Histamine H1 receptor ( IC50 > 32 μM )

Lidocaine (Lignocaine) blocks the tail nerve entirely and reversibly in rats. Thermal nociception block has a faster recovery rate and a slower onset than mechanical nociception block, which is produced by lidocaine[3].

Cell Line: The human gastric cancer cell line MKN45
Concentration: 10 nM
Incubation Time: 48 hours
Result: Decreased significantly cell proliferation.

Absorption, Distribution and Excretion
In general, lidocaine is readily absorbed across mucous membranes and damaged skin but poorly through intact skin. The agent is quickly absorbed from the upper airway, tracheobronchial tree, and alveoli into the bloodstream. 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. 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. 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. Subsequently, the systemic absorption of lidocaine is determined by the site of injection, the dosage given, and its pharmacological profile. 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. The total dose injected regardless of the site is the primary determinant of the absorption rate and blood levels achieved. There is a linear relationship between the amount of lidocaine injected and the resultant peak anesthetic blood levels. 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. Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration. Additionally, lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion.
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. The renal clearance is inversely related to its protein binding affinity and the pH of the urine. This suggests by the latter that excretion of lidocaine occurs by non-ionic diffusion.
The volume of distribution determined for lidocaine is 0.7 to 1.5 L/kg. In particular, lidocaine is distributed throughout the total body water. Its rate of disappearance from the blood can be described by a two or possibly even three-compartment model. 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). The slower phase is related to distribution to slowly equilibrating tissues (beta phase) and to its metabolism and excretion (gamma phase). Lidocaine's distribution is ultimately throughout all body tissues. In general, the more highly perfused organs will show higher concentrations of the agent. The highest percentage of this drug will be found in skeletal muscle, mainly due to the mass of muscle rather than an affinity.
The mean systemic clearance observed for intravenously administered lidocaine in a study of 15 adults was approximately 0.64 +/- 0.18 L/min.
Binding of lidocaine to plasma proteins is variable and concentration dependent. At concentrations of 1-4 ug/mL, the drug is approximately 60-80% bound to plasma proteins. Lidocaine is partially bound to a1-acid glycoprotein (a1-AGP), and the extent of binding to a1-AGP depends on the plasma concentration of the protein. In patients with myocardial infarction, increases in plasma a1-AGP concentration are associated with increased lidocaine binding and increased total plasma concentrations of the drug, but only small increases in plasma concentration of free drug; these changes in a1-AGP concentration and lidocaine binding are believed to account in part for accumulation of the drug observed in patients with myocardial infarction receiving prolonged infusions.
The volume of distribution is decreased in patients with congestive heart failure and increased in patients with liver disease.
Lidocaine is widely distributed into body tissues. After an IV bolus, there is an early, rapid decline in plasma concentrations of the drug, principally associated with distribution into highly perfused tissues such as the kidneys, lungs, liver, and heart, followed by a slower elimination phase in which metabolism and redistribution into skeletal muscle and adipose tissue occur. Lidocaine has a high affinity for fat and adipose tissue. As plasma concentrations of the drug fall, the diffusion gradient from tissue to blood increases and the lidocaine that initially entered the highly perfused tissues and fat diffuses back into the blood.
Plasma lidocaine concentrations of approximately 1-5 ug/mL are required to suppress ventricular arrhythmias. Toxicity has been associated with plasma lidocaine concentrations greater than 5 ug/mL. Following IV administration of a bolus dose of 50-100 mg of lidocaine hydrochloride, the drug has an onset of action within 45-90 seconds and a duration of action of 10-20 minutes. If an IV infusion is begun without an initial bolus dose, the attainment of therapeutic plasma concentrations is relatively slow. For example, therapeutic plasma concentrations are achieved in 30-60 minutes after the start of a continuous infusion of 60-70 ug/kg per minute when no loading dose is given. Plasma concentrations of 1.5-5.5 ug/mL have been reported to be maintained with an initial IV bolus of 1.5 mg/kg followed by infusion of 50 ug/kg per minute in patients with heart disease.
For more Absorption, Distribution and Excretion (Complete) data for LIDOCAINE (17 total), please visit the HSDB record page.

