porphyria]], especially [[Acute Intermittent Porphyria|Acute Intermittent Porphyria (AIP)]]; lidocaine has been classified as porphyrogenic because of the hepatic enzymes it induces;<ref name="url_www.merckmanuals.com">{{cite web | url = http://www.merckmanuals.com/media/professional/pdf/Drugs_porphyria.pdf | title = Table 96–4. Drugs and Porphyria | year = 2011 | work = Merck Manual | publisher = Merck & Company, Inc. | pages = | quote = | accessdate = }}</ref> although clinical evidence suggests that it is not.<ref name="urlLidocaine - N01BB02 - Drug porphyrinogenicity monograph">{{cite web | url = http://www.drugs-porphyria.org/monograph.php?id=3448 | title = Lidocaine - N01BB02 | format = | work = Drug porphyrinogenicity monograph | publisher = The Norwegian Porphyria Centre (NAPOS) and The Swedish Porphyria Centre | pages = | language = | archiveurl = | archivedate = | quote = strong clinical evidence points to lidocaine as probably not porphyrinogenic | accessdate = }}</ref> [[Bupivacaine]] is a safe alternative in this case.
* Impaired liver function - people with lowered hepatic function may have an adverse reaction with repeated administration of lidocaine because the drug is metabolized by the liver. Adverse reactions may include neurological symptoms (e.g. dizziness, nausea, muscle twitches, vomiting, or seizures).<ref name=Khan>{{cite book|last=Khan|first=M. Gabriel|title=Cardiac Drug Therapy|date=2007|publisher=Humana Press|location=Totowa, NJ|isbn=9781597452380|edition=7th ed.}}</ref>
== Adverse Effects ==
[[Adverse drug reaction]]s (ADRs) are rare when lidocaine is used as a local anesthetic and is administered correctly. Most ADRs associated with lidocaine for anesthesia relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, and [[allergy|allergic]] reactions only rarely occur.<ref name="pmid7844301">{{cite journal | author = Jackson D, Chen AH, Bennett CR | title = Identifying true lidocaine allergy | journal = J Am Dent Assoc | volume = 125 | issue = 10 | pages = 1362–6 | date = October 1994 | pmid = 7844301 | doi = }}</ref> Systemic exposure to excessive quantities of lidocaine mainly result in [[central nervous system]] (CNS) and [[cardiovascular]] effects – CNS effects usually occur at lower [[blood plasma]] concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations. ADRS are listed below by system:
CNS excitation: nervousness, agitation, anxiety, apprehension, tingling around the mouth (circumoral paraesthesia), headache, [[hyperesthesia]], tremor, dizziness, pupillary changes, psychosis, euphoria, hallucinations, and seizures
CNS depression with increasingly heavier exposure: drowsiness, lethargy, slurred speech, [[hypoesthesia]], confusion, disorientation, loss of consciousness, [[respiratory depression]] and [[apnoea]].
Cardiovascular: [[hypotension]], [[bradycardia]], [[arrhythmia]]s, flushing, venous insufficiency, increased defibrillator threshold, [[edema]], and/or [[cardiac arrest]] – some of which may be due to [[Hypoxia (medical)|hypoxemia]] secondary to respiratory depression.<ref name="rossi">{{cite book | author = | title = [[Australian Medicines Handbook]] | publisher = Australian Medicines Handbook Pty Ltd | location = Adelaide, S. Aust | year = 2006 | pages = | isbn = 0-9757919-2-3 }}{{page needed|date=May 2013}}</ref>
Respiratory: Bronchospasm, dyspnea, respiratory depression or arrest
Skin: itching, depigmentation, rash, [[urticaria]], edema, angioedema, bruising, [[thrombophlebitis|inflammation of the vein]] at the injection site, irritation of the skin when applied topically
Blood: [[methemoglobinemia]]
Allergic
ADRs associated with the use of intravenous lidocaine are similar to toxic effects from systemic exposure above. These are dose-related and more frequent at high infusion rates (≥3 mg/minute). Common ADRs include: headache, dizziness, drowsiness, confusion, visual disturbances, [[tinnitus]], tremor, and/or [[paraesthesia]]. Infrequent ADRs associated with the use of lidocaine include: [[hypotension]], [[bradycardia]], [[arrhythmia]]s, [[cardiac arrest]], muscle twitching, [[seizure]]s, [[coma]], and/or respiratory depression.<ref name = rossi/>
Traditionally physicians have always advocated against using epinephrine with local anesthesia in end arterial structures (fingers, toes, nose, and penis) because vasospasm combined with a lack of collateral circulation in these areas may result in tissue necrosis. No clinical evidence has implicated lidocaine in particular as a cause of this adverse reaction.<ref>{{cite journal | author = Chowdhry S, Seidenstricker L, Cooney DS, Hazani R, Wilhelmi BJ | title = Do not use epinephrine in digital blocks: myth or truth? Part II. A retrospective review of 1111 cases. | journal = Plastic and reconstructive surgery | volume = 126 | issue = 6 | pages = 2031–4 | date = Dec 2010 | pmid = 20697319 }}</ref>
