Alcohol

From Ganfyd

Common Name:Ethanol

Alternative Name:Alcohol

Other Names, such as IUPAC Name

C₂H₅OH

Biochemical Information

Molecular Structure

Ethanol Molecule

PubChem on Ethanol

CTD (Comparative Toxicogenomics Database) on Ethanol

Chemical Information on Ethanol

Protein Structural Information on Ethanol

Biological Information (GenomeNet) on Ethanol and some on Alcohol

Protein Knowledgebase (UniProtKB) on Alcohol

Online Mendelian Inheritence in Man (OMIM) on Alcohol

Important Issues in Man

Enjoyable sedative with considerable potential for acute and chronic toxicity

Data limitations

Relevant Clinical Literature

Pubmed on Alcohol

RCT with Alcohol

Systematic reviews of Alcohol

Alcohol in N Eng J Med, Lancet, JAMA, BMJ

Alcohol in Cochrane Collaboration

TRIP Database on Alcohol

Google Scholar on Alcohol

Bandolier on Alcohol

UK Guidance

SNOMED search

NHS Evidence on Ethanol

Centre for Reviews and Dissemination databases -DARE & NHS EED (evaluates reliability of research)

Nice Guidance on Alcohol

Prodigy Guidance on Alcohol

Other Wikis

Medpedia on Alcohol (Less technical, good quality control)

Wikipedia on Alcohol (Less technical, ? quality control)

Strictly speaking, an alcohol is any organic compound with the R-OH formula. However, in common usage, alcohol refers to ethanol (C₂H₅OH) and ethanol-containing fermented beverages. Other small chain alcohols include methanol (CH₃OH) and propanol (C₂H₅OH).

Metabolism

Comparison of kinetics after single oral dose ethanol iv verus oral verus oral with anticholinergic to delay gastric emptying

It is well known that there is variability in the rate and extent of absorption, distribution and elimination of alcohol. Up to 98% of ingested alcohol is metabolised and the remainder is excreted in breath, urine and sweat.

Elimination

The bulk of ethanol is broken down in the liver. However gastric mucosal metabolism is not negligible^[1]. Alcohol dehydrogenase of which there are multiple isoenzymes is the main enzyme, but microsomal enzymes play a smaller role. Alcohol dehydrogenase converts ethanol to acetyldehyde, which in turns is rapidly degraded into acetic acid by acetyldehyde dehydrogenase. Alcohol is unusual in pharmacokinetic terms as its breakdown is usually governed by zero-order kinetics, i.e. the amount of alcohol metabolised is fixed. The explanation for this is that at the amounts of alcohol that most people drink, the liver's capacity to metabolise alcohol, principally with cytosolic alcohol dehydrogenase (ADH), is overwhelmed and the amount of alcohol metabolised per unit time is therefore constant. This amount in individual normal adults varies two fold due to ADH polymorphism, but the differential metabolism has been well characterised and is open to fairly accurate estimation for forensic purposes^[2]. This rate-limiting step in oxidation has a Michaelis-Menten constant (Km) of 0.05-0.1 g/L^[3]. Another ethanol-metabolising cytochrome P450 enzyme CYP2E1, has a higher Km (0.5-0.8 g/L) and is inducible, so that the clearance of ethanol is increased in heavy drinkers.

Absorption

Absorption of ethanol from the gut depends on:

• Time of day
• Drinking pattern
• Dose form^[4]
• Concentration of ethanol in the beverage
• Recent and current food (it tends to be much higher in fasting)
• Gastric emptying time (drugs or pathology that alter gastric emptying change alcohol metabolism and indeed can prevent a proportion ever getting into the blood).

Subject to the caveats above, consumption of 1ml/kg (=0.8g/kg) of alcohol can be expected to raise the blood levels by 100-150mg/dL. In a 60kg person, this equates to approximately 6 alcohol units. The UK legal limit of driving is 80mg/dL, but is 50mg/dL in many other countries.^[5]

Distribution

The rate of equilibration is governed by the ratio of blood flow to tissue mass and body composition. Ethanol has low solubility in lipids and does not bind to plasma proteins, so volume of distribution is closely related to the amount of water in the body, contributing to sex- and age-related differences. Recent work confirms that a multicompartment model to describe the disposition of ethanol is more accurate than the traditional one-compartment model with zero-order elimination^[6].