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Metabolism / Metabolites
Lidocaine is metabolized predominantly and rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of lidocaine HCl. Approximately 90% of lidocaine HCl administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate of 4-hydroxy-2,6-dimethylaniline.
Approximately 90% of a parenteral dose of lidocaine is rapidly metabolized in the liver by de-ethylation to form MEGX and GX followed by cleavage of the amide bond to form xylidine and 4-hydroxyxylidine which are excreted in urine. Less than 10% of a dose is excreted unchanged in urine.
The rate of lidocaine metabolism may also be decreased in patients with liver disease, possibly because of altered perfusion in the liver or hepatic tissue necrosis. Distribution and elimination of lidocaine and /monoethylglycinexylidide/ MEGX appear to remain normal in patients with renal failure, but /glycinexylidide/ GX may accumulate in these patients when lidocaine is administered IV for several days.
... The purpose of this study is to determine the amount of lidocaine and its metabolite monoethyl-glycinexylidide (MEGX) in breast milk after local anesthesia during dental procedures. The study population consisted of seven nursing mothers (age, 23-39 years) who received 3.6 to 7.2 mL 2% lidocaine without adrenaline. Blood and milk concentrations of lidocaine and its metabolite MEGX were assayed using high-performance liquid chromatography. The milk-to-plasma ratio and the possible daily doses in infants for both lidocaine and MEGX were calculated. The lidocaine concentration in maternal plasma 2 hours after injection was 347.6 +/- 221.8 ug/L, the lidocaine concentration in maternal milk ranged from 120.5 +/- 54.1 ug/L (3 hours after injection) to 58.3 +/- 22.8 ug/L (6 hours after injection), the MEGX concentration in maternal plasma 2 hours after injection was 58.9 +/- 30.3 ug/L, and the MEGX concentration in maternal milk ranged from 97.5 +/- 39.6 ug/L (3 hours after injection) to 52.7 +/- 23.8 ug/L (6 hours after injection). According to these data and considering an intake of 90 mL breast milk every 3 hours, the daily infant dosages of lidocaine and MEGX were 73.41 +/- 38.94 ug/L/day and 66.1 +/- 28.5 ug/L/day respectively. This study suggests that even if a nursing mother undergoes dental treatment with local anesthesia using lidocaine without adrenaline, she can safely continue breastfeeding.
... To determine the time/concentration profile of lidocaine and its active metabolites glycinexylidide (GX) and monoethylglycinexylidide (MEGX) during a 96 hr lidocaine infusion. lidocaine was administered to 8 mature healthy horses as a continuous rate infusion (0.05 mg/kg bwt/min) for 96 hr. Blood concentrations of lidocaine, GX and MEGX were determined using high performance liquid chromatography during and after discontinuation of the infusion. Serum lidocaine concentrations reached steady state by 3 hr and did not accumulate thereafter. Concentrations were above the target therapeutic concentration (980 ng/mL) only at 6 and 48 hr, and did not reach the range described as potentially causing toxicity (>1850 ng/mL) at any time. MEGX did not accumulate over time, while the GX accumulated significantly up to 48 hr and then remained constant. The serum concentrations of lidocaine, MEGX and GX were below the limit of detection within 24 hr of discontinuation of the infusion. None of the horses developed any signs of lidocaine toxicity during the study. The metabolism of lidocaine was not significantly impaired by prolonged infusion and no adverse effects were observed. Prolonged infusions appear to be safe in normal horses but the accumulation of GX, a potentially toxic active metabolite, is cause for concern.
For more Metabolism/Metabolites (Complete) data for LIDOCAINE (11 total), please visit the HSDB record page.
Lidocaine has known human metabolites that include Monoethylglycinexylidide and 3-Hydroxylidocaine.
Primarily hepatic.
Route of Elimination: Lidocaine and its metabolites are excreted by the kidneys.
Half Life: 109 minutes

