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What is Lidocaine and explain in detail?
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. 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. Lidocaine mixtures may also be applied directly to the skin or mucous membranes to numb the area. It is often used mixed with a small amount of adrenaline (epinephrine) to prolong its local effects and to decrease bleeding.If injected intravenously, it may cause cerebral effects such as 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. This means it works by blocking sodium channels and thus decreasing the rate of contractions of the heart. When injected near nerves, the nerves cannot conduct signals to or from the brain.Lidocaine was discovered in 1946 and went on sale in 1948. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. In 2019, it was the 219th most commonly prescribed medication in the United States, with more than 2 million prescriptions.

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.
Lidocaine is one of the most commonly used local anaesthetics in dentistry. It can be administered in multiple ways, most often as a nerve block or infiltration, depending on the type of treatment carried out and the area of the mouth worked on.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. There is tentative evidence for topical lidocaine for neuropathic pain and skin graft donor site pain. As a local numbing agent, it is used for the treatment of premature ejaculation.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. 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 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 preventive dose is no longer recommended after a myocardial infarction as the overall benefit is not convincing.

Epilepsy
A 2013 review on treatment for neonatal seizures recommended intravenous lidocaine as a second-line treatment, if phenobarbital fails to stop seizures.

Other
Intravenous lidocaine infusions are also used to treat chronic pain and acute surgical pain as an opiate sparing technique. The quality of evidence for this use is poor so it is difficult to compare it to placebo or an epidural.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.Lidocaine, along with ethanol, ammonia, and acetic acid, may also help in treating jellyfish stings, both numbing the affected area and preventing further nematocyst discharge.For gastritis, drinking a viscous lidocaine formulation may help with the pain.

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. 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
AllergyADRs 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 adrenaline, 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.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. 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.  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.

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 a contraindication, as they may increase the serum levels, but hundreds of other drugs require monitoring for interaction.

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
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
Bradycardia
Accelerated idioventricular rhythm
Elderly
Ehlers–Danlos syndromes; efficiency of local anesthetics can be reduced
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).

Overdosage
Overdoses of lidocaine may result from 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 from prolonged use of subcutaneous infiltration anesthesia during cosmetic surgery.
Such overdoses 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 forensic investigation in a case of fatal overdose.
Lidocaine is often given intravenously as an antiarrhythmic agent in critical cardiac-care situations. Treatment with intravenous lipid emulsions (used for parenteral feeding) to reverse the effects of local anaesthetic toxicity is becoming more common.

Postarthroscopic glenohumeral chondrolysis
Lidocaine in large amounts may be toxic to cartilage and intra-articular infusions can lead to postarthroscopic glenohumeral chondrolysis.

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. 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.
The same principle applies for this drugs 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.

Pharmacokinetics
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).

History
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
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