Effects of Alcohol

It is classified as a sedative, but is often taken for the pleasure of the drink as well as its for its disinhibiting effect. Acute ingestion of a toxic fatal quantity is possible without the person ingesting it being aware of this risk, although most attributable fatalities are associated with secondary consequences such as accidents, inhalation of vomit or seizures.

The increase in reaction time has proved particularly problematical with driving and other skilled tasks. An advanced state of alcoholic intoxication is termed being "drunk" and is very familiar in most Western Societies. Children, the elderly, those with small amounts of body fat and those taking most medications will be at higher risk of alcohol toxicity.

There is quite a large literature on the association between a moderate alcohol consumption and lower risk of a number of conditions. This leads to the J shaped curve where both low and high alcohol consumption is associated with health loss.^[7] There is often the potential for confounding in such studies. The pattern of drinking, type of drink^[8][9] and selection by the disease against or for alcohol consumption might be such confounders^[10]. Such fragile associations have been demonstrated for cognition^[11], ischaemic heart disease^[12], ischaemic stroke^[13], insulin resistence^[14], hip fracture^[15], mental health^[16], elderly well being ^[17], healthcare costs^[18] and all cause mortality^[19]. This area gets even more interesting given malignacy risk is increased^[20].

Chronic Effects

The metabolism of alcohol can provide energy at the risk of disturbance of normal energy metabolism and toxicity. Acute alcoholic hepatitis is different from alcoholic cirrhosis, although the two may coexist. There is a higher incidence of trauma presentations, cardiomyopathy, neuropathy, cerebellar degeneration and many other diseases in those with a high prolonged intake of alcohol. Many common medical presentations, such as gastro-intestinal bleeds, atrial fibrillation, hyponatraemia and confusion are associated with alcohol use.

Fetal alcohol syndrome

This is rather important to be aware of in pregnancy and for the mother to be advised accordingly.

Alcohol Dependence

(follow heading link for main article)

(AKA alcoholism, alcoholic state.) See description of dependence syndromes.

Diagnosis

History

Special Questionnaires

• FAST test^[21][22][23]
• CAGE and other tests^[24]
• Alcohol Use Disorders Identification Test (AUDIT) test^[25]

Clinical examination

Laboratory tests

[e.g. Gamma GT]

Predisposing Factors

• Genetics
  • Higher concordance in MZ twins than DZ
  • Adoption studies show higher­ rates in adopted children from alcoholic parents
• Personality
• Advertising
• Peer group pressures
• Psychiatric illness
  • Depression
  • Anxiety disorders
  • Phobic disorders
  • Schizophrenia (more rarely)
  • Bipolar affective disorder (particularly when hypomanic/manic)
• Social factors
  • Religion
  • Tradition / cultural factors
  • Economic factors (cheap price leads to greater­ consumption)
  • Occupation
    • Availability of alcohol (Landlords, bartenders etc)
    • Stress of job (Doctors!)

Complications of Alcohol Dependence

• Liver problems in 50% of alcoholics
  • Fatty liver (reversible; may progress to cirrhosis); Hepatitis (80% progress to cirrhosis); Cirrhosis; Jaundice; increased risk of hepatocellular carcinoma
• CNS/nerve/muscle disorders
  • Poor memory/cognition; Cortical atrophy; Retrobulbar neuropathy; Dementia; Fits; Falls; Wide-based gait; Neuropathy; Korsakoff’s encephalopathy; Wernicke’s encephalopathy; Myopathy; Cerebellar degeneration; Epilepsy; Optic atrophy; Central pontine myelinolysis; Marchiafava-Bignami disease
• GI tract
  • Nausea & Vomiting (particularly in the morning; can be prevented by drinking more alcohol); Obesity; Diarrhoea; Gastric erosions; Peptic ulcer disease; Mallory-Weiss tears; Oesophageal varices; Pancreatitis (acute/chronic/calcific); Malnutrition due to poor diet, GI disorders; folate deficiency; Vitamin K deficiency
• Blood
  • Macrocytic anaemia; Bone marrow depression; Haemolysis; Sideroblastic anaemia; Impaired clotting; Reduced platelet function
• Cardiovascular
  • Arrhythmias; **prolongation of QTc interval; Hypertension; Cardiomyopathy; Sudden death in binge drinkers
• Genito-urinary
  • Men - Erectile dysfunction; Delayed ejaculation; Low libido; reduced size of testes & penis; Loss of body hair; Gynaecomastia
  • Women - Abnormalities of menstruation; Loss of breast tissue; Vaginal dryness; Fetal alcohol syndrome in children
• Cancer
  • Oropharynx; Oesophagus; Pancreas; Liver; Lung
• Psychiatric
  • Depression; increased ­risk of suicide (x 50); Deterioration in personality; Short-term amnesia (blackouts); Psychosexual disorders; Pathological jealousy; Fugue state
• Social morbidity
  • Family/relationship breakdown; Effect on children; Poor performance at work; Crime; Accidents & trauma

