Lidocaine preparations

Table 69.1. Other lidocaine preparations indications and dosage Lidocaine form Dosage...

Fig. 12 Flow curves of 0.2 % carbomer hydrogels loaded with increasing proportions of lidocaine prepared in situ. Black diamond) C-lidocaineioo black square) C-hdocaineys black triangle), C-lidocainesol black circle) C-lidocaine25. Data adapted from reference [16])...

Lidocaine hydrochloride [73-78-9] (Xylocaine), is the most versatile local anesthetic agent because of its moderate potency and duration of action, rapid onset, topical activity, and low toxicity. Its main indications are for infiltration, peripheral nerve blocks, extradural anesthesia, and in spinal anesthesia where a duration of 30 to 60 min is desirable. Because of its vasodilator activity, addition of the vasoconstrictor, epinephrine, increases the duration of action of Hdocaine markedly. It is also available in ointment or aerosol preparations for a variety of topical appHcations. 

It will be recalled that certain local anesthetic amides, such as procainamide and lidocaine, are active antiarrythmic agents. Annelation of a second aromatic ring is consistent with bioactivity. Bunaftine (21) is such an agent, prepared simply from reaction of the acid chloride of 1-naphthoic acid and... 

Lozenges and troehes are solid preparations designed to dissolve or disintegrate slowly in the mouth their base is usually flavored and sweetened. Examples of eom-pounded troehes include anesthetic (lidocaine), hormonal (testosterone), analgesie (ketamine), and antifungal (nystatin) preparations (Table 2). 

Mueller-Goymann, C.C., and Frank, S.G., Interaction of lidocaine and lidocaine-hydrochloride with the liquid crystal structure of topical preparations, Int. J. Pharm., 29 147-159 (1986). 

Bupivacaine is an anaesthetic with a slow onset but a long duration of action. It is indicated for continuous epidural analgesia in labour. Xylocoine is the proprietary preparation of lidocaine (lignocoine). Lidocoine injections ore used in dentistry. 

Replacement therapy-As soon as possible, change patient to IV lidocaine or to an oral antiarrhythmic preparation for maintenance therapy. However, if necessary, an additional IM injection may be administered after 60 to 90 minutes. 

EMLA cream (lidocaine 2.5% and prilocaine 2.5%) consists of a eutectic mixture of focal anesthetics. It is used to provide topical anesthetic to intact skin. Other topical preparations are effective only on mucosal surfaces. EMLA has been shown to reduce pain on venipuncture and provide substantial anesthesia for skin graft donor sites. No significant local or systemic toxicity has been demonstrated. 

Bupivacaine is an amide compound with a duration of nerve blocking effect of around 3 hours. It is about four times more potent than lidocaine (lignocaine) and has an intermediate-to-slow onset of action. Bupivacaine is prepared as the hydrochloride salt in aqueous solutions in concentrations of 0.25%, 0.50%, and 0.75%. The incidence of motor block increases with increasing concentration. High doses of bupivacaine are associated with cardiac toxicity. Particular care must be exercised to avoid inadvertent overdosage or when the drug is administered to patients taking concurrent cardioactive medication. 

Lidocaine (synonyme lignocaine) was introduced as the first amide in 1944 and is the most commonly used LA today. It has a rapid onset of action with intermediate duration and an intermediate toxicity. The maximum tolerated dose with infiltration or injection is 200 mg (500 mg when combined with adrenaline). Lidocaine is dealkylated in the liver to monoethylglycine xylidide and glycine xylidide which retain local anesthetic activity. It is available in a variety of preparations including creams, gels, patches and solutions, often in combination with adrenaline. 

Bicchi and Bertolino [193] analyzed a variety of pharmaceuticals for residual solvents. Samples were equilibrated directly or dissolved in a suitable solvent with a boiling point higher than that of the residual solvent to be determined. Equilibration conditions were 90 or 100°C for 20 min. A Perkin-Elmer HS-6 headspace sampler was used. The chromatographic phase chosen was a 6 x Vs in. column packed with Carbopack coated with 0.1% SP 1000. Residual ethanol in phenobarbital sodium was determined by a direct desorption method. An internal standard, /-butanol, was used. Typically, 0.44% of ethanol was detected (compared to a detection limit of 0.02 ppm). The standard deviation of six determinations was 0.026. Pharmaceutical preparations which were analyzed by the solution method included lidocaine hydrochloride, calcium pantothenate, methyl nicotinate, sodium ascorbate, nicotinamide, and phenylbutazone. Acetone, ethanol, and isopropanol were determined with typical concentrations ranging from 14 ppm for ethanol to 0.27% for acetone. Detection limits were as low as 0.03 ppm (methanol in methyl nicotinate). 

The selectivity of amperometric detection has been useful in simplifying the sample pretreatment steps in the determination of a number of drug products [82-86]. A method requiring no sample preparation using an amperometric detector and UV detector in series was developed for lido-caine hydrochloride injectable solutions [87]. The drug epinephrine is quantified with the amperometric detector, whereas lidocaine and methyl para-ben are detected by ultraviolet light. Disodium EDTA had to be added to the mobile phase to eliminate a peak response from iron leached from the stainless steel. 

However signs do change with the "handedness" of the natural isomer so a higher level of distinction is achieved using CD or polarimetric detection. An enormous advantage is derived from the fact that achiral excipients, such as lidocaine, procaine, and benzocaine, often deliberately added to illicit drug preparations to complicate the chromatographic identifications of amphetamine and methamphetamine, present no interference problem whatsoever to CD detection. ORD detection was developed for the analysis of mixtures of pseudoephedrine and ephedrine [47], which because of the connection between anomalous ORD and CD, should be applicable to CD detection in the UV. 

Yahagi, R. Onishih, H. Machida, Y. Preparation and evaluation of double-phased mucoadhesive suppositories of lidocaine utilizing carbopol and white beeswax. J. Controlled Release 1999, 61, 1-8. 

In preparation for transesophageal echocardiogram, a 73-year-old woman was given 15 ml of lidocaine solution 2% and lidocaine spray 4% to anesthetize the oropharynx, plus intravenous midazolam 1 mg and pethidine 12.5 mg. She very rapidly became cyanosed, but remained... 

A 5-year-old child had 35 g of Emla apphed under an occlusive dressing to eczematous skin in preparation for cryotherapy for molluscum contagiosum (3). Within 1 hour, the child had a generalized seizure that lasted 10 minutes. The plasma concentrations of lidocaine and prilocaine 30 minutes later were 5.5 and 2.0 pg/ml, respectively, and 6 hours later, the methemoglobin concentration was 19%. The child was given vitamin C 500 mg intravenously, and 2 days later had a methemoglobin concentration of 0.3%. 

Local anesthetics make use of the lipophobic property of an aromatic amine moiety, or its acyl derivative, that links with a hydrophilic amino acid. The products include the anilide lidocaine, or 2-(diethylamino)-A-(2,6-dimethylphenyl)acetamide (153), the toluidine derivative prilocaine and the century-old procaine, 2-diethylaminoethyl 4-aminobenzoate (154)84. The ester is prepared by reacting p-aminobenzoic acid with ethylene chlorohydrin and diethylamine. 

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