Lidocain Chemische Eigenschaften,Einsatz,Produktion Methoden
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Chemische Eigenschaften
solid
Verwenden
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
Definition
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.
Indications
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.
Allgemeine Beschreibung
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.
Biologische Aktivität
Anasthetic and class Ib antiarrhythmic agent.? Blocks voltage-gated sodium channels in the inactivated state.
Kontakt-Allergie
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.
Pharmakologie
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.
Pharmakokinetik
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.
Clinical Use
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.
Nebenwirkungen
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.
Sicherheitsprofil
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.
Synthese
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
Elektrophysiologische Effekte
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.
Arzneimittelwechselwirkung
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.
Stoffwechsel
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.
Vorsichtsmaßnahmen
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.
Lidocain Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
