|Systematic (IUPAC) name|
|Routes||intravenous, subcutaneous, topical, oral|
|Metabolism||Hepatic, 90% CYP1A2-mediated|
|ATC code||C01 C05 D04 N01 R02 S01 S02|
|Mol. mass||234.34 g/mol|
|Melt. point||68 °C (154 °F)|
|(what is this?)|
Lidocaine (INN, BAN) //, xylocaine, or lignocaine (AAN, former BAN) // is a common local anesthetic and class-1b antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning, and pain from skin inflammations, injected as a dental anesthetic, or as a local anesthetic for minor surgery.
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.
- 1 Medical uses
- 2 Contraindications
- 3 Adverse effects
- 4 Overdosage
- 5 Interactions
- 6 Dosage forms
- 7 Preparation
- 8 Pharmacokinetics
- 9 Pharmacodynamics
- 10 History
- 11 Recreational use
- 12 Compendial status
- 13 See also
- 14 References
- 15 External links
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, though, has the advantage of a rapid onset of action. Epinephrine (adrenaline) vasoconstricts arteries, reducing bleeding and also delays the resorption of lidocaine, almost doubling the duration of anaesthesia. For surface anesthesia, several available formulations can be used e.g. for endoscopies, before intubations, etc. Buffering the pH of lidocaine makes local freezing less painful. 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 not enough study evidence exists to recommend it as a first-line treatment. Intravenous 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.
Lidocaine is also the most important class-1b antiarrhythmic drug; it is used intravenously for the treatment of ventricular arrhythmias (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. 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 who have to be intubated, as it reduces the incidence of coughing and any tracheal damage it might cause when emerging from anesthesia.
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.
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. 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.
Absolute contraindications for the use of lidocaine include:
- 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 mixed injections)
- Concurrent treatment with quinidine, flecainide, disopyramide, procainamide (class I antiarrhythmic agents)
- Prior use of amiodarone hydrochloride
- Adams-Stokes syndrome
- Wolff-Parkinson-White syndrome
- Lidocaine viscous is not recommended by the FDA to treat tooth pain in children and infants.
Exercise caution in patients with any of these:
- Hypotension not due to arrhythmia
- 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; lidocaine has been classified as porphyrogenic because of the hepatic enzymes it induces, although clinical evidence suggests it is not. 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).
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. 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 by system are:
- 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, arrhythmias, flushing, venous insufficiency, increased defibrillator threshold, edema, and/or cardiac arrest – some of which may be due to hypoxemia secondary to respiratory depression.
- Respiratory: Bronchospasm, dyspnea, respiratory depression or arrest
- Gastrointestinal: metallic taste, nausea, vomiting
- Ears: tinnitus
- Eyes: local burning, Conjunctival hyperemia, corneal epithelial changes/ulceration, diplopia, visual changes (opacification)
- Skin: itching, depigmentation, rash, urticaria, edema, angioedema, bruising, inflammation of the vein at the injection site, irritation of the skin when applied topically
- Blood: methemoglobinemia
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/min). 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.
Traditionally, physicians have always advocated not 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.
Overdoses with lidocaine can be a result of excessive administration by 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 overdose. 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. Treatment with intravenous lipid emulsions (used for parental feeding) to reverse the effects of local anaesthetic toxicity is becoming more commonplace.
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 hundreds of other drugs require monitoring for interaction.
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
- Topical gel (as with aloe vera gels that include lidocaine)
- 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 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 by 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. Cocaine numbs the gums when applied, and since lidocaine causes stronger numbness, a user gets the impression of high-quality cocaine when in actuality, the user is receiving a diluted product.
The onset of action of lidocaine is about 45 to 90 sec and its duration is 10 to 20 min. It is about 95% metabolized (dealkylated) in the liver mainly by CYP3A4 to the pharmacologically active 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. The volume of distribution is 1.1-2.1 l/kg, but congestive heart failure can decrease it. About 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 around 90–120 min in most patients. This may be prolonged in patients with hepatic impairment (average 343 min) or congestive heart failure (average 136 min). Lidocaine is excreted in the urine (90% as metabolites and 10% as unchanged drug).
Lidocaine alters signal conduction in neurons by blocking the fast voltage-gated Na+ channels in the neuronal cell membrane responsible for signal propagation. 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 also affect other modalities of neuron signaling.
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.
Lidocaine, the first amino amide–type local anesthetic, was first synthesized under the name 'xylocaine' by Swedish chemist Nils Löfgren in 1943. His colleague Bengt Lundqvist performed the first injection anesthesia experiments on himself. It was first marketed in 1949.
- "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
- 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. PMID 21154371.
- 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. PMID 17443559.
- "New hope for tinnitus sufferers". BBC News. 9 January 2008.
- Kalcioglu MT, Bayindir T, Erdem T, Ozturan O. (2005). "Objective evaluation of the effects of intravenous lidocaine on tinnitus.". Hearing Research 199 (1-2): 81–8. doi:10.1016/j.heares.2004.08.004. PMID 15574302.
