Lidocaine, also known aslignocaine and sold under the brand nameXylocaine among others, is alocal anesthetic of theaminoamide type.[11] It is also used to treatventricular tachycardia andventricular fibrillation.[8][9] When used for local anaesthesia or in nerve blocks, lidocaine typically begins working within several minutes and lasts for half an hour to three hours.[9][10] Lidocaine mixtures may also be applied directly to the skin ormucous membranes to numb the area.[11][9] It is often used mixed with a small amount ofadrenaline (epinephrine) to prolong its local effects and to decrease bleeding.[9]
If injected intravenously, it may cause cerebral effects such as confusion, changes in vision, numbness, tingling, and vomiting.[11][8] It can causelow blood pressure and an irregular heart rate.[8] There are concerns that injecting it into a joint can cause problems with thecartilage.[9] It appears to be generally safe for use inpregnancy.[8] A lower dose may be required in those with liver problems.[8] It is generally safe to use in those allergic totetracaine orbenzocaine.[9] Lidocaine is anantiarrhythmic medication of the class Ib type.[8] This means it works byblocking sodium channels thus decreasing the rate of contractions of the heart.[11][8] When injected near nerves, the nerves cannot conduct signals to or fromthe brain.[9]
The efficacy profile of lidocaine as a local anaesthetic is characterized by a rapid onset of action and intermediate duration of efficacy.[11] Therefore, lidocaine is suitable for infiltration, block, and surface anaesthesia. Longer-acting substances such asbupivacaine are sometimes given preference for spinal andepidural anaesthesias; lidocaine, though, has the advantage of a rapid onset of action.[11]
Lidocaine is one of the most commonly used local anaesthetics in dentistry. It can be administered in multiple ways, most often as anerve block orinfiltration, depending on the type of treatment carried out and the area of the mouth worked on.[11]
An adhesivetransdermal patch containing a 5% concentration of lidocaine in ahydrogel bandage, is approved by the US FDA for reducingnerve pain caused by shingles.[20] The transdermal patch is also used for pain from other causes, such as compressed nerves and persistent nerve pain after some surgeries.
A 2013 review on treatment forneonatal seizures recommended intravenous lidocaine as a second-line treatment, ifphenobarbital fails to stop seizures.[22]
Intravenous lidocaine infusions are also used to treatchronic pain andacute surgical pain as anopiate sparing technique. The quality of evidence for this use is poor so it is difficult to compare it toplacebo or anepidural.[23]
Inhaled lidocaine can be used as acough suppressor acting peripherally to reduce thecough reflex. This application can be implemented as a safety and comfort measure for people needingintubation, as it reduces the incidence of coughing and any tracheal damage it might cause when emerging from anaesthesia.[24]
A 2019 systematic review of the literature found that intraurethral lidocaine reduces pain in men who undergocystoscopic procedures.[25]
Forgastritis, drinking a viscous lidocaine formulation may help with the pain.[28]
A 2021 study found that lidocaine 5% spray on glans penis 10-20 minutes prior to sexual intercourse significantly improves premature ejaculation.[29] Another study found that lidocaine-prilocaine cream 5% is effective in premature ejaculation and 20 minutes of application time before sexual intercourse.[30]
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, andallergic reactions only rarely occur.[31] Systemic exposure to excessive quantities of lidocaine mainly results incentral nervous system (CNS) andcardiovascular effects – CNS effects usually occur at lowerblood plasma concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations. ADRs by individual organ systems 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 heavier exposure: drowsiness, lethargy, slurred speech,hypoesthesia, confusion, disorientation, loss of consciousness,respiratory depression, andapnoea.
