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1.
J Psychosoc Nurs Ment Health Serv ; 59(12): 7-11, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1547521

ABSTRACT

Alcohol use disorder (AUD) is a serious, prevalent disorder that affects millions of people. There are numerous evidence-based treatments and strategies to treat AUD, but they are under-utilized for a variety of reasons, including provider stigma, lack of knowledge, lack of professional support, shortage of willing providers, and patient barriers. Disulfiram, naltrexone, and acamprosate are approved but underused medications for the treatment of AUD. Nonpharmacological strategies and treatments include the use of motivational interviewing when talking to patients about their alcohol use, peer support or mutual help groups, and individualized therapy. Nurses are in a prime position to educate themselves and patients on evidence-based treatments for AUD and to help patients access those treatments. [Journal of Psychosocial Nursing and Mental Health Services, 59(12), 7-11.].


Subject(s)
Alcohol Deterrents , Alcoholism , Acamprosate/therapeutic use , Alcohol Deterrents/therapeutic use , Disulfiram/therapeutic use , Humans , Naltrexone/therapeutic use
2.
PLoS One ; 16(10): e0259061, 2021.
Article in English | MEDLINE | ID: covidwho-1496526

ABSTRACT

Effective, low-cost therapeutics are needed to prevent and treat COVID-19. Severe COVID-19 disease is linked to excessive inflammation. Disulfiram is an approved oral drug used to treat alcohol use disorder that is a potent anti-inflammatory agent and an inhibitor of the viral proteases. We investigated the potential effects of disulfiram on SARS-CoV-2 infection and disease severity in an observational study using a large database of clinical records from the national US Veterans Affairs healthcare system. A multivariable Cox regression adjusted for demographic information and diagnosis of alcohol use disorder revealed a reduced risk of SARS-CoV-2 infection with disulfiram use at a hazard ratio of 0.66 (34% lower risk, 95% confidence interval 24-43%). There were no COVID-19 related deaths among the 188 SARS-CoV-2 positive patients treated with disulfiram, in contrast to 5-6 statistically expected deaths based on the untreated population (P = 0.03). Our epidemiological results suggest that disulfiram may contribute to the reduced incidence and severity of COVID-19. These results support carefully planned clinical trials to assess the potential therapeutic effects of disulfiram in COVID-19.


Subject(s)
COVID-19/drug therapy , Disulfiram/therapeutic use , Adult , Alcoholism/complications , COVID-19/epidemiology , COVID-19/metabolism , Cohort Studies , Disulfiram/metabolism , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Severity of Illness Index , Veterans
3.
Eur J Pharmacol ; 904: 174143, 2021 Aug 05.
Article in English | MEDLINE | ID: covidwho-1487708

ABSTRACT

Disulfiram (DSF) is a well-known anti-alcohol agent that inhibits aldehyde dehydrogenase and results in extreme 'hangover' symptoms when consumed with alcohol. This drug, however, has been suggested as useful in other forms of drug addiction due to its beneficial potential in both drug abuse reduction and withdrawal. However, among other drugs used in alcohol dependence, it carries the greatest risk of pharmacological interactions. Concomitant use of DSF and central nervous system stimulants usually leads to harmful, undesirable effects. To date, there is still limited data regarding the detailed safety profile of DSF as a concomitant drug. In this review article, we outline the current state of knowledge about DSF, its broad pharmacological action, as well as therapeutic effects, with a particular emphasis on the molecular understanding of its potential pharmacodynamic interactions with common addictive substances (e.g., alcohol, cocaine, cannabinoids, opioids) supported by relevant examples.


Subject(s)
Acetaldehyde Dehydrogenase Inhibitors/pharmacology , Acetaldehyde Dehydrogenase Inhibitors/therapeutic use , Disulfiram/pharmacology , Disulfiram/therapeutic use , Substance-Related Disorders/drug therapy , Alcohol Drinking/prevention & control , Alcoholism/drug therapy , Animals , Disulfiram/adverse effects , Drug Interactions , Humans
4.
Blood ; 138(25): 2702-2713, 2021 12 23.
Article in English | MEDLINE | ID: covidwho-1365304

ABSTRACT

Multiple organ dysfunction is the most severe outcome of sepsis progression and is highly correlated with a worse prognosis. Excessive neutrophil extracellular traps (NETs) are critical players in the development of organ failure during sepsis. Therefore, interventions targeting NET release would likely effectively prevent NET-based organ injury associated with this disease. Herein, we demonstrate that the pore-forming protein gasdermin D (GSDMD) is active in neutrophils from septic humans and mice and plays a crucial role in NET release. Inhibition of GSDMD with disulfiram or genic deletion abrogated NET formation, reducing multiple organ dysfunction and sepsis lethality. Mechanistically, we demonstrate that during sepsis, activation of the caspase-11/GSDMD pathway controls NET release by neutrophils during sepsis. In summary, our findings uncover a novel therapeutic use for disulfiram and suggest that GSDMD is a therapeutic target to improve sepsis treatment.


Subject(s)
Extracellular Traps/genetics , Gene Deletion , Intracellular Signaling Peptides and Proteins/genetics , Multiple Organ Failure/genetics , Phosphate-Binding Proteins/genetics , Sepsis/genetics , Acetaldehyde Dehydrogenase Inhibitors/therapeutic use , Adoptive Transfer , Aged , Animals , Cells, Cultured , Disulfiram/therapeutic use , Female , Humans , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Male , Mice, Inbred C57BL , Middle Aged , Multiple Organ Failure/pathology , Multiple Organ Failure/therapy , Phosphate-Binding Proteins/antagonists & inhibitors , Sepsis/pathology , Sepsis/therapy
6.
Alcohol Alcohol ; 55(4): 354-356, 2020 Jun 25.
Article in English | MEDLINE | ID: covidwho-245703

ABSTRACT

AIM: In view of the increase in the use of ethanol-containing hand sanitizers throughout the world due to the current COVID-19 pandemic, we wished to review the possible risks to patients treated with disulfiram, following a case report in which an apparent DER (disulfiram-ethanol reaction) was attributed to the cutaneous absorption of alcohol from hand sanitizers as well as by inhalation of vapour. METHOD: Simple experiments to assess the levels of absorption by each route separately. RESULTS: Our results strongly suggest that while amounts of alcohol sufficient to cause a DER may be inhaled when hand sanitizers are used in confined spaces, absorption can be avoided by dispersal of the fumes, and absorption from the skin alone does not occur in pharmacologically significant quantities. CONCLUSION: Warnings about absorption of alcohol through the skin from hand sanitizers and products such as perfumes, deodorants and after-shave (whose use is often warned against when disulfiram is prescribed) should be modified accordingly.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Disulfiram/adverse effects , Disulfiram/chemistry , Ethanol/chemistry , Ethanol/pharmacokinetics , Hand Sanitizers/adverse effects , Hand Sanitizers/pharmacokinetics , Pneumonia, Viral/complications , Administration, Inhalation , Breath Tests/methods , COVID-19 , Disulfiram/pharmacokinetics , Disulfiram/therapeutic use , Ethanol/administration & dosage , Ethanol/adverse effects , Hand Sanitizers/administration & dosage , Hand Sanitizers/chemistry , Humans , Pandemics , SARS-CoV-2 , Skin Absorption/drug effects
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