2. greater than three standard drinks per day enhances the risk
for cancer and vascular disease, and alcohol use disorders
decrease the life span by about 10 years
2
.
3. ROUND FIGURES
A standard drink is 10–12 g
as seen in
1. 340 mL of beer
2. 115 mL of wine
3. 43 mL of whisky
0.5 L (1 pint) of 80-proof beverage contains ~160 g of ethanol
(about 16 standard drinks), and 750 mL of wine contains ~60 g
of ethanol.
Congeners include methanol, butanol, acetalde-hyde, histamine,
tannins, iron, and lead
3
4. METABOLISM OF ALCOHOL
Absorbed from
1. Mucous membranes of mouth & esophagus (in small
amounts)
2. Stomach and large bowel (in modest amounts)
3. Proximal portion of the small intestine (the major site).
The rate of absorption is increased by
1. Rapid gastric emptying (as seen with carbonation)
2. Absence of proteins, fats or carbohydrates (which interfere
with absorption)
3. Dilution to a modest percentage of ethanol (maximum at
~20% by volume).
4
5. METABOLISM OF ALCOHOL
1. Ethanol is excreted directly through the lungs, urine, or
sweat
2. Most of it metabolized to acetaldehyde, in liver.
3. The most important pathway occurs in the cell cytosol
where alcohol dehydrogenase (ADH) produces
acetaldehyde,
4. which is then rapidly destroyed by aldehyde
dehydrogenase (ALDH) in the cytosol and mitochondria
5
6. A second pathway
occurs in the microsomes of the smooth endoplasmic reticulum
(microsomal ethanol-oxidizing system i.e. MEOS)
It is responsible for ≥10% of ethanol oxidation at high blood
alcohol concentrations
6
8. 1. Although a drink contains ~300 kJ, or 70–100 kcal
2. These are devoid of minerals, proteins, and vitamins.
3. In addition, alcohol interferes with:
• Absorption of vitamins in the small intestine and
• Decreases their storage in the liver
E.g.
Folate (folacin or folic acid),
Pyridoxine (B6),
Thiamine (B1),
Nicotinic acid (niacin, B3)
Vitamin A
8
9. ALCOHOLIC KETOACIDOSIS
Heavy drinking in a fasting, can produce transient
hypoglycemia within 6–36 h, because ethanol inhibits hepatic
gluconeogenesis
Alcohol ketoacidosisc (AKA) d/t decrease in fatty acid
oxidation + poor diet or recurrent vomiting, can be
misdiagnosed as diabetic ketosis.
AKA:
1. patients show an increase in serum ketones along with a
mild increased glucose but a large anion gap, a mild to
moderate increase in serum lactate.
2. β-hydroxybutyrate/lactate ratio of between 2:1 and 9:1
(with normal being 1:1).
9
10. NEUROTRANSMITTER
CHANGES
Alcohol affects almost all neurotransmitter systems.
Boosting GABA activity, especially at GABA-A receptors.
Enhancement of chloride channel system
Anticonvulsant, sleep-inducing, antianxiety, and muscle
relaxation effects of all GABA-boosting drugs.
1. Acutely administered produces a release of GABA, and
2. Continued Alcohol use increases density of GABA A
receptors
3. Withdrawal states decreased GABA activity..
10
11. Acute alcoholism Inhibit postsynaptic NMDA (N-methyl-d-
aspartate) excitatory glutamate receptors
Chronic drinking upregulate NMDA excitatory receptors.
The relationships between greater GABA and diminished
NMDA receptor activity during acute intoxication and
diminished GABA with enhanced NMDA actions during
alcohol withdrawal explain intoxication and withdrawal
phenomena.
11
12. Alcohol acutely increases dopamine levels in the ventral
tegmentum and related brain regions, and this effect plays an
important role in continued alcohol use, craving, and relapse.
The changes in dopamine also increases “stress hormones”
including cortisol & ACTH during intoxication and
withdrawal.
Such alterations contribute to both feelings of reward during
intoxication & depression during falling blood alcohol
concentrations.