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Biological Half-Life
The elimination half-life of lidocaine hydrochloride following an intravenous bolus injection is typically 1.5 to 2.0 hours. Because of the rapid rate at which lidocaine hydrochloride is metabolized, any condition that affects liver function may alter lidocaine HCl kinetics. The half-life may be prolonged two-fold or more in patients with liver dysfunction.
... In 30 patients (aged 18-70 yr) undergoing surgery ... mean half-life ... lidocaine was ... 94 min.
... In patients with myocardial infarction (with or without cardiac failure), the half-lives of lidocaine and MEGX have been reported to be prolonged; the half-life of GX is reportedly prolonged in patients with cardiac failure secondary to myocardial infarction. The half-life of lidocaine is reportedly also prolonged in patients with congestive heart failure or liver disease and may be prolonged following continuous IV infusions lasting longer than 24 hours.
Lidocaine has an initial half-life of 7-30 minutes and a terminal half-life of 1.5-2 hours. In healthy individuals, the elimination half-lives of the active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX) are 2 hours and 10 hours, respectively...
Lidocaine is extensively metabolized by the liver; heaptic disease and reduced hepatic blood flow prolong the half life, which is normally < 1 hr in dogs.
The elimination half-life of lidocaine in the newborn following maternal epidual anesthesia averaged 3 hr.

Toxicity Summary
IDENTIFICATION AND USE: Lidocaine is a white or slightly yellow, crystalline powder or needle with a characteristic odor. It is commonly used as a medication including for local anesthetics, anti-arrhythmia agent, or as a voltage-gated sodium channel blocker. Lidocaine may also be used in the treatment of hypertensive emergencies, or acute coronary syndrome associated with the toxicity of various stimulants and antiarrhythmic agents. A lidocaine transdermal patch is used for relief of pain associated with postherpetic neuralgia. An oral patch is available for application to accessible mucous membranes of the mouth prior to superficial dental procedures. The combination of lidocaine (2.5%) and prilocaine (2.5%) in an occlusive dressing is used as an anesthetic prior to venipuncture, skin graft harvesting, and infiltration of anesthetics into genitalia. Lidocaine in combination with tetracaine in a formulation that generates a "peel" is approved for topical local analgesia prior to superficial dermatological procedures. HUMAN EXPOSURE AND TOXICITY: Adverse effects of the drug mainly involve the CNS because of its rapid entry in the brain. Adverse CNS reactions may be manifested by drowsiness; dizziness; disorientation; confusion; lightheadedness; tremulousness; psychosis; nervousness; apprehension; agitation; euphoria; tinnitus; visual disturbances including blurred or double vision; nausea; vomiting; paresthesia; sensations of neat, cold or numbness; difficulty swallowing; dyspnea; and slurred speech. Muscle twitching or tremors, seizures, unconsciousness, coma, and respiratory depression and arrest may also occur. Shortly following the CNS effects, patients with lidocaine toxicity may also experience cardiovascular effects. If the patient is supported through this period, the drug rapidly distributes away from the heart, and spontaneous cardiac function returns. Lidocaine, when administered to a baby may induce convulsions. Lidocaine intoxication in the neonate, occurring as a result of inadvertent injection into the fetal scalp or cranium during local anesthesia (caudal or paracervical block or episiotomy), produces apnea, hypotonia, and seizures. Dilated pupils and loss of the oculocephalic reflex may also be observed. The more severe of these effects develop when serum lidocaine concentrations exceed 5 ug/mL and are often preceded by paresthesias or somnolence. Continuous application for 72 hours of four lidocaine patches 5%, changed every 12 or 24 hours, produced mild application-site erythema in most patients, but no systemic adverse reactions. No loss in sensation at the application site was reported. Systemic exposure to lidocaine and monoethylglycinexylidide (MEGX), the primary active metabolite of lidocaine, after application of lidocaine gel or patches was minimal in normal volunteers, patients with post-herpetic neuralgia, and patients with acute herpes zoster. In human SH-SY5Y neuroblastoma cells, local anesthesia caused rapid cell death, which was primarily due to necrosis. Lidocaine can trigger apoptosis with either increased time of exposure or increased concentration. ANIMAL STUDIES: In rats persistent functional impairment and histologic damage in the nerve roots and the spinal cord was less severe after epidural lidocaine than after intrathecal lidocaine. In 8 New Zealand Rabbits receiving 0.2 mL 1% lidocaine hydrochloride applied intracamerally to the lenses, had morphological abnormalities in both cornea and iris of the lidocaine injected eyes. Another experiment in rabbits with 2% lidocaine HCl applied intracamerally on the corneal endothelium found that lidocaine caused statistically significant corneal thickening and clinically significant corneal opacification. Lidocaine injection into the dorsal root ganglion of rats produced hyperalgesia, possibly due to activation of resident satellite glial cells. One-hour exposure of primary rabbit urothelial cells (PRUC) culture to 0.5 or 1.0% lidocaine decreased cell viability. Lidocaine rapidly crosses the placenta in pregnant guinea pigs. High concentrations are found in the fetal liver, heart, and brain. High myocardial levels of drug in the fetus may possibly account for marked depressant effects that local anesthetics produce. In another study, no significant effects were observed in offspring of rats administered lidocaine at by constant infusion for 2 weeks before mating and throughout pregnancy. Additionally, pregnancy did not enhance the CNS and cardiovascular toxic effects of lidocaine when studied in pregnant sheep receiving continuous IV drug infusion and compared to data from nonpregnant ewes. Lidocaine did not induce genotoxicity in the wing somatic mutation and recombination test in Drosophila melanogaster, which detects point and chromosomal mutations as well as recombination induced by the activity of genotoxins of direct and indirect action. Lidocaine 0.25% did decrease cell viability and caused DNA degradation in murine fibroblasts 3T6. Lidocaine was not oncogenic when administered topically weekly to the dorsal skin of mice for 26 weeks.
Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action. Lidocaine alters signal conduction in neurons by blocking the fast voltage gated sodium (Na+) channels in the neuronal cell membrane that are 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 aborting their birth in the first place.

