Alcohol tolerance refers to the bodily responses to the functional effects of ethanol in alcoholic beverages. This includes direct tolerance, speed of recovery from insobriety and resistance to the development of alcoholism.

Different concentrations of alcohol in the human body have different effects on the subject.

The following lists the common effects of alcohol on the body, depending on the blood alcohol concentration (BAC). However, tolerance varies considerably between individuals, as does individual response to a given dosage; the effects of alcohol differ widely between people. Hence, BAC percentages are just estimates used for illustrative purposes.

- Euphoria (BAC = 0.03% to 0.12%):

- Overall improvement in mood and possible euphoria

- Increased self-confidence

- Increased sociability

- Decreased anxiety

- Shortened attention span

- Flushed appearance

- Impaired judgment

- Impaired fine muscle coordination

- Lethargy (BAC = 0.09% to 0.25%)

- Sedation

- Impaired memory and comprehension

- Delayed reactions

- Ataxia; balance difficulty; unbalanced walk

- Blurred vision; other senses may be impaired

- Confusion (BAC = 0.18% to 0.30%)

- Profound confusion

- Impaired senses

- Analgesia

- Increased ataxia; impaired speech; staggering

- Dizziness often associated with nausea ("the spins")

- Vomiting (emesis)

- Stupor (BAC = 0.25% to 0.40%)

- Severe ataxia

- Lapses in and out of consciousness

- Unconsciousness

- Anterograde amnesia

- Vomiting (death may occur due to inhalation of vomit (pulmonary aspiration) while unconscious)

- Respiratory depression (potentially life-threatening)

- Decreased heart rate (usually results in coldness and/or numbness of the limbs)

- Urinary incontinence

- Coma (BAC = 0.35% to 0.80%)

- Unconsciousness (coma)

- Depressed reflexes (i.e., pupils do not respond appropriately to changes in light)

- Marked and life-threatening respiratory depression

- Markedly decreased heart rate

- Most deaths from alcohol poisoning are caused by dosage levels in this range.

The long-term effects of alcohol (also known formally as ethanol) consumption range from cardioprotective health benefits for low to moderate alcohol consumption in industrialized societies with higher rates of cardiovascular disease to severe detrimental effects in cases of chronic alcohol abuse. Health effects associated with alcohol intake in large amounts include an increased risk of alcoholism, malnutrition, chronic pancreatitis, ], and cancer. In addition, damage to the central nervous system and peripheral nervous system can occur from chronic alcohol abuse. The long-term use of alcohol is capable of damaging nearly every organ and system in the body. The developing adolescent brain is particularly vulnerable to the toxic effects of alcohol. In addition, the developing fetal brain is also vulnerable, and fetal alcohol spectrum disorders (FASDs) may result if pregnant mothers consume alcohol.

The inverse relation in Western cultures between alcohol consumption and cardiovascular disease has been known for over 100 years. Many physicians do not promote alcohol consumption, however, given the many health concerns associated with it, some suggest that alcohol should be regarded as a recreational drug, and promote exercise and good nutrition to combat cardiovascular disease. Others have argued that the benefits of moderate alcohol consumption may be outweighed by other increased risks, including those of injuries, violence, fetal damage, liver disease, and certain forms of cancer. Alcohol liver disease (ALD) accounted for four fifths of all chronic diseases in Ireland in 2013.

