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Lidocaine hydrochloride was synthesized by Löfgren and Lundquist in 1943, and was clinically introduced in 1948. It remains one of the most widely used local anaesthetics. It can be administered parenterally for a peripheral nerve block (PNB), intravenously, or applied topically at strengths of 2–4%. The addition of epinephrine 1:200 000 to 1:100 000 slows the vascular absorption of lidocaine and prolongs its effects.
Lidocaine hydrochloride is white and odorless crystal with bitter and numb taste. It is easily soluble in water, ethanol and organic solvents, but insoluble in ether. Aqueous solution in the case of acid and alkali do not break down, repeated autoclave rarely go bad.
Lidocaine hydrochloride is a local anesthetic and antiarrhythmic drug. It is clinically used for infiltration anesthesia, epidural anesthesia, surface anesthesia (including in the thoracoscopy or abdominal surgery for mucosal anesthesia) and nerve conduction block. The drug can also be used for acute myocardial infarction after ventricular premature beats and ventricular tachycardia, and for digitalis poisoning, cardiac surgery and ventricular arrhythmias caused by cardiac catheterization. But it is usually ineffective for supraventricular arrhythmias.
Lidocaine hydrochloride is an amide local anesthetic. After blood absorption or intravenous administration, the drug has obvious excitement and inhibition of biphasic effects for the central nervous system, and no excitement of the pioneer. With the dose increased, the role or toxicity increased, there is an anti-convulsive effect with sub-poisoning plasma concentration; Blood concentration of more than 5μg • ml-1 can occur convulsions. Lidocaine hydrochloride in low doses can promote outflow of K+ in cardiomyocytes, reduce myocardial autonomy, and has antiarrhythmic effects. In the treatment dose, lidocaine hydrochloride has no significant effect for the electrical activity of cardiomyocytes, atrioventricular conduction and myocardial contraction. Increased plasma concentration may cause slowing of heart conduction, atrioventricular block, inhibition of myocardial contractility and decreased cardiac output.
Lidocaine hydrochloride is characterized by strong penetration, strong dispersion, rapidly onset. The anesthetic performance is twice that of procaine and the toxicity is1. There is an anesthetic effect after 5 minutes treatments, and anesthesia can last 1 to 1.5 hours, 50% longer than procaine. The drug is effective on the heart of the disease or arrhythmia caused by cardiac glycoside, but on the supraventricular tachycardia is poor. This product is fast and oral ineffective, with short duration, and often used as intravenous administration.
Lidocaine is metabolized by the liver with only a small amount (3%) found unchanged in urine. The three main mechanisms of metabolism are shown below: N-de-ethylation > monoethylglycinexylidide (MEGX) > glycinexylidide Hydrolysis of glycinexylidide 5-hydroxylation of lidocaine’s benzene ring Lidocaine possesses convulsant activity. Hepatic disease or reduced hepatic blood flow (as in congestive cardiac failure) will lower metabolic capacity.
Surface anesthesia with solution of 2% to 5%.Infiltration anesthesia with solution of 0.25% to 0.5%, conduction anesthesia with 2%, each injection point, horse, cattle 8 to 12 ml, sheep 3 to 4 ml. Epidural anesthesia with 2% solution, horse, cow, 8 to 12 ml, dog, cat, 0.22 ml per kilogram of body weight. Subcutaneous injection with 2% solution, pig, sheep, 80 ml, horse, cow, 400 ml, dog,25 ml, cat, 8.5 ml.
Treatment of arrhythmia, intravenous injection: Per kg of dog’s body weight of the initial dose is 2 to 4 mg, followed by 25 to 75 micrograms per minute intravenous infusion; Cat initial dose of 250 to 500 micrograms, followed by intravenous infusion of 20 micrograms per minute.
The incidence of adverse effect with lidocaine hydrochloride was about 6.3%. Most adverse effects are dose dependent. Adverse effects are drowsiness, dizziness, nausea, vomiting, burnout, euphoria, insanity, muscle convulsions, syncope, blurred vision, confusion and difficulty breathing. Large doses lead to severe sinus bradycardia, cardiac arrest, severe atrioventricular block and weakened myocardial contractility, reduced blood pressure and so on. Excess concentrations of lidocaine hydrochloride in the blood cause some problems. For example, atrial conduction slows, atrioventricular blocks (A-V-B), and inhibits myocardial contractility and cardiac output decreases. There are little allergic effects, such as erythema rash, angioneurotic edema and so on.