==Overdosage==
Overdosage with lidocaine can be a result of excessive administration via topical or parenteral routes, accidental oral ingestion of topical preparations by children who are more susceptible to overdose, accidental intravenous (rather than subcutaneous, intrathecal or paracervical) injection or prolonged use of subcutaneous infiltration anesthesia during cosmetic surgical procedures. These occurrences have often led to severe toxicity or death in both children and adults. Lidocaine and its two major metabolites may be quantified in blood, plasma or serum to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage. It is important in the interpretation of analytical results to recognize that lidocaine is often routinely administered intravenously as an antiarrhythmic agent in critical cardiac care situations.<ref name="isbn0-9626523-7-7">{{cite book | author = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | year = 2008 | pages = 840–4 | isbn = 0-9626523-7-7 }}</ref> Treatment with intravenous lipid emulsions (used for parental feeding) to reverse the effects of local anaesthetic toxicity is becoming more commonplace.<ref name="pmid19143686">{{cite journal | author = Picard J, Ward SC, Zumpe R, Meek T, Barlow J, Harrop-Griffiths W | title = Guidelines and the adoption of 'lipid rescue' therapy for local anaesthetic toxicity | journal = Anaesthesia | volume = 64 | issue = 2 | pages = 122–5 | date = February 2009 | pmid = 19143686 | doi = 10.1111/j.1365-2044.2008.05816.x }}</ref>
== Interactions ==
Any drugs that are also ligands of [[CYP3A4]] and CYP1A2 can potentially increase serum levels and potential for toxicity or decrease serum levels and the efficacy depending on whether they induce or inhibit the enzymes respectively. Drugs that may increase the chance of [[methemoglobinemia]] should also be considered carefully. Dronedarone and
liposomal morphine are both absolutely contraindicated as they may increase the serum levels but there are hundreds of other drugs that have to be monitored for interaction.<ref name=epocrates>{{cite web|url=https://online.epocrates.com/u/104316/lidocaine/Drug+Interactions|accessdate=April 2014}}</ref>
== Dosage Forms ==
[[File:Lidocaine HCl local anesthetic cartridge.JPG|thumbnail|right|Lidocaine hydrochloride 2% epinephrine 1:80,000 solution for injection in a cartridge]]
[[File:Lidocaine hci.jpg|thumbnail|right|Lidocaine hydrochloride 1% solution for injection]]
Lidocaine, usually in the form of lidocaine hydrochloride, is available in various forms including:
* Injected local anesthetic (sometimes combined with [[epinephrine]] to reduce bleeding)
* Dermal patch (sometimes combined with [[prilocaine]])
* Intravenous injection
* Intravenous infusion
* Intraosseous infusion
* Nasal instillation/spray (combined with [[phenylephrine]])
* Oral gel (often referred to as "viscous lidocaine" or abbreviated "lidocaine visc" or "lidocaine hcl visc" in pharmacology; used as teething gel)
* Oral liquid
* Oral and topical ointments, with and without flavoring, respectively<ref name="url_www.taro.com">{{cite web | url = http://www.taro.com/media/oMedia/Lidocaine-ointmentUSP_05.pdf | title = Product information for lidocaine ointment, USP 5%, spearmint flavored | work = Product Insert | publisher = Taro Pharmaceutical Industries Ltd. | accessdate = July 27, 2009 }}</ref><ref name="urlLidocaine Ointment Official FDA information, side effects and uses.">{{cite web | url = http://www.drugs.com/pro/lidocaine-ointment.html | title = Lidocaine Ointment Prescribing Information | publisher = Drugs.com | accessdate = January 22, 2012 }}</ref>
* Topical gel (as with [[Aloe vera]] gels that include lidocaine)<ref name="urlwww.solarcaine.com">{{cite web | url = http://www.solarcaine.com | title = Solarcaine | work = | publisher = Schering-Plough Healthcare Products, Inc. | accessdate = July 27, 2009 }}</ref>
* Topical liquid
* Lidocaine HCl 2% Jelly, combined with hypromellose, to anesthetize and lubricate the urethra, etc., for inserting a catheter or instrument
* Topical patch (lidocaine 5%), marketed since 1999 in the US by [[Endo Pharmaceuticals]]<ref name="urlEndo Pharmaceuticals | All Products of Endo Pharmaceuticals">{{cite web | url = http://www.endo.com/endopharma/our-products/all-products | title = Lidoderm (Lidocaine Patch 5%) | work = Our Products | publisher = Endo Pharmaceuticals | accessdate = 18 October 2012 }}</ref> as "Lidoderm" - and since 2007 in the UK by Grünenthal as "Versatis"
* Topical ointment (lidocaine 5%) as a temporary reliever of discomfort associated [[anorectal disorder]]s, such as [[hemorrhoids]], marketed as an over-the-counter product in the US as "[[RectiCare]]" since 2012 by Ferndale Healthcare, Inc.