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Toxicity Data
LD50: 459 (346-773) mg/kg (oral, non-fasted female rats)
LD50: 214 (159-324) mg/kg (oral, fasted female rats)

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Interactions
EMLA cream is a topical formulation based upon the eutectic mixture of lidocaine and prilocaine and is used in clinical settings to produce local analgesia after application under occlusive dressing. A blanching reaction has been reported to occur locally after application, but it is not clear whether this reaction is caused by the anesthetic mixture, by the vehicle or the occlusion. This blanching reaction was studied in 50 healthy volunteers in a double-blind randomized assay: EMLA versus placebo, under occlusive dressing for 1 hr, each subject being his own control. 33 Cases (66%) of blanching after application of EMLA cream were observed versus 3 cases (6%) after placebo, this difference being highly significant. Blanching was observed without delay, after removal of the dressing, and was very transient, disappearing in less than 3 hr in all cases. It is concluded that the blanching reaction is (1) frequent but very transient, and (2) determined by the anesthetic mixture included in EMLA cream and not by the vehicle alone, nor by the occlusion, since it is not found with the placebo. The precise mechanism of this reaction is unknown.
Recent studies have suggested that cytochrome P-450 isoenzyme 1A2 has an important role in lidocaine biotransformation. /This research/ studied the effect of a cytochrome P-450 1A2 inhibitor, ciprofloxacin, on the pharmacokinetics of lidocaine. In a randomized, double-blinded, cross-over study, nine healthy volunteers ingested for 2.5 days 500 mg oral ciprofloxacin or placebo twice daily. On day 3, they received a single dose of 1.5 mg/kg lidocaine intravenously over 60 min. Plasma concentrations of lidocaine, 3-hydroxylidocaine and monoethylglycinexylidide were determined for 11 hr after the start of the lidocaine infusion. Ciprofloxacin increased the mean peak concentration and area under plasma concentration-time curve of lidocaine by 12% (range [-6] to 46%; P<0.05) and 26% (8 to 59%; P 0.01), respectively. The mean plasma clearance of lidocaine was decreased by ciprofloxacin by 22% (7 to 38%; P<0.01). Ciprofloxacin decreased the area under the plasma concentration-time curve of monoethylglycinexylidide by 21% (P<0.01) and that of 3-hydroxylidocaine by 14% (P< 0.01). The plasma decay of intravenously administered lidocaine is modestly delayed by concomitantly administered ciprofloxacin. Ciprofloxacin may increase the systemic toxicity of lidocaine.
Epinephrine is commonly added to lidocaine solutions to increase the duration of spinal anesthesia. Despite this common usage, the effect of epinephrine on the neurotoxic potential of this anesthetic is not known. The current experiments investigated whether adding epinephrine increases functional impairment or histologic damage induced by spinal administration of lidocaine in the rat. Eighty rats were divided into four groups to receive an intrathecal injection of normal saline containing either 5% lidocaine, 5% lidocaine with 0.2 mg/mL of epinephrine, 0.2 mg/mL of epinephrine, or normal saline alone. Animals were assessed for persistent sensory impairment using the tail-flick test administered 4 and 7 days after infusion. Animals were then killed, and the spinal cord and nerve roots were prepared for neuropathologic evaluation. Rats given 5% lidocaine developed persistent sensory impairment and histologic damage, and the addition of epinephrine resulted in a further significant increase in injury. Sensory function in animals given epinephrine without anesthetic was similar to baseline and did not differ from saline. Histologic changes in animals treated with epinephrine alone did not differ significantly from saline controls. The neurotoxicity of intrathecally administered lidocaine is increased by the addition of epinephrine. When making clinical recommendations for maximum safe intrathecal dose of this anesthetic, one may need to consider whether the solution contains epinephrine.
PURPOSE: During continuous epidural anesthesia with lidocaine, plasma monoethylglycinexylidide (MEGX), an active metabolite of lidocaine, increases continuously. /This study/ assessed the effect of epinephrine on the absorption of lidocaine and the accumulation of MEGX during continuous epidural anesthesia in children. Anesthesia was administered as an initial bolus of 5 mg/kg of 1% lidocaine solution followed by continuous infusion at 2.5 mg/kg/hr. Patients in the control group (n = 8) received lidocaine alone, while patients in the epinephrine group (n = 8) received lidocaine + epinephrine (5 ug/mL). Concentrations of lidocaine and its active metabolite, MEGX, were measured in plasma samples obtained after 15 min, 30 min, and one, two, three, four, and five hours of infusion using high-performance liquid chromatography with ultraviolet detection. Plasma lidocaine concentrations were higher in samples from the control group for the first hour; however, after two hours the levels were the same in all samples. Plasma MEGX levels increased continuously in both groups and were significantly higher in the control group samples. The sum of lidocaine + MEGX was higher in the control group for the first two hours but there was no significant difference between groups after three hours. Reduction of the potential for systemic toxicity by the addition of epinephrine to lidocaine is limited, because the reduction of the sum of the plasma concentrations of lidocaine and its active metabolite MEGX is small and limited to the initial phase of infusion.
For more Interactions (Complete) data for LIDOCAINE (33 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Mouse oral 292 mg/kg
LD50 Mouse ip 105 mg/kg
LD50 Mouse iv 19.5 mg/kg
LD50 Rat oral 317 mg/kg
For more Non-Human Toxicity Values (Complete) data for LIDOCAINE (8 total), please visit the HSDB record page.