Lidocaine is contraindicated in patients with known hypersensitivity to local anaesthetics of the amide type and in patients with porphyria. Reactions due to overdose with lidocaine (high plasma levels) are systemic and involve the central nervous and cardiovascular systems. Effects include medullary depression, tonic and clonic convulsions, and cardiovascular collapse Solutions in multidose vials may contain hydrobenzoate derivatives and have been associated with allergic reactions in some patients. As with all of the amide local anaesthetics protein binding is reduced in the neonate (50% versus 64% in the adult), which necessitates reduced doses if adverse reactions are to be avoided.
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https://en.wikipedia.org/wiki/Lidocaine
White to Off-White Solid
Xylocaine,Astra,US,1949
Apply to affected site 5 to 10 minutes before procedure. Duration of anesthesia is relatively short (<1 hour).
Local anesthesic;Na+ channel blocker
Anesthetic (local); antiarrhythmic (class IB). Long-acting, membrane stabilizing agent against ventricular arrhythmia. Originally developed as a local anesthetic.
ChEBI: Lidocaine hydrochloride is the anhydrous form of the hydrochloride salt of lidocaine. It functions as both a local anesthetic and cardiac depressant, and is commonly used as an antiarrhythmic agent. Its potency is higher and its effects last longer than those of procaine, but its duration of action is shorter than that of bupivacaine or prilocaine.
One mol of 2,6-xylidine is dissolved in 800 ml glacial acetic acid. The mixture
is cooled to 10°C, after which 1.1 mol chloracetyl chloride is added at one
time. The mixture is stirred vigorously during a few moments after which
1,000 ml half-saturated sodium acetate solution, or other buffering or
alkalizing substance, is added at one time. The reaction mixture is shaken
during half an hour. The precipitate formed which consists of ω-chloro-2,6-
dimethyl-acetanilide is filtered off, washed with water and dried. The product
is sufficiently pure for further treatment. The yield amounts to 70 to 80% of
the theoretical amount.
One mole of the chloracetyl xylidide thus prepared and 2.5 to 3 mols diethyl
amine are dissolved in 1,000 ml dry benzene. The mixture is refluxed for 4 to
5 hours. The separated diethyl amine hydrochloride is filtered off. The benzene
solution is shaken out two times with 3N hydrochloric acid, the first time with
800 ml and the second time with 400 ml acid. To the combined acid extracts
is added an approximately 30% solution of sodium hydroxide until the
precipitate does not increase.
The precipitate, which sometimes is an oil, is taken up in ether. The ether
solution is dried with anhydrous potassium carbonate after which the ether is
driven off. The remaining crude substance is purified by vacuum distillation.
During the distillation practically the entire quantity of the substance is carried
over within a temperature interval of 1° to 2°C. The yield approaches the
theoretical amount. MP 68° to 69°C. BP 180° to 182°C at 4 mm Hg; 159° to
160°C at 2 mm Hg. (Procedure is from US Patent 2,441,498.)
Alpha caine Hydrochloride (Carlisle); Anestacon (Polymedica); Laryng-O-Jet (International Medication); Lidocaton (Phar maton); Lidopen (Meridian); Xylocaine (Abraxis); Xylo caine (AstraZeneca); Xylocaine (Dentsply).
Local anesthetic, Antiarrhythmic
Lidocaine hydrochloride (Xylocaine) is the most commonly used local anesthetic. It is well tolerated, and in addition to its use in infiltration and regional nerve blocks, it is commonly used for spinal and topical anesthesia and as an antiarrhythmic agent. Lidocaine has a more rapidly occurring, more intense, and more prolonged duration of action than does procaine.
Lidocaine hydrochloride,2-(diethylamino)-2 ,6 -acetoxylidide monohydrochloride(Xylocaine), was conceived as a derivative of gramine(3-dimethylaminomethylindole) and introduced as a localanesthetic. It is now being used intravenously as a standardparenteral agent for suppression of arrhythmias associatedwith acute myocardial infarction and cardiac surgery.It isthe drug of choice for the parenteral treatment of prematureventricular contractions.
