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|Trade names||Xylocaine, others|
|Other names||N-(2,6-dimethylphenyl)-N2,N2-diethylglycinamide, lignocaine (AAN AU)|
|AHFS/Drugs.com||Local Monograph Injectable Monograph|
|intravenous, subcutaneous, topical, oral|
|Bioavailability||35% (by mouth)|
|Metabolism||Liver, 90% CYP3A4-mediated|
|Onset of action||within 1.5 min (IV)|
|Elimination half-life||1.5 h to 2 h|
|Duration of action||10 min to 20 min(IV), 0.5 h to 3 h (injection)|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||234.34 g/mol g·mol−1|
|3D model (JSmol)|
|Melting point||68 °C (154 °F)|
Lidocaine, also known as xylocaine and lignocaine is a medication used to numb tissue in a specific area. It is also used to treat ventricular tachycardia and to perform nerve blocks. Lidocaine mixed with a small amount of adrenaline (epinephrine) is available to allow larger doses for numbing, to decrease bleeding, and to make the numbing effect last longer. When used as an injectable, it typically begins working within four minutes and lasts for half an hour to three hours. Lidocaine mixtures may also be applied directly to the skin or mucous membranes to numb the area.
Common side effects with intravenous use include sleepiness, muscle twitching, confusion, changes in vision, numbness, tingling, and vomiting. It can cause low blood pressure and an irregular heart rate. There are concerns that injecting it into a joint can cause problems with the cartilage. It appears to be generally safe for use in pregnancy. A lower dose may be required in those with liver problems. It is generally safe to use in those allergic to tetracaine or benzocaine. Lidocaine is an antiarrhythmic medication of the class Ib type. Lidocaine works by blocking sodium channels and thus decreasing the rate of contractions of the heart. When used locally as a numbing agent, local neurons cannot signal the brain.
Lidocaine was discovered in 1946 and went on sale in 1948. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication and is not very expensive. The wholesale cost in the developing world in 2014 was US$0.45 to $1.05 wholesale per 20ml vial of medication.
- 1 Medical uses
- 2 Adverse effects
- 3 Pharmacology
- 4 History
- 5 Society and culture
- 6 Veterinary use
- 7 See also
- 8 References
- 9 External links
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 delays the resorption of lidocaine, almost doubling the duration of anaesthesia. For surface anaesthesia, several formulations can be used for endoscopies, before intubations, etc. Buffering the pH of lidocaine makes local numbing less painful. Lidocaine drops can be used on the eyes for short ophthalmic procedures.
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 preventative dose is no longer recommended after a myocardial infarction as the overall benefit is not convincing.
Inhaled lidocaine can be used as a 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 anaesthesia.
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 anaesthesia, 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.
Lidocaine, usually in the form of lignocaine hydrochloride, is available in various forms including:
- Injected local anaesthetic (sometimes combined with adrenaline (epinephrine) to reduce bleeding)
- Dermal patch (sometimes combined with prilocaine in a eutectic mixture)
- 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 "lignocaine 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) such as 4% lignocaine base, marketed since 1996 by ESBA Laboratories Inc.
- Topical liquid
- Lignocaine HCl 2% jelly, combined with hypromellose, to anesthetize and lubricate the urethra, etc., for inserting a catheter or instrument
- Topical patch (lignocaine 5%), marketed since 1999 in the US by Endo Pharmaceuticals as "Lidoderm" - and since 2007 in the UK by Grünenthal as "Versatis".
- Over the counter patch (lignocaine 4%) since 2015.
- Topical ointment (lignocaine 5%) as a temporary reliever of discomfort associated anorectal disorders, such as hemorrhoids, and to prevent premature ejaculation marketed as an over-the-counter product in the US
- Topical aerosol spray
- Inhaled by nebulizer
- As a component of a GI cocktail used in emergency rooms
- Ophthalmic solution
- Ear drops
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.
It is generally safe to use lidocaine with vasoconstrictor such as epinephrine including in regions such as the nose, ears, fingers and toes. While concerns of tissue death if used in these areas have been raised evidence does not support these concerns.
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.
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 teething 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).
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 than it was in the past.
Mechanism of action
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.
When used as an injectable it typically begins working within four minutes and lasts for half an hour to three hours. 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. 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). Lidocaine is excreted in the urine (90% as metabolites and 10% as unchanged drug).
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.
Society and culture
Xylocaine is a brandname.
Lidocaine is not currently listed by the World Anti-Doping Agency as an illegal substance. It is used as an adjuvant, adulterant, and diluent to street drugs such as cocaine and heroin. It is one of the three common ingredients in site enhancement oil used by bodybuilders.
Adulterant in cocaine
Lidocaine is often added to cocaine as a diluent. Cocaine numbs the gums when applied. Lidocaine causes a similar numbing sensation when applied to the gums and is sometimes used as an adulterant in cocaine. This gives the user the impression of high-quality cocaine when in actuality, the user is receiving a diluted product. 
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