Alkohol und seine Wirkung im Körper

Wurst et al 2006 SUCHT

ETG im Urin bis zu 5 Tagen PEth im Vollblut bis 3 Wochen nachweisbar. Beides in Haaren noch nach Monaten. Beides valide und sensitive Alkoholmarker.

Wurst et al 2006 Addiction

Promising nonoxidative ethanol metablolites: fatty acid ethyl esters (FAEEs), ethanol glucuronide (EtG) and phosphatidyl ethanol (PEth). Each remains positive in serum and urine for a characteristic time spectrum after the cessation of ethanol intake. FAEEs 24 h. EtG 5 days and PEth more than 2 weeks. All can be detected in hair for months. Ethyl sulphate (EtS) also promising. Figure P 207. In US EtG urine testing at workplace increasignly widespread (Skipper et al 2004).

Politi et al 2006 Addiction

Ethyl glucuronide (EtG) a phase II metabolite of ethanol. Measured in hair. Teetotallers negative, cutoff level discriminating between moderte and non moderate drinkers.

Dräger 2006 Suchtmed.

DrugCheck durch Speichelprobe Minuten bis Tage nachweisbar.

Hartmann et al 2007 Addiction Biology

Phosphatidylethanol PEth a direct ethanol metabilite is decetable in blood for more than 2 weeks after sustained ethanol intake. N=56. Has potential to be a sensitive and specific biomarker having been found in previous studies to indicate longer lasting intake of higher amounts of alcohol.

Bentele et al 2007 Addiction Biology

N=2940. Combination of the markers gammaGT and CDT with physicians judgement of condition as reference was superior to the use of single markers. The detection of at risk drinking before the disease process progresses towards more severe, harmful or dependent drinking patterns is essential for early primary or secorndary prevention in primary care. The prevalence of at risk drinking is around 10-14% in the general population and approximately 15-17% in primary care settings. Many patients tend to either underestimate or underreport their alcohol intake. Examminations are not easily integrated into the routine care of patients because some are rather time consuming. With common cut off points Gamma GT has a relatively loww specifity and mean corpuscular volume a low sensitivity. CDT shows increase serum concentration after regular intake of 60-80g aof ethanol per day for at least 1 week, which then normalizes slowly during abstinence. Koch et al 2004; validity still questionalbe.

Klein 2008 SUCHt

N=259 CDT eher als Grenzwert für Chronizität des Alkoholkonsums aber nicht für die Schwere des Konsums. Nicht geeignet, um kurze Rückfälle innerhalb eines Studienprogramms aufzudecken.

Skoop 2008 SUCHT

Prinzipiell hängt der im Urin vorhande, körperfremende Stof ab von;- der Wirkstoffmenge- der Häufigkeit des Konsums- der Zeit seit Aufnahme- individuellen AbbauDer pH-Wert einer frischen Urinprobe schwankt zwischen 4,5-7,5. Messergebnissse auf den Kreatiningehalt beziehen, um tageszeitliche Konzentrationsschwankungen ausgleichen und eine Aufnahme erheblicher Flüssigkeitsmengen erkennen zu können. Proben mit einer relativen Dichte unter 1,001 und einer Kreatininkonzentration unter 5mg Kreatinein/dL Urin sollten nicht in ein Drogenscreening eingesetzt werden, da diese Werte für eine Substitution oder Manipulation der Probe sprechen und allenfalls bei schwer erkrankten Personen vorkommen. Haarprobe ab 6 cm Länge. Einmaliger Cocainkonsum lässt sich heute sicher nachweisen. Ein einmaliger Cannabiskonsum lässt sich auch mit modernen Analyseverfahren nicht zuverlässig belegen. Übersichtsanalysen, die eine ganze Palette von Substanzen erfassen können, nicht hinreichend empfindlich. Fahrtenschreibermodell des Haares. Analyse erst 6-12 Monate nach Konsumende durchführen. Bei Langzeitkontrolle daher preiswerter als regelmäßige Urinkontrollen.

Wurst et al 2008 SUCHT

Urin Ethylglucuronid UEtG und Haar Fettsäureethylester HFAEE und Haar Ethlglucuronid HEtG. Mit HEtg wurden 20 Fälle täglichen Alkoholkonsum von mehr als 20g entdeckt, die mit den Fragen 1 und 2 des AUDIT übersehen worden wären.