Withdrawal effects and dependence are also almost identical. Alcohol at moderate levels has some positive and negative effects on health. The negative effects include increased risk of liver diseases, oropharyngeal cancer, esophageal cancer and pancreatitis. Conversely moderate intake of alcohol may have some beneficial effects on gastritis and cholelithiasis. Of the total number of deaths and diseases caused by alcohol, most happen to the majority of the population who are moderate drinkers, rather than the heavy drinker minority. Chronic alcohol misuse and abuse has serious effects on physical and mental health. Chronic excess alcohol intake, or alcohol dependence, can lead to a wide range of neuropsychiatric or neurological impairment, cardiovascular disease, liver disease, and malignant neoplasms. The psychiatric disorders which are associated with alcoholism include major depression, dysthymia, mania, hypomania, panic disorder, phobias, generalized anxiety disorder, personality disorders, schizophrenia, suicide, neurologic deficits (e.g. impairments of working memory, emotions, executive functions, visuospatial abilities and gait and balance) and brain damage. Alcohol dependence is associated with hypertension, coronary heart disease, and ischemic stroke, cancer of the respiratory system, and also cancers of the digestive system, liver, breast and ovaries. Heavy drinking is associated with liver disease, such as cirrhosis. Excessive alcohol consumption can have a negative impact on aging.

Recent studies have focused on understanding the mechanisms by which moderate alcohol consumption confers cardiovascular benefit.

The short-term effects of alcohol (also known formally as ethanol) consumption–due to drinking beer, wine, distilled spirits or other alcoholic beverages–range from a decrease in anxiety and motor skills and euphoria at lower doses to intoxication (drunkenness), stupor, unconsciousness, anterograde amnesia (memory "blackouts"), and central nervous system depression at higher doses. Cell membranes are highly permeable to alcohol, so once alcohol is in the bloodstream it can diffuse into nearly every cell in the body.

The concentration of alcohol in blood is measured via blood alcohol content (BAC). The amount and circumstances of consumption play a large part in determining the extent of intoxication; for example, eating a heavy meal before alcohol consumption causes alcohol to absorb more slowly. The amount of alcohol consumed largely determines the extent of hangovers, although hydration also plays a role. After excessive drinking, stupor and unconsciousness can occur. Extreme levels of consumption can lead to alcohol poisoning and death (a concentration in the blood stream of 0.40% will kill half of those affected). Alcohol may also cause death indirectly, by asphyxiation from vomit.

Alcohol can greatly exacerbate sleep problems. During abstinence, residual disruptions in sleep regularity and sleep patterns are the greatest predictors of relapse.

Binge drinking, or heavy episodic drinking, is a modern epithet for drinking alcoholic beverages with an intention of becoming intoxicated by heavy consumption of alcohol over a short period of time.

Binge drinking is a style of drinking that is popular in several countries worldwide, and overlaps somewhat with social drinking since it is often done in groups. The degree of intoxication, however, varies between and within various cultures that engage in this practice. A binge on alcohol can occur over hours, last up to several days, or in the event of extended abuse, even weeks. Due to the long-term effects of alcohol misuse, binge drinking is considered to be a major public health issue.

Binge drinking is associated with a profound social harm, economic costs as well as increased disease burden. Binge drinking is more common in males, during adolescence and young adulthood. Heavy regular binge drinking is associated with adverse effects on neurologic, cardiac, gastrointestinal, hematologic, immune, musculoskeletal organ systems as well as increasing the risk of alcohol induced psychiatric disorders. A US-based review of the literature found that up to one-third of adolescents binge-drink, with six percent reaching the threshold of having an alcohol-related substance use disorder. Approximately one in 25 women binge-drinks during pregnancy, which can lead to fetal alcohol syndrome and fetal alcohol spectrum disorders. Binge drinking during adolescence is associated with traffic accidents and other types of accidents, violent behavior as well as suicide. The more often a child or adolescent binge drinks and the younger they are the more likely that they will develop an alcohol use disorder including alcoholism. A large number of adolescents who binge-drink also consume other psychotropic substances.

Essential tremors—or, in the case of essential tremors on a background of family history of essential tremors, familial tremors—can be temporarily relieved in up to two-thirds of patients by drinking small amounts of alcohol.

Ethanol is known to activate aminobutyric acid type A (GABAA) and inhibit N-methyl-D-aspartate (NMDA) glutamate receptors, which are both implicated in essential tremor pathology and could underlie the ameliorative effects. Additionally, the effects of ethanol have been studied in different animal essential tremor models. (For more details on this topic, see Essential tremor.)