* Topical aerosol spray
* Inhaled via a nebulizer
* As a component of a [[GI cocktail]] used in emergency rooms
* Ophthalmic solution
=== Adulterant in Cocaine ===
Lidocaine is often added to [[cocaine]] as a [[diluent]].<ref>{{cite journal | author = Bernardo NP, Siqueira MEPB, De Paiva MJN, Maia PP | title = Caffeine and other adulterants in seizures of street cocaine in Brazil |year=2003 | journal = International Journal of Drug Policy | volume = 14 | issue = 4 | pages = 331–4 | doi = 10.1016/S0955-3959(03)00083-5 }}</ref> Cocaine numbs the [[gums]] when applied, and since lidocaine causes stronger numbness,<ref>{{cite web | author = Kimberly H | title = Take a big-picture approach when dealing with corneal sensation | url = http://www.eyefacialplasticsurgery.com/topics/201-Latest%20News/File/corneal_sensation.htm | date = 1997-12-15 | accessdate = 2009-04-23 | quote = Lidocaine is more potent, with rapid diffusion and penetration.}}</ref> a user gets the impression of high-quality cocaine when in actuality, the user is receiving a diluted product.<ref name="url599 F.2d 635">{{cite web | url = https://bulk.resource.org/courts.gov/c/F2/599/599.F2d.635.78-5314.html | title = UNITED STATES of America, Plaintiff-Appellee, v. Luis A. CUELLO, Alvaro Bastides-Benitez, John Doe, a/k/a Hugo Hurtado, and Alvaro Carvajal, Defendants-Appellants | author = | date = 1979-07-25 | work = Docket No. 78-5314 | publisher = United States Court of Appeals, Fifth Circuit }}</ref>
== Preparation ==
Lidocaine may be prepared in two steps by the reaction of [[2,6-xylidine]] with [[chloroacetyl chloride]], followed by the reaction with [[diethylamine]]:<ref>{{cite journal |doi=10.1021/ed076p1557 |title=The Preparation of Lidocaine | year = 1999 | author = Reilly TJ | journal = Journal of Chemical Education | volume = 76 | issue = 11 | pages = 1557}}</ref><ref>{{ cite patent | country = US | number = 2441498 | status = patent | title = Alkyl glycinanilides | gdate = 1948-05-11 | inventor = Bengt JL, Niels, ML | assign1 = Astra Apotekarnes Kem FAB}}</ref>
:[[File:Synthesis of lidocaine.png|700px|thumb|center|Preparation of Lidocaine: {{US patent|2441498}}, Bengt JL, Niels, ML, [[Astra Apotekarnes Kem Fab]] (1948).]]
== Pharmacokinetics ==
==Category==
The onset of action of lidocaine is about 45 to 90 seconds and its duration is 10 to 20 minutes. It is approximately 95% metabolized (dealkylated) in the [[liver]] mainly by [[CYP3A4]] to the pharmacologically-active [[Metabolomics#Metabolites|metabolites]] [[monoethylglycinexylidide]] (MEGX) and then subsequently to the inactive [[glycine xylidide]]. MEGX has a longer half life than lidocaine but also is a less potent sodium channel blocker.<ref name="isbn0-07-143763-0">{{cite book | editor = Flomenbaum N, Goldfrank LR, Hoffman RL, Howland MD, Lewin NA, Nelson LH | title = Goldfrank's Toxicologic Emergencies | edition = 8th | publisher = McGraw-Hill | location = New York | year = 2006 | pages = 963–4 | author = Lewin NA, Nelson LH | chapter = Chapter 61: Antidysrhythmics | isbn = 0-07-143763-0 }}</ref> The [[volume of distribution]] is 1.1-2.1 L/kg but congestive heart failure can decrease it. 60-80% circulates bound to the protein alpha<sub>1</sub> acid glycoprotein. The oral bioavailability is 35% and the topical bioavailability is 3%.