Geringer Wassergehalt im Körper bei alten Menschen führt zu stärkerer Alkoholwirkung.

Spanagel 2001 (Suchttherapie)

Naltrexon (Revia) besonders bei intermettierender Gabe effektiv. Naltrexon positives Verlangen, Acamprosat negatives Verlangen

White, 2003 Addiction

Vielzahl von Pillen gegen Sucht in Amerika des 19. JahrhundertsI know of no class of people who have been so victimized by the quack as the inebiate (Rogers 1913)

Soyka 2003 Suchtmedizin

zitierfähige Zusmmenfassung der bisherigen Ergebnisse

Krahl et al 2004 Suchtmedizin

Revival von Antabus durch GOAL Therapie. Anatabus als psychotherapeutische Substanz wie bei ALITA

Hulse et al 2004 Addiction Biology

Naltrexonimplantat wegen Complianceproblemen. Hohe Dosierung vorteilhaft.

Bouza et al 2004 Addiction

Metaanalyse von 36 Studien: Acamprosat odds ration 1.88 Abstinenzrate. Naltrexon eher geeignet, um Trinkexzess zu reduzieren. Mehr Nebenwirkungen. Allerdings hohe Abbruchraten. Keine Substanz überlegen. Notwendigkeit zusätzlicher Psychotherapie nicht ganz klar.

Cowen et al 2005 Addiction Biology

Recent metaanalyses (Kranzler & Van Krik 2001, Mann 2004) are positive for acamporsate. Hypothesized by preventing conditioned withdrawal induced by enviromental stimuli, secundarily conditioned by ethanaol (Littleton 1995). Acamporsat also decreased the ethanol reinforcement process. However these effects undergo tolerance. This may explain why the effect size of acamprosate treatment is relatively moderate (Mann 2005). Acamprosate does not alter the the recognition but the salience of cues.

Huang et al 2005 Addiction Biology

Double blind placebo controlled study: naltrexone safe and effective in craving reduction in alcoholics.

Mann et al 2006 SUCHT

Predict Studie: Bildung von Subtypen von Patienten nach reward vs relief craving zur Vorhersage von Acamprosat vs Naltrexon.

Paslakis et al 2006 SUCHT

Übersicht Wirksamkeit von Anticravingsubstanzen. Keine wirksamkeit bei dopaminergen Substanzen (Lisurid) und antidopaminergen Substanzen (Taprid, Flupentixol) sowie Antidepressiva und Anxiolytika. Insbesondere bei selektiven Serotonin Wiederaufnahmehemmern und Buspiron, Ritanserin und Nefazodon.

Spanagel 2006 SUCHT

Erhöhter Glutamatspiegel Indikator für Ansprechen auf Acamprosat

Karanzler 2006 Addiction

Naltrexone just prescribed to 3,8% of alcohoics demonstrating very limited by practitioners in the use of medication to treat alcohol dependence. Modest efficacy when compared with the effects of antidepressants in the treatment of major depression. On the other hand NRT with similar modest effect is considered first choice in smoking cessation. One reason: naltrexone is available only as generic drug. In contrast acamprosate is marketed actively and overtaking in prescriptions within 13 weeks.

Morley et al 2006 Addiction

169 alcohol dependent subjects. No difference between naltrexone and acomprosate on outcome of drinking, craving or biochemical markers. Similarly analyses of the 94 subjects that completetd the study in full and demonstrated 80% compliance revealed not significant treatment effects. A significant tretment effect on time to first relapse was revealed for subjects with no depression allocated to naltrexone. Support for some limited efficacy of naltrexone but no effect of acomporsate. Some indication to define subgroups to optimize pharmacological treatemnt for alcohol dependence.

Escher % Mittleman 2006 Addiction Biology
The efects of acamprosate and naltrexone are relatively nonspecific in that they involve both nonregulary and regulatory ingestion and may affect both hunger and thirst.