Individuals with an alcohol use disorder will often complain of difficulty with interpersonal relationships, problems at work or school, and legal problems. Additionally, people may complain of irritability and insomnia. Alcohol abuse is also an important cause of chronic fatigue.

Signs of alcohol abuse are related to alcohol's effects on organ systems. However, while these findings are often present, they are not necessary to make a diagnosis of alcohol abuse. Signs of alcohol abuse show its drastic effects on the central nervous system, including inebriation and poor judgment; chronic anxiety, irritability, and insomnia. Alcohol's effects on the liver include elevated liver function tests (classically AST is at least twice as high as ALT). Prolonged use leads to cirrhosis and liver failure. With cirrhosis, patients develop an inability to process hormones and toxins. The skin of a patient with alcoholic cirrhosis can feature cherry angiomas, palmar erythema and — in acute liver failure — jaundice and ascites. The derangements of the endocrine system lead to the enlargement of the male breasts. The inability to process toxins leads to liver disease, such as hepatic encephalopathy.

Alcohol abuse can result in brain damage which causes impairments in executive functioning such as impairments to working memory, visuospatial skills, and can cause an abnormal personality as well as affective disorders to develop. Binge drinking is associated with individuals reporting fair to poor health compared to non-binge drinking individuals and which may progressively worsen over time. Alcohol also causes impairment in a person's critical thinking. A person's ability to reason in stressful situations is compromised, and they seem very inattentive to what is going on around them. Social skills are significantly impaired in people suffering from alcoholism due to the neurotoxic effects of alcohol on the brain, especially the prefrontal cortex area of the brain. The social skills that are impaired by alcohol abuse include impairments in perceiving facial emotions, difficulty with perceiving vocal emotions and theory of mind deficits; the ability to understand humour is also impaired in alcohol abusers. Adolescent binge drinkers are most sensitive to damaging neurocognitive functions especially executive functions and memory. People who abuse alcohol are less likely to survive critical illness with a higher risk for having sepsis and were more likely to die during hospitalization.

Warning signs of alcoholism include the consumption of increasing amounts of alcohol and frequent intoxication, preoccupation with drinking to the exclusion of other activities, promises to quit drinking and failure to keep those promises, the inability to remember what was said or done while drinking (colloquially known as "blackouts"), personality changes associated with drinking, denial or the making of excuses for drinking, the refusal to admit excessive drinking, dysfunction or other problems at work or school, the loss of interest in personal appearance or hygiene, marital and economic problems, and the complaint of poor health, with loss of appetite, respiratory infections, or increased anxiety.

The risk of alcohol dependence begins at low levels of drinking and increases directly with both the volume of alcohol consumed and a pattern of drinking larger amounts on an occasion, to the point of intoxication, which is sometimes called "binge drinking". Young adults are particularly at risk of engaging in binge drinking.

Alcohol abuse among pregnant women causes their baby to develop fetal alcohol syndrome. Fetal alcohol syndrome is the pattern of physical abnormalities and the impairment of mental development which is seen with increasing frequency among children with alcoholic mothers. Alcohol exposure in a developing fetus can result in slowed development of the fetal brain, resulting in severe retardation or death. Surviving infants may suffer severe abnormalities such as abnormal eyes, fissures, lips and incomplete cerebella. Some infants may develop lung disease. It is even possible that the baby throughout pregnancy will develop heart defects such as ventricular septal defect or atrial septal defect. Experts suggest that pregnant women take no more than one unit of alcohol per day. However, other organizations advise complete abstinence from alcohol while pregnant.