Anesthetic and Antiarrythmic
==FDA Package Insert<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = XYLOCAINE (LIDOCAINE HYDROCHLORIDE) INJECTION [ASTRAZENECA LP] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=723c8e7e-75eb-4119-4ab0-ab52955869f7#nlm34067-9 | publisher = | date = | accessdate = }}</ref>==
The elimination [[half-life]] of lidocaine is biphasic and approximately 90–120 minutes in most patients. This may be prolonged in patients with [[liver failure|hepatic impairment]] (average 343 minutes) or [[heart failure|congestive heart failure]] (average 136 minutes).<ref name="pmid4694036">{{cite journal | author = Thomson PD, Melmon KL, Richardson JA, Cohn K, Steinbrunn W, Cudihee R, Rowland M | title = Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans | journal = Ann. Intern. Med. | volume = 78 | issue = 4 | pages = 499–508 | date = April 1973 | pmid = 4694036 | doi = 10.7326/0003-4819-78-4-499 }}</ref> Lidocaine is excreted in the urine (90% as metabolites and 10% as unchanged drug).<ref name="pmid4609637">{{cite journal | author = Collinsworth KA, Kalman SM, Harrison DC | title = The clinical pharmacology of lidocaine as an antiarrhythymic drug | journal = Circulation | volume = 50 | issue = 6 | pages = 1217–30 | year = 1974 | pmid = 4609637 | doi = 10.1161/01.CIR.50.6.1217 }}</ref>
'''| [[Lidocaine indications and usage|Indications and Usage]]'''
== Pharmacodynamics ==
'''| [[Lidocaine dosage and administration|Dosage and Administration]]'''
'''| [[Lidocaine labels and packages|Labels and Packages]]'''
==Mechanism of Action==
=== Anaesthesia ===
Lidocaine alters signal conduction in [[neuron]]s by blocking the fast [[sodium channel|voltage gated sodium (Na<sup>+</sup>) channels]] in the neuronal cell membrane that are responsible for signal propagation.<ref name="novartis">{{cite journal |doi=10.1002/0470846682.ch14 |chapter=Molecular Mechanisms of Gating and Drug Block of Sodium Channels |title=Sodium Channels and Neuronal Hyperexcitability |series=Novartis Foundation Symposia |year=2001 |last1=Carterall |first1=William A. |isbn=9780470846681 |volume=241 |pages=206}}</ref> With sufficient blockage the membrane of the postsynaptic neuron will not depolarize and will thus fail to transmit an [[action potential]]. This creates the [[anaesthetic]] effect by not merely preventing pain signals from propagating to the brain but by stopping them before they begin. Careful titration allows for a high degree of selectivity in the blockage of sensory neurons, whereas higher concentrations will also affect other modalities of neuron signaling.
Lidocaine alters signal conduction in [[neuron]]s by blocking the fast [[sodium channel|voltage gated sodium (Na<sup>+</sup>) channels]] in the neuronal cell membrane that are responsible for signal propagation.<ref name="novartis">{{cite journal |doi=10.1002/0470846682.ch14 |chapter=Molecular Mechanisms of Gating and Drug Block of Sodium Channels |title=Sodium Channels and Neuronal Hyperexcitability |series=Novartis Foundation Symposia |year=2001 |last1=Carterall |first1=William A. |isbn=9780470846681 |volume=241 |pages=206}}</ref> With sufficient blockage the membrane of the postsynaptic neuron will not depolarize and will thus fail to transmit an [[action potential]]. This creates the [[anaesthetic]] effect by not merely preventing pain signals from propagating to the brain but by stopping them before they begin. Careful titration allows for a high degree of selectivity in the blockage of sensory neurons, whereas higher concentrations will also affect other modalities of neuron signaling.
