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Higher pretreatment blood pressure is associated with greater alcohol drinking reduction in alcohol-dependent individuals treated with doxazosin.

ABSTRACT: BACKGROUND:Preclinical and clinical research suggest that the ?1 receptor antagonist prazosin reduces alcohol consumption. Furthermore, clinical studies indicate a role for prazosin in treating Post-Traumatic Stress Disorder (PTSD) symptoms and a recent trial suggested that pre-treatment blood pressure (BP) predicts therapeutic response for prazosin in PTSD patients. Whether pre-treatment BP may predict response to ?1 blockers in alcohol-dependent (AD) patients is unknown. We previously reported a randomized controlled trial (RCT) where doxazosin, an ?1 receptor antagonist with a more favorable pharmacokinetic profile than prazosin, reduced drinks per week (DPW) and heavy drinking days (HDD) in AD patients with a high family history density of alcoholism. In this study, we tested pre-treatment BP as another potentially valuable clinical moderator of doxazosin's response on alcohol consumption. METHODS:This was a double-blind placebo-controlled RCT testing doxazosin up to 16mg/day in AD treatment-seeking patients (N=41). The hypothesized moderator effect of baseline standing systolic and diastolic BP on DPW and HDD was tested. RESULTS:With pre-treatment standing diastolic BP as a moderator, there were significant BP x medication interactions for both DPW [**p=0.009, d=0.80] and HDD [*p=0.018, d=1.11]. Post-hoc analyses indicated significant doxazosin effects in patients with higher standing BP in reducing both DPW and HDD. CONCLUSION:These findings suggest that higher standing diastolic BP at baseline (pre-treatment) may represent a predictor of doxazosin's response on alcohol consumption in AD patients. These results further elucidate the possible efficacy and mechanisms of action of ?1 receptor antagonism in AD individuals.

SUBMITTER: Haass-Koffler CL

PROVIDER: S-EPMC5534374 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Higher pretreatment blood pressure is associated with greater alcohol drinking reduction in alcohol-dependent individuals treated with doxazosin.

Haass-Koffler Carolina L CL Goodyear Kimberly K Zywiak William H WH Magill Molly M Eltinge Sarah E SE Wallace Paul M PM Long Victoria M VM Jayaram-Lindström Nitya N Swift Robert M RM Kenna George A GA Leggio Lorenzo L

Drug and alcohol dependence 20170516

<h4>Background</h4>Preclinical and clinical research suggest that the α<sub>1</sub> receptor antagonist prazosin reduces alcohol consumption. Furthermore, clinical studies indicate a role for prazosin in treating Post-Traumatic Stress Disorder (PTSD) symptoms and a recent trial suggested that pre-treatment blood pressure (BP) predicts therapeutic response for prazosin in PTSD patients. Whether pre-treatment BP may predict response to α<sub>1</sub> blockers in alcohol-dependent (AD) patients is u ...[more]

PMID: 28551590

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Project description:IntroductionChronic alcohol consumption is known to cause gut dysbiosis (changes in microbiota composition and/or function, disruptive of the normal host-microbiota interactions). However, little is known about the changes that alcohol binge drinking induces in the gut microbiota. Here, we have tested the hypothesis that a protocol of alcohol binge drinking, known to induce neuroinflammation in previous studies, also promotes intestinal dysbiosis, and we explored how oleoylethanolamide (OEA, an acylethanolamide proven to counteract alcohol binge drinking-induced neuroinflammation) pretreatment modulates alcohol-induced dysbiosis.MethodsAlcohol binges were forced by gavage three times per day during 4 consecutive days; OEA pretreatment (intraperitoneal or intragastric) was administered before each alcohol gavage. Stool microbiota composition was assessed by next-generation 16S rRNA gene sequencing, prior and after the 4-day alcohol binge protocol.ResultsAlcohol binge drinking reduced the richness of the gut microbiota and changed the microbial community, reducing Lactobacillus among other genera. Pretreatment with OEA in the alcohol-administered rats decreased the richness, evenness, and Shannon indices to a greater extent with respect to alcohol alone, also changing the community structure. Microbial interactions in the association network were further decreased following OEA administration in the alcohol group, with respect to the water administration. The synergistic interaction between alcohol binge and OEA was affected by the route of administration of OEA, since oral and i.p. administrations differently changed the community structure.ConclusionResults suggest that alcohol binge drinking produces a clear dysbiosis in animals; we observed that the well-known protective actions of OEA in the context of alcohol abuse might not be related to OEA-induced changes in alcohol-induced dysbiosis. These are observational results, and thus, further research will be needed for a complete understanding of the biological significance of the observed changes.