12
13. BEHAVIORAL EFFECTS, TOLERANCE & WITHDRAWAL
“Legal intoxication” with alcohol
requires a blood alcohol concentration of 0.08 g/dL
1. Behavioral, psychomotor, cognitive changes are seen at
0.02–0.04 g/dL (i.e. after one to two drinks)
2. Deep & disturbed sleep can be seen at 0.04 – 0.08g/dl.
3. Death can occur with levels between 0.30 - 0.40 g/dL.
13
15. ACQUIRED TOLERANCE
Repeated use of alcohol Acquired tolerance
iInvolve 3 compensatory mechanisms.
(1) Metabolic tolerance After 1–2 weeks of daily drinking, up
to 30% increase in the rate of hepatic ethanol metabolism
(2) Cellular tolerance develops through neurochemical
changes that maintains relatively normal physiologic
functioning despite the presence of alcohol. Subsequent
decreases in blood levels contribute to symptoms of
withdrawal.
(3) Behavioral tolerance Individuals learn to adapt their
behavior so that they can function better than expected
under influence of the drug (learned T.)
15
.
16. THE EFFECTS OF ETHANOL ON ORGAN SYSTEMS
Low doses of alcohol (1 or 2 drinks / day) beneficial effects :-
1. Increasing high-density lipoprotein cholesterol
2. Decreasing aggregation of platelets
3. Resulting decrease in risk for occlusive coronary disease
and embolic strokes.
Red wine has potential health-promoting qualities at low
doses due to flavinols and related substances.
Modest drinking decrease risk for : vascular dementia &
Alzheimer’s disease.
16
17. NERVOUS SYSTEM
1) Approximately 35% experience a blackout, an episode of
temporary anterograde amnesia, in which the person forgets all
or part of what occurred during a drinking evening.
2) disturbed sleep:- initially help a person fall asleep, it disrupts
sleep. The stages of sleep are altered, Time spent in REM & deep
sleep is reduced.
3) Alcohol relaxes muscles in the pharynx, which cause snoring
and exacerbate sleep apnea; 75% of alcoholic men older than
age 60.
4) impaired judgment & coordination
5) Hangover : headache, thirst, nausea, vomiting, and fatigue the
following day
6) Brain atrophy, evident as ventricular enlargement and widened
cortical sulci on MRI are usually reversible if abstinence is
maintained.
17
18. PSYCHIATRIC
1. Impulsivity and disinhibition
2. Intense sadness lasting for days to weeks
3. Severe anxiety
4. Auditory hallucina-tions and/or paranoid delusions
18
19. GIT
1. Inflammation of esophagus & stomach causing epigastric
distress and gastrointestinal bleeding, hemorrhagic
gastritis.
2. Violent vomiting :-- Mallory-Weiss lesion
3. Acute pancreatitis (~25 per 1000 per year) 3 fold higher
in alcoholics
4. Alcohol impairs gluconeogenesis in the liver, increased
lactate production, and decreased oxidation of fatty
acids. This L/T fat accumulation in liver cells.
5. With repeated exposure to ethanol, causes alcohol-
induced hepatitis, perivenular sclerosis, and cirrhosis
6. Vulnerability to infections
19
20. HEMATOPOIETIC SYSTEM
1. Increase in red blood cell size MCV
2. If folic acid deficiency, there can also be
• Hyper segmented neutrophils
• Reticulo cytopenia
• Hyperplastic bone marrow
20
21. CVS
decreases myocardial contractility
peripheral vasodilation
Resulting mild decrease in blood pressure and a compensatory
increase in cardiac output.
Cardiac oxygen consumption is higher.
Dose-dependent increase in blood pressure, which normalised
within weeks of abstinence.
Chronic heavy drinkers have 6 fold increased risk for CAD &
cardiomyopathy.
21
22. CVS
Symptoms :
1. Unexplained arrhythmias in the presence of left
ventricular impairment
2. Heart failure
3. Dilation of all four heart chambers with associated mural
thrombi and mitral valve regurgitation.
