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DOI: 10.1055/s-2007-1016438
Klinische Pharmakologie von Disulfiram - eine aktuelle Übersicht[1]
Pharmacology of Disulfiram - An UpdatePublication History
Publication Date:
07 February 2008 (online)

Zusammenfassung
Der gegenwärtig zu beobachtende Anstieg an Verschreibungen von Disulfiram setzt ärztliche Kenntnisse bezüglich Pharmakodynamik, -kinetik, Nebenwirkung und Wechselwirkung der Substanz voraus. Wir geben eine Übersicht über die Pharmakologie und unerwünschte Nebenwirkungen der Substanz Disulfiram. Beispielhaft wird ein Fall vorgestellt, bei welchem ein akutes neurologisches Defizit zunächst als Nebenwirkung von Disulfiram verkannt wurde. Diskutiert werden mögliche Perspektiven von Disulfiram in der Suchtmedizin.
Abstract
Recently, we have been observing an increase in prescription of Disulfiram requiring medical knowledge concerning the overall effects, side effects and drug interactions of this substance. In the following report, we give an overview about the pharmacology and the side effects of Disulfiram. As an example we demonstrate a case, in which an acute neurological deficit was misjudged as a side effect of Disulfiram. Furthermore, the potential of Disulfiram as a promising treatment in addiction medicine will be discussed.
Schlüsselwörter
Disulfiram - Alkohol - Nebenwirkungen - Wechselwirkungen - Arzneimittel-Interaktionen
Key words
Disulfiram - alcohol - side effects - adverse drug reactions - drug interactions
1 Interessenkonflikt. Es besteht kein Interessenkonflikt. Die Autoren versichern, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.
Literatur
- 1
De Sousa A, De Sousa A.
A one-year pragmatic trial of naltrexone vs disulfiram in the treatment of alcohol
dependence.
Alcohol Alcohol.
2004;
39
528-531
MissingFormLabel
- 2
De Sousa A, De Sousa A.
An open randomized study comparing disulfiram and acamprosate in the treatment of
alcohol dependence.
Alcohol Alcohol.
2005;
40
545-548
MissingFormLabel
- 3
Krampe H, Stawicki S, Wagner T. et al .
Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment:
impact of alcohol deterrents on outcome.
Alcohol Clin Exp Res.
2006;
30
86-95
MissingFormLabel
- 4
Chick J, Gough K, Falkowski W. et al .
Disulfiram treatment of alcoholism.
Br J Psychiatry.
1992;
161
84-89
MissingFormLabel
- 5 Datenlieferungen nach § 300 SGB V, Wissenschaftliches Institut der AOK WldO. 2007
MissingFormLabel
- 6
Johansson B.
A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites.
Acta Psychiatr Scand Suppl.
1992;
369
15-26
MissingFormLabel
- 7
Brewer C.
How effective is the standard dose of disulfiram? A review of the alcohol-disulfiram
reaction in practice.
Br J Psychiatry.
1984;
144
200-202
MissingFormLabel
- 8
Madan A, Parkinson A, Faiman M D.
Identification of the human P-450 enzymes responsible for the sulfoxidation and thiono-oxidation
of diethyldithiocarbamate methyl ester: role of P-450 enzymes in disulfiram bioactivation.
Alcohol Clin Exp Res.
1998;
22
1212-1219
MissingFormLabel
- 9
Elenbaas R M.
Drug therapy reviews: management of the disulfiram-alcohol reaction.
Am J Hosp Pharm.
1977;
34
827-831
MissingFormLabel
- 10
Amadoe M, Gazdar A.
Sudden death during disulfiram-alcohol reaction.
Q J Stud Alcohol.
1967;
28
649-654
MissingFormLabel
- 11
Guild J, Epstein N B.
Psychosis during the treatment of alcoholism with tetraethylthiuram disulfide.
Q J Stud Alcohol.
1951;
12
360-366
MissingFormLabel
- 12
Jacobsen E.
Deaths of alcoholic patients treated with disulfiram (tetraethylthiuram disulfide)
in Denmark.
Q J Stud Alcohol.
1952;
13
16-26
MissingFormLabel
- 13
Fuller R K, Branchey L, Brightwell D R. et al .
Disulfiram treatment of alcoholism. A Veterans Administration cooperative study.
JAMA.
1986;
256
1449-1455
MissingFormLabel
- 14
Fuller R K, Gordis E.
Does disulfiram have a role in alcoholism treatment today?.
Addiction.
2004;
99
21-24
MissingFormLabel
- 15
Green A L.
The inhibition of dopamine-B-oxidase by chelating agents.
Biochem biophys Acta.
1964;
81
394-397
MissingFormLabel
- 16
Mays D C, Ortiz-Bermudez P, Lam J P, Tong I H, Fauq A H, Lipsky J J.
Inhibition of recombinant human mitochondrial aldehyde dehydrogenase by two intermediate
metabolites of disulfiram.
