The biological reason for this gender difference is based on different ethanol absorption rates, distribution pattern, and metabolism in women compared to men . It does not suppose a risk of ACM development unless consumed over a large period of time (more than 10 years) 19,52. Wine is considered less damaging compared to other alcohol beverages, probably because of its antioxidant polyphenolic content, with molecules such as resveratrol 79,80. Therefore, because of its multiple actions, acetaldehyde may influence ACM pathogenesis in addition to ethanol effect itself 20,76,77. Before recognizing that ethanol itself is the etiological factor of ACM, different theories and hypotheses emerged 1,66. Mortality in ACM is related to the progression of heart failure and malignant arrhythmias 58,65.

One of the most relevant targets of ethanol in the membrane is the disruption of membrane receptor composition and activities . More than 30% of the myocyte ventricular fraction can be replaced by fibrotic tissue, thus decreasing the heart elasticity and contractile capacity (Figure 2). In fact, ethanol itself decreases the myocyte regeneration capacity and increases the fibrogenic process 52,126.

Alcohol (General Term)

Many published studies of non-approved medications included patients on psychotropic agents (eg, antipsychotics, antidepressants, anticonvulsants), suggesting the presence of a comorbid psychiatric illness and dual diagnosis of AUD with a mood or thought disorder. Nalmefene has been recorded to reduce the number of drinks per drinking day in alcohol-dependent subjects;44 however, when measuring days abstinent,44,45 number of heavy drinking days,45–47 time to relapse,44–46 and subjective cravings44,47 the data are controversial. In animal models, alcohol administration was shown to promote β-endorphin release in regions of the brain that are involved in reward.38 Relief of the tonic inhibiting effects of GABA neurons by β-endorphins in the VTA promotes dopaminergic signaling from this area of the brain to the NAc. These effects may be due to some combination of antagonizing NMDA glutamate receptors, modulating type 5 metabotropic glutamate receptors, or reducing glutamate accumulation during repeated episodes of alcohol withdrawal.31 Acamprosate is structurally similar to the endogenous amino acids (eg, glutamate, GABA, glycine) that act as neurotransmitters or neuromodulators in several different brain regions.31 The primary beneficial mechanism of action remains unclear; however, acamprosate is believed to normalize the balance between excitatory and inhibitory pathways that become adapted to chronic alcohol use and alleviate psychological and physiological discomfort that follows withdrawal. Metabolites of disulfiram can alter neurotransmitter levels in the NAc that are implicated in the response to alcohol, and other studies suggest the acetaldehyde reaction may not be necessary to achieve favorable treatment outcomes.29,30

The Effects of Ethanol on the Heart: Alcoholic Cardiomyopathy

This induces a variety of effects, since more than 14 different sites in the myocyte can be affected by ethanol 19,98. At the experimental level, some gender differences also are evident in functional proteomic analysis, with sex-dependent differences in structural and energy-producing myocardial proteins in a rat model of alcoholic cardiomyopathy . It causes acute myocardial effects with a temporary depression of LV EF evident in experimental 85,86 and clinical models 87,88. Until the second part of the 20th century, there was no scientific evidence on the direct and dose-dependent effect of ethanol on the heart as cause of ACM 6,38. In addition, acetaldehyde is able to interact with proteins and produce protein-adduct compounds that are highly reactive and may induce additional inflammatory and immunologic heart damage . Acetaldehyde is produced at a lower quantity in the heart as compared to the liver, and systemic acetaldehyde does not achieve toxic heart concentrations .

How is alcohol use disorder treated?

  • Flupenthixol intramuscular injection,66,67 amisulpride,68 and tiapride69 all performed poorly in placebo-controlled studies on measures of alcohol intake, craving, and abstinence.
  • Alcohol use disorder (sometimes called alcoholism) is a common medical condition.
  • In spite of increasing knowledge of the neurobiological disturbances caused by habitual drinking, a common etiological cause for AUD has not been established.
  • Heavy drinking in this population is five or more drinks in one day or 15 or more drinks in a week.

Ethanol withdrawal is thought to occur only in persons with ethanol dependence. Clinical intoxication is related to the rate of blood ethanol increase and the individual’s ethanol tolerance. Ethanol follows zero-order kinetics, with 70 mg to 150 mg of ethanol being metabolized per kilogram of the drinker’s body weight per hour, equivalent to 10 mg/dL to 25 mg/dL blood ethanol per hour.2 Acute ethanol intoxication induces CNS depression, perhaps initially in the reticular formation, followed by cerebral cortical involvement. Frequent alcohol abuse and frank alcoholism are very common among adults in the United States.