=== Antiarrhythmic ===
The same principle applies for this drug's actions in the heart. Blocking sodium channels in the conduction system as well as the muscle cells of the heart raises the depolarization threshold making the heart less likely to initiate or conduct early action potentials that may cause an arrhythmia.<ref>{{cite journal | author = Sheu SS, Lederer WJ | title = Lidocaine's negative inotropic and antiarrhythmic actions. Dependence on shortening of action potential duration and reduction of intracellular sodium activity. | journal = Circulation research | volume = 57 | issue = 4 | pages = 578–90 | date = Oct 1985 | pmid = 2412723 }}</ref>
== History ==
Lidocaine, the first [[amino]] [[amide]]–type local anesthetic, was first synthesized under the name ''xylocaine'' by Swedish chemist [[Nils Löfgren]] in 1943.<ref name="lofgren_1948">{{cite book | author = Löfgren N|title=Studies on local anesthetics: Xylocaine: a new synthetic drug |type=Inaugural dissertation |publisher=Ivar Heggstroms |location=Stockholm, Sweden |year=1948 |oclc=646046738}}{{page needed|date=May 2013}}</ref><ref>{{cite journal | author = Löfgren N, Lundqvist B | year = 1946 | title = Studies on local anaesthetics II | journal = Svensk Kemisk Tidskrift | volume = 58 | pages = 206–17}}</ref><ref>{{cite journal | author = Wildsmith JAW |year=2011 | title = Lidocaine: A more complex story than 'simple' chemistry suggests | journal = The Proceedings of the History of Anaesthesia Society | url = http://www.histansoc.org.uk/uploads/9/5/5/2/9552670/vol_43.pdf | volume = 43 | pages = 9–16 }}</ref> His colleague Bengt Lundqvist performed the first injection anesthesia experiments on himself.<ref name="lofgren_1948"/> It was first marketed in 1949.
== Recreational use ==
Lidocaine is not currently listed by the [[World Anti-Doping Agency]] as an illegal substance.<ref name="url_www.wada-ama.org">{{cite web | url = http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/WADA_Prohibited_List_2010_EN.pdf | title =The 2010 Prohibited List International Standard | author = | date = 19 September 2009 | work = The World Anti-Doping Code | publisher = World Anti-Doping Agency (WADA) }}</ref> Lidocaine is used as an adjuvant, adulterant, and diluent to street drugs such as [[cocaine]] and [[heroin]].<ref>{{cite web | url = http://www.justice.gov/archive/ndic/pubs2/2580/heroin.htm | publisher = National Drug Intelligence Center | title = New York Drug Threat Assessment | date = November 2002}}</ref>
== Compendial Status ==
* [[Japanese Pharmacopoeia]] 15
* [[United States Pharmacopeia]] 31<ref>{{cite web |url=http://www.usp.org/usp-nf/official-text/accelerated-revision-process/accelerated-revision-history/lidocaine-and-prilocaine-cream-revision-related |title=Revision Bulletin: Lidocaine and Prilocaine Cream–Revision to Related Compounds Test |date=November 30, 2007 |publisher=The United States Pharmacopeial Convention}}</ref>
== See Also ==
* [[Lidocaine/prilocaine]]
* [[QX-314]]<ref>{{cite journal | author = Lim TK, Macleod BA, Ries CR, Schwarz SK | title = The quaternary lidocaine derivative, QX-314, produces long-lasting local anesthesia in animal models in vivo. |year=2007 | journal = Anesthesiology | volume = 107 | issue = 2 | pages = 305–11 | url=http://www.ncbi.nlm.nih.gov/pubmed/17667576 }}</ref>
*[[Dimethocaine]] (has some [[DRI]] activity)
*[[Procaine]]
== External Links ==
* [http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Lidocaine U.S. National Library of Medicine: Drug Information Portal - Lidocaine]
The efficacy profile of lidocaine as a local anesthetic is characterized by a rapid onset of action and intermediate duration of efficacy. Therefore, lidocaine is suitable for infiltration, block and surface anesthesia. Longer-acting substances such as bupivacaine are sometimes given preference for subdural and epidural anesthesias; lidocaine, on the other hand, has the advantage of a rapid onset of action. Epinephrine (aka adrenaline) vasoconstricts arteries reducing bleeding and also delays the resorption of lidocaine, almost doubling the duration of anaesthesia. For surface anesthesia several formulations are available that can be used e.g. for endoscopies, before intubations etc. Buffering the pH of lidocaine makes local freezing less painful.[2] Lidocaine drops can be used on the eyes for short ophthalmic procedures.
Topical lidocaine has been shown in some patients to relieve the pain of postherpetic neuralgia (a complication of shingles), though there is not enough study evidence to recommend it as a first-line treatment.[3]IV lidocaine also has uses as a temporary fix for tinnitus. Although not completely curing the disorder, it has been shown to reduce the effects by around two thirds.[4][5]
A routine prophylactic administration is no longer recommended for acute cardiac infarction; the overall benefit of this measure is not convincing.
