rifampin and Substance-Withdrawal-Syndrome

Topics: Adult; Aged; Chromatography, Gas; Drug Interactions; Feces; Female; Heroin Dependence; Humans; Liver; Male; Mass Spectrometry; Methadone; Methods; Middle Aged; Naloxone; Rifampin; Substance Withdrawal Syndrome; Tuberculosis, Pulmonary

Nucleus accumbens (NAc) is the ventral part of the striatum of the brain; it is an important part of the mesolimbic pathway involved in the reward system that mediates the formation of various forms of addiction, in particular alcohol addiction. Neuroimaging data and in vitro studies indicate the development of a pronounced neurodegenerative process in the NAc, with long-term alcohol use, but the key mechanisms mediating this process remain unknown. In recent years, the attention of researchers has been focused on studying the system of Toll-like receptors (TLRs), the increased activity of which is clearly shown in the cerebral cortex and hippocampus during prolonged alcohol exposure, but there is a need to study the role of this system in other brain structures. In this study, we have shown that prolonged alcohol exposure (2 months) with moderate doses of ethanol (2 g/kg) promotes a pronounced increase in the expression of the Tlr4 gene and its endogenous ligand Hmgb1 in NAc during the period of alcohol withdrawal in rats. Injections of rifampicin (100 mg/kg) reduced the elevated expression level of Hmgb1, Tlr4, as well as pro-inflammatory cytokine genes (IL1β, IL6), while the administration of the drug increased the reduced level of mRNA of anti-inflammatory cytokines (IL10, IL11).. Prilezhashchee iadro (nucleus accumbens, NAc) — ventral'naia chast' striatuma golovnogo mozga, kotoraia iavliaetsia vazhnoĭ chast'iu mezolimbicheskogo puti, uchastvuiushchego v sisteme vnutrennego podkrepleniia, oposreduiushcheĭ formirovanie razlichnykh form addiktsii, v chastnosti alkogol'noĭ addiktsii. Dannye neĭrovizualizatsii i issledovaniia in vitro svidetel'stvuiut o razvitii vyrazhennogo neĭrodegenerativnogo protsessa v NAc pri dlitel'nom upotreblenii alkogolia, odnako kliuchevye mekhanizmy, oposreduiushchie étot protsess, ostaiutsia neizvestnymi. V poslednie gody vnimanie issledovateleĭ sosredotocheno na izuchenii sistemy Toll-podobnykh retseptorov (TLR), povyshennaia aktivnost' kotorykh vyiavlena v kore i gippokampe golovnogo mozga pri dlitel'noĭ alkogolizatsii, odnako sushchestvuet neobkhodimost' v issledovanii étoĭ sistemy v drugikh strukturakh mozga. V dannoĭ rabote pokazano, chto dlitel'naia alkogolizatsiia (2 mesiatsa) umerennymi ezhednevnymi dozami étanola (2 g/kg) sposobstvuet vyrazhennomu povysheniiu ékspressii gena Tlr4 i ego éndogennogo liganda Hmgb1 v NAc u krys v period otmeny alkogolia. In"ektsii rifampitsina (Rif; 100 mg/kg) snizhali povyshennyĭ uroven' ékspressii Hmgb1, Tlr4, a takzhe genov provospalitel'nykh tsitokinov (IL1β, IL6) v NAc u dlitel'no alkogolizirovannykh krys v period otmeny alkogolia. Pri étom otmecheno uvelichenie ponizhennogo urovnia mRNK protivovospalitel'nykh tsitokinov (IL10, IL11).

Topics: Alcoholism; Animals; Brain; Ethanol; HMGB1 Protein; Nucleus Accumbens; Rats; Rifampin; Substance Withdrawal Syndrome; Toll-Like Receptor 4