Atrial or ventricular arrhythmias, especially paroxysmal
tachycardia, temporarily after heavy drinking with no other
evidence of heart disease— known as the “holiday heart”
22
23. GENITOURINARY SYSTEM CHANGES,
SEXUAL FUNCTIONING,
AND FETAL DEVELOPMENT
1. Affect normal sexual development & reproductive onset.
2. At any age, modest ethanol doses (e.g. 0.06 g/dL) can increase
sexual drive but decrease erectile capacity in men
3. Irreversible testicular atrophy & shrinkage of the seminiferous
tubules, decreases in ejaculate volume & lowers sperm count
4. Women amenorrhea, a decrease in ovarian size, infertility, &
spontaneous abortion.
23
24. Heavy drinking during pregnancy rapid placental transfer
of both ethanol and acetaldehyde
Fetal alcohol syndrome (FAS) ~5%
1. facial changes with
1. epicanthal eye folds
2. poorly formed ear concha
3. small teeth with faulty enamel
2. Cardiac : atrial or ventricular septal defects
3. Aberrant palmar crease
4. Limitation in joint movement
5. Microcephaly with mental retardation.
24
25. OTHER EFFECTS
Skeletal muscle weakness i.e. acute alcoholic myopathy
improves with abstinence.
Effects on skeletal system :--
1. Changes in calcium metabolism, lower bone density, and
decreased growth in epiphyses
2. Increased risk for fractures and osteonecrosis femoral head
25
26. ALCOHOL USE DISORDER
• Alcohol use disorder is defined as
1. Repeated alcohol-related difficulties
2. In at least 2 of 11 life areas
3. That cluster together in the same12-month period
• Criterias were taken directly from the 7 dependence and 4
abuse criteria in DSM-IV
• The lifetime risk is about 10–15% for men and 5–8% for
women
• Severity of an alcohol use disorder
1. Mild - two or three items
2. Moderate - four or five
3. Severe - six or more
26
28. TREATMENT
The approach to treating alcohol-related conditions is relatively
straightforward:
(1) recognize that at least 20% of all patients have an alcohol use
disorder;
(2) learn how to identify and treat acute alcohol-related conditions;
(3) know how to help patients begin to address their alcohol
problems; and
(4) know enough about treating alcoholism to appropriately
refer patients for additional help.
28
29. IDENTIFICATION OF THE
ALCOHOLIC
by asking questions about alcohol problems & noting laboratory
test results.
The two blood tests with ≥60% sensitivity and specificity for heavy
alcohol consumption are
1. γ-glutamyl transferase (GGT) (>35 U) and
2. Carbohydrate deficient transferrin (CDT) (>20 U/L or >2.6%)
Other useful blood tests
high-normal : MCVs (≥91 μm3) & uric acid (>416 mol/L, or 7
mg/dL).
29
31. TREATMENT : ALCOHOL-RELATED CONDITIONS
ACUTE INTOXICATION
Assess vital signs
Manage respiratory depression
Cardiac arrhythmias or
Blood pressure instability
Aggressive behavior T/t : reassurance & low doses of a short-
acting benzodiazepine such as lorazepam (e.g., 1–2 mg PO or
IV) & repeated as needed.
An alternative approach : antipsychotic (e.g., 0.5–5 mg of
haloperidol PO or IM every 4–8 h as needed, or olanzapine 2.5–
10 mg IM repeated at 2 and 6 h, if needed).
31
32. INTERVENTION
Two main elements :
motivational interviewing and brief interventions.
1. Motivational interviewing:- clinician helps patient to think
through the assets (e.g., comfort in social situations) & liabilities
(e.g., health- and interpersonal-related problems) of the current
pattern of drinking, helping to weigh options & encouraging the patient to
take responsibility for needed changes.
2. Brief intervention:- summarized as FRAMES:
32
33. BRIEF INYTERVENTION
FRAMES
Feedback to the patient
Responsibility to be taken by patient
Advice, on what needs to be done
Menus of options that might be considered;
Empathy for understanding patient’s thoughts and feelings &
Self-efficacy, i.e., offering support for the capacity of the patient to
make changes.
33
34. INTERVENTION
Once the patient begins to consider change, the emphasis shifts
to brief interventions.
