Alcohol, or more specifically, ethanol, is probably our very first synthetic (in a very loose sense of the word as it is not humans that synthesize it, but rather bacterial organisms) drug and has been used by humans for thousands of years (with the earliest record of such use dating further back than 10,000 BC), despite this its pharmacology is so complex that even now we do not fully understand precisely how it elicits its various effects.:28-29 It is very easily the most popularly consumed drug in the world, aside from caffeine. Approximately 3.3 million people die every year, worldwide, from alcohol consumption, accounting for 5.9% of worldwide deaths. In the age bracket 20-39 years it accounts for one in four deaths, worldwide. Alcohol consumption is causally related to over 200 different diseases and injuries (most of which are unintentional). Of these liver cirrhosis, alcohol dependence (‘alcoholism’), cancers and injuries are perhaps the best known. It accounts for 5.1% of global burden of disease and injury. While there is evidence for possible health benefits from light drinking, there is also evidence for health dangers associated with light alcohol consumption.:12
It is also worth noting that it is impossible to blind people with a convincing placebo in the any clinical trial involving alcohol, additionally many abstainers from alcohol are abstainers due to pre-existing illnesses that could be exacerbated by alcohol consumption, while others are abstainers because they once drank, it damaged their health and they gave it up as a result. Plus what many people consider to be drinking in moderation might actually be excessive.
- Improved mood
- Improved sociability
- Impaired coordination and judgement
- Stimulant effects, including increased movement
Whereas moderate doses can produce:
- Significantly impaired coordination, memory and judgement
- Emotional or aggressive behaviours
- Nausea or vomiting
And high doses can cause:
- People to feel dizzy and potentially pass out.
- Respiratory depression
It also inhibits the production and the release of antidiuretic hormone (ADH), leading to diuresis which can cause dehydration. This is likely partially (but not fully, low blood sugar and sleep disturbances are also believed to contribute) responsible for the hangover effect the morning after a night of heavy drinking.
Hangovers consist of the following symptoms: fatigue, headache, increased sensitivity to light and sound, redness of the eyes, muscle aches, thirst, increased blood pressure, nausea, vomiting, rapid heartbeat, tremor, sweating, dizziness, vertigo, memory impairment, depression, anxiety and irritability.
Long-term consequences of alcohol consumptionEdit
Drinking in moderation may reduce one’s risk of the following diseases:
- Reduces the risk of developing Alzheimer’s disease/dementia by 25-40%
- Autoimmune hypothyroidism
- Cardiovascular disease, reduced by, at most, 30%
- Colorectal cancer
- Common cold
- Ischaemic heart disease
- Type 2 diabetes mellitus
- Hearing loss
- Liver cirrhosis
- Low birth weight, prematurity
- Lower urinary tract symptoms (in men)
- Metabolic syndrome
- Negative child development
- Psychiatric disorders
- Renal cell cancer (RCC; the most common form of kidney cancer)
- Rheumatoid arthritis
It may also reduce one’s risk of death from any cause, improve general health status and cause an overall reduction in cancer-related mortality. But as mentioned above, it is impossible to blind anyone in these trials and many abstainers are abstainers for a medical reason, including the fact that alcohol has adversely affected their health in the past. It is also worth noting, however, these studies were all cohort/observational studies, not randomized placebo-controlled trials, hence, see these limitations.
Light wine consumption may protect from additional health conditions including:
- Stomach cancer
- Lung cancer
- Upper digestive cancers (probably oesophageal)
- Hip fracture
It is worth noting, however, that a recently published observational study that followed 783 elderly patients over the period of 9 years found no evidence of improved survival or any other benefits imparted by the consumption of wine, in moderation.
Adverse consequences from alcohol consumption are far better studied than any health benefits from modest consumption. Light alcohol consumption is known to increase one’s risk of the following cancers: oesophageal (22% of deaths worldwide attributable to this cause are due to alcohol abuse), oropharyngeal (throat) (alcohol abuse accounts for 30% of deaths due to this cancer) and female breast cancers (8% of worldwide deaths can be attributed to alcohol abuse).:12 It is worth noting that alcohol consumption is often understated when self-reported, hence as these studies were also observational it is possible that these results were for heavier consumption than what the participants reported. Whereas heavy alcohol consumption is associated with these risks, plus (the % in brackets is the percentage of worldwide deaths caused by said condition that are believed to be caused by alcohol abuse)::12
- Intentional physical injuries (it is estimated that 40% of such injuries are alcohol-related)
- Child abuse
- Cancer of digestive tract (including colorectal [10%]), pancreas and liver (12%).