Inhaled lidocaine can be used as an antitussive (cough suppressor) acting peripherally to reduce the cough reflex. This application can be implemented as a safety and comfort measure for patients that have to be intubated as it reduces the incidence of coughing and any tracheal damage it might cause when emerging from anesthesia.[6][7][8]
Lidocaine along with ethanol, ammonia, and acetic acid has also been proven to be effective in treating jellyfish stings, both numbing the affected area and preventing further nematocyst discharge.[9][10]
Intra-articular infusion (this is not an approved indication and can cause chondrolysis)
Porphyria, especially Acute Intermittent Porphyria (AIP); lidocaine has been classified as porphyrogenic because of the hepatic enzymes it induces;[15] although clinical evidence suggests that it is not.[16]Bupivacaine is a safe alternative in this case.
Impaired liver function - people with lowered hepatic function may have an adverse reaction with repeated administration of lidocaine because the drug is metabolized by the liver. Adverse reactions may include neurological symptoms (e.g. dizziness, nausea, muscle twitches, vomiting, or seizures).[17]
Adverse Effects
Adverse drug reactions (ADRs) are rare when lidocaine is used as a local anesthetic and is administered correctly. Most ADRs associated with lidocaine for anesthesia relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, and allergic reactions only rarely occur.[18] Systemic exposure to excessive quantities of lidocaine mainly result in central nervous system (CNS) and cardiovascular effects – CNS effects usually occur at lower blood plasma concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations. ADRS are listed below by system:
CNS excitation: nervousness, agitation, anxiety, apprehension, tingling around the mouth (circumoral paraesthesia), headache, hyperesthesia, tremor, dizziness, pupillary changes, psychosis, euphoria, hallucinations, and seizures
CNS depression with increasingly heavier exposure: drowsiness, lethargy, slurred speech, hypoesthesia, confusion, disorientation, loss of consciousness, respiratory depression and apnoea.
Skin: itching, depigmentation, rash, urticaria, edema, angioedema, bruising, inflammation of the vein at the injection site, irritation of the skin when applied topically
ADRs associated with the use of intravenous lidocaine are similar to toxic effects from systemic exposure above. These are dose-related and more frequent at high infusion rates (≥3 mg/minute). Common ADRs include: headache, dizziness, drowsiness, confusion, visual disturbances, tinnitus, tremor, and/or paraesthesia. Infrequent ADRs associated with the use of lidocaine include: hypotension, bradycardia, arrhythmias, cardiac arrest, muscle twitching, seizures, coma, and/or respiratory depression.[19]
Traditionally physicians have always advocated against using epinephrine with local anesthesia in end arterial structures (fingers, toes, nose, and penis) because vasospasm combined with a lack of collateral circulation in these areas may result in tissue necrosis. No clinical evidence has implicated lidocaine in particular as a cause of this adverse reaction.[20]
Overdosage
Overdosage with lidocaine can be a result of excessive administration via topical or parenteral routes, accidental oral ingestion of topical preparations by children who are more susceptible to overdose, accidental intravenous (rather than subcutaneous, intrathecal or paracervical) injection or prolonged use of subcutaneous infiltration anesthesia during cosmetic surgical procedures. These occurrences have often led to severe toxicity or death in both children and adults. Lidocaine and its two major metabolites may be quantified in blood, plasma or serum to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage. It is important in the interpretation of analytical results to recognize that lidocaine is often routinely administered intravenously as an antiarrhythmic agent in critical cardiac care situations.[21] Treatment with intravenous lipid emulsions (used for parental feeding) to reverse the effects of local anaesthetic toxicity is becoming more commonplace.[22]
Interactions
Any drugs that are also ligands of CYP3A4 and CYP1A2 can potentially increase serum levels and potential for toxicity or decrease serum levels and the efficacy depending on whether they induce or inhibit the enzymes respectively. Drugs that may increase the chance of methemoglobinemia should also be considered carefully. Dronedarone and
liposomal morphine are both absolutely contraindicated as they may increase the serum levels but there are hundreds of other drugs that have to be monitored for interaction.[23]
Nasal instillation/spray (combined with phenylephrine)
Oral gel (often referred to as "viscous lidocaine" or abbreviated "lidocaine visc" or "lidocaine hcl visc" in pharmacology; used as teething gel)
Oral liquid
Oral and topical ointments, with and without flavoring, respectively[24][25]
Topical gel (as with Aloe vera gels that include lidocaine)[26]
Topical liquid
Lidocaine HCl 2% Jelly, combined with hypromellose, to anesthetize and lubricate the urethra, etc., for inserting a catheter or instrument
Topical patch (lidocaine 5%), marketed since 1999 in the US by Endo Pharmaceuticals[27] as "Lidoderm" - and since 2007 in the UK by Grünenthal as "Versatis"
Topical ointment (lidocaine 5%) as a temporary reliever of discomfort associated anorectal disorders, such as hemorrhoids, marketed as an over-the-counter product in the US as "RectiCare" since 2012 by Ferndale Healthcare, Inc.
