リドカイン

外観

白色〜わずかにうすい黄色, 結晶〜結晶性粉末

溶解性

エタノール、クロロホルムに易溶、エーテル、オリーブ油、ゴマ油に可溶。水に不溶。

解説

2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide．C14H22N2O(234.34)．リグノカインともいう．2,6-ジメチルアニリンにモノクロロ酢酸クロリド，ジエチルアミンを順次縮合させて合成する．"融点68～69 ℃，沸点159～160 ℃(266 Pa)．水に不溶，エタノールに可溶．表面麻酔および脊椎麻酔作用があり，プロカインの数倍の強さを示す．塩酸塩(融点127～129 ℃)は作用発現が迅速で持続時間も長いことから，注射用局所麻酔に使用される．LD50 292 mg/kg(マウス，経口)．[CAS 137-58-6]
森北出版「化学辞典（第2版）

用途

ナトリウム透過性抑制作用を 示します。

用途

ナトリウム透過性抑制作用を 示します。

用途

局所麻酔剤、抗不整脈剤

用途

神経化学研究用。

用途

薬理・生理作用研究用。

用途

局所麻酔剤として開発されたが、その後各種疾患に伴う不整脈の治療にも用いられるようになった。塩酸リドカイン注射液として脊椎(せきつい)麻酔、硬膜外麻酔、伝達麻酔、浸潤麻酔に用いられ、また1～2％液として表面麻酔に塗布または噴霧する。歯科用には塩酸エピネフリンを配合した2％注射液がよく用いられる。外傷、熱傷、刺傷、凍傷、痔疾(じしつ)の疼痛(とうつう)には5％軟膏(なんこう)が用いられる。なお、不整脈には点滴静脈注射で使用される。リドカインは白色ないし微黄色の結晶または結晶性粉末で、わずかに特異臭があり、味はわずかに苦く、舌を麻痺(まひ)する。劇薬で、極量1回0.2グラム（硬膜外・伝達・浸潤麻酔）および1回毎分4ミリグラム（点滴静注）。

リドカインは，強力な局所麻酔薬。空気中で安定で，酸，アルカリにも安定である。作用発現が迅速，確実で，作用持続時間も長く，表面麻酔作用も強く，脊髄，伝導，浸潤，表面など，各局所麻酔の麻酔薬として，各科領域で広範囲に使用される。局所麻酔作用はプロカインの2～4倍強力であり，毒性の強さはプロカインと同程度である。組織刺激作用はほとんどなく，プロカインに過敏な患者にも使用しうる。アドレナリンを併用すれば，吸収が遅延し，副作用はほとんど現れない。全身的な投与では抗不整脈作用を示し，かつ速効性なので，手術中や緊急の場合に利用されている。［幸保文治］

効能

表面麻酔薬, 抗不整脈薬, ナトリウムチャネル遮断薬

商品名

ペンレス (日東電工)

化学的特性

solid

使用

Lidocaine (Alphacaine)is a selective inverse peripheral histamine H1-receptor agonist with an IC50 of >32 μM. [1] Histamine is responsible for many features of allergic reactions. Lidocaine (Alphacaine)is a second-generation antihistamine agent closely st

定義

ChEBI: Lidocaine is the monocarboxylic acid amide resulting from the formal condensation of N,N-diethylglycine with 2,6-dimethylaniline. It has a role as a local anaesthetic, an anti-arrhythmia drug, an environmental contaminant, a xenobiotic and a drug allergen. It is a monocarboxylic acid amide, a tertiary amino compound and a member of benzenes. It derives from a glycinamide.

適応症

Experimentally, lidocaine has been found to prevent VF arising during myocardial ischemia or infarction by preventing the fragmentation of organized largewavefronts into heterogeneous wavelets. Although lidocaine is of proven benefit in preventing VF early after clinical myocardial infarction, there is no evidence that it reduces mortality. To the contrary, lidocaine may increase mortality after myocardial infarction by approximately 40% to 60%.There are no controlled studies of lidocaine in secondary prevention of recurrence of VT or VF.
Lidocaine terminates organized monomorphic spontaneous VT or induced sustained VT in only approximately 20% of cases and is less effective than many other antiarrhythmic drugs. In a blinded, randomized study of intravenous lidocaine versus intravenous amiodarone in out-of-hospital VF resistant to defibrillation, lidocaine was associated with half the likelihood of survival to hospital admission compared with amiodarone.

一般的な説明

Lidocaine was the first amino amide synthesized in 1948and has become the most widely used local anesthetic. Thetertiary amine has a pKa of 7.8 and it is formulated as thehydrochloride salt with a pH between 5.0 and 5.5. When lidocaineis formulated premixed with epinephrine the pH ofthe solution is adjusted to between 2.0 and 2.5 to prevent the hydrolysis of the epinephrine. Lidocaine is also availablewith or without preservatives. Some formulations of lidocainecontain a methylparaben preservative that maycause allergic reactions in PABA-sensitive individuals. Thelow pKa and medium water solubility provide intermediateduration of topical anesthesia of mucous membranes.Lidocaine can also be used for infiltration, peripheral nerveand plexus blockade, and epidural anesthesia.

生物活性

Anasthetic and class Ib antiarrhythmic agent.? Blocks voltage-gated sodium channels in the inactivated state.

接触アレルゲン

Lidocaine is an anesthetic of the amide group, like articaine or bupivacaine. Immediate-type IgE-dependent reactions are rare, and delayed-type contact dermatitis is exceptional. Cross-reactivity between the different amide anesthetics is not systematic.