Project description:BackgroundGhrelin may influence several alcohol-related behaviors in animals and humans by modulating central and/or peripheral biological pathways. The aim of this exploratory analysis was to investigate associations between ghrelin administration and the human circulating metabolome during alcohol exposure in nontreatment seeking, heavy drinking individuals with alcohol use disorder (AUD).MethodsWe used serum samples from a randomized, crossover, double-blind, placebo-controlled human laboratory study with intravenous (IV) ghrelin or placebo infusion in two experiments. During each session, participants received a loading dose (3 µg/kg) followed by continuous infusion (16.9 ng/kg/min) of acyl ghrelin or placebo. The first experiment included an IV alcohol self-administration (IV-ASA) session and the second experiment included an IV alcohol clamp (IV-AC) session, both with the counterbalanced infusion of ghrelin or placebo. Serum metabolite profiles were analyzed from repeated blood samples collected during each session.ResultsIn both experiments, ghrelin infusion was associated with an altered serum metabolite profile, including significantly increased levels of cortisol (IV-ASA q-value = 0.0003 and IV-AC q < 0.0001), corticosterone (IV-ASA q = 0.0202 and IV-AC q < 0.0001), and glycochenodeoxycholic acid (IV-ASA q = 0.0375 and IV-AC q = 0.0013). In the IV-ASA experiment, ghrelin infusion increased levels of cortisone (q = 0.0352) and fatty acids 18:1 (q = 0.0406) and 18:3 (q = 0.0320). Moreover, in the IV-AC experiment, ghrelin infusion significantly increased levels of glycocholic acid (q < 0.0001) and phenylalanine (q = 0.0458).ConclusionIV ghrelin infusion, combined with IV alcohol administration, was associated with increases in the circulating metabolite levels of corticosteroids and glycine-conjugated bile acids, among other changes. Further research is needed to understand the role that metabolomic changes play in the complex interaction between ghrelin and alcohol.

Project description:ObjectivesTo explore awareness of alcohol marketing and ownership of alcohol branded merchandise in adolescents and young adults in the UK, what factors are associated with awareness and ownership, and what association awareness and ownership have with alcohol consumption, higher-risk drinking and susceptibility.DesignOnline cross-sectional survey conducted during April-May 2017.SettingThe UK.ParticipantsAdolescents and young adults aged 11-19 years in the UK (n=3399).Main outcome measuresAlcohol Use Disorders Identification Test-Consumption (AUDIT-C) (0-12) and indication of higher-risk consumption (>5 AUDIT-C) in current drinkers. Susceptibility to drink (yes/no) in never drinkers.ResultsEighty-two per cent of respondents were aware of at least one form of alcohol marketing in the past month and 17% owned branded merchandise. χ2 tests found that awareness of marketing and ownership of branded merchandise varied within drinking variables. For example, higher awareness of alcohol marketing was associated with being a current drinker (χ2=114.04, p<0.001), higher-risk drinking (χ2=85.84, p<0.001), and perceived parental (χ2=63.06, p<0.001) and peer approval of consumption (χ2=73.08, p<0.001). Among current drinkers, multivariate regressions (controlling for demographics and covariates) found that marketing awareness and owning branded merchandise was positively associated with AUDIT-C score and higher-risk consumption. For example, current drinkers reporting medium marketing awareness were twice as likely to be higher-risk drinkers as those reporting low awareness (adjusted OR (AOR)=2.18, 95% CI 1.39 to 3.42, p<0.001). Among never drinkers, respondents who owned branded merchandise were twice as likely to be susceptible to drinking as those who did not (AOR=1.98, 95% CI 1.20 to 3.24, p<0.01).ConclusionsYoung people, above and below the legal purchasing age, are aware of a range of alcohol marketing and almost one in five own alcohol branded merchandise. In current drinkers, alcohol marketing awareness was associated with increased consumption and greater likelihood of higher-risk consumption. In never drinkers, ownership of branded merchandise was associated with susceptibility.

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Higher pretreatment blood pressure is associated with greater alcohol drinking reduction in alcohol-dependent individuals treated with doxazosin.

Publications

Higher pretreatment blood pressure is associated with greater alcohol drinking reduction in alcohol-dependent individuals treated with doxazosin.

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