Typically the severity of the symptoms experienced will depend on the amount and duration of prior alcohol consumption, as well as the number and severity of previous withdrawals. Even the most severe of these symptoms can occur in as little as 2 hours after cessation; therefore, the overall unpredictability necessitates either pre-planned hospitalization, treatment coordinated with a doctor, or at the very least rapid access to medical care, and a supporting system of friends or family should be introduced prior to addressing detoxification. In many cases, however, symptoms follow a reasonably predictable time frame as exampled below:

Six to 12 hours after the ingestion of the last drink, withdrawal symptoms such as shaking, headache, sweating, anxiety, nausea or vomiting occur. Other comparable symptoms may also exist in this period. Twelve to 24 hours after cessation, the condition may progress to such major symptoms as confusion, hallucinations (with awareness of reality), tremor, agitation, and similar ailments.

At 24 to 48 hours following the last ethanol ingestion, the possibility of seizures should be anticipated. Meanwhile, none of the earlier withdrawal symptoms will have abated. Seizures carry the risk of death for the alcoholic.

Although, most often, the patient's condition begins to improve past the 48-hour mark, it can sometimes continue to increase in severity to delirium tremens, characterized by hallucinations that are indistinguishable from reality, severe confusion, more seizures, high blood pressure and fever which can persist anywhere from 4 to 12 days.

Signs and symptoms of alcohol withdrawal occur primarily in the central nervous system. The severity of withdrawal can vary from mild symptoms such as sleep disturbances and anxiety to severe and life-threatening symptoms such as delirium, hallucinations, and autonomic instability.

Withdrawal usually begins 6 to 24 hours after the last drink. It can last for up to one week. To be classified as alcohol withdrawal syndrome, patients must exhibit at least two of the following symptoms: increased hand tremor, insomnia, nausea or vomiting, transient hallucinations (auditory, visual or tactile), psychomotor agitation, anxiety, tonic-clonic seizures, and autonomic instability.

The severity of symptoms is dictated by a number of factors, the most important of which are degree of alcohol intake, length of time the individual has been using alcohol, and previous history of alcohol withdrawal. Symptoms are also grouped together and classified:

- Alcohol hallucinosis: patients have transient visual, auditory, or tactile hallucinations, but are otherwise clear.

- Withdrawal seizures: seizures occur within 48 hours of alcohol cessations and occur either as a single generalized tonic-clonic seizure or as a brief episode of multiple seizures.

- Delirium tremens: hyperadrenergic state, disorientation, tremors, diaphoresis, impaired attention/consciousness, and visual and auditory hallucinations. This usually occurs 24 to 72 hours after alcohol cessation. Delirium tremens is the most severe form of withdrawal and occurs in 5 to 20% of patients experiencing detoxification and 1/3 of patients experiencing withdrawal seizures.

Acute alcohol poisoning is a related medical term used to indicate a dangerously high concentration of alcohol in the blood, high enough to induce coma, respiratory depression, or even death. It is considered a medical emergency. The term is mostly used by healthcare providers. Toxicologists use the term "alcohol intoxication" to discriminate between alcohol and other toxins.

The signs and symptoms of acute alcohol poisoning include:

- severe confusion, unpredictable behavior and stupor

- sudden lapses into and out of unconsciousness or semi-consciousness (with later alcoholic amnesia)

- vomiting while unconscious or semi-conscious

- seizures

- respiratory depression (fewer than eight breaths a minute)

- pale, bluish, cold and clammy skin due to insufficient oxygen

Stolle, Sack and Thomasius define binge drinking as episodic excessive drinking. There is currently no worldwide consensus on how many drinks constitute a "binge", but in the United States, the term has been described in academic research to mean consuming five or more standard drinks (male), or four or more drinks (female), over a 2-hour period. In 2015, the US Centers for Disease Control and Prevention, citing the National Institute on Alcohol Abuse and Alcoholism, defines binge drinking as "a pattern of drinking that brings a person’s blood alcohol concentration (BAC) to 0.08 grams percent or above. This typically happens when men consume 5 or more drinks, and when women consume 4 or more drinks, in about 2 hours." and estimated that about 16% of American adults met these binge drinking criteria four times per month. One 2001 definition from the publication "Psychology of Addictive Behavior" states that 5 drinks for men and 4 drinks for women must be consumed on one occasion at least once in a two-week period for it to be classed as binge drinking. This is colloquially known as the "5/4 definition", and depending on the source, the timeframe can vary. In the United Kingdom, binge drinking is defined by one academic publication as drinking more than twice the daily limit, that is, drinking eight units or more for men or six units or more for women (roughly equivalent to five or four American standard drinks, respectively). In Australia, binge drinking is also known as risky single occasion drinking (RSOD) and can be classified by the drinking of seven or more standard drinks (by males) and 5 or more standard drinks (by females) within a single day. When BEACH (Bettering the Evaluation of care and health) conducted a study which gathered information of people over the age of 18, it defined binge drinkers as those who consumed six or more standard drinks on one occasion whether that be weekly or monthly.

