Lidocaine
Clinical data | |
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Pronunciation | Lidocaine /ˈlaɪdəˌkeɪn/[1][2] Lignocaine /ˈlɪɡnəˌkeɪn/ |
Trade names | Xylocaine, Ztlido, others |
Other names | lignocaine |
AHFS/Drugs.com | Local Monograph
Systemic Monograph Ophthalmic Professional Drug Facts |
MedlinePlus | a682701 |
License data | |
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ATC code | |
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Pharmacokinetic data | |
Bioavailability | 35% (by mouth) 3% (topical) |
Metabolism | Liver,[7] 90% CYP3A4-mediated |
Onset of action | within 1.5 min (IV)[7] |
Elimination half-life | 1.5 h to 2 h |
Duration of action | 10 min to 20 min(IV),[7] 0.5 h to 3 h (local)[8][9] |
Excretion | Kidney[7] |
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JSmol) | |
Melting point | 68 °C (154 °F) |
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Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a
If injected intravenously, it may cause cerebral effects such as confusion, changes in vision, numbness, tingling, and vomiting.
Lidocaine was discovered in 1946 and went on sale in 1948.[10] It is on the World Health Organization's List of Essential Medicines.[11] It is available as a generic medication.[8][12] In 2021, it was the 267th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[13][14]
Medical uses
Local numbing agent
The efficacy profile of lidocaine as a local anaesthetic is characterized by a rapid onset of action and intermediate duration of efficacy. Therefore, lidocaine is suitable for infiltration, block, and surface anaesthesia. Longer-acting substances such as bupivacaine are sometimes given preference for spinal and epidural anaesthesias; lidocaine, though, has the advantage of a rapid onset of action. Adrenaline vasoconstricts arteries, reducing bleeding and also delaying the resorption of lidocaine, almost doubling the duration of anaesthesia.[citation needed]
Lidocaine is one of the most commonly used local anaesthetics in dentistry. It can be administered in multiple ways, most often as a
For surface anaesthesia, several formulations can be used for
An adhesive transdermal patch containing a 5% concentration of lidocaine in a hydrogel bandage, is approved by the US FDA for reducing nerve pain caused by shingles.[19] The transdermal patch is also used for pain from other causes, such as compressed nerves and persistent nerve pain after some surgeries.
Heart arrhythmia
Lidocaine is also the most important
Epilepsy
A 2013 review on treatment for neonatal seizures recommended intravenous lidocaine as a second-line treatment, if phenobarbital fails to stop seizures.[21]
Other
Intravenous lidocaine infusions are also used to treat
Inhaled lidocaine can be used as a
A 2019 systematic review of the literature found that intraurethral lidocaine reduces pain in men who undergo cystoscopic procedures.[24]
Lidocaine, along with
For gastritis, drinking a viscous lidocaine formulation may help with the pain.[27]
Adverse effects
- 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, apnoea.
- Cardiovascular: hypoxemia secondary to respiratory depression.[29]
- Respiratory: bronchospasm, dyspnea, respiratory depression or arrest
- Gastrointestinal: metallic taste, nausea, vomiting, agita, and diarrhea
- 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 veinat the injection site, irritation of the skin when applied topically
- Blood: methemoglobinemia
- Allergy
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
It is generally safe to use lidocaine with vasoconstrictor such as adrenaline, including in regions such as the
The use of lidocaine for spinal anesthesia may lead to an increased risk of transient neurological symptoms, a painful condition that is sometimes experienced immediately after surgery.[31] There is some weak evidence to suggest that the use of alternative anesthetic medications such as prilocaine, procaine, bupivacaine, ropivacaine, or levobupivacaine may decrease the risk of a person developing transient neurological symptoms.[31] Low quality evidence suggests that 2‐chloroprocaine and mepivacaine when used for spinal anesthetic have a similar risk of the person developing transient neurological symptoms as lidocaine.[31]
Interactions
Any drugs that are also
Contraindications
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[33]
- Wolff–Parkinson–White syndrome[33]
- Lidocaine viscous is not recommended by the FDA to treat teething pain in children and infants.[34]
Exercise caution in patients with any of these:
- arrhythmia
- Bradycardia
- Accelerated idioventricular rhythm
- Elderly
- Ehlers–Danlos syndromes; efficiency of local anesthetics can be reduced[35]
- 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,[36] although clinical evidence suggests it is not.[37] 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).[38]
Overdosage
Overdoses of lidocaine may result from excessive administration by topical or
Such overdoses have often led to severe toxicity or death in both children and adults (local anesthetic systemic toxicity).[39] Symptoms include central nervous system manifestations such as numbness of the tongue, dizziness, tinnitus, visual disturbances, convulsions, reduced consciousness progressing to coma, as well as respiratory arrest and cardiovascular disturbances.[40] 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 forensic investigation in a case of fatal overdose.[citation needed]
Lidocaine is often given intravenously as an antiarrhythmic agent in critical cardiac-care situations.