- Liver cirrhosis (50%)
- Irreversible damage to the brain, heart and pancreas. Stroke (both ischaemic [4%] and haemorrhagic [11%]), hypertension and heart attacks are more common in those that heavily consume alcohol. Alcohol is the second leading cause of dementia, after Alzheimer’s disease. Pancreatitis (swelling of the pancreas; 25%) is also more common in drunks.
- Nerve damage
- Alcoholism, also known as alcohol addiction
- Type II diabetes mellitus, especially common in binge drinkers
- Hormonal imbalances, including increased cortisol and aldosterone production, reduced testosterone levels (perhaps due to an increased production of oestrogen from testosterone) and reduced growth hormone production. This can lead to sexual dysfunction, amongst other effects.
- Domestic violence (22%)
- Drowning (13%)
- Tuberculosis (12%)
- Pneumonia (4%)
- HIV/AIDS (1%)
- Seizures (12%)
- Self-harm (22%)
- Hypertensive heart disease (8%)
- Poor judgement
- Traffic accident (15%)
- Fetal alcohol spectrum disorder (FASD; see below for details)
- Nutritional deficiencies including of thiamine (vitamin B1) and niacin (vitamin B3).
Overall female alcoholics are, on average (across their potential ages), 4.6 times more likely to die during any given time period than their sober counterparts, whereas male alcoholics are 3.4 times more likely to die during any given time period than their sober counterparts.
Fetal alcohol spectrum disorderEdit
FASD is basically what it sounds like, it is a spectrum of potential birth defects or abnormalities that are seen in children exposed to alcohol in utero (in the womb). It is especially common in the children of alcoholics or binge-drinking mothers. They include fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), alcohol-related neuro-developmental disorders (ARND) and alcohol-related birth defects (ARBD).
FAS is basically a constellation of symptoms due to alcohol exposure in utero (that is, in the womb), including craniofacial features (see figure 40), heart defects (potentially fatal ones too), stunted growth and neurodevelopmental defects (like mental retardation and behavioural anomalies). pFAS is, well what it sounds like, it is when a child exhibits some of the symptoms characteristic of FAS, but not all of them. ARND is when a child exhibits stunted development, including mental retardation and behavioural problems (both of which can closely resemble ADHD), but has no other physical abnormalities. ARBD are physical abnormalities experienced by some children exposed to alcohol in utero.
As you can probably guess it is recommended by virtually every health organisation worldwide that pregnant women abstain from alcohol, this includes the World Health Organization and the National Health and Medical Research Council (NHMRC; an Australian government organisation that is concerned with medical research and health). Despite these warnings some 20-30% of women in English-speaking countries consume alcohol while pregnant.
In the United States approximately 1% of children are afflicted by FASD, whereas in Australia this rate seems to be substantially less at 0.001-0.068%. South Africa has a FASD rate of 6.8-8.9%, Russia 14.1% and Italy 12%.
It is a clear, colourless, very mobile and flammable liquid, with a mild, pleasant smell and a burning taste. It has a density of 0.7893 g/cm3 (at 20℃), an acid dissociation constant (pK) of 15.9 and is miscible with water and most organic solvents. Its melting point is -114.14℃ and its boiling point is 78.29℃.
It is rapidly absorbed by the gut and reaches peak concentrations in the bloodstream within 30-60 minutes of oral administration.:28 Its metabolism is in the liver and is via alcohol dehydrogenase (to acetaldehyde) and aldehyde dehydrogenase (from acetaldehyde to acetic acid) and is such that the time it takes to eliminate a quantity of ethanol goes up linearly with said quantity and in this case that relationship is such that twice as much alcohol takes twice as long for the body to eliminate:28 is primarily excreted in urine, sweat and breath.:28
Mechanism of actionEdit
It is believed to exert its effects via a variety of different mechanisms, including::29
- GABAA receptor potentiation, especially of the α1,2,4,5 and β2 subunits, leading to anxiolysis, amnesia, incoordination, muscle relaxation, euphoria, sedation, etc.
- GABA release potentiation via a metabotropic mechanism. Likely leading to the effects list above.
- NMDA receptor antagonism. Likely leading to sedation, amnesia, euphoria, psychosis, analgesia and aggressive behaviour. This action might also be partly responsible for the brain damage caused by alcohol abused.
- AMPA receptor potentiation/antagonism.
- Potentiation of nAChRs, especially the α3β4 and α4β2 subtypes. Probably contributing to the euphoria and potential for dependence produced by alcohol and potentially the ability of alcohol to induce seizures at higher doses and in susceptible individuals.
- Potentiation of glycine receptors, leading to muscle relaxation and potentially contributing to dependence.
- Induction of the release of endorphins, which act at the mu opioid receptors. Producing euphoria, anxiolysis and analgesia.