Alcohol Withdrawal

(follow heading link for main article)

WHEN TO USE PARENTAL VITAMIN B Incipient Wernicke's encephalopathy confusion ± ataxia memory disturbance ophthalmoplegia At risk group Significant weight loss Poor diet Signs of malnutrition[26]

A common cause of confusion, both in patients and the doctor who fails to recognise the reason for a patient's new confusion. The diagnosis may not be straight forward due to the stigmata associated with admitting to excess alcohol use. While much alcohol withdrawal can be managed in the community there are catches. The most important are:

1. the prevention of Wernicke's encephalopathy. In those at risk this requires 3 days of parental thiamine, not just oral thiamine
2. in advanced hepatitic disease or alcoholic hepatitis chlordiazepoxide is safer than diazepam or lorazepam.
3. use of iv benzodiazepines is not without risk
4. Clomethiazole (chlormethiazole), particularily the iv preparation, is associated with a higher life-threatening complication rate than benzodiazipines

Chronic alcohol use leads to gradual upregulation of N-methyl-d-aspartate receptors; withdrawal of alcohol leads to overwhelming excitatory action mediated by the glutamatergic system.

Symptoms & Signs

Acute withdrawal usually occurs between 6 and 12 hours after last alcohol consumption. Symptoms may last 4-5 days.

• Autonomic hyperactivity
  • Hand tremor, insomnia, sweating, tachycardia, hypertension, anxiety
• Perceptual disturbances
  • Transient visual, tactile or auditory hallucinations or illusions
  • Reality testing is generally intact i.e. person recognises these as hallucinations
• Withdrawal seizures
  • These are not associated with "latent epilepsy" as EEG is normal before and after seizures

Delirium Tremens

An acute confusional state caused by withdrawal from alcohol. Usually begins 3-4 days after withdrawal, though may occur while individual is still drinking (possibly due to a reduced alcohol level). It is either of sudden onset or there is a prodromal phase of restlessness, anxiety and insomnia, with above symptoms of alcohol withdrawal. Additionally there is reduced level of consciousness, disorientation in time and place, impairment of sensory stimuli with hallucinations. Visual hallucinations may be Lilliputian, complex, frightening or vivid. The symptoms are worse at night and last for 2-3 days. If untreated, they may end with a deep prolonged sleep, waking symptom-free & with no memory of delirium.

Management of Alcohol Withdrawal

• Rehydration
• Correct any electrolyte imbalance
• Correct hypoglycaemia with caution
  • Risk of precipitating Wernicke’s encephalopathy
• Oral/parenteral thiamine
• Reducing regimen of benzodiazepines or Chlordiazepoxide
• Treat seizures with rectal or IV diazepam
  • Consider anticonvulsant for elective withdrawal if there is a history of withdrawal seizures

Medicinal Uses of Alcohol

Traditionally ethanol has been used in the treatment of methanol poisoning. Methanol is broken down by alcohol dehydrogenase to formaldehyde, a toxic metabolite which can cause serious morbidity including blindness. Ethanol is given as this will overwhelm the alcohol dehydrogenase, thus reducing the levels of formaldehyde produced by methanol metabolism.

Laboratory Uses of Alcohol

Ethanol is used as a fixative and solvent within the microbiology laboratory.

A 70% ethanol or propanol solution has disinfectant properties, possibly through denaturation of bacterial proteins. Either compound may be found in hand disinfectant gels. Ethanol is also commonly used in conjunction with other antiseptics such as chlorhexidine or povidone-iodine. When used, it should be allowed to dry before a procedure is undertaken. This is because some of the action may depend on evapouration, but also because it is flammable and there is a risk of ignition if diathermy is to be used.

References