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 the toxic effects of 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/orparaesthesia. Infrequent ADRs associated with the use of lidocaine include:hypotension,bradycardia,arrhythmias,cardiac arrest, muscle twitching,seizures,coma, and/or respiratory depression.[32]
It is generally safe to use lidocaine with vasoconstrictors such as adrenaline, including in regions such as thenose, ears,fingers, andtoes.[33] While concerns of tissue death, if used in these areas, have been raised, the evidence does not support these concerns.[33]
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.[34] There is some weak evidence to suggest that the use of alternative anesthetic medications such asprilocaine,procaine,bupivacaine,ropivacaine, orlevobupivacaine may decrease the risk of a person developing transient neurological symptoms.[34] Low-quality evidence suggests that 2‐chloroprocaine andmepivacaine when used for spinal anesthetic have a similar risk of the person developing transient neurological symptoms as lidocaine.[34]
Any drugs that are alsoligands ofCYP3A4 andCYP1A2 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 ofmethemoglobinemia should also be considered carefully.Dronedarone andliposomalmorphine are both absolutely acontraindication, as they may increase the serum levels, but hundreds of other drugs require monitoring for interaction.[35]
Intra-articular infusion (this is not an approved indication and can causechondrolysis)
Porphyria, especiallyacute intermittent porphyria; lidocaine has been classified as porphyrogenic because of the hepatic enzymes it induces,[39] although clinical evidence suggests it is not.[40]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).[41]
Overdoses of lidocaine may result from excessive administration by topical orparenteral 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 from prolonged use of subcutaneous infiltration anesthesia during cosmetic surgery.[citation needed] The maximum safe dose is 3 mg per kg.[11]
Such overdoses have often led to severe toxicity or death in both children and adults (local anesthetic systemic toxicity).[42] 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.[43] 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.[44] Treatment with intravenous lipid emulsions (used forparenteral feeding) to reverse the effects of local anaesthetic toxicity is becoming more common.[45][46]
Lidocaine has been used by veterinarians foreuthanasia ofhorses,livestock, and more recently ofdogs andcats.[47] Due to its side effects,intravenous lidocaine can be given only to anesthetized patients, making it less attractive perhaps thanpentobarbital, that can be given intravenously to awake patients. In 2025Russian Army nurses have reported the use of 1-2 %intravenous lidocaine in 60 mL dosage formercy killing of mortally wounded servicemen.[48]
Lidocaine alters signal conduction inneurons by prolonging the inactivation of the fastvoltage-gated Na+ channels in the neuronal cell membrane responsible foraction potential propagation.[11][50] 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 to 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.[51]
When used as an injectable it typically begins working within four minutes and lasts for half an hour to three hours.[9][10] Lidocaine is about 95% metabolized (dealkylated) in theliver mainly by CYP3A4 to the pharmacologically activemetabolites monoethylglycinexylidide (MEGX) and then subsequently to the inactive glycine xylidide. MEGX has a longerhalf-life than lidocaine, but also is a less potent sodium channel blocker.[52] Thevolume 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 proteinalpha1 acid glycoprotein. The oralbioavailability is 35% and the topical bioavailability is 3%. Lidocaine efficacy may be reduced in tissues that areinflamed, due to competing inflammatory mediators.[11]
The elimination half-life of lidocaine is biphasic and around 90 min to 120 min in most people. This may be prolonged in people withhepatic impairment (average 343 min) orcongestive heart failure (average 136 min).[53] Lidocaine is excreted in the urine (90% as metabolites and 10% as unchanged drug).[54]
Lidocaine's 1,5-dimethylbenzene group gives ithydrophobic properties. In addition to this aromatic unit, lidocaine has an aliphatic section comprising amide, carbonyl, and enyl groups.
Lidocaine exhibits a remarkable degree of conformational flexibility, resulting in more than 60 probable conformers.[55] 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[55] and temperature.[56] 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.[57]
Lidocaine is commonly used in veterinary medicine in both companion and production animals around the world and is listed as an essential veterinary medicine by the World Veterinary Association and also the World Small Animal Veterinary Association.[1][58]
In veterinary medicine, it is commonly used as a local anaesthetic both as an injectable or topical product. It provides excellent local anaesthesia when given by local infiltration into a tissue or via specific nerve blocks. These are commonly applied to nerves of the head, limbs, thorax, and spine. It can also be used to treat ventricular arrhythmias when given intravenously. In most veterinary species, when given via injection, it has a rapid onset of action (2-10 minutes) with a duration of action of 30-60 minutes.[59]
In veterinary species, its metabolism is much the same as humans with rapid metabolism in the liver to the major metabolites MEGX (monoethylglycine xylidide) and GX (glycine xylidide) that retain partial activity against sodium channels. These compounds are further metabolized to monoethylglycine and xylidide, respectively.[59]
Toxicity in animals is similar to that seen in humans with both toxicity to the central nervous system (CNS) and cardiovascular system observed. General the CNS signs are seen first with agitation and muscle twitching seen before the cardiovascular signs of hypotension, myocardial depression, and arrhythmias. Further CNS depression will result from higher doses with seizures and convulsions and eventually apnea and death.[59]
Lidocaine, the firstaminoamide–type local anesthetic (previous were amino esters), was first synthesized under the name 'xylocaine' by Swedish chemistNils Löfgren in 1943.[62][63][64] His colleague Bengt Lundqvist performed the first injection anesthesia experiments on himself.[62] It was first marketed in 1949.
Xylocaine is a brand name, referring to the major synthetic building block2,6-xylidine. The "ligno" prefix is chosen because "xylo" meanswood in Greek while "ligno" means the same in Latin. The "lido" prefix instead refers to the fact that the drug is chemically related toacetanilide.[64]
Lidocaine is often added tococaine as adiluent.[71][72] Cocaine and lidocaine both numb thegums when applied. This gives the user the impression of high-quality cocaine when in actuality the user is receiving a diluted product.[73]
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US patent 2441498, Nils Magnus Loefgren & Bengt Josef Lundqvist, "Alkyl glycinanilides", published 11 May 1948, issued 11 May 1948, assigned to ASTRA APOTEKARNES KEM FAB[permanent dead link]