Lidocaine can block Na+ and K+ ion channels and regulate intracellular and extracellular calcium concentrations through other ligand-gated ion channels. Lidocaine was the first sodium channel blocker to be identified. Its main mechanism of action is blocking voltage-gated Na+ channels (VGSC/NaVs).
Lidocaine hydrochloride is a class IB antiarrhythmicagent with a different effect on the electrophysiologicalproperties of myocardial cells from that of procainamideand quinidine. It binds with equal affinity to the active (A)and inactive (I) Na+ ion channels. It depresses diastolic depolarizationand automaticity in the Purkinje fiber networkand increases the functional refractory period relative toaction potential duration, as do procainamide and quinidine.It differs from the latter two drugs, however, in that it doesnot decrease, and may even enhance, conduction velocity and increase membrane responsiveness to stimulation.There are fewer data available on the subcellular mechanismsresponsible for the antiarrhythmic actions of lidocainethan on the more established drug quinidine. It has been proposedthat lidocaine has little effect on membrane cation exchangeof the atria. Sodium ion entrance into ventricularcells during excitation is not influenced by lidocaine becauseit does not alter conduction velocity in this area.Lidocaine hydrochloride does depress Na+ influx duringdiastole, as do all other antiarrhythmic drugs, to diminishautomaticity in myocardial tissue. It also alters membraneresponsiveness in Purkinje fibers, allowing increased conductionvelocity and ample membrane potential at the timeof excitation.
Poison by ingestion, intraperitoneal, intravenous, subcutaneous, intramuscular, and intratracheal routes. Human systemic effects: somnolence, respiratory depression, low blood pressure, cardiomyopathy includmg infarction, pulse rate increase. An experimental teratogen. Other experimental reproductive effects. A skin and eye irritant. An anesthetic. When heated to decomposition it emits very toxic fumes of NOx and HCl.
Store in a tightly closed container at room temperature away from light and moisture. Do not store in the bathroom. Do not freeze. Keep all medications away from children and pets.
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Regardless, lidocaine is currently available as a relatively non-expensive generic medication that is written for in millions of prescriptions internationally on a yearly basis. It is even included in the World Health Organization's List of Essential Medicines 9 .
Ever since its discovery and availability for sale and use in the late 1940s, lidocaine has become an exceptionally commonly used medication 6 . In particular, lidocaine's principal mode of action in acting as a local anesthetic that numbs the sensations of tissues means the agent is indicated for facilitating local anesthesia for a large variety of surgical procedures 10 , 7 , 8 . It ultimately elicits its numbing activity by blocking sodium channels so that the neurons of local tissues that have the medication applied on are transiently incapable of signaling the brain regarding sensations 10 , 7 , 8 . In doing so, however, it can block or decrease muscle contractile, resulting in effects like vasodilation, hypotension, and irregular heart rate, among others 10 , 7 , 8 . As a result, lidocaine is also considered a class Ib anti-arrhythmic agent 7 , 8 , 12 . Nevertheless, lidocaine's local anesthetic action sees its use in many medical situations or circumstances that may benefit from its action, including the treatment of premature ejaculation 5 .
Excessive blood levels of lidocaine can cause changes in cardiac output, total peripheral resistance, and mean arterial pressure 10,7. With central neural blockade these changes may be attributable to the block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine when present 10,7. The net effect is normally a modest hypotension when the recommended dosages are not exceeded 10,7.
In particular, such cardiac effects are likely associated with the principal effect that lidocaine elicits when it binds and blocks sodium channels, inhibiting the ionic fluxes required for the initiation and conduction of electrical action potential impulses necessary to facilitate muscle contraction 10,7,8. Subsequently, in cardiac myocytes, lidocaine can potentially block or otherwise slow the rise of cardiac action potentials and their associated cardiac myocyte contractions, resulting in possible effects like hypotension, bradycardia, myocardial depression, cardiac arrhythmias, and perhaps cardiac arrest or circulatory collapse 10,7,8.
