Lidocaine, determination

E. H. M. Koster, C. Wemes, J. B. Morsink and G. J. de Jong, Determination of lidocaine in plasma by direct solid-phase microexti action combined with gas chromatography , J. Chromatogr. B 739 175-182 (2000). 

Mr. Summers has a ventricular arrhythmia and is placed on a cardiac monitor. The primary health care provider prescribes IV lidocaine. Discuss preadministration assessments you would perform on Mr. Summers. Analyze which adverse reactions would be most important to monitor for during the ongoing assessment. Determine what reactions should be reported immediately. 

The primary site of action of epidurally administered agents is on the spinal nerve roots. As with spinal anesthesia, the choice of drug to be used is determined primarily by the duration of anesthesia desired. However, when a catheter has been placed, short-acting drugs can be administered repeatedly. Bupivacaine is typically used when a long duration of surgical block is needed. Lidocaine is used most often for intermediate length procedures chloroprocaine is used when only a very short duration of anesthesia is required. 

The liver, known as the chemical reactor of the body, serves to eliminate drugs and other compounds from the body. In one such process, lidocaine (a drag given to heart attack patients) may be converted either into MEGX by deethylation, or into hydroxylidocaine (OHLDD) by hydroxylation. Assuming that the liver may be represented by a CSTR, determine the... 

Anderson, M. S., Lu, B., Abdel-Rehim, M., Blomberg, S., and Blomberg, L. G. (2004). Utility of nonaqueous capillary electrophoresis for the determination of lidocaine and its metabolites in human plasma a comparison of ultraviolet and mass spectrometric detection. Rapid Commun. Mass Spectrom. 18, 2612—2618. 

Meta-analysis is a method often used to determine the effectiveness of a drug but to date it has rarely been used to assess safety. One case illustrates how this technique can help. Six studies examining the use of intravenous lidocaine for acute myocardial infarction did not, on an individual basis, give strong enough evidence to support the hypothesis that this technique could cause excess mortality. The meta-analysis, however, was able to demonstrate this. ... 

Ambient pH in the extracellular fluid (ECF) is approximately 7.4 but the value varies and this determines the proportions of ionised and unionised local anaesthetic drug. A decrease in ambient pH will increase the amount of ionised drug and reduce the unionised fraction available for transfer across the cell membrane. A common example of this is when infection or inflammation reduces the ambient pH. In the case of lidocaine (lignocaine), a fall in tissue pH from 7.4 to 7.0 will halve the amount of unionised drug. This has obvious implications for efficacy. Similar effects occur following repeated administrations of acidified local anaesthetic solutions. 

In patients with heart failure, lidocaine s volume of distribution and total body clearance may both be decreased. Thus, both loading and maintenance doses should be decreased. Since these effects counterbalance each other, the half-life may not be increased as much as predicted from clearance changes alone. In patients with liver disease, plasma clearance is markedly reduced and the volume of distribution is often increased the elimination half-life in such cases may be increased threefold or more. In liver disease, the maintenance dose should be decreased, but usual loading doses can be given. Elimination half-life determines the time to steady state. Thus, although steady-state concentrations may be achieved in 8-10 hours in normal patients and patients with heart failure, 24-36 hours may be required in those with liver disease. Drugs that decrease liver blood flow (eg, propranolol, cimetidine) reduce lidocaine clearance and so increase the risk of toxicity unless infusion rates are decreased. With infusions lasting more than 24 hours, clearance falls and plasma concentrations rise. Renal disease has no major effect on lidocaine disposition. 

The action of several anesthetics has also been associated with a modulation of K+ channels. In addition to blocking Na+ currents in spinal neurones of the superficial dorsal horn the local anesthetics bupivacaine, lidocaine and mepivacaine reduce transient, A-type K+ currents in these cells whereas delayed rectifier K+ currents proved to be resistant (Olschewski et al., 1998). Since the A-type K+ current determines the frequency pattern of repetitively firing neurones (Hille, 2001) their suppression in dorsal... 

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. 

PURPOSE AND RATIONALE Surface anesthesia is used to anesthetize the cornea and conjunctiva of the eye and the mucous membranes in the mouth. The classical pharmacological test is the blockade of the rabbit corneal reflex as described by Regnier (1923) that has become a standard test method for evaluating local anesthetics (FuBganger and Schaumann 1931 Ther 1953a Quevauviller 1971 Muschaweck et al. 1986). These pharmacological methods are only partially suitable to determine the irritancy potential of local anesthetic on mucus membranes. Luduena et al. (1960) compared the mucus membrane irritancy of mepivacaine and lidocaine by the eye irritation method according to Hoppe (1950) and Draize et al. (1944). 

Arts IC, Sesink AL, Faassen-Peters M, Hollman PC (2004) The type of sugar moiety is a major determinant of the small intestinal uptake and subsequent biliary excretion of dietary quercetin glycosides. Br J Nutr 91 841-847 Berggren S, Hoogstraate J, Fagerholm U, Lennemas H (2004) Characterization of jejunal absorption and apical efflux of ropivacaine, lidocaine and bupivacaine in the rat using in situ and in vitro absorption models. Eur J Pharm Sd 21 553-560... 

Riviere, J. E., Monteiro-Riviere, N. A., and Inman. A. Determination of lidocaine concentrations in skin after transdermal iontophoresis Effects of vasoactive drugs. Pharm. Res. 9 211, 1992. 

Orlando R, Piccoli P, De Martin S, Padrini R, Ploreani M, Palatini P. Cytochrome P50 1A2 is a major determinant of lidocaine metabolism in vivo Effects of liver ftmction. Clin Pharmacol Ther 2004 75 80-8. 

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