Biochem Pharmacol.
1998;
55
1099-1103
MissingFormLabel
- 17
Karamanakos P N, Pappas P, Stephanou P, Marselos M.
Differentiation of disulfiram effects on central catecholamines and hepatic ethanol
metabolism.
Pharmacol Toxicol.
2001;
88
106-110
MissingFormLabel
- 18
Musacchio J M, Goldstein M, Anagnoste B, Poch G, Kopin I J.
Inhibition of dopamine-beta-hydroxylase by disulfiram in vivo.
J Pharmacol Exp Ther.
1966;
152
56-61
MissingFormLabel
- 19
Paradisi R, Grossi G, Pintore A. et al .
Evidence for a pathological reduction in brain dopamine metabolism in idiopathic hyperprolactinemia.
Acta Endocrinol (Copenh).
1991;
125
246-252
MissingFormLabel
- 20
Rosen G F, Lobo R A.
Further evidence against dopamine deficiency as the cause of inappropriate gonadotropin
secretion in patients with polycystic ovary syndrome.
J Clin Endocrinol Metab.
1987;
65
891-895
MissingFormLabel
- 21
Amit Z, Levitan D E, Lindros K O.
Suppression of ethanol intake following administration of dopamine-beta-hydroxylase
inhibitors in rats.
Arch Int Pharmacodyn Ther.
1976;
223
114-119
MissingFormLabel
- 22
Kohnke M D, Zabetian C P, Anderson G M. et al .
A genotype-controlled analysis of plasma dopamine beta-hydroxylase in healthy and
alcoholic subjects: evidence for alcohol-related differences in noradrenergic function.
Biol Psychiatry.
2002;
52
1151-1158
MissingFormLabel
- 23
Kohnke M D, Kolb W, Kohnke A M, Lutz U, Schick S, Batra A.
DBH*444G/A polymorphism of the dopamine-beta-hydroxylase gene is associated with alcoholism
but not with severe alcohol withdrawal symptoms.
J Neural Transm.
2006;
113
869-876
MissingFormLabel
- 24
Ewing J A, Rouse B A, Mueller R A, Silver D.
Can dopamine beta-hydroxylase levels predict adverse reactions to disulfiram?.
Alcohol Clin Exp Res.
1978;
2
93-94
MissingFormLabel
- 25
Heath R G, Nesselhof Jr W, Bishop M P, Byers L W.
Behavioral and metabolic changes associated with administration of tetraethylthiuram
disulfide (antabuse).
Dis Nerv Syst.
1965;
26
99-105
MissingFormLabel
- 26
Major L F, Lerner P, Ballenger J C, Brown G L, Goodwin F K, Lovenberg W.
Dopamine-beta-hydroxylase in the cerebrospinal fluid: relationship to disulfiram-induced
psychosis.
Biol Psychiatry.
1979;
14
337-344
MissingFormLabel
- 27
Cubells J F, Kranzler H R, Cance-Katz E. et al .
A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase
activity, also associates with cocaine-induced paranoia.
Mol Psychiatry.
2000;
5
56-63
MissingFormLabel
- 28
Poikolainen K.
The disulfiram-ethanol reaction (DER) experience.
Addiction.
2004;
99
6-28
MissingFormLabel
- 29
Ehrenreich H, Krampe H.
Does disulfiram have a role in alcoholism treatment today? Not to forget about disulfiram's
psychological effects.
Addiction.
2004;
99
26-27
MissingFormLabel
- 30
Martensen-Larsen O.
Psychotic phenomena provoked by tetraethylthiuram disulfide.
Q J Stud Alcohol.
1951;
12
206-216
MissingFormLabel
- 31
Christensen J K, Ronsted P, Vaag U H.
Side effects after disulfiram. Comparison of disulfiram and placebo in a double-blind
multicentre study.
Acta Psychiatr Scand.
1984;
69
265-273
MissingFormLabel
- 32
Fuller R K, Branchey L, Brightwell D R. et al .
Disulfiram treatment of alcoholism. A Veterans Administration cooperative study.
JAMA.
1986;
256
1449-1455
MissingFormLabel
- 33
Poulsen H E.
Disulfiram therapy - adverse drug reactions and interactions. Loft S, Andersen JR,
Andersen M (eds).
Acta Psychiatr Scand.
1992;
86
59-66
MissingFormLabel
- 34
Branchey L, Davis W, Lee K K, Fuller R K.
Psychiatric complications of disulfiram treatment.
Am J Psychiatry.
1987;
144
1310-1312
MissingFormLabel
- 35
Bjornsson E, Nordlinder H, Olsson R.
Clinical characteristics and prognostic markers in disulfiram-induced liver injury.
J Hepatol.
2006;
44
791-797
MissingFormLabel
- 36
Frisoni G B, Di Monda V.
Disulfiram neuropathy: a review (1971 - 1988) and report of a case.
Alcohol Alcohol.