Postarthroscopic glenohumeral chondrolysis
Lidocaine in large amounts may be toxic to cartilage and intra-articular infusions can lead to postarthroscopic glenohumeral chondrolysis.[44]
Pharmacology
Mechanism of action
Lidocaine alters signal conduction in neurons by prolonging the inactivation of the fast voltage-gated Na+ channels in the neuronal cell membrane responsible for action potential propagation.[45] With sufficient blockage, the voltage-gated sodium channels will not open and an action potential will not be generated. Careful titration allows for a high degree of selectivity in the blockage of sensory neurons, whereas higher concentrations also affect other types of neurons.[citation needed]
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.[46]
Pharmacokinetics
When used as an injectable it typically begins working within four minutes and lasts for half an hour to three hours.[8][9] Lidocaine 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.[47] The volume of distribution is 1.1 L/kg to 2.1 L/kg, but congestive heart failure can decrease it. About 60% to 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 min to 120 min in most patients. This may be prolonged in patients with hepatic impairment (average 343 min) or congestive heart failure (average 136 min).[48] Lidocaine is excreted in the urine (90% as metabolites and 10% as unchanged drug).[49]
Chemistry
Molecular structure and conformational flexibility
At the heart of lidocaine's molecular structure lies a lipophilic group featuring a 1,5-dimethylbenzene core, contributing to the molecule's hydrophobic characteristics. In addition to this aromatic unit, lidocaine incorporates an aliphatic section comprising amide, carbonyl, and enyl groups. This multifaceted arrangement endows the molecule with unique properties and a capacity to interact with biological systems.
Lidocaine exhibits a remarkable degree of conformational flexibility, resulting in more than 60 probable conformers.[50] This adaptability arises from the high lability of the amide and ethyl groups within the molecule. These groups can undergo shifts in their positions, leading to significant variations in the overall molecular configuration.
Influence of temperature and pressure on conformational preference
The dynamic transformation of lidocaine conformers in supercritical carbon dioxide (scCO2) highly depends on external factors such as pressure[50] and temperature.[51] Alterations in these conditions can lead to distinct conformations, impacting the molecule's physicochemical properties. One notable consequence of these variations is the particle size of lidocaine when produced through micronization using scCO2. Changes in the position of the amide group within the molecule can trigger a redistribution of intra- and intermolecular hydrogen bonds, affecting the outcome of the micronization process and the resultant particle size.[52]
History
Lidocaine, the first
Society and culture
Dosage forms
Lidocaine, usually in the form of its hydrochloride salt, is available in various forms including many topical formulations and solutions for injection or infusion.[56] It is also available as a transdermal patch, which is applied directly to the skin.[citation needed]
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Lidocaine hydrochloride 2% epinephrine 1:80,000 solution for injection in a cartridge
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Lidocaine hydrochloride 1% solution for injection
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Topical lidocaine spray
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2% viscous lidocaine
Names
Lidocaine is the
Xylocaine is a brand name, referring to the major synthetic building block
Recreational use
As of 2021,[update] lidocaine is not listed by the World Anti-Doping Agency as a substance whose use is banned in sport.[59] It is used as an adjuvant, adulterant, and diluent to street drugs such as cocaine and heroin.[60] It is one of the three common ingredients in site enhancement oil used by bodybuilders.[61]
Adulterant in cocaine
Lidocaine is often added to cocaine as a diluent.[62][63] Cocaine and lidocaine both numb the gums when applied. This gives the user the impression of high-quality cocaine, when in actuality the user is receiving a diluted product.[64]
Compendial status
Veterinary use
It is a component of the
References
- ^ "Lidocaine". Merriam-Webster.com Dictionary.
- ^ "Lidocaine". Dictionary.com Unabridged (Online). n.d.
- ^ "Poisons Standard February 2021". Federal Register of Legislation. 1 January 2021. Retrieved 11 April 2021.
- ^ "Lidocaine Hydrochloride Injection BP 1% w/v - Summary of Product Characteristics (SmPC)". (emc). 29 June 2020. Retrieved 11 April 2021.
- ^ "Xylocaine MPF- lidocaine hydrochloride injection, solution Xylocaine- lidocaine hydrochloride injection, solution Xylocaine- lidocaine hydrochloride,epinephrine bitartrate injection, solution". DailyMed. Retrieved 11 April 2021.
- ^ "Ztlido- lidocaine patch". DailyMed. Retrieved 11 April 2021.
- ^ a b c d e f g h i j k "Lidocaine Hydrochloride (Antiarrhythmic)". The American Society of Health-System Pharmacists. Archived from the original on 10 August 2015. Retrieved 26 August 2015.