- Adcock JJ, Douglas GJ, Garabette M, Gascoigne M, Beatch G, Walker M, Page CP (February 2003). "RSD931, a novel anti-tussive agent acting on airway sensory nerves". Br. J. Pharmacol. 138 (3): 407–16. doi:10.1038/sj.bjp.0705056. PMC 1573683. PMID 12569065.
- 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. ISBN 978-0-7817-9595-1. "Inhaled lidocaine is used to suppress cough during bronchoscopy. Animal studies and a few human studies suggest that lidocaine has an antitussive effect…"
- 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. doi:10.1213/01.ANE.0000132779.27085.52. PMID 15385385.
- 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. PMID 20116454.
- 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. doi:10.1016/j.toxicon.2014.03.002. PMID 24637105.
- Segal MM, Rogers GF, Needleman HL, Chapman CA (Dec 2007). "Hypokalemic sensory overstimulation.". Journal of child neurology 22 (12): 1408–10. doi:10.1177/0883073807307095. PMID 18174562.
- Hakim AJ, Grahame R, Norris P, Hopper C (February 2005). "Local anaesthetic failure in joint hypermobility syndrome". J R Soc Med 98 (2): 84–5. doi:10.1258/jrsm.98.2.84. PMC 1079398. PMID 15684369.
- "Lidocaine Hydrochloride and 5% Dextrose Injection". Safety Labeling Changes. FDA Center for Drug Evaluation and Research (CDER). January 2014.
- "Lidocaine Viscous: Drug Safety Communication - Boxed Warning Required - Should Not Be Used to Treat Teething Pain". FDA Center for Drug Evaluation and Research (CDER). June 2014.
- "Table 96–4. Drugs and Porphyria". Merck Manual. Merck & Company, Inc. 2011.
- "Lidocaine - N01BB02". Drug porphyrinogenicity monograph. The Norwegian Porphyria Centre 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. ISBN 9781597452380.
- Jackson D, Chen AH, Bennett CR (October 1994). "Identifying true lidocaine allergy". J Am Dent Assoc 125 (10): 1362–6. PMID 7844301.
- Australian Medicines Handbook. Adelaide, S. Aust: Australian Medicines Handbook Pty Ltd. 2006. ISBN 0-9757919-2-3.[page needed]
- 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. doi:10.1097/PRS.0b013e3181f44486. PMID 20697319.
- Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 840–4. ISBN 0-9626523-7-7.
- 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. PMID 19143686.
- https://online.epocrates.com/u/104316/lidocaine/Drug+Interactions. Retrieved April 2014. Missing or empty
- "Product information for lidocaine ointment, USP 5%, spearmint flavored". Product Insert. Taro Pharmaceutical Industries Ltd. Retrieved July 27, 2009.
- "Lidocaine Ointment Prescribing Information". Drugs.com. Retrieved January 22, 2012.
- "Solarcaine". Schering-Plough Healthcare Products, Inc. Retrieved July 27, 2009.
- "Lidoderm (Lidocaine Patch 5%)". Our Products. Endo Pharmaceuticals. Retrieved 18 October 2012.
- 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.
- Kimberly H (1997-12-15). "Take a big-picture approach when dealing with corneal sensation". Retrieved 2009-04-23. "Lidocaine is more potent, with rapid diffusion and penetration."
- "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". Docket No. 78-5314. United States Court of Appeals, Fifth Circuit. 1979-07-25.
- 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. ISBN 0-07-143763-0.
- 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. PMID 4694036.
- 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. PMID 4609637.
- Carterall, William A. (2001). "Molecular Mechanisms of Gating and Drug Block of Sodium Channels". "Sodium Channels and Neuronal Hyperexcitability". Novartis Foundation Symposia 241. p. 206. doi:10.1002/0470846682.ch14. ISBN 9780470846681.
- 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. doi:10.1161/01.res.57.4.578. PMID 2412723.
- Löfgren N (1948). Studies on local anesthetics: Xylocaine: a new synthetic drug (Inaugural dissertation). Stockholm, Sweden: Ivar Heggstroms. OCLC 646046738.[page needed]
- Löfgren N, Lundqvist B (1946). "Studies on local anaesthetics II". Svensk Kemisk Tidskrift 58: 206–17.
- Wildsmith JAW (2011). "Lidocaine: A more complex story than 'simple' chemistry suggests". The Proceedings of the History of Anaesthesia Society 43: 9–16.
- "The 2010 Prohibited List International Standard". The World Anti-Doping Code. World Anti-Doping Agency (WADA). 19 September 2009.
- "New York Drug Threat Assessment". National Drug Intelligence Center. November 2002.
- "Revision Bulletin: Lidocaine and Prilocaine Cream–Revision to Related Compounds Test". The United States Pharmacopeial Convention. November 30, 2007.
- U.S. National Library of Medicine: Drug Information Portal - Lidocaine
- Endo Pharmaceuticals' Lidoderm website