EtOH (Ethanol) Abuse Clarified

People with this condition can’t stop drinking, even if their alcohol use upends their lives and the lives of those around them. Alcohol use disorder (sometimes called alcoholism) is a common medical condition. However, areas of uncertainty in this complex disease are still present and should be further explored . New strategies aiming to control apoptosis, autophagy and pathological heart remodeling, and increase myocyte regeneration may be promising in the near future 112,133. However, these new strategies have not yet demonstrated their real effectiveness in clinical trials, require further evaluation, and are not approved for clinical use . They aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis, and persistent apoptosis.

Clinically, patients with alcohol-related dementia typically present at an earlier age than other acquired or late-onset forms of dementia. As with Wernicke encephalopathy, its epidemiology, including the proportion with antecedent Wernicke encephalopathy, is not well known; cases of undiagnosed Wernicke syndrome can progress to Korsakoff syndrome. MRI may reveal restricted diffusion or fluid-attenuated inversion recovery (FLAIR) signal abnormalities in areas implicated in the syndrome, including the thalamus, hypothalamus (mammillary bodies), midbrain (periaqueductal gray and oculomotor regions), and pons (abducens and medial vestibular nuclei). Death occurs in nearly 20% of patients with delayed treatment.9 EEG and CSF analysis may exclude other explanatory or concomitant conditions, but these tests are generally unrevealing in central thiamine deficiency states.

Care at Cleveland Clinic

Heavy, long-term consumption of beverages containing alcohol increases your risk of developing esophageal cancer. However, genetic polymorphisms, the use of other concomitant drugs (tobacco, cocaine), and the presence of other cardiac risk factors (hypertension, diabetes) may influence and worsen the natural course of ACM in each specific individual 27,72,98. Therefore, efforts for the prevention, early detection, and specific treatment in this relevant disease should be established . Recently, new cardiomyokines (FGF21, Metrnl) and several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCKs inhibitors) have been described as being able to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms 112,119. However, most programs of alcohol transplantation require the guarantee of a long period of ethanol abstinence (almost 3 months), a condition not accomplished by most subjects with ACM, who are alcohol-dependent 9,66.

Is alcohol use disorder treatment different for pregnant women and mothers of newborns?

These deaths are obviously upsetting for the family, resulting in unanswered questions and are also frustrating for the pathologist. One would logically infer from this that alcohol induced arrhythmias are a commonly stated cause of death. The only findings at post mortem are fatty liver and a negative or low blood alcohol. Recovering from EtOH addiction, EtOH dependence, or alcohol use disorder is a challenging but possible journey. These symptoms often worsen over time, signaling the potential development of alcohol use disorder (AUD).

Short-and Long-Term Effects of EtOH Addiction

The clinical efficacy of disulfiram to reduce craving and prevent relapse to drinking may be related to changes in neurotransmission. After ethyl alcohol is absorbed by the body, it becomes converted to acetaldehyde, which is oxidized in the liver by the mitochondrial enzyme aldehyde dehydrogenase (ALDH).24 Disulfiram produces an irreversible inhibition of ALDH activity. Pharmacologic strategies for treating alcohol dependence include generating an aversive physiological reaction to alcohol to mask positive subjective effects and administering medications that block alcohol reinforcement. Consumption of alcoholic beverages in the US is common, with two-thirds of adults over 18 years of age having consumed alcoholic beverages within the past year, according to the 2011 National Health Interview survey.19 The highest prevalence of heavy use (13.7%) is observed in the age group from 18 to 25 years.20 Estimates in the general population are similar or higher in Europe, according to the World Health Organization.21 Alternatively, compounds that target reward pathways may compensate for the plasticity in dopamine signaling that enhances the drinking experience of patients with AUD. The desire to relieve anxiety and negative sensations of withdrawal can contribute to relapse to drinking and lead to the repetitive and compulsive behaviors that characterize alcohol dependence.9

In addition to a 12-week open-label study,114 baclofen 30 mg daily has shown positive benefit compared to placebo in abstinence,115–117 craving, and daily alcohol intake.115 Higher doses (60 mg/day) produced a more robust response in reduction of number of drinks per day compared to 30 mg daily.118 Studies that failed to replicate the benefits of baclofen used patients with a lower daily drink intake and no comorbid liver problems who were recruited via advertisements,119 as opposed to subjects seeking treatment. Binge drinking (eg, a single exposure to 90 mL of 80-proof whiskey) can produce atrial or ventricular arrhythmias, even in individuals who have no other evidence of heart disease, a syndrome known as “holiday heart.”17 Even in otherwise healthy individuals, alcohol is toxic to most organ systems at doses above one to two drinks per day.11 Long-term exposure to alcohol generally increases the risk of damage to the gastrointestinal, cardiovascular, immune, nervous, and other systems.