[1]. Setting up for the block: the mechanism underlying lidocaine's use-dependent inhibition of sodium channels. J Physiol. 2007 Jul 1;582(Pt 1):11.

[2]. Lidocaine inhibits growth, migration and invasion of gastric carcinoma cells by up-regulation of miR-145. BMC Cancer. 2019 Mar 15;19(1):233.

[3]. Evaluation of the antinociceptive effects of lidocaine and bupivacaine on the tail nerves of healthy rats. Basic Clin Pharmacol Toxicol. 2013 Jul;113(1):31-6.

Therapeutic Uses
Anesthetics, Local; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers
Lidocaine hydrochloride is used for infiltration anesthesia and for nerve block techniques including peripheral, sympathetic, epidural (including caudal), and spinal block anesthesia. /Included in US product label/
Lidocaine has been administered intraperitoneally for anesthesia of the peritoneum and pelvic viscera. /NOT included in US product label/
Lidocaine is considered an alternative antiarrhythmic agent to amiodarone in the treatment of cardiac arrest secondary to ventricular fibrillation or pulseless ventricular tachycardia resistant to cardiopulmonary resuscitation (CPR), electrical cardioversion (e.g., after 2 to 3 shocks) and a vasopressor (epinephrine, vasopressin). /Included in US product label/
For more Therapeutic Uses (Complete) data for LIDOCAINE (21 total), please visit the HSDB record page.