The above definitions are limited in that they do not take into account the time period over which the drinking occurs or the body mass of the person drinking. A person could be defined as a binge drinker even if he or she never becomes intoxicated. The term, however, has succeeded in drawing public awareness to the problem of excess drinking..

Other, less common definitions rely on blood alcohol concentration (BAC). For example, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines the term "binge drinking" as a pattern of drinking that brings a person’s blood alcohol concentration (BAC) to 0.08 grams percent or above. Whatever the numerical definition used, heavy drinking or rapid consumption over a short period of time with the intention of becoming intoxicated is often implied when the term is used colloquially, since four or five drinks consumed over the course of a whole day and as an accompaniment to meals will not have the same effects as the same amount consumed over a couple of hours on an empty stomach.

An alternative colloquial term for binge drinking, "going on a bender", formerly implied a drinking spree of several days.

Alcohol-induced respiratory reactions, also termed alcohol-induced asthma and alcohol-induced respiratory symptoms, are increasingly recognized as a pathological bronchoconstriction response to the consumption of alcohol that afflicts many people with a "classical" form of asthma, the airway constriction disease evoked by the inhalation of allergens. Alcohol-induced respiratory reactions reflect the operation of different and often racially related mechanisms that differ from those of classical, allergen-induced asthma.

Alcohol-related brain damage is the damage that occurs to brain structures or function of the central nervous system as a result of the direct neurotoxic effects of alcohol intoxication or acute withdrawal. The frontal lobes are the most damaged region of the brains of alcohol abusers but other regions of the brain are also affected. The damage that occurs from heavy drinking/high blood alcohol levels causes impairments in judgement and decision making and social skills. These brain changes are linked to poor behavioural control and impulsivity, which tend to worsen the existing addiction problem.

The problems of alcoholism are well known, such as memory disorders, liver disease, high blood pressure, muscle weakness, heart problems, anaemia, low immune function, disorders of the digestive system and pancreatic problems as well as depression, unemployment and family problems including child abuse. Recently attention has been increasingly focused on binge drinking by adolescents and young adults due to neurochemical changes and brain damage which, unlike with alcoholism, can occur after a relatively short period of time; the damage is particularly evident in the corticolimbic region. This brain damage increases the risk of abnormalities in mood and cognitive abilities, increases the risk of dementia and additionally binge drinkers have an increased risk of developing chronic alcoholism.

Individuals who are impulsive are at high risk of addiction due to impaired behavioural control and increased sensation seeking behaviour. Alcohol abuse, especially during adolescence, causes a deterioration of executive functions in the frontal lobe. This brain damage from alcohol actually increases impulsivity and therefore worsens the addictive disorder.

There are five main stages of alcoholism. The first stage,occasional abuse and binge drinking, in this stage one may want to just experiment with alcohol and test their limits. These drinkers may be new to different forms of alcohol. This experimental stage is commonly seen in teens and young adults. These experimental drinkers also frequently engage in binge drinking. While they may not drink regularly, they consume exceptionally enormous amounts of alcohol at one time.