  • Alcohol use disorder is a chronic brain disease, and people who have the disorder and stop drinking are prone to relapse.
  • In placebo-controlled, blinded studies using target doses of topiramate of 300 mg daily, topiramate outperformed placebo in multiple drinking measures89–91 and craving.91 Topiramate was equivalent to naltrexone in a blinded design measuring relapse and abstinence.92 Craving93 and intake94 were superior in naturalistic open designs.
  • These disorders include several encephalopathic states related to alcohol intoxication, withdrawal, and related nutritional deficiencies; acute and chronic toxic and nutritional peripheral neuropathies; and myopathy.

It may account for around 1,000 deaths per annum in England and Wales with many of these deaths currently misattributed to other causes or simply unexplained. Although alcoholic ketoacidosis was the link between alcohol and suicide originally described almost 70 years ago , it has only gained widespread recognition in more recent years. A number of previous studies have examined the relationship between sudden death and fatty liver. In 2005, 230,000 deaths were referred to Coroners in England and Wales, accounting for 45% of all deaths . These seven cases represented 0.5% of deaths undergoing coroner’s post mortem. In this study, five of our seven highlighted arrhythmic deaths were in Davies category 5.

Attacks can be recurrent, correlating with additional episodes of heavy drinking. Muscle destruction may be enhanced by fasting, which commonly occurs in binge drinking. Most cases of the syndrome are asymptomatic, but when apparent, the syndrome consists of painful, swollen muscles, variable weakness, usually with myoglobinuria (as evidenced sometimes by tea- or cola-colored urine), and markedly elevated CK that normalizes within 1 to 2 weeks. Ethanol is a common and important cause of rhabdomyolysis; estimates are that alcohol is the underlying cause of 20% or more of recognized cases of rhabdomyolysis in some series. Older patients with coexisting peripheral neuropathy have a less favorable outcome in this setting. A causal but unproven association with ethanol exists, and most cases have no report of thiamine levels.

In this disorder, people can’t stop drinking, even when drinking affects their health, puts their safety at risk and damages their personal relationships. Since ethanol is a drug with systemic toxic effects, the evaluation of global alcohol-related systemic damage is necessary in ACM . The multiple sites of myocyte damage from alcohol 11,19,23 and the genetically mediated individual predisposition 32,153 create a large individual clinical variability and make it difficult to establish a simple effective treatment for ACM 27,30,52. The direct dose-dependent effect between alcohol intake and development of ACM is clearly established 50,52, women being more sensitive than men to the toxic effects of ethanol on the heart . Since ethanol consumption of the global population is not currently under control , the incidence of alcoholic cardiomyopathy is expected to be maintained in the future, especially in specific population groups, such as adolescents and young people . Since ethanol has multiple cell targets with different pathological mechanisms implicated, those different strategies to directly target alcohol-induced heart damage are only partially effective and can only be used as support medication in a multidisciplinary approach .

Ritanserin is a 5-HT2 receptor antagonist with documented use to improve sleep, mood, and vigilance.109 The feedback inhibition of dopaminergic activity related to blocking 5-HT receptors may act as a substitute for alcohol effects.110 Carbamazepine and zonisamide have placebo-controlled trials supporting their potential use in alcohol dependence.105,106 Zonisamide was significantly better than placebo in reducing number of heavy drinking days, reduction in number of drinks per week, and urge to drink. VPA significantly decreased relapse to heavy drinking in a blinded study against placebo and also decreased amount of drinking and craving compared to baseline.103 A small non-blinded study found VPA treatment increased abstinence at 6 weeks post-detoxification, though this was not statistically significant.104 At higher doses, 1,500–1,800 mg daily, oxcarbazepine was superior to naltrexone in a number of patients who remained alcohol-free.102 There are currently no placebo-controlled blinded studies testing oxcarbazepine’s place in alcohol dependence. An open-label trial with levetiracetam on alcohol dependence found positive results;97 however, double-blind, placebo-controlled trials failed to find a benefit of levetiracetam for alcohol dependence.98,99 One study found that moderate-to-heavy drinkers taking levetiracetam increased their drinking during the study period.100 Anticonvulsants are used for seizure disorders and several have indications for chronic pain conditions and mood stabilization.

Treatment with thiamine repletion, currently recommended at 1 gram of IV thiamine per 24 hours for alcoholics with suspected Wernicke encephalopathy,9 should not be delayed while awaiting diagnostic laboratory results such as blood transketolase levels, which may be normal unless assessed prior to treatment. Delirium tremens represents the most advanced, deadly, and prolonged form of alcohol withdrawal and includes features of alcoholic hallucinosis and agitation, delirium, and autonomic disarray (including tachycardia, fever, hypertension, and diaphoresis). Seizures, occurring within 48 hours of last intoxication, are thought to be the earliest manifestation of alcohol withdrawal, but seizures may occur while the person remains inebriated with decreasing blood ethanol levels.5 Ethanol may additionally increase seizure risk among epileptics, typically following either brief use or overt intoxication. Other aspects of alcoholism, including secondary neurologic effects through its medical complications such as cirrhosis, as well as prevention, are reviewed elsewhere.