Moreover, lidocaine possesses a dissociation constant (pKa) of 7.7 and is considered a weak base 8. As a result, about 25% of lidocaine molecules will be un-ionized and available at the physiological pH of 7.4 to translocate inside nerve cells, which means lidocaine elicits an onset of action more rapidly than other local anesthetics that have higher pKa values 8. This rapid onset of action is demonstrated in about one minute following intravenous injection and fifteen minutes following intramuscular injection 7. The administered lidocaine subsequently spreads rapidly through the surrounding tissues and the anesthetic effect lasts approximately ten to twenty minutes when given intravenously and about sixty to ninety minutes after intramuscular injection 7.
Nevertheless, it appears that the efficacy of lidocaine may be minimized in the presence of inflammation 8. This effect could be due to acidosis decreasing the amount of un-ionized lidocaine molecules, a more rapid reduction in lidocaine concentration as a result of increased blood flow, or potentially also because of increased production of inflammatory mediators like peroxynitrite that elicit direct actions on sodium channels 8.
In general, lidocaine is readily absorbed across mucous membranes and damaged skin but poorly through intact skin 12. The agent is quickly absorbed from the upper airway, tracheobronchial tree, and alveoli into the bloodstream 12. And although lidocaine is also well absorbed across the gastrointestinal tract the oral bioavailability is only about 35% as a result of a high degree of first-pass metabolism 12. After injection into tissues, lidocaine is also rapidly absorbed and the absorption rate is affected by both vascularity and the presence of tissue and fat capable of binding lidocaine in the particular tissues 12.
The concentration of lidocaine in the blood is subsequently affected by a variety of aspects, including its rate of absorption from the site of injection, the rate of tissue distribution, and the rate of metabolism and excretion 10,7,8. Subsequently, the systemic absorption of lidocaine is determined by the site of injection, the dosage given, and its pharmacological profile 10,7,8. The maximum blood concentration occurs following intercostal nerve blockade followed in order of decreasing concentration, the lumbar epidural space, brachial plexus site, and subcutaneous tissue 10,7,8. The total dose injected regardless of the site is the primary determinant of the absorption rate and blood levels achieved 10,7,8. There is a linear relationship between the amount of lidocaine injected and the resultant peak anesthetic blood levels 10,7,8.
Nevertheless, it has been observed that lidocaine hydrochloride is completely absorbed following parenteral administration, its rate of absorption depending also on lipid solubility and the presence or absence of a vasoconstrictor agent 10,7,8. Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration 10,7,8.
Additionally, lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion 10.
The volume of distribution determined for lidocaine is 0.7 to 1.5 L/kg 8.
In particular, lidocaine is distributed throughout the total body water 7. Its rate of disappearance from the blood can be described by a two or possibly even three-compartment model 7. There is a rapid disappearance (alpha phase) which is believed to be related to uptake by rapidly equilibrating tissues (tissues with high vascular perfusion, for example) 7. The slower phase is related to distribution to slowly equilibrating tissues (beta phase) and to its metabolism and excretion (gamma phase) 7.
Lidocaine's distribution is ultimately throughout all body tissues 7. In general, the more highly perfused organs will show higher concentrations of the agent 7. The highest percentage of this drug will be found in skeletal muscle, mainly due to the mass of muscle rather than an affinity 7.
The protein binding recorded for lidocaine is about 60 to 80% and is dependent upon the plasma concentration of alpha-1-acid glycoprotein 10,8. Such percentage protein binding bestows lidocaine with a medium duration of action when placed in comparison to other local anesthetic agents 8.
The excretion of unchanged lidocaine and its metabolites occurs predominantly via the kidney with less than 5% in the unchanged form appearing in the urine 10,7. The renal clearance is inversely related to its protein binding affinity and the pH of the urine 7. This suggests by the latter that excretion of lidocaine occurs by non-ionic diffusion 7.
The elimination half-life of lidocaine hydrochloride following an intravenous bolus injection is typically 1.5 to 2.0 hours 10. Because of the rapid rate at which lidocaine hydrochloride is metabolized, any condition that affects liver function may alter lidocaine HCl kinetics 10. The half-life may be prolonged two-fold or more in patients with liver dysfunction 10.
The mean systemic clearance observed for intravenously administered lidocaine in a study of 15 adults was approximately 0.64 +/- 0.18 L/min 11.