Oslin et al 2006 Addiction Biology

Genetic variation in the mu-opiod receptor has a significant invluence on clinical presentation of alcohol problems and response to treatment with an opoid antagonist. A118G polymorphisms of the mureceptor gene has been demonstrated to predict clinical response to naltrexone in alcoholdependent individuals. Despite the better group response to naltrexone in clinical trials there is significant variability in response among individuals prescirbed the medication. While some of this variability is due to differences in adherence and obtaining a functionally significant dose, there remain intradinividual differences in patient response that have not yet been accounted for or predicted. A critical aim of the field is not to find the single treatment that is beneficial for all patients but rather to determine under what cicrumstances or for which patients a particial treatment will have the greatest effect. Increasing the cost effectiveness of patient treatment matching. Animal studies have shown that alcohl is ingested after rather than during a stressful event and that there is a rebound reduction in endorphin levels after stress. Moreover alcohol consumption leads to an increase in betaendorphin release. Thus for most people during periods when endorphins are praticularly low eg after stress alcohol may be most reinforceing. Nalterxone may reduce the reinforcing or pleasurable effects of alcohol in social drinkers. Demonstrated greater levels of plasma beta endorphin after alcohol challenge in non alcohol dependent adults who were at high risk for alcoholism basted on family history compared with low risk individuals. Naltrexone blinte the subjective stimulation or high experienced after alcohol consumption in HR individuals relative to LR individuals as measured by the Biphasic Alcohol Effects Scale. Naltrexone preferentially binds to the mu opioid receptor which is hypothesized to be the principal site of action of the medication. Polymorphisms may moderate treatment response to mu poioid rectptor blockage. 3,5 Time responded to treatemnt, but no difference in rates of abstinence. 2 promises of pharmacogenetics: 1) to reduce expsoure to medication that has adverse effects 2) to increase the specificity of treatment respons. Ifts determine subtype of alcoholism. Than adaptive treatemnt strategy.

Ma et al 2006 Addiction

N=75. alcoholics who received topiramate achieved more likely longer periods of safe drinking (less thean 1/2 drinks per day) compared to placebo in an abstinene orienteated treatemnt program.

Fletcher et al 2006 Addiction

only 20% of all patients were fully compliant with antabus.

Olbrich & Olbrich 2007 SuCHT

Durch das Zusammentreffen von Ethanol und Disulfiram im menschlichen Organismus wird eine Akkumulaton von Acetaldehyd und damit eine Symptomatik herbeigeführt, die va. durch Übelkeit, Kopfschmerz, Schwindel, Herzklopfen, Blutdruckabfall und eine Tachykardie gekennzeichnet ist. Entdeckt von Williams 1937. Überblick über Studien S 74. Durchgängig hohe methodischer Standard. Meistens im Sinne des Intention to Treat Prinzips alle Patietnen einbezogen. Antabus deutliche Effekte gegenübe Placebo und gegenüber Acamprosat. Fazit: Potential: missbräuchlichen Alkoholkonsum bei Suchtkranken deutlich zu verringern. In Effektstärken Anticravingsubtanzen ebenbürtig bis überlegen. Breite Reaktionsvarianz auf Probetrunk. In Extremfälllen Anwendung nicht sinnvoll.

Kiefer 2007 Suchtmedizin

Bei chronischem Alkoholkonsum Upregulation in Dichte und Affinität von Rezeptoren im glutamartergen und eine Downregulation im GABAergen System.

Roozen et al 2007 European Addiction Research

Oral delivery of naltrexon is associated with poor compliance and adverse events. Possible solution is the use of injectable extendet-release naltrexone (1 month). Metaanlysis: Reduction of alcohol consumption. But inconstistent findings about mechanism (reduction of relapse through blocking of reinforcing effects of alcohol). No sign effect on relapse after 3 months. No superiority of injection proven.

Burattini et al 2008 Addiction Biology

Acute adminsitration of acomprosate has minimal effects on reducing alcohol consumption and or relapse like behaviors in rodents and nonhuman primates and that repeated dosing procedures are needed to obtain more robust effects. Some studies have shown that repeated or chronic administration of naltrexone actually results in tolerance to its ability to reduce alcohol consumption in rodents.Acute administration of acamporsate (100 or 300 mg/kg) results in extracellular levles of this drug in the low micormolar range 

Mutschler et al. 2008 SUCHT

Deutlich zunehmende Zahl von Pat. zu verzeichnen, die eine Behandlung mit Disulfiram wünschen.

Richardson et al 2008 Addiction

169 alcoholdependent subjects. Naltrexone had a greater effect on drinking when craving was high. These results support the role of naltrexone in reducing craving when that craving is highly salient. The role of acomprosate in reducing craving was not supported by these findings. Baseline level of depression was the strongest predictor of subjective daily craving over the course of treatment.

Quintanilla et al 2008 Addiction Biology

Baclofen reduces ethanol intake in high alcohol drinking rats.

