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Ethanol affects multiple cellular targets and neural networks; and abrupt cessation results in generalized brain hyper excitability, due to unchecked excitation and impaired inhibition.
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In medically ill, hospitalized subjects, most AWS cases (80%) are relatively mild and uncomplicated, requiring only symptomatic management.
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The incidence of complicated AWS among patients admitted to medical or critical care units, severe enough to require pharmacologic treatment, is between 5% and 20%.
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Despite
Novel Algorithms for the Prophylaxis and Management of Alcohol Withdrawal Syndromes–Beyond Benzodiazepines
Section snippets
Key points
Background
Alcohol use disorders (AUDs) are maladaptive patterns of alcohol consumption manifested by symptoms leading to clinically significant impairment or distress.1 Ethanol is the second most commonly abused psychoactive substance (second to caffeine) and AUD is the most serious drug abuse problem in the United States2 and worldwide.3 The lifetime prevalences of Diagnostic and Statistical Manual of Mental Disorders, 4th edition, alcohol abuse and dependence were 17.8% and 12.5%, respectively; the
Neurobiological effects of alcohol
Alcohol has varying effects in the central nervous system (CNS), depending on volume ingested and the chronicity of its use. Ethanol acts on many cellular targets of several neuromodulators within many neural networks in the brain.19 The abrupt cessation of alcohol results in generalized brain hyperexcitability because receptors previously inhibited by alcohol are no longer inhibited and inhibitory systems are not functioning properly (Fig. 1). AWS is mediated by several neurochemical
Overview of alcohol withdrawal syndromes
AWS occurs after a period of absolute or, in some cases, relative abstinence from alcohol (ie, as soon as the blood alcohol level decreases significantly in habituated individuals). Therefore, it is possible for patients to experience AWS even with elevated blood alcohol concentration (BAC). Approximately 50% of alcohol-dependent patients develop clinically relevant AWS.24, 25 Moreover, 10% to 30% of patients admitted to the hospital ICU experience AWS7, 8, 26, 27; which is associated with
Clinical dilemma
Studies have shown that in medically ill, hospitalized subjects, most AWS cases are relatively mild and uncomplicated, requiring only symptomatic management (eg, anxiety, tremulousness, insomnia). Usually, the symptoms of uncomplicated AWS do not require medical intervention and disappear within 2 to 7 days. The unnecessary prophylaxis or treatment of patients feared to be at risk or experiencing AWS may lead to several unintended consequences, including sedation, falls, respiratory depression,
Alcohol withdrawal treatment
The effective management of AWS includes a combination of supportive and pharmacologic measures. Supportive measures include the stabilization and management of comorbid medical problems, assessment and management of concurrent substance intoxication or withdrawal syndrome, and nutritional supplementation.
A recently published Cochrane Review, including 64 studies (n = 4309), evaluated benzodiazepine (BZDP) against placebos, BZDPs against other medications (including other anticonvulsants), and
Benzodiazepine-sparing alternative for the treatment of alcohol withdrawal
The effectiveness of BZDP in managing AWS has been covered elsewhere and will not be repeated here.71 Despite their proven usefulness in the management of complicated AWS, the use of BZDP is fraught with potential complications (Box 1). In an attempt to avoid the extremes of undersedation or oversedation, and some of their side effects, the author decided to search for pharmacologic agents effective in the management of AWS beyond conventional BZDP-based protocols.
The author found that the
Development of a novel algorithm for the prophylaxis and treatment of alcohol withdrawal
The author’s institution created a multidisciplinary taskforce, including members from all clinical departments, tasked with reviewing the available literature regarding AWS assessment methods and treatment algorithms. Concerns regarding potential problems with oversedation, negative neurologic sequelae, development of medication-induced delirium, and codependence issues between alcohol and BZDP sparked interest in developing a BZDP-sparing protocol. Based on the taskforce findings, we
Summary
Current guidelines for the prophylaxis and management of AWS are based on the use of BZDPs. The rationale has always been that BZDPs effectively cover all phases of alcohol withdrawal. Yet clinical experience with the use of BZDPs suggests difficulties in implementing prophylaxis and treatment protocols adequately. The problem seems related to the way BZDPs are administered, whether objective physiologic or psychological methods are used to time dosing, and the type of BZDP agent used.
The
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2023, Results in ChemistryCitation Excerpt :Diazepine is a such kind of molecular fragment that has multiple biological activities [3,5,8,9,18,21], and some activities are extensively explored such as central depressants, anxiolytics, anticonvulsants and anticancer activity [2,4,11,19,22]. After the first introduction of benzodiazepine as its potential to treat anxiety, barbiturates were replaced with diazepine derivatives because of their comparatively considerable safety profile, Drugs like alprazolam (Fig. 1, compound 1) which is a triazole based derivative of benzodiazepine used in the treatment of psychiatric conditions is the first choice of prescription [14], also it used to treat alcohol withdrawal syndrome [10]. various derivatives of benzodiazepine (Fig. 1, Compound 2 & 3) possess multiple biological properties such as anxiolytic, anticonvulsant, sedative-hypnotic, reduce anxiety, induce and maintain sleep, reduce seizures, and induce conscious sedation [20,1].(