The second stage, increased drinking, in this stage one will leave the experimental stage and start drinking on a regular basis. Instead of just drinking at parties occasionally, one may find themselves drinking every weekend. Increased alcohol consumption can also lead to drinking for these reasons: as an excuse to get together with friends, to alleviate stress, out of boredom, or to combat sadness or loneliness.

The third stage, problem drinking, one will drink to get rid of their problems for them at any moment. As increased drinking continues, one becomes more dependent on alcohol and are at risk of developing alcoholism.

The fourth stage, alcohol dependence, this forms after the problem drinking stage. At this point, one has an attachment to alcohol that has taken over their regular routine. They are aware of the adverse effects, but no longer have control over their alcohol consumption. Alcohol dependence also means that one has developed a tolerance to drinking. As a result, they may have to consume larger quantities to get “buzzed” or drunk.

The fifth stage, addiction and alcoholism, this is the final and most harmful stage. One is addicted and dependent and must have alcohol all the time, if not they have withdrawals. Alcohol withdrawal is the changes the body goes through when a person suddenly stops drinking after prolonged alcohol abuse, or if one does not have alcohol for a period of time. Symptoms include trembling (shakes), insomnia, anxiety, and other physical and mental symptoms. If the alcohol is withdrawn suddenly, the brain is like an accelerated vehicle that has lost its brakes. Not surprisingly, most symptoms of withdrawal are symptoms that occur when the brain is overstimulated (Drugs.com). People with alcohol addiction physically crave the substance and are often inconsolable until they start drinking again. With prolonged abstinence neurogenesis occurs which can potentially reverse the damage from alcohol abuse.

Alcohol intoxication, also known as drunkenness among other names, is a physiological condition that may result in psychological alterations of consciousness. Drunkenness is induced by the ingestion or consumption of alcohol in a living body. Alcohol intoxication is the result of alcohol entering the bloodstream faster than it can be metabolized by the body. Metabolism results in breaking down the ethanol into non-intoxicating byproducts.

Some effects of alcohol intoxication, such as euphoria and lowered social inhibition, are central to alcohol's desirability as a beverage and its history as one of the world's most widespread recreational drugs. Despite this widespread use and alcohol's legality in most countries, many medical sources tend to describe any level of alcohol intoxication as a form of poisoning due to ethanol's damaging effects on the body in large doses. Some religions consider alcohol intoxication to be a sin.

Symptoms of alcohol intoxication include euphoria, flushed skin, and decreased social inhibition at lower doses, with larger doses producing progressively severe impairments of balance, and decision-making ability as well as nausea or vomiting from alcohol's disruptive effect on the semicircular canals of the inner ear and chemical irritation of the gastric mucosa.

Sufficiently extreme levels of blood-borne alcohol may result in coma or death.

Include the following:

- Depression

- Shaking

- Feeling unreal

- Appetite loss

- Muscle twitching

- Memory loss

- Motor impairment

- Nausea

- Muscle pains

- Dizziness

- Apparent movement of still objects

- Feeling faint

- Noise sensitivity

- Light sensitivity

- Peculiar taste

- Pins and needles

- Touch sensitivity

- Sore eyes

- Hallucinations

- Smell sensitivity

All sedative-hypnotics, e.g. alcohol, barbiturates, benzodiazepines and the nonbenzodiazepine Z-drugs have a similar mechanism of action, working on the GABA receptor complex and are cross tolerant with each other and also have abuse potential. Use of prescription sedative-hypnotics; for example the nonbenzodiazepine Z-drugs often leads to a relapse back into substance misuse with one author stating this occurs in over a quarter of those who have achieved abstinence.

