Is chronic ethanol consumption associated with tolerance to intrathecal lidocaine in the rat? 1990

A Fassoulaki, and K Drasner, and E I Eger
Department of Anesthesia, University of California, San Francisco 94143-0464.

Intoxication with alcohols can produce anesthesia. In contrast, chronic ethanol consumption can produce tolerance to inhaled and other general anesthetics. We tested whether ongoing consumption decreased, and whether withdrawal from such consumption increased, the intrathecal dose of lidocaine that induces sensory and motor blockade in female Sprague-Dawley rats. Sensory blockade was assessed using the tail-flick test, and motor blockade by the animal's inability to move its hind limbs. Rats were tested before commencing ethanol intake; during ethanol ingestion (9 days after beginning ingestion); and on the 15th day of ingestion, 14 h after withdrawing ethanol from their diet. Pair-fed control rats were tested at the same intervals. Ongoing administration of ethanol decreased the dose of lidocaine required to produce sensory blockade, but this difference was not significant relative to the control group (i.e., the difference was significant within group but not across groups). Withdrawal of ethanol increased the dose requirements for sensory and motor blockade by 80% and 53% (P less than 0.01 and P less than 0.0001) and decreased the duration of the motor blockade (P less than 0.01). Dose requirements producing sensory block differed between alcoholic and control groups (P less than 0.0001). These results suggest that chronic ethanol intake produces tolerance to the local anesthetic effects of lidocaine. Whether this change results from a change in kinetics or in sensitivity is not known, but the latter would seem more likely, because duration of blockade was minimally affected or unaffected.

UI MeSH Term Description Entries
D007278 Injections, Spinal Introduction of therapeutic agents into the spinal region using a needle and syringe. Injections, Intraspinal,Injections, Intrathecal,Intraspinal Injections,Intrathecal Injections,Spinal Injections,Injection, Intraspinal,Injection, Intrathecal,Injection, Spinal,Intraspinal Injection,Intrathecal Injection,Spinal Injection
D008012 Lidocaine A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE. Lignocaine,2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide,2-2EtN-2MePhAcN,Dalcaine,Lidocaine Carbonate,Lidocaine Carbonate (2:1),Lidocaine Hydrocarbonate,Lidocaine Hydrochloride,Lidocaine Monoacetate,Lidocaine Monohydrochloride,Lidocaine Monohydrochloride, Monohydrate,Lidocaine Sulfate (1:1),Octocaine,Xylesthesin,Xylocaine,Xylocitin,Xyloneural
D009407 Nerve Block Interruption of NEURAL CONDUCTION in peripheral nerves or nerve trunks by the injection of a local anesthetic agent (e.g., LIDOCAINE; PHENOL; BOTULINUM TOXINS) to manage or treat pain. Chemical Neurolysis,Chemodenervation,Nerve Blockade,Block, Nerve,Blockade, Nerve,Blockades, Nerve,Blocks, Nerve,Chemical Neurolyses,Chemodenervations,Nerve Blockades,Nerve Blocks,Neurolyses, Chemical,Neurolysis, Chemical
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004361 Drug Tolerance Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL. Drug Tolerances,Tolerance, Drug,Tolerances, Drug
D005260 Female Females
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000437 Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4) Alcohol Abuse,Alcoholic Intoxication, Chronic,Ethanol Abuse,Alcohol Addiction,Alcohol Dependence,Alcohol Use Disorder,Abuse, Alcohol,Abuse, Ethanol,Addiction, Alcohol,Alcohol Use Disorders,Chronic Alcoholic Intoxication,Dependence, Alcohol,Intoxication, Chronic Alcoholic,Use Disorders, Alcohol
D000772 Anesthesia, Local A blocking of nerve conduction to a specific area by an injection of an anesthetic agent. Anesthesia, Infiltration,Local Anesthesia,Neural Therapy of Huneke,Huneke Neural Therapy,Infiltration Anesthesia

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