This document provides an overview of alcohol including its chemical properties, effects on the body, risks of abuse and dependence, and medical uses and risks. Key points include: - Alcohol is a central nervous system depressant that can cause impairment at high doses and is linked to many health and social problems. - Chronic heavy drinking can damage major organs like the liver, heart and brain and increase risks of certain cancers. - Dependence and withdrawal involve physical and psychological risks that require medical management in some cases. - Fetal alcohol syndrome is a serious risk for pregnant women who drink alcohol.

1. ALCOHOAL PROF DR SHAH MURAD

2. 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).

3. Whether most people know it or not, ethyl alcohol (or eth-anol) is a real drug, one that causes more deaths, crime, and health and behavioral problems than all illegal drugs combined.

4. Produced by the fermentation and distillation of grain, fruit, and other plant products, alcohol is used throughout the world, except in Islamic countries, which oppose its use.

5. Actions/Effects Ethanol is a central nervous system depressant that triggers a range of physical, emotional, and behavioral changes.

6. The rate at which it enters the bloodstream (and exerts its psychoactive effects) is influenced by various factors, including gender and body size and whether drinking is done on a full or empty stomach.

7. As blood-alcohol levels rise, effects increase. At low doses, effects includes a loosening of inhibitions along with feelings of relaxation and well-being. At higher doses, intoxication is linked to progressive levels of impairment.

8. Duration Depends on the amount consumed. Since the liver can only metabolize about one drink per hour, drinking more than that causes intoxication and impairment.

9. Medical Uses Alcohol has a long history of medical uses, but is no longer used as a medicine in its own right. When used at all today, it's combined with other ingredients in cough syrups or elixirs.

10. Risks/Side Effects All body systems are affected by alcohol. Side effects include dilation of blood vessels (which causes flushed skin) and increased gastric secretion in the stomach.

11. At high doses, side effects include mood swings, unrestrained behavior, and inability to control motor functions as basic as walking.

12. Other effects include blackouts, sleep problems (including impaired REM sleep), and hangovers. Side effects increase in severity with chronic abuse.

13. Heavy drinkers suffer a variety of alcohol-related problems, including damage to the brain, stomach, pancreas, heart, and liver.

14. Demographics All socioeconomic and ethnic groups in society are affected, but overuse is most common among young people.

15. According to a recent survey, about 16 million Americans are considered "heavy" drinkers, while 26.8 percent of the high school class of 2010 reported being drunk at least once during the month preceding an annual survey.

16. It is well known that there is variability in the rate and extent of absorption, distribution and elimination of alcohol.

17. Up to 98% of ingested alcohol is metabolised and the remainder is excreted in breath, urine and sweat.

19. Elimination The bulk of ethanol is broken down in the liver. However gastric mucosal metabolism is not negligible. Alcohol dehydrogenase of which there are multiple isoenzymes is the main enzyme, but microsomal enzymes play a smaller role.

20. Alcohol dehydrogenase converts ethanol to acetyldehyde, which in turns is rapidly degraded into acetic acid by acetyldehyde dehydrogenase.

21. 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.

22. 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.

23. 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. This rate-limiting step in oxidation has a Michaelis-Menten constant (Km) of 0.05-0.1 g/L.

24. 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

25. Absorption

26. Absorption of ethanol from the gut depends on: Time of day Drinking pattern Dose form Concentration of ethanol in the beverage Recent and current food (it tends to be much higher in fasting) Gastric emptying time

27. Distribution The rate of equilibration is governed by the ratio of blood flow to tissue mass and body composition.

28. 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.

29. A multicompartment model to describe the disposition of ethanol is more accurate than the traditional one-compartment model with zero-order elimination

30. 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.

31. 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.

32. 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.

33. Children, the elderly, those with small amounts of body fat and those taking most medications will be at higher risk of alcohol toxicity.

34. There is quite a large literature on the association between a moderate alcohol consumption and lower risk of a number of conditions.

35. Such fragile associations have been demonstrated for cognition, ischaemic heart disease, ischaemic stroke, insulin resistence, hip fracture, mental health, elderly well being , healthcare costs and all cause mortality. This area gets even more interesting given malignacy risk is increased.

36. 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.

37. 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.

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

39. Alcohol Dependence, alcoholism, Alcohol dependence syndrome Diagnosis FAST test CAGE and other tests Alcohol Use Disorders Identification Test ( AUDIT )

40. 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)

41. 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!)

42. 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

43. 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

44. 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; folatate deficiency; Vitamin K deficiency

45. Blood Macrocytic anaemia ; Bone marrow depression; Haemolysis; Sideroblastic anaemia ; Impaired clotting; Reduced platelet function

46. Cardiovascular Arrhythmias; **prolongation of QTc interval; Hypertension; Cardiomyopathy; Sudden death in binge drinkers

47. 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

48. 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

49. Social morbidity Family/relationship breakdown; Effect on children; Poor performance at work; Crime; Accidents & trauma

50. Alcohol Withdrawal 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

51. 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

52. The most important are the prevention of Wernicke's encephalopathy. In those at risk this requires 3 days of parental thiamine, not just oral thiamine in advanced hepatitic disease or alcoholic hepatitis chlordiazepoxide is safer than diazepam or lorazepam.

53. use of iv benzodiazepines is not without risk Clomethiazole (chlormethiazole), particularily the iv preparation, is associated with a higher life-threatening complication rate than benzodiazipines

54. 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.

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

56. 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

57. 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.

58. 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.

59. 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

60. 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.

61. 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.

62. 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