In 1973, Breslin et al. tested the effects of alcoholic beverage consumption on the respiratory symptoms of 11 asthmatic subjects who gave a history of asthma attacks following certain alcoholic beverages. In response to ingesting the type of beverage that the subjects reported to provoke their symptoms, six developed the asthmatic symptom of chest tightness, two developed a symptom often associated with asthma, rhinitis, and one subject developed both chest tightness and rhinitis. Symptoms developed almost immediately after ingestion, inhalation of fumes from the beverages did not precipitate symptoms, and bronchoconstriction in response to the ingestion was confirmed in the three patients evaluated by pulmonary function tests. The study suggested that these reactions were induced by non-alcoholic allergens that were contained in or contaminated the beverages. In 1978 a non-asthmatic female of Japanese descent with a history of moderately severe bronchoconstriction responses to various alcoholic beverages and in 1981 an asthmatic Japanese male with a similar history beer or 95% pure ethanol were studied and found to develop bronchoconstriction after drinking apple juice but not after drinking apple juice per se; intravenous infusion or inhalation of ethanol also caused bronchospasm responses in the male subject. These studies suggested that alcohol itself caused the asthmatic symptoms triggered by alcoholic beverages. A subsequent study in 1986 found that 9 of 18 patients with a history of red wine-induced asthma symptoms showed bronchoconstriction in response to ingesting red wine; the response correlated positively with the amount of sulfur dioxide contained in the provocative wine. The study suggested that the reaction was not allergen-induced but rather triggered by sulfur dioxide, a sulfur dioxide-related agent, or an agent whose levels in alcohol beverages correlated positively with those of sulfur dioxide. Finally, a questionnaire survey of 366 asthmatic patients conducted in 2000 found that 33% reported asthma symptoms in response to alcoholic beverages; there was a significant association between wine-induced asthma and asthma triggered by sulfite-containing foods, by aspirin, and by nonsteroidal anti-inflammatory drugs (NSAID) other than aspirin. The study suggested the salicylate-"contaminates" in wine may contribute to these responses. In other studies, D.P. Agarwal and colleagues associated race-based variations in the activity alcohol-metabolizing enzymes with the occurrence of alcohol flush reactions to alcohol and alcoholic beverages in certain Asian populations. This early work is the basis for further studies that have defined not only many alcohol-induced flush reactions but also many alcohol-induced respiratory reactions as due to racially associated genetic differences in alcohol-metabolizing enzymes.

The signs and symptoms of paracetamol toxicity occur in three phases. The first phase begins within hours of overdose, and consists of nausea, vomiting, a pale appearance, and sweating. However, patients often have no specific symptoms or only mild symptoms in the first 24 hours of poisoning. Rarely, after massive overdoses, patients may develop symptoms of metabolic acidosis and coma early in the course of poisoning.

The second phase occurs between 24 h and 72 h following overdose and consists of signs of increasing liver damage. In general, damage occurs in liver cells as they metabolize the paracetamol. The individual may experience right upper quadrant abdominal pain. The increasing liver damage also changes biochemical markers of liver function; International normalized ratio (INR) and the liver transaminases ALT and AST rise to abnormal levels. Acute kidney failure may also occur during this phase, typically caused by either hepatorenal syndrome or multiple organ dysfunction syndrome. In some cases, acute kidney failure may be the primary clinical manifestation of toxicity. In these cases, it has been suggested that the toxic metabolite is produced more in the kidneys than in the liver.

The third phase follows at 3 to 5 days, and is marked by complications of massive liver necrosis leading to fulminant liver failure with complications of coagulation defects, low blood sugar, kidney failure, hepatic encephalopathy, brain swelling, sepsis, multiple organ failure, and death. If the third phase is survived, the liver necrosis runs its course, and liver and kidney function typically return to normal in a few weeks. The severity of paracetamol toxicity varies depending on the dose and whether appropriate treatment is received.

Alcohol tolerance is increased by regular drinking. This reduced sensitivity requires that higher quantities of alcohol be consumed in order to achieve the same effects as before tolerance was established. Alcohol tolerance may lead to (or be a sign of) alcohol dependency.

Heavy alcohol consumption over a period of years can lead to "reverse tolerance". A liver can be damaged by chronic alcohol use, leading to a buildup of fat and scar tissue. The reduced ability of such a liver to metabolize or break down alcohol means that small amounts can lead to a high blood alcohol concentration (BAC) and more rapid intoxication.