薬物動態学

Lidocaine is administered intravenously because extensive first-pass transformation by the liver prevents clinically effective plasma concentrations orally. The drug is dealkylated and eliminated almost entirely by the liver; therefore, dosage adjustments are necessary in the presence of hepatic disease or dysfunction. Lidocaine clearance exhibits the time dependency common to high-clearance agents. With a continuous infusion lasting more than 24 hours, there is a decrease in total lidocaine clearance and an increase in elimination half-life compared with a single dose. Lidocaine free plasma levels can vary in certain patients owing to binding with albumin and the acutephase reactant a1-acid glycoprotein. Levels of a1-acid glycoprotein are increased in patients after surgery or acute myocardial infarction, whereas levels of both a1-acid glycoprotein and serum albumin are decreased in chronic hepatic disease or heart failure and in those who are malnourished. This is an essential consideration because it is the unbound fraction that is pharmacologically active.

薬理学

Lidocaine is the most widely used local anaesthetic. It has a rapid onset and short duration of action. Lidocaine is rapidly and extensively metabolised in the liver and is safe at recommended doses. Efficacy is enhanced markedly and duration of action prolonged by addition of adrenaline. Lidocaine is less toxic than bupivacaine; a testament to this relative safety is that lidocaine is used intravenously as a class 1b antiarrhythmic and as an i.v. infusion to treat refractory chronic pain. Lidocaine solutions for injection are available in concentrations of 1% and 2%, with or without adrenaline. It is also available as a spray (4% or 10%), cream (2% or 4%), ointment or medicated plaster (both 5%) for topical application.

臨床応用

The metabolism of lidocaine is typical of the amino amideanesthetics . The liver is responsiblefor most of the metabolism of lidocaine and any decreasein liver function will decrease metabolism. Lidocaineis primarily metabolized by de-ethylation of the tertiary nitrogento form monoethylglycinexylidide (MEGX). At lowlidocaine concentrations, CYP1A2 is the enzyme responsiblefor most MEGX formation. At high lidocaine concentrations,both CYP1A2 and CYP3A4 are responsible for the formationof MEGX.

副作用

Central nervous system side effects such as drowsiness, slurred speech, paresthesias, agitation, and confusion predominate. These symptoms may progress to convulsions and respiratory arrest with higher plasma concentrations. A rare adverse effect is malignant hyperthermia.
Cimetidine significantly reduces the systemic clearance of lidocaine as well as the volume of distribution at steady state and the degree of plasma protein binding. Beta blockers also reduce lidocaine clearance owing to a decrease in hepatic blood flow. For the same reason, clearance is reduced in congestive heart failure or low-output states.
Amiodarone may also influence the pharmacokinetics of lidocaine. In patients receiving amiodarone, single doses of intravenous lidocaine do not influence the pharmacokinetics of either agent. When amiodarone treatment is started in patients who are already receiving lidocaine infusion, there is a decrease in lidocaine clearance, which can result in toxic lidocaine levels.

安全性プロファイル

Poison by ingestion, intravenous, intraperitoneal, and subcutaneous routes. Human systemic effects: blood pressure lowering, changes in heart rate, coma, convulsions, dlstorted perceptions, dyspnea, excitement, hallucinations, muscle contraction or spasticity, pulse rate, respiratory depression, toxic psychosis. An experimental teratogen. Other experimental reproductive effects. A local anesthetic. Mutation data reported. When heated to decomposition it emits toxic fumes of NOx.

合成

Lidocaine, 2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide (2.2.2), is synthesized from 2,6-dimethylaniline upon reaction with chloroacetic acid chloride, which gives |á-chloro-2,6-dimethylacetanilide (2.1.1), and its subsequent reaction with diethylamine [11].

Synthesis of Lidocaine

電気生理学的効果

Experimentally, lidocaine has been found to prevent VF arising during myocardial ischemia or infarction by preventing the fragmentation of organized largewavefronts into heterogeneous wavelets. Although lidocaine is of proven benefit in preventing VF early after clinical myocardial infarction, there is no evidence that it reduces mortality. To the contrary, lidocaine may increase mortality after myocardial infarction by approximately 40% to 60%.There are no controlled studies of lidocaine in secondary prevention of recurrence of VT or VF.
Lidocaine terminates organized monomorphic spontaneous VT or induced sustained VT in only approximately 20% of cases and is less effective than many other antiarrhythmic drugs. In a blinded, randomized study of intravenous lidocaine versus intravenous amiodarone in out-of-hospital VF resistant to defibrillation, lidocaine was associated with half the likelihood of survival to hospital admission compared with amiodarone.

薬物相互作用

The concurrent administration of lidocaine with cimetidine but not ranitidine may cause an increase (15%) in the plasma concentration of lidocaine. This effect is a manifestation of cimetidine reducing the clearance and volume of distribution of lidocaine. The myocardial depressant effect of lidocaine is enhanced by phenytoin administration.

代謝

Lidocaine is extensively metabolized in the liver by N-dealkylation and aromatic hydroxylations catalyzed by CYP1A2 isozymes. Lidocaine also possesses a weak inhibitory activity toward the CYP1A2 isozymes and, therefore, may interfere with metabolism of other medications.

予防処置

Contraindications include hypersensitivity to local anesthetics of the amide type (a very rare occurrence), severe hepatic dysfunction, a history of grand mal seizures due to lidocaine, and age 70 or older. Lidocaine is contraindicated in the presence of second- or thirddegree heart block, since it may increase the degree of block and can abolish the idioventricular pacemaker responsible for maintaining the cardiac rhythm.