- Antagonism of adenosine receptors: A1 and A2A. Perhaps contributing to aggression.
- Potentiation of dopamine release, especially in the mesolimbic circuit, producing euphoria and dependence.:29
- Potentiation of 5-HT3 receptors, producing emesis and potentially potentiating the addictive potential of alcohol.
- Inhibition of AMPK, leading to liver damage.
Alcohol is very effective disinfectant at high concentrations, hence it is often used in hand sanitizers. Alcohol is also used in the treatment of methanol (a simpler, but far more toxic alcohol also known as wood alcohol) poisoning by competing with it for alcohol dehydrogenase and aldehyde dehydrogenase, slowing the toxic metabolism of methanol into formic acid.
Treatments for addictionEdit
The major treatment for alcohol abuse is psychosocial interventions like Alcoholics Anonymous. There are three drug treatments available for alcohol abuse that have received regulatory approval, naltrexone, acamprosate and disulfiram. Acamprosate has complex effects at the NMDA receptors, serving as a partial agonist, so it increases activity of the receptor when glutamate is scarce, whereas when it is in abundance it reduces the activity of the receptor.167 Additional positive results in clinical trials have been achieved with the use of topiramate and baclofen.168-170 Unfortunately, their effectiveness is generally modest, hence the psychosocial interventions are still the cornerstones of the modern medical treatment of alcoholics.168-170 One treatment that is particularly promising, is depot naltrexone. See depots are long-acting injections of a drug that are made into a large muscle like those in one’s buttocks or thigh. They slowly release the drug into the body, over a period of weeks or months. In the case of depot naltrexone it is capable of reducing the pleasurable effects of alcohol over the period of a month. It is sort of a commitment for the alcoholics as there is no way for them to remove the depot themselves. Ondansetron and sodium oxybate might also reduce alcohol usage in alcoholics.
- NCBI Bookshelf provides free book resources on this topic.
- PubMed provides review articles from the past five years (limit to free review articles or to systematic reviews)
- The TRIP database provides clinical publications about evidence-based medicine.
- ↑ Patrick, CH (1970). Alcohol, culture, and society. New York, USA: AMS Press. pp. 26–27. ISBN 978-0-40-404906-5.
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- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 National Collaborating Centre for Mental Health (2011). Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence. London, UK: British Psychological Society/Royal College of Psychiatrists. ISBN 978-1-904671-26-8. PMID 22624177.
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- ↑ Stokowski, LA (30 April 2014). "No Amount of Alcohol Is Safe". Medscape Oncology. United States of America: WebMD. Retrieved 20 July 2014.
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- ↑ Meredith, V; Price-Robertson, R (December 2011). "Alcohol misuse and child maltreatment" (PDF). AIFS.gov.au. Canberra, Australia: Australian Institute of Family Studies. Retrieved 25 June 2014.
- ↑ Varela-Rey, M; Woodhoo, A; Martinez-Chantar, ML; Mato, JM; Lu, SC (2013). "Alcohol, DNA methylation, and cancer.". Alcohol Research 35 (1): 25–35. PMC 3860423. PMID 24313162.
- ↑ 15.0 15.1 Sid, B; Verrax, J; Calderon, PB (July 2013). "Role of AMPK activation in oxidative cell damage: Implications for alcohol-induced liver disease.". Biochemical Pharmacology 86 (2): 200–9. PMID 23688501. doi:10.1016/j.bcp.2013.05.007.
- ↑ Ji, C (2014). "New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases.". International Journal of Hepatology 2014: 513787. PMC 4020372. PMID 24868470. doi:10.1155/2014/513787.
- ↑ Husain, K; Ansari, RA; Ferder, L (May 2014). "Alcohol-induced hypertension: Mechanism and prevention.". World Journal of Cardiology 6 (5): 245–252. PMC 4038773. PMID 24891935. doi:10.4330/wjc.v6.i5.245.
- ↑ Kazimir, M; Talano, JV; Hayes, S (19 July 2013). Sander, GE; Talavera, F; Ooi, HH, ed. "Cocaine-Related Cardiomyopathy". Medscape Reference. WebMD. Retrieved 8 June 2014.
- ↑ Krenz, M; Korthuis, RJ (January 2012). "Moderate ethanol ingestion and cardiovascular protection: from epidemiologic associations to cellular mechanisms." (PDF). Journal of Molecular and Cellular Cardiology 52 (1): 93–104. PMC 3246046. PMID 22041278. doi:10.1016/j.yjmcc.2011.10.011.
- ↑ Walker, RK; Cousins, VM; Umoh, NA; Jeffress, MA; Taghipour, D; Al-Rubaiee, M; Haddad, GE (August 2013). "The good, the bad, and the ugly with alcohol use and abuse on the heart.". Alcoholism, Clinical and Experimental Research 37 (8): 1253–60. PMID 23527963. doi:10.1111/acer.12109.
