- 1. ALCOHOALPROF DR SHAH MURAD
2.
- Strictly speaking, an alcohol is any organic compound with the
R-OH formula.
- However, in common usage,alcoholrefers 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.
18. 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:
- Concentration of ethanol in the beverage
- Recent and current food (it tends to be much higher in
fasting)
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.
- Amulticompartment 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, Alcoholdependence
syndrome
- Alcohol Use Disorders Identification Test ( AUDIT )
40. Predisposing Factors
-
- Higher concordance in MZ twins than DZ
-
- Adoption studies show higher rates in adopted children from
alcoholic parents
-
- Schizophrenia (more rarely)
-
- Bipolar affective disorder (particularly when
hypomanic/manic)
41.
-
- Tradition / cultural factors
-
- Economic factors (cheap price leads to greater
consumption)
-
-
- Availability of alcohol (Landlords, bartenders etc)
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; Korsakoffs
encephalopathy; Wernickes encephalopathy; Myopathy; Cerebellar
degeneration; Epilepsy; Optic atrophy; Central pontine
myelinolysis; Marchiafava-Bignami disease
44.
-
- 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;folatatedeficiency; Vitamin K
deficiency
45.
-
- Macrocytic anaemia ; Bone marrow depression;
Haemolysis;Sideroblastic anaemia ; Impaired clotting; Reduced
platelet function
46.
-
- Arrhythmias; **prolongation of QTc interval; Hypertension;
Cardiomyopathy; Sudden death in binge drinkers
47.
-
- Men - Erectile dysfunction;Delayed ejaculation ; Low libido;
reduced size of testes & penis; Loss of body hair;
Gynaecomastia
-
- Women - Abnormalities ofmenstruation ; Loss of breast tissue;
Vaginal dryness; Fetal alcohol syndrome in children
48.
-
- Oropharynx; Oesophagus; Pancreas; Liver; Lung
-
- Depression; increased risk of suicide (x 50); Deterioration
inpersonality ; Short-termamnesia(blackouts); Psychosexual
disorders;Pathological jealousy ; Fugue state
49.
-
- 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
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.
-
- Hand tremor, insomnia, sweating, tachycardia, hypertension,
anxiety
-
- Transient visual, tactile or auditory hallucinations or
illusions
-
- Reality testing is generally intact i.e. person recognises
these as hallucinations
-
- These are not associated with "latent epilepsy" as EEG is
normal before and after seizures
57. Delirium Tremens
- Anacute confusional statecaused 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
- Correct any electrolyte imbalance
- Correct hypoglycaemia with caution
-
- Risk of precipitating Wernickes encephalopathy
- 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
includingblindness .
- 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 orpropanolsolution 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
63.