Biological Approaches
Tricia L. Chandler, Fredrick Dombrowski, Tara G. Matthews in Co-occurring Mental Illness and Substance Use Disorders, 2022
Disulfiram is one of the more common drugs used to treat alcohol use disorder and the first medication approved by the US Food and Drug Administration (FDA). It works by inhibiting aldehyde dehydrogenase – a key enzyme involved in the breakdown of ethyl alcohol (Schatzberg & Nemeroff, 2013). It is considered most effective for individuals who have completed detoxification and are in the initial stage of abstinence. There are some common unpleasant side effects that can occur as soon as ten minutes after drinking even a small amount of alcohol and can last one or more hours. These side effects include nausea, headache, vomiting, chest pains, and difficulty breathing. The half-life of Disulfiram is 60 to 120 hours. It is contraindicated if an individual has been diagnosed with cardiovascular disease or a psychosis (Stahl, 2017).
Stimulant Use Disorder
James MacKillop, George A. Kenna, Lorenzo Leggio, Lara A. Ray in Integrating Psychological and Pharmacological Treatments for Addictive Disorders, 2017
Disulfiram is an FDA-approved treatment for alcohol dependence. Disulfiram was first used in PUD to reduce alcohol intake in individuals with PUD [108], and further studies investigated whether this would extend to reducing psychostimulant use as well [109]. Studies to date on this have yielded inconclusive results. One study [110] tested the effects of disulfiram given in combination with CBT, or 12-step facilitation, or clinical management versus CBT alone, or 12-step facilitation alone in patients with cocaine dependence and comorbid alcohol use disorder. In this study, disulfiram was associated with better retention in treatment, as well as longer duration of abstinence from cocaine and alcohol. Cocaine-dependent, methadone-maintained individuals treated with disulfiram reported on average three less stimulant-using days compared to placebo [111]. In another trial, in which everyone received individual CBT and either adjunctive disulfiram, CM, both, or placebo, disulfiram reduced stimulant use compared to the double placebo group [112]. In this study, disulfiram did not reduce stimulant use compared with individuals that received CM only, and there were no additive effects of disulfiram when it was used with CM. However, in two other randomized trials comparing disulfiram to placebo samples, there were no differences in stimulant abstinence or use [113, 114].
Treating the Substance-Addicted Offender: Theory and Practice
Barbara Sims in Substance Abuse Treatment with Correctional Clients, 2012
Administering drugs to alcohol- or drug-dependent individuals is usually a first step taken to alleviate the adverse effects of abstinence. During detoxification, some patients are, for example, administered such drugs as Librium or Valium to relieve the symptoms of anxiety and depression (Jung, 2001). Sometimes, however, drugs are administered to purposefully cause severe physical discomfort in the presence of other drugs. For alcoholics, disulfiram is often administered to block the elimination from the liver of toxins associated with drinking alcohol. Drinking while taking this drug causes extreme nausea and vomiting in the drinker (Brewer, 1993). Also, other drugs, such as naltrexone, have been found to block the effects of alcohol and thus reduce cravings and relapses (Volpicelli, Clay, Watson, & Volpicelli, 1995).
Promising treatment strategies to combat Staphylococcus aureus biofilm infections: an updated review
Published in Biofouling, 2020
P. S. Seethalakshmi, Riya Rajeev, George Seghal Kiran, Joseph Selvin
Disulfiram is an FDA approved medication used as an aversive agent in patients with chronic alcoholism (Ellis and Dronsfield 2013). Recent studies have proven that disulfiram has antimicrobial potential against antibiotic-resistant bacteria such as Mycobacterium tuberculosis and S. aureus (Horita et al. 2012; Long 2017). Disulfiram eradicated S. aureus biofilms much more effectively than the antibiotics levofloxacin, and vancomycin (Thakare et al. 2019). Besides biofilms, intracellular reservoirs of S. aureus can also lead to recurrent infections (Fowler et al. 2005). Disulfiram showed efficient elimination of intracellular S. aureus from infected mouse macrophage cells and a reduced bacterial load in mouse models. The MIC value of disulfiram did not differ with respect to virulence factors and was equally effective against antibiotic-resistant and sensitive strains of S. aureus, suggesting a novel inhibitory mechanism (Thakare et al. 2019). Given below is a summary of drugs that have been repurposed as anti-biofilm agents of S. aureus (Table 2; Figure 3).
State-of-the-art behavioral and pharmacological treatments for alcohol use disorder
Published in The American Journal of Drug and Alcohol Abuse, 2019
Lara A. Ray, Spencer Bujarski, Erica Grodin, Emily Hartwell, ReJoyce Green, Alexandra Venegas, Aaron C. Lim, Artha Gillis, Karen Miotto
Disulfiram was the first medication approved for the treatment of AUD in 1951. Disulfiram is an aldehyde dehydrogenase inhibitor that exerts its clinical effect by blocking the metabolism of alcohol, which produces an aversive unpleasant response after alcohol intake that results in severe nausea and vomiting (110). Disulfiram has demonstrated mixed clinical efficacy, largely due to poor adherence (111,112); however, a recent meta-analysis reported a significant effect of disulfiram in open-label trials (113). Supervised administration of disulfiram has been suggested to still have a role in AUD treatment if an individual is having difficulty attaining sobriety (114); however, compliance and medical management (MM) issues, including the risk for severe medical complications when the medication is combined with alcohol, limit the widespread utilization of disulfiram in clinical practice for AUD.
Pharmacotherapeutic management of co-morbid alcohol and opioid use
Published in Expert Opinion on Pharmacotherapy, 2020
Lauren E. Hood, Jonna M. Leyrer-Jackson, M. Foster Olive
Disulfiram is intended to provide aversive conditioning against alcohol to promote abstinence. Disulfiram causes increased sensitivity to the negative effects of alcohol by inhibiting acetaldehyde dehydrogenase 2 (ALDH2), an important enzyme for metabolizing acetaldehyde to acetate. Acetaldehyde is the first byproduct of alcohol oxidation, and when disulfiram is metabolized in the presence of alcohol, the lack of functional ALDH2 leads to the accumulation of acetaldehyde in the bloodstream. The increased concentration of acetaldehyde causes unpleasant symptoms characteristic of a severe hangover, including nausea, vomiting, headaches, and low blood pressure [2]. The severity of the reaction experienced is dependent on the dose of disulfiram and the amount of alcohol consumed, and has the potential to be fatal under some circumstances [81]. In the absence of alcohol, disulfiram induces minor side effects including drowsiness, headaches and an increased risk for heptatoxicity that is preventable if monitored properly [81]. In the same mechanistic vein, mutations in the Aldh2 gene that impede acetaldehyde metabolism appear to be protective against AUDs. For example, the ALDH2.2 allele, predominantly expressed in Asian populations, encodes a nonfunctional form of the enzyme and confers sensitivity to alcohol, most frequently characterized by facial flushing [83,84].
Related Knowledge Centers
- Alcoholism
- Aldehyde Dehydrogenase
- Enzyme
- Enzyme Inhibitor
- Ethanol
- Shortness of Breath
- Tachycardia
- Hyperventilation
- Medication
- Hangover
- Shortness of Breath