Topical aerosol spray
Inhaled via a nebulizer
As a component of a GI cocktail used in emergency rooms
Ophthalmic solution
Adulterant in Cocaine
Lidocaine is often added to cocaine as a diluent.[28] Cocaine numbs the gums when applied, and since lidocaine causes stronger numbness,[29] a user gets the impression of high-quality cocaine when in actuality, the user is receiving a diluted product.[30]
The onset of action of lidocaine is about 45 to 90 seconds and its duration is 10 to 20 minutes. It is approximately 95% metabolized (dealkylated) in the liver mainly by CYP3A4 to the pharmacologically-active metabolitesmonoethylglycinexylidide (MEGX) and then subsequently to the inactive glycine xylidide. MEGX has a longer half life than lidocaine but also is a less potent sodium channel blocker.[33] The volume of distribution is 1.1-2.1 L/kg but congestive heart failure can decrease it. 60-80% circulates bound to the protein alpha1 acid glycoprotein. The oral bioavailability is 35% and the topical bioavailability is 3%.
The elimination half-life of lidocaine is biphasic and approximately 90–120 minutes in most patients. This may be prolonged in patients with hepatic impairment (average 343 minutes) or congestive heart failure (average 136 minutes).[34] Lidocaine is excreted in the urine (90% as metabolites and 10% as unchanged drug).[35]
Pharmacodynamics
Anaesthesia
Lidocaine alters signal conduction in neurons by blocking the fast voltage gated sodium (Na+) channels in the neuronal cell membrane that are responsible for signal propagation.[36] With sufficient blockage the membrane of the postsynaptic neuron will not depolarize and will thus fail to transmit an action potential. This creates the anaesthetic effect by not merely preventing pain signals from propagating to the brain but by stopping them before they begin. Careful titration allows for a high degree of selectivity in the blockage of sensory neurons, whereas higher concentrations will also affect other modalities of neuron signaling.
Antiarrhythmic
The same principle applies for this drug's actions in the heart. Blocking sodium channels in the conduction system as well as the muscle cells of the heart raises the depolarization threshold making the heart less likely to initiate or conduct early action potentials that may cause an arrhythmia.[37]
History
Lidocaine, the first aminoamide–type local anesthetic, was first synthesized under the name xylocaine by Swedish chemist Nils Löfgren in 1943.[38][39][40] His colleague Bengt Lundqvist performed the first injection anesthesia experiments on himself.[38] It was first marketed in 1949.
Recreational use
Lidocaine is not currently listed by the World Anti-Doping Agency as an illegal substance.[41] Lidocaine is used as an adjuvant, adulterant, and diluent to street drugs such as cocaine and heroin.[42]
↑Cepeda MS, Tzortzopoulou A, Thackrey M, Hudcova J, Arora Gandhi P, Schumann R (2010). "Adjusting the pH of lidocaine for reducing pain on injection". Cochrane Database Syst Rev (12): CD006581. doi:10.1002/14651858.CD006581.pub2. PMID21154371.CS1 maint: Multiple names: authors list (link)
↑Khaliq W, Alam S, Puri N (2007). "Topical lidocaine for the treatment of postherpetic neuralgia". Cochrane Database Syst Rev (2): CD004846. doi:10.1002/14651858.CD004846.pub2. PMID17443559.CS1 maint: Multiple names: authors list (link)
↑Biller JA (2007). "Airway obstruction, bronchospasm, and cough". In Berger AM, Shuster JL, Von Roenn JH. Principles and practice of palliative care and supportive oncology. Hagerstwon, MD: Lippincott Williams & Wilkins. pp. 297–307. ISBN978-0-7817-9595-1. Inhaled lidocaine is used to suppress cough during bronchoscopy. Animal studies and a few human studies suggest that lidocaine has an antitussive effect…CS1 maint: Multiple names: editors list (link)
↑Minogue SC, Ralph J, Lampa MJ (Oct 2004). "Laryngotracheal topicalization with lidocaine before intubation decreases the incidence of coughing on emergence from general anesthesia". Anesthesia and analgesia. 99 (4): 1253–7, table of contents. PMID15385385.CS1 maint: Multiple names: authors list (link)