Rösner 2008 Suchtmedizin

Metaanalyose: 21 Acamporsat und 20 Naltrexonstudien zu über 5280 bzw 2475 Pat.

Diehl et al 2008 SUCHT

Unter Galanthamin wie unter Rivastigmine zeigte sich eine sign Reduktion des Tabakkonsums,ohne jegliche weitere  spezifische Therapie zur Unterstützung des Rauchausstiegs. Über den Tabakreduktionsansatz mit Nikotinersatztherapie könnten deutlich mehr Alkoholabhängige Patienten noch während der aktuellen Entzugsbehandlung zu einer Raucherentwöhnung motiviert werden im Vergleich zu Rauchstopansatz.

Kranzler et al 2008 Addiction

N=1138. over 6month period 85,8% of patients who filled an initial prescription of naltrexone did not persist. Need to educate physicians in the use of medications with demonstratd efficacy for the treatment of alcohol dependence and in methods to enhance patients adherence with the treatments.

Baltieri et al 2008 Addiciton

N=155. Support the efficacy of topiramate in the relapse prevention of alcoholism. Superiority of topiramate vs naltrexone. Topiramate is an anticonvulsant that facilates the inhibitory action of the neurostransmitter GABA at its nonbenzodiazepine receptor and reduces th exitorary action on glutamate receptors of the alpha amino 3 hydroxy 5 methylisoxazole 4 propionic acis AMPA and kainate types. Similar to the approved medication acamprosate. Sign more effective than placebo in delaying time to the first alcohol driking relapse increasing treatemnt retention and abstinence duration during a 12 weeks randomized efficacy evaluation and reducing mean duration of heavy drinking. Reduced the odds of relapse by 39%. Favourable side effect profile. Lack of sign effects of naltrexone vs placebo in the present trial. Relatively smaller effect for naltrexone than for topiramate.

Mason et al 2008 Addiction Biology

Gabapentin was associated with sign greater reductions than placebo on several measures of subjective craving for alcohol as well as for affectively evoced craving. Gabapentin was also associated with sig improvements on several measures of sleep quality. Anticonvulsant drug gabapentin (Neurontin). Like acamprosate it acts on GABA and glutamate systems to normilize CNS actiity. Reports have suggested that it may have efficacy as an offlabled treatment for depression, anxiety and insomnia, all of which have been identified as symptoms of protracted abstinence and which can increase risk of relapse in abstinent alcoholics. If gabapentin were found to attenuate such protracted withdrawal symptoms such a finding would tend to confim the hypothsized sign of GABA and glutamatae system dysregulation in alcohol dependence because gabapentin and acomporsate have theses mechanisms in common. We included only cue reactive subjects in the study. Cure reactivity method descirbed in Mason et al 2008.

• Verstärkte Alkoholtoleranz und verstärkter AKonsum durch unterschiedlichen Metabolismus von Acetaldehyd durch ALDH im Gehirn bei Vieltrinkern. Verheul et al 1999 reward (Hypersensitivität von opioidem und dopaminergem System), relief (GABAerge Dysfunktion, die zu erhöhter Stressanfälligkeit führt) und obsessive craving (Serotonindefizit, Ciccocioppo, 1999)) mit jeweils unterschiedlicher neurochemischer Verursachung 
  Implizites Gedächtnis, das der bewussten Verarbeitung nicht zugänglich ist.
  Quelle: Tampier & Quintillana 2003 Addiction Biology
• Permanente Alkoholtoleranz bei abhängigen Ratten. Dauerhafte empfindlichkeit gegenüber Stress und Anfälligkeit gegenübe mehr Alkohol. hat nichts mit MEOS zu tun, sondern mit neurophysiologischer Veränderung im Belohnungssystem.
  Quelle: Rimondini et al 2008 Add Biol
• N=172. 1,5% promille. 25-30% of drinkers may be resistant to hangover. Survey of college students found that 25% reported hangover during the previous week. Congener differences between beverages did not account for differences in hangover severety. Lack of difference in hangover incidences by gender. No relationship between selfrepored daily drinking qunatitiy and hangover incidence. The lack of sign individual difference predictors despite observed variation in hangover intensity demonstrates the need of furhter research to determine individual differences that account for differing levels of hangover severety after about the same peak BAC levle.
  Quelle: Howland et al 2008 Addiction