This series of studies examines the pharmacokinetic/pharmacodynamic interactions between buprenorphine, an opioid partial agonist increasingly used in treatment of opioid dependence, and rifampin, a medication used as a first line treatment for tuberculosis; or rifabutin, an alternative antituberculosis medication.. Opioid-dependent individuals on stable doses of buprenorphine/naloxone underwent two, 24-h blood sampling studies: (1) for buprenorphine pharmacokinetics and (2) following 15 days of rifampin 600 mg daily or rifabutin 300 mg daily for buprenorphine and rifampin or rifabutin pharmacokinetics.. Rifampin administration produced significant reduction in plasma buprenorphine concentrations (70% reduction in mean area under the curve (AUC); p=<0.001) and onset of opiate withdrawal symptoms in 50% of participants (p=0.02). While rifabutin administration to buprenorphine-maintained subjects resulted in a significant decrease in buprenorphine plasma concentrations (35% decrease in AUC; p<0.001) no opiate withdrawal was seen. Compared with historical control data, buprenorphine had no significant effect on rifampin pharmacokinetics, but was associated with 22% lower rifabutin mean AUC (p=0.009), although rifabutin and its active metabolite concentrations remained in the therapeutic range.. Rifampin is a more potent inducer of buprenorphine metabolism than rifabutin with pharmacokinetic and pharmacodynamic adverse consequences. Those patients requiring rifampin treatment for tuberculosis and receiving buprenorphine therapy are likely to require an increase in buprenorphine dose to prevent withdrawal symptoms. Rifabutin administration was associated with decreases in buprenorphine plasma concentrations, but no clinically significant adverse events were observed.

Topics: Adult; Antitubercular Agents; Buprenorphine; Drug Interactions; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Rifabutin; Rifampin; Substance Withdrawal Syndrome

Topics: Adult; Antibiotics, Antitubercular; Anxiety Disorders; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Male; Rifampin; Selective Serotonin Reuptake Inhibitors; Sertraline; Substance Withdrawal Syndrome

All patients with culture-confirmed, rifampin-susceptible Mycobacterium tuberculosis diagnosed during a 20-month period in New York City, who were started on a rifampin-containing regimen and received > or =60 days of treatment.. To identify rates of and reasons for rifampin discontinuation.. Retrospective case-control study using surveillance data and medical record reviews. Discontinuation due to thrombocytopenia, creatinine >2.0 mg/dl, bilirubin >2.0 mg/dl or severe reactions (generalized rash, persistent drug fever, or severe interference with methadone metabolism) were defined as appropriate for discontinuation of rifampin. All other reactions were classified as inappropriate.. Of 3,520 patients, rifampin was discontinued in 68 (1.9%); of these, 57% had rifampin discontinued unnecessarily. Treatment by an inexperienced provider (adjusted odds ratio [ORadj] 4.0; 95% confidence interval [CI] 1.9-8.5), race (ORadj 3.1; 95%CI 1.4-6.9), history of previous treatment (ORadj 4.8; 95%CI 1.9-12.5), and history of methadone drug treatment (ORadj 12.6; 95%CI 5.3-29.9) were all associated with inappropriate rifampin discontinuation.. True intolerance was rare, even among those patients infected with the human immunodeficiency virus. Most patients with minor reactions can successfully complete treatment with rifampin, particularly if managed by a physician experienced in the treatment of tuberculosis.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antibiotics, Antitubercular; Case-Control Studies; Child; Confidence Intervals; Drug Utilization; Female; Hispanic or Latino; Humans; Incidence; Logistic Models; Male; Middle Aged; Multivariate Analysis; New York City; Odds Ratio; Patient Compliance; Retrospective Studies; Rifampin; Risk Factors; Substance Withdrawal Syndrome; Tuberculosis, Pulmonary; White People

Topics: Adult; Antibiotics, Antitubercular; Female; Humans; Methadone; Opioid-Related Disorders; Rifampin; Substance Withdrawal Syndrome; Tuberculosis, Pulmonary

Topics: Acquired Immunodeficiency Syndrome; Adult; Female; Humans; Male; Methadone; Mycobacterium avium-intracellulare Infection; Opioid-Related Disorders; Rifampin; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

Topics: Adult; Drug Interactions; Heroin Dependence; Humans; Male; Methadone; Rifampin; Substance Withdrawal Syndrome; Tuberculosis, Cutaneous

Topics: Adult; Bronchopneumonia; Drug Interactions; Female; Humans; Methadone; Rifampin; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Aged; Drug Interactions; Heroin Dependence; Humans; Isoniazid; Male; Methadone; Middle Aged; Rifampin; Substance Withdrawal Syndrome; Tuberculosis, Pulmonary