- ↑ 21.0 21.1 Roerecke, M; Rehm, J (September 2013). "Alcohol use disorders and mortality: a systematic review and meta-analysis.". Addiction 108 (9): 1562–78. PMID 23627868. doi:10.1111/add.12231.
- ↑ Rundio, A, Jr (September 2013). "Understanding alcoholism.". The Nursing Clinics of North America 48 (3): 385–90, v. PMID 23998765. doi:10.1016/j.cnur.2013.05.001.
- ↑ 23.0 23.1 Tabakoff, B; Hoffman, PL (November 2013). "The neurobiology of alcohol consumption and alcoholism: an integrative history.". Pharmacology, Biochemistry, and Behavior 113: 20–37. PMID 24141171. doi:10.1016/j.pbb.2013.10.009.
- ↑ Wackernah, RC; Minnick, MJ; Clapp, P (2014). "Alcohol use disorder: pathophysiology, effects, and pharmacologic options for treatment.". Substance Abuse and Rehabilitation 5: 1–12. PMC 3931699. PMID 24648792. doi:10.2147/SAR.S37907.
- ↑ Pietraszek, A; Gregersen, S; Hermansen, K (June 2010). "Alcohol and type 2 diabetes. A review.". Nutrition, Metabolism, and Cardiovascular Diseases 20 (5): 366–75. PMID 20556883. doi:10.1016/j.numecd.2010.05.001.
- ↑ Bianco, A; Thomas, E; Pomara, F; Tabacchi, G; Karsten, B; Paoli, A; Palma, A (2014). "Alcohol consumption and hormonal alterations related to muscle hypertrophy: a review.". Nutrition & Metabolism 11: 26. PMC 4056249. PMID 24932207. doi:10.1186/1743-7075-11-26.
- ↑ 27.0 27.1 27.2 27.3 Burns, L; Breen, C; Bower, C; O' Leary, C; Elliott, EJ (September 2013). "Counting fetal alcohol spectrum disorder in Australia: the evidence and the challenges.". Drug and Alcohol Review 32 (5): 461–7. PMID 23617437. doi:10.1111/dar.12047.
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- ↑ 29.0 29.1 29.2 "Ethanol". PubChem. Bethesda, USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 23 June 2014.
- ↑ Kumar, S; Porcu, P; Werner, DF; Matthews, DB; Diaz-Granados, JL; Helfand, RS; Morrow, AL (September 2009). "The role of GABA(A) receptors in the acute and chronic effects of ethanol: a decade of progress.". Psychopharmacology 205 (4): 529–64. PMC 2814770. PMID 19455309. doi:10.1007/s00213-009-1562-z.
- ↑ Kelm, MK; Criswell, HE; Breese, GR (January 2011). "Ethanol-enhanced GABA release: a focus on G protein-coupled receptors.". Brain Research Reviews 65 (2): 113–23. PMC 3005894. PMID 20837058. doi:10.1016/j.brainresrev.2010.09.003.
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- ↑ Rahman, S; Prendergast, MA (August 2012). "Cholinergic receptor system as a target for treating alcohol abuse and dependence.". Recent Patents on CNS Drug Discovery 7 (2): 145–50. PMID 22574675. doi:10.2174/157488912800673173.
- ↑ Rahman, S (August 2013). "Nicotinic receptors as therapeutic targets for drug addictive disorders.". CNS & Neurological Disorders Drug Targets 12 (5): 633–40. PMID 23574176. doi:10.2174/1871527311312050011.
- ↑ Doyon, WM; Thomas, AM; Ostroumov, A; Dong, Y; Dani, JA (October 2013). "Potential substrates for nicotine and alcohol interactions: a focus on the mesocorticolimbic dopamine system.". Biochemical Pharmacology 86 (8): 1181–93. PMID 23876345. doi:10.1016/j.bcp.2013.07.007.
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- ↑ Bodnar, RJ (December 2013). "Endogenous opiates and behavior: 2012.". Peptides 50: 55–95. PMID 24126281. doi:10.1016/j.peptides.2013.10.001.
- ↑ Nam, HW; Bruner, RC; Choi, DS (September 2013). "Adenosine signaling in striatal circuits and alcohol use disorders.". Molecules and Cells 36 (3): 195–202. PMID 23912595. doi:10.1007/s10059-013-0192-9.
- ↑ Kenna, GA (2010). "Medications acting on the serotonergic system for the treatment of alcohol dependent patients.". Current Pharmaceutical Design 16 (19): 2126–35. PMID 20482508. doi:10.2174/138161210791516396.