↑Birsa LM, Verity PG, Lee RF (May 2010). "Evaluation of the effects of various chemicals on discharge of and pain caused by jellyfish nematocysts". Comp. Biochem. Physiol. C Toxicol. Pharmacol. 151 (4): 426–30. doi:10.1016/j.cbpc.2010.01.007. PMID20116454.CS1 maint: Multiple names: authors list (link)
↑Morabito R, Marino A, Dossena S, La Spada G (Jun 2014). "Nematocyst discharge in Pelagia noctiluca (Cnidaria, Scyphozoa) oral arms can be affected by lidocaine, ethanol, ammonia and acetic acid". Toxicon : official journal of the International Society on Toxinology. 83: 52–8. PMID24637105.CS1 maint: Multiple names: authors list (link)
↑Segal MM, Rogers GF, Needleman HL, Chapman CA (Dec 2007). "Hypokalemic sensory overstimulation". Journal of child neurology. 22 (12): 1408–10. PMID18174562.CS1 maint: Multiple names: authors list (link)
↑"Lidocaine - N01BB02". Drug porphyrinogenicity monograph. The Norwegian Porphyria Centre (NAPOS) and The Swedish Porphyria Centre. strong clinical evidence points to lidocaine as probably not porphyrinogenic
↑Khan, M. Gabriel (2007). Cardiac Drug Therapy (7th ed. ed.). Totowa, NJ: Humana Press. ISBN9781597452380.CS1 maint: Extra text (link)
↑Chowdhry S, Seidenstricker L, Cooney DS, Hazani R, Wilhelmi BJ (Dec 2010). "Do not use epinephrine in digital blocks: myth or truth? Part II. A retrospective review of 1111 cases". Plastic and reconstructive surgery. 126 (6): 2031–4. PMID20697319.CS1 maint: Multiple names: authors list (link)
↑Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 840–4. ISBN0-9626523-7-7.
↑Picard J, Ward SC, Zumpe R, Meek T, Barlow J, Harrop-Griffiths W (February 2009). "Guidelines and the adoption of 'lipid rescue' therapy for local anaesthetic toxicity". Anaesthesia. 64 (2): 122–5. doi:10.1111/j.1365-2044.2008.05816.x. PMID19143686.CS1 maint: Multiple names: authors list (link)
↑Bernardo NP, Siqueira MEPB, De Paiva MJN, Maia PP (2003). "Caffeine and other adulterants in seizures of street cocaine in Brazil". International Journal of Drug Policy. 14 (4): 331–4. doi:10.1016/S0955-3959(03)00083-5.CS1 maint: Multiple names: authors list (link)
↑Reilly TJ (1999). "The Preparation of Lidocaine". Journal of Chemical Education. 76 (11): 1557. doi:10.1021/ed076p1557.
↑US patent 2441498, Bengt JL, Niels, ML, "Alkyl glycinanilides", issued 1948-05-11, assigned to Astra Apotekarnes Kem FAB
↑Lewin NA, Nelson LH (2006). "Chapter 61: Antidysrhythmics". In Flomenbaum N, Goldfrank LR, Hoffman RL, Howland MD, Lewin NA, Nelson LH. Goldfrank's Toxicologic Emergencies (8th ed.). New York: McGraw-Hill. pp. 963–4. ISBN0-07-143763-0.CS1 maint: Multiple names: editors list (link)
↑Thomson PD, Melmon KL, Richardson JA, Cohn K, Steinbrunn W, Cudihee R, Rowland M (April 1973). "Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans". Ann. Intern. Med. 78 (4): 499–508. doi:10.7326/0003-4819-78-4-499. PMID4694036.CS1 maint: Multiple names: authors list (link)
↑Collinsworth KA, Kalman SM, Harrison DC (1974). "The clinical pharmacology of lidocaine as an antiarrhythymic drug". Circulation. 50 (6): 1217–30. doi:10.1161/01.CIR.50.6.1217. PMID4609637.CS1 maint: Multiple names: authors list (link)
↑Carterall, William A. (2001). "Sodium Channels and Neuronal Hyperexcitability". Novartis Foundation Symposia. 241: 206. doi:10.1002/0470846682.ch14. ISBN9780470846681. |chapter= ignored (help)
↑Sheu SS, Lederer WJ (Oct 1985). "Lidocaine's negative inotropic and antiarrhythmic actions. Dependence on shortening of action potential duration and reduction of intracellular sodium activity". Circulation research. 57 (4): 578–90. PMID2412723.
↑ 38.038.1Löfgren N (1948). Studies on local anesthetics: Xylocaine: a new synthetic drug (Inaugural dissertation). Stockholm, Sweden: Ivar Heggstroms. OCLC646046738.[page needed]
↑Löfgren N, Lundqvist B (1946). "Studies on local anaesthetics II". Svensk Kemisk Tidskrift. 58: 206–17.