- ^ a b c d e f g h i j "Lidocaine Hydrochloride (Local)". The American Society of Health-System Pharmacists. Archived from the original on 6 September 2015. Retrieved 26 August 2015.
- ^ ISBN 9780521433792. Archivedfrom the original on 8 September 2017.
- ISBN 9780941901215. Archivedfrom the original on 8 September 2017.
- hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
- ISBN 9781284057560.
- ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
- ^ "Lidocaine - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
- ^ "Local anaesthetic drugs".
- PMID 25058164.
- S2CID 44520644.
- S2CID 19110955.
- PMID 26702198.
- PMID 26295202.
- PMID 23318696.
- PMID 29864216.
- 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…
- S2CID 195192577.
- PMID 20116454.
- PMID 24637105.
- ISBN 9781455733941. Archivedfrom the original on 8 September 2017.
- PMID 7844301.
- ^ ISBN 978-0-9757919-2-9.[page needed]
- ^ PMID 25354008.
- ^ PMID 31786810.
- ^ "Lidocaine". Epocrates. Archived from the original on 22 April 2014.
- ^ a b "Lidocaine Hydrochloride and 5% Dextrose Injection". Safety Labeling Changes. FDA Center for Drug Evaluation and Research (CDER). January 2014. Archived from the original on 3 April 2013.
- ^ "FDA Drug Safety Communication: FDA recommends not using lidocaine to treat teething pain and requires new Boxed Warning". FDA Center for Drug Evaluation and Research (CDER). June 2014. Archived from the original on 14 July 2014.
- PMID 31723666.
- ^ "Table 96–4. Drugs and Porphyria" (PDF). Merck Manual. Merck & Company, Inc. 2011. Archived from the original on 20 April 2014.
- ^ "Lidocaine - N01BB02". Drug porphyrinogenicity monograph. The Norwegian Porphyria Centre and the Swedish Porphyria Centre. Archived from the original on 20 April 2014.
strong clinical evidence points to lidocaine as probably not porphyrinogenic
- ISBN 9781597452380.
- PMID 30122981.
- PMID 18265791.
- ISBN 978-0-9626523-7-0.
- S2CID 25581037.
- PMID 30122981.
- PMID 27047224.
- ISBN 9780470846681.
- PMID 2412723.
- ISBN 978-0-07-143763-9.
- PMID 4694036.
- PMID 4609637.
- ^ S2CID 252799787.
- S2CID 260069284.
- S2CID 213017906.
- ^ OCLC 646046738.[page needed]
- ^ Löfgren N, Lundqvist B (1946). "Studies on local anaesthetics II". Svensk Kemisk Tidskrift. 58: 206–17.
- ^ a b Wildsmith JA (2011). "Lidocaine: A more complex story than 'simple' chemistry suggests" (PDF). The Proceedings of the History of Anaesthesia Society. 43: 9–16. Archived (PDF) from the original on 22 April 2014.
- ^ "Lidocaine international forms and names". Drugs.com. Retrieved 29 October 2017.
- ^ "Lidocaine Ingredient Summary". Therapeutic Goods Administration. Retrieved 20 September 2018.
- ^ "Updating medicine ingredient names - list of affected ingredients". Therapeutic Goods Administration. 24 June 2019. Archived from the original on 28 August 2021. Retrieved 16 February 2020.
- ^ "The 2021 Prohibited List International Standard" (PDF). The World Anti-Doping Code. World Anti-Doping Agency (WADA). 1 January 2021. Archived from the original (PDF) on 13 May 2021. Retrieved 18 May 2021.
- ^ "New York Drug Threat Assessment". National Drug Intelligence Center. November 2002. Archived from the original on 12 August 2012.
- PMID 19580174.
- .
- ^ "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. 25 July 1979. Archived from the original on 24 May 2012.
- ^ Winterman D (7 September 2010). "How cutting drugs became big business". BBC News Online. BBC News Magazine. Archived from the original on 2 February 2017. Retrieved 20 January 2017.
- ^ "Revision Bulletin: Lidocaine and Prilocaine Cream–Revision to Related Compounds Test". The United States Pharmacopeial Convention. 30 November 2007. Archived from the original on 1 May 2013.
- ISBN 978-0323241984. Archivedfrom the original on 8 September 2017.
- ^ "FDA Freedom of Information Summary - Tributame" (PDF). Food and Drug Administration. Archived from the original (PDF) on 18 May 2015.
External links
- "Lidocaine Transdermal Patch". MedlinePlus.
- US patent 2441498, Nils Magnus Loefgren & Bengt Josef Lundqvist, "Alkyl glycinanilides", published 1948-05-11, issued 1948-05-11, assigned to ASTRA APOTEKARNES KEM FAB