Symptoms of overdose and/or acute systemic toxicity involves central nervous system toxicity that presents with symptoms of increasing severity 7. Patients may present initially with circumoral paraesthesia, numbness of the tongue, light-headedness, hyperacusis, and tinnitus 7. Visual disturbance and muscular tremors or muscle twitching are more serious and precede the onset of generalized convulsions 7. These signs must not be mistaken for neurotic behavior 7. Unconsciousness and grand mal convulsions may follow, which may last from a few seconds to several minutes 7. Hypoxia and hypercapnia occur rapidly following convulsions due to increased muscular activity, together with the interference with normal respiration and loss of the airway 7. In severe cases, apnoea may occur. Acidosis increases the toxic effects of local anesthetics 7. Effects on the cardiovascular system may be seen in severe cases 7. Hypotension, bradycardia, arrhythmia and cardiac arrest may occur as a result of high systemic concentrations, with potentially fatal outcome 7.
Pregnancy Category B has been established for the use of lidocaine in pregnancy, although there are no formal, adequate, and well-controlled studies in pregnant women 10. General consideration should be given to this fact before administering lidocaine to women of childbearing potential, especially during early pregnancy when maximum organogenesis takes place 10. Ultimately, although animal studies have revealed no evidence of harm to the fetus, lidocaine should not be administered during early pregnancy unless the benefits are considered to outweigh the risks 7. Lidocaine readily crosses the placental barrier after epidural or intravenous administration to the mother 7. The ratio of umbilical to maternal venous concentration is 0.5 to 0.6 7. The fetus appears to be capable of metabolizing lidocaine at term 7. The elimination half-life in the newborn of the drug received in utero is about three hours, compared with 100 minutes in the adult 7. Elevated lidocaine levels may persist in the newborn for at least 48 hours after delivery 7. Fetal bradycardia or tachycardia, neonatal bradycardia, hypotonia or respiratory depression may occur 7.
Local anesthetics rapidly cross the placenta and when used for epidural, paracervical, pudendal or caudal block anesthesia, can cause varying degrees of maternal, fetal and neonatal toxicity 10. The potential for toxicity depends upon the procedure performed, the type and amount of drug used, and the technique of drug administration 10. Adverse reactions in the parturient, fetus and neonate involve alterations of the central nervous system, peripheral vascular tone, and cardiac function 10.
Maternal hypotension has resulted from regional anesthesia 10. Local anesthetics produce vasodilation by blocking sympathetic nerves 10. Elevating the patient’s legs and positioning her on her left side will help prevent decreases in blood pressure 10. The fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable 10.
Epidural, spinal, paracervical, or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts 10. In one study, paracervical block anesthesia was associated with a decrease in the mean duration of first stage labor and facilitation of cervical dilation 10. However, spinal and epidural anesthesia have also been reported to prolong the second stage of labor by removing the parturient’s reflex urge to bear down or by interfering with motor function 10. The use of obstetrical anesthesia may increase the need for forceps assistance 10.
The use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life 10. The long-term significance of these observations is unknown 10. Fetal bradycardia may occur in 20 to 30 percent of patients receiving paracervical nerve block anesthesia with the amide-type local anesthetics and may be associated with fetal acidosis 10. Fetal heart rate should always be monitored during paracervical anesthesia 10. The physician should weigh the possible advantages against risks when considering a paracervical block in prematurity, toxemia of pregnancy, and fetal distress 10. Careful adherence to the recommended dosage is of the utmost importance in obstetrical paracervical block 10. Failure to achieve adequate analgesia with recommended doses should arouse suspicion of intravascular or fetal intracranial injection 10. Cases compatible with unintended fetal intracranial injection of local anesthetic solution have been reported following intended paracervical or pudendal block or both. Babies so affected present with unexplained neonatal depression at birth, which correlates with high local anesthetic serum levels, and often manifest seizures within six hours 10. Prompt use of supportive measures combined with forced urinary excretion of the local anesthetic has been used successfully to manage this complication 10.
It is not known whether this drug is excreted in human milk 10. Because many drugs are excreted in human milk, caution should be exercised when lidocaine is administered to a nursing woman 10.
Dosages in children should be reduced, commensurate with age, body weight and physical condition 10.
The oral LD 50 of lidocaine HCl in non-fasted female rats is 459 (346-773) mg/kg (as the salt) and 214 (159-324) mg/kg (as the salt) in fasted female rats 10.
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