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Drug Warnings
WARNING: Life-threatening and fatal events in infants and young children. Postmarketing cases of seizures, cardiopulmonary arrest, and death in patients under the age of 3 years have been reported with use of Xylocaine 2% Viscous Solution when it was not administered in strict adherence to the dosing and administration recommendations. In the setting of teething pain, Xylocaine 2% Viscous Solution should generally not be used. For other conditions, the use of the product in patients less than 3 years of age should be limited to those situations where safer alternatives are not available or have been tried but failed. To decrease the risk of serious adverse events with use of Xylocaine 2% Viscous Solution, instruct caregivers to strictly adhere to the prescribed dose and frequency of administration and store the prescription bottle safely out of reach of children.
Life-threatening adverse effects (e.g., irregular heart beat, seizures, breathing difficulties, coma, death) may occur when topical anesthetics are applied to a large area of skin, when the area of application is covered with an occlusive dressing, if a large amount of topical anesthetic is applied, if the anesthetic is applied to irritated or broken skin, or if the skin temperature increases (from exercise or use of a heating pad).101 102 When applied in such a manner, the amount of anesthetic that is absorbed systemically is unpredictable and the plasma concentrations achieved may be high enough to cause life-threatening adverse effects.
The Food and Drug Administration (FDA) has reviewed 35 reports of chondrolysis (necrosis and destruction of cartilage) in patients given continuous intra-articular infusions of local anesthetics with elastomeric infusion devices to control post-surgical pain. The significance of this injury to otherwise healthy young adults warrants notification to health care professionals. The local anesthetics (with and without epinephrine) were infused for extended periods of time (48 to 72 hours) directly into the intra-articular space using an elastomeric pump. Chondrolysis was diagnosed within a median of 8.5 months after the infusion. Almost all of the reported cases of chondrolysis (97%) occurred following shoulder surgeries. Joint pain, stiffness, and loss of motion were reported as early as the second month after receiving the infusion. In more than half of these reports, the patients required additional surgery, including arthroscopy or arthroplasty (joint replacement). It is not known which specific factor or combination of factors contributed to the development of chondrolysis in these cases. The infused local anesthetic drugs, the device materials, and/or other sources may have resulted in the development of chondrolysis. It is important to note that single intra-articular injections of local anesthetics in orthopedic procedures have been used for many years without any reported occurrence of chondrolysis. Local anesthetics are approved as injections for the production of local or regional anesthesia or analgesia. Neither local anesthetics nor infusion devices are approved for an indication of continuous intra-articular infusion.
Local anesthetics should only be administered by clinicians who are experienced in the diagnosis and management of dose-related toxicities and other acute emergencies associated with these agents. Resuscitative equipment, oxygen, drugs, and personnel required for treatment of adverse reactions should be immediately available when lidocaine is administered. Proper positioning of the patient is extremely important in spinal anesthesia.
For more Drug Warnings (Complete) data for LIDOCAINE (31 total), please visit the HSDB record page.

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Pharmacodynamics
Excessive blood levels of lidocaine can cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. 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. The net effect is normally a modest hypotension when the recommended dosages are not exceeded. 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. 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. Moreover, lidocaine possesses a dissociation constant (pKa) of 7.7 and is considered a weak base. 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. This rapid onset of action is demonstrated in about one minute following intravenous injection and fifteen minutes following intramuscular injection. 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. Nevertheless, it appears that the efficacy of lidocaine may be minimized in the presence of inflammation. 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.

C14H22N2O

234.34

234.173

C, 71.76; H, 9.46; N, 11.95; O, 6.83

137-58-6

Lidocaine hydrochloride; 73-78-9;Lidocaine (Standard); 137-58-6; Lidocaine hydrochloride hydrate; 6108-05-0; Lidocaine; 137-58-6; N-Oxide Lidocaine-d10; 851528-10-4; Lidocaine-d10; 851528-09-1

3676

White to off-white solid powder

1.0±0.1 g/cm3

372.7±52.0 °C at 760 mmHg

66-69°C

179.2±30.7 °C

0.0±0.9 mmHg at 25°C

1.512

3.63

1

2

5

17

228

0

O=C(NC1=C(C)C=CC=C1C)CN(CC)CC

NNJVILVZKWQKPM-UHFFFAOYSA-N

InChI=1S/C14H22N2O/c1-5-16(6-2)10-13(17)15-14-11(3)8-7-9-12(14)4/h7-9H,5-6,10H2,1-4H3,(H,15,17)

2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (10.67 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (10.67 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 4.35 mg/mL (18.56 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)