1989;
24
429-437
MissingFormLabel
- 37
Berglund M.
A better widget? Three lessons for improving addiction treatment from a meta-analytical
study.
Addiction.
2005;
100
742-750
MissingFormLabel
- 38
Mann K, Lehert P, Morgan M Y.
The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent
individuals: results of a meta-analysis.
Alcohol Clin Exp Res.
2004;
28 (1)
51-63
MissingFormLabel
- 39
Kiefer F, Jahn H, Tarnaske T. et al .
Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism:
a double-blind, placebo-controlled study.
Arch Gen Psychiatry.
2003;
60
92-99
MissingFormLabel
- 40
Besson J, Aeby F, Kasas A, Lehert P, Potgieter A.
Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a
controlled study.
Alcohol Clin Exp Res.
1998;
22
573-579
MissingFormLabel
- 41
Landabaso M A, Iraurgi I, Sanz J. et al .
Naltrexone in the treatment of alcoholism. Two-year follow up results.
Eur J Psychiatry.
1999;
13
97-105
MissingFormLabel
- 42
Petrakis I L, Poling J, Levinson C, Nich C, Carroll K, Rounsaville B.
Naltrexone and disulfiram in patients with alcohol dependence and comorbid psychiatric
disorders.
Biol Psychiatry.
2005;
57
1128-1137
MissingFormLabel
- 43
Petrakis I L, Poling J, Levinson C. et al .
Naltrexone and disulfiram in patients with alcohol dependence and comorbid post-traumatic
stress disorder.
Biol Psychiatry.
2006;
60
777-783
MissingFormLabel
- 44
Weinshenker D, Schroeder J P.
There and Back Again: A Tale of Norepinephrine and Drug Addiction.
Neuropsychopharmacology.
2007;
32
1433-1451
MissingFormLabel
- 45
Finney J W, Monahan S C.
The cost-effectiveness of treatment for alcoholism: a second approximation.
J Stud Alcohol.
1996;
57
229-243
MissingFormLabel
- 46
Miller W R, Wilbourne P L.
Mesa Grande: a methodological analysis of clinical trials of treatments for alcohol
use disorders.
Addiction.
2002;
97
265-277
MissingFormLabel
- 47
Fuller R K, Branchey L, Brightwell D R. et al .
Disulfiram treatment of alcoholism. A Veterans Administration cooperative study.
JAMA.
1986;
256
1449-1455
MissingFormLabel
- 48
Kellam A M, Wesolkowski J M.
Disulfiram implantation for alcoholism.
Lancet.
1968;
1
925-926
MissingFormLabel
- 49
Wilson A, Davidson W J, Blanchard R, White J.
Disulfiram implantation. A placebo-controlled trial with two-year follow-up.
J Stud Alcohol.
1978;
39
809-819
MissingFormLabel
- 50
Hughes J C, Cook C C.
The efficacy of disulfiram: a review of outcome studies.
Addiction.
1997;
92
381-395
MissingFormLabel
- 51
Suh J J, Pettinati H M, Kampman K M, O"Brien C P.
The status of disulfiram: a half of a century later.
J Clin Psychopharmacol.
2006;
26
290-302
MissingFormLabel
- 52
Matching Alcoholism Treatments to Client Heterogeneity .
Project MATCH posttreatment drinking outcomes.
J Stud Alcohol.
1997;
58
7-29
MissingFormLabel
- 53
Moos R H, Finney J W, Ouimette P C, Suchinsky R T.
A comparative evaluation of substance abuse treatment: I. Treatment orientation, amount
of care, and 1-year outcomes.
Alcohol Clin Exp Res.
1999;
23
529-536
MissingFormLabel
- 54
Brewer C.
Long-term, high-dose disulfiram in the treatment of alcohol abuse.
Br J Psychiatry.
1993;
163
687-689
MissingFormLabel
- 55
Carroll K M, Fenton L R, Ball S A. et al .
Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients:
a randomized placebo-controlled trial.
Arch Gen Psychiatry.
2004;
61
264-272
MissingFormLabel
- 56
Fritze J.
Psychopharmaka-Verordnungen - Ergebnisse und Kommentare zum Arzneiverordnungsreport
2005.
Psychoneuro.
2006;
32
44-53
MissingFormLabel
- 57
Kiefer F, Jahn H, Holzbach R, Briken P, Stracke R, Wiedemann K.
Die NALCAM-Studie: Wirksamkeit, Verträglichkeit, Outcome.
Sucht.
2003;
49 (6)
342-351
MissingFormLabel
1 Interessenkonflikt. Es besteht kein Interessenkonflikt. Die Autoren versichern, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.
Dr. med. Alexander Diehl
Klinik für Abhängiges Verhalten und Suchtmedizin, Ärztlicher Direktor Prof. Dr. Karl
Mann, Zentralinstitut für Seelische Gesundheit
Quadrat J 5
68159 Mannheim
Email: alexander.diehl@zi-mannheim.de