Combined drug intoxication (CDI), also known as multiple drug intake (MDI) or lethal polydrug/polypharmacy intoxication, is an unnatural cause of human death. CDI is often confused with drug overdose, but it is a completely different phenomenon. It is distinct in that it is due to the simultaneous use of multiple drugs, whether the drugs are prescription, over-the-counter, recreational, or some other combination. Alcohol can exacerbate the symptoms and may directly contribute to increased severity of symptoms. The reasons for toxicity vary depending on the mixture of drugs. Usually, most victims die after using two or more drugs in combination that suppress breathing, and the low blood oxygen level causes brain death.

The CDI/MDI phenomenon seems to be becoming more common in recent years. In December 2007, according to Dr. John Mendelson, a pharmacologist at the California Pacific Medical Center Research Institute, deaths by combined drug intoxication were relatively "rare" ("one in several million"), though they appeared then to be "on the rise". In July 2008, the Associated Press and CNN reported on a medical study showing that over two decades, from 1983 to 2004, such deaths have soared. It has also become a prevalent risk for older patients.

People who engage in polypharmacy and other hypochondriac behaviors are at an elevated risk of death from CDI. Elderly people are at the highest risk of CDI, because of having many age-related health problems requiring many medications combined with age-impaired judgment, leading to confusion in taking medications.

A drug-related blackout is a phenomenon caused by the intake of any substance or medication in which short term and long term memory creation is impaired, therefore causing a complete inability to recall the past. Blackouts are most frequently associated with GABAergic drugs. Blackouts are frequently described as having effects similar to that of anterograde amnesia, in which the subject cannot recall any events after the event that caused amnesia. Research on alcohol blackouts was begun by E. M. Jellinek in the 1940s. Using data from a survey of Alcoholics Anonymous (AA) members, he came to believe that blackouts would be a good determinant of alcoholism. However, there are conflicting views whether this is true. The negative psychological effects of an alcohol-related blackout are often worsened by those who suffer from anxiety disorders. Impairment of the liver will also allow more alcohol to reach the brain and hasten the individual's blackout.

The term "blackout" can also refer to a complete loss of consciousness, or syncope.

Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. This may include feeling tired, abdominal pain, or nausea. This is typically followed by a couple of days without any symptoms after which yellowish skin, blood clotting problems, and confusion occurs. Additional complications may include kidney failure, pancreatitis, low blood sugar, and lactic acidosis. If death does not occur, people tend to recover fully over a couple of weeks. Without treatment some cases will resolve while others will result in death.

Paracetamol poisoning can occur accidentally or as an attempt to end one's life. Risk factors for toxicity include alcoholism, malnutrition, and the taking of certain other medications. Liver damage results not from paracetamol itself, but from one of its metabolites, "N"-acetyl-"p"-benzoquinone imine (NAPQI). NAPQI decreases the liver's glutathione and directly damages cells in the liver. Diagnosis is based on the blood level of paracetamol at specific times after the medication was taken. These values are often plotted on the Rumack-Matthew nomogram to determine level of concern.

Treatment may include activated charcoal if the person presents soon after the overdose. Attempting to force the person to vomit is not recommended. If there is a potential for toxicity, the antidote acetylcysteine is recommended. The medication is generally given for at least 24 hours. Psychiatric care may be required following recovery. A liver transplant may be required if damage to the liver becomes severe. The need for transplant is often based on low blood pH, high blood lactate, poor blood clotting, or significant hepatic encephalopathy. With early treatment liver failure is rare. Death occurs in about 0.1% of cases.

Paracetamol poisoning was first described in the 1960s. Rates of poisoning vary significantly between regions of the world. In the United States more than 100,000 cases occur a year. In the United Kingdom it is the medication responsible for the greatest number of overdoses. Young children are most commonly affected. In the United States and the United Kingdom paracetamol is the most common cause of acute liver failure.