Discussions focus on
1. consequences of high alcohol consumption
2. approaches to stopping drinking
3. help in recognizing and avoiding situations likely to lead
to heavy drinking.
carried out in 15-min sessions, multiple meetings to explain the
problem, discuss optimal treatments and explain the benefits of
abstinence
34
35. ALCOHOL WITHDRAWAL
If the patient stop drinking, can produce withdrawal symptoms.
Features include
1. Tremor of the hands (shakes)
2. agitation and anxiety
3. autonomic nervous system overactivity (increase in pulse,
respiratory rate, sweating, and body temperature; and insomnia.)
Symptoms
1. begin within 5–10 h of decreasing ethanol intake,
2. peak on day 2 or 3, and
3. improve by day 4 or 5
4. may persist for 4–6 months (protracted abstinence Syndrome)
35
36. About 2% of alcoholics experience a
withdrawal seizure & similar rate of
delirium tremens
mental confusion,
Agitation
fluctuating levels of consciousness
associated with tremor and autonomic
overactivity
36
37. PHYSICAL EXAMINATION IN ALL
ALCOHOLICS
1. Search for evidence of liver failure
2. Gastrointestinal bleeding
3. Cardiac arrhythmia
4. Infection
5. Glucose or electrolyte imbalances.
Adequate nutrition and oral multiple B vitamins
50–100 mg thiamine daily for a week or more
37
38. 1. Rapid removal of alcohol
2. Administer depressant in doses that decrease symptoms (e.g., a rapid
pulse and tremor) and then tapering the dose over 3–5 days.
3. Benzodiazepines have the highest margin of safety and lowest cost
4. Short-half-life benzodiazepines for patients with serious liver
impairment / significant brain damage, given every 4 h to avoid risk
for seizures.
5. use drugs with longer half-lives
1. Chlordiazepoxide 25–50 mg or
2. Diazepam 10mg given PO every 4–6 h on the first day
doses then decreased over the next 5 days.
38
39. TREATMENT OF
DELERIUM TREMENS
1. Challenging & Likely to run a course of 3–5 days regardless of the
therapy
2. High dose benzodiazepine max 800 mg/d of chlordiazepoxide has
been given.
3. Use of antipsychotics E.g. haloperidol or olanzapine
• Antipsychotics are less likely to exacerbate confusion but may
increase risk of seizure
• they have no role in treatnig mild withdrawal symptoms.
• Little evidence anticonvulsants such as phenytoin or gabapentin are
more effective in drug-withdrawal seizures
39
40. REHABILITATION OF
ALCOHOLICS
≥60% of alcoholics, maintain abstinence for at least a year, and many
achieve lifetime.
The core of treatment
Cognitive-behavioral approaches
motivation toward abstinence
Instructing family members to stop protecting the patient
from problems caused by alcohol.
try self-help groups as Alcoholics Anonymous (AA) to help them to learn
how to deal with life’s stresses
40
41. RELAPSE
PREVENTION
helps the patient identify situations in which a return to drinking is likely
formulate ways of managing these risks
develop coping strategies that increase the chances of a return to abstinence if a
slip occurs.
Counseling focuses on improving functioning in the absence of alcohol
Helping to manage free time without alcohol
Develop a nondrinking peer group & handle stresses.
41
42. INSOMNIA
Teach elements of “sleep hygiene” :-
Maintaining consistent schedules for bedtime and awakening.
Sedating antidepressants (e.g., trazodone); not be used
because they interfere with cognitive functioning & disturb the
normal sleep architecture.
42
43. MEDICATIONS FOR
REHABILITATION
1. Naltrexone(Opioid antagonist) 50–150 mg/d orally shorten
relapses, oral form or as once per month 380-mg injection
MOA: By blocking opioid receptors, decreases dopaminergic activity in
the ventral tegmental reward system & decreases pleasure .
2. Acamprosate ~2 g/d divided into three oral doses : similar effects
MOA: inhibits NMDA receptors, decreasing symptoms of withdrawal.
3. Disulfiram (ALDH inhibitor) 250 mg/d : produces vomiting and
autonomic nervous system instability with alcohol.
Can be dangerous in patients with heart disease, stroke, diabetes
mellitus or hypertension.
S/E:- depression, psychotic symptoms, peripheral neuropathy, and liver
damage
43
