This document discusses alcohol use, dependence, and treatment. It begins with an overview of the pharmacokinetics of alcohol and its effects on different body systems. Alcohol dependence is characterized by craving, loss of control, tolerance, and withdrawal symptoms. Treatment involves detoxification, counseling, mutual support groups, and pharmacotherapy using benzodiazepines, acamprosate, naltrexone, disulfiram, and other medications. The combination of pharmacological and psychosocial therapies provides the most effective management of alcohol dependence.

1. ALCOHOL AND MANAGEMENT OF
ALCOHOLISM
Dr Manjuprasad
Moderator: Dr Nicole Periera
1

2. OVERVIEW
 Introduction
 Pharmacokinetics
 Action on different system
 Alcohol dependence
 Treatment
 conclusion
2

3. INTRODUCTION
 Documented 10,000 B.C
 Used as beverages of pleasure
-to facilitate socialization
-as a source of nutrition
-as a part of medicinal practices
3

4.  Wine – 10-15%
 Beer – 4-6%
 Brandy – 35-60%
 Vodka – 35-50%
 Rum – 37-70%
 Whisky – 40-60%
4

5.  Ethanol ERA: Ethanol in blood
 Blood ethanol levels influenced by
- rate of drinking
- sex
- rates of metabolism
- stomach emptying
5

6. METABOLISM
Ethanol
NAD
ADH
NADH
Acetaldehyde
NAD
ALDH
NADH
Acetic acid
6

7. ↑ in NADH:NAD
↓
Lactate accumulates & activity of TCA↓
↓
Acetyl Co A accumulates
↓
Acetyl Co A+↑NADH → fatty acid synthesis
↓
Accumulation of triglycerides
7

8. ON CNS
 Depressant
 Behavioral disinhibition
 Antianxiety
 Impairs cognitive functioning and judgment
 Neurotoxic
 Disturbs balance between excitatory and inhibitory
influences
8

9.  Ion channels:
-- Acts through GABAA receptor → sleepiness, muscle
relaxation and anticonvulsant properties
-- Results in GABA release
-- intoxication → GABA rich state
-- withdrawal phenomena → GABA activity deficiency
9

10.  Nicotinic Ach receptor is also sensitive to ethanol
 Ethanol - ↑Ach in ventral tegmental area
- ↑DA in nucleus accumbens
 Varenicline : a partial agonist at 4β2 subunit ↓ethanol
seeking behavior & consumption in rodent models
10

11. ON CNS
 Large doses : anterograde amnesia
 Disturbance in sleep
 Hangover
 Chronic heavy drinking → permanent cognitive deficits
 Korsakoffs psychosis
 Peripheral neuropathy
11

12. CVS
 ↑HDL & ↓LDL,VLDL
 Ethanol ↑tissue plasminogen activator
 >3 standard drinks/day elevates risk of heart attacks and &
bleeding related strokes
 6 fold ↑in CAD
 Cardiac arrhythmias
 cardiomyopathy
12

13.  Stroke
 Diuresis – ↓release of vasopressin from ant pituitary
 Gastritis, malabsorption, diarrhea
 Acute and Chronic Pancreatitis
 Liver- accumulation of fat, fibrosis, necrosis, chronic
inflammation
 osteoporosis
13

14. SEXUAL FUNCTION
 Initially increased libido
 Both acute and chronic alcohol use leads to
impotence in men
50% in chronic alcoholics
 Decreased sexual arousal, ↑ejaculatory latency,
↓orgasmic pleasure.
 Testicular atrophy & decreased fertility
 ↓libido, ↓vaginal lubrication and menstrual
abnormalities
 Lower fertility rates 14

15. USES OF ALCOHOL
 As antiseptic
 Rubefacient & counterirritant
 To prevent bed sores
 Alcoholic sponges
 Intractable neuralgias
 Appetite stimulant
 To treat methanol poisoning
15

16. ALCOHOL DEPENDENCE
 Alcohol dependence is a substance related
disorder in which an individual is addicted to alcohol
either physically or mentally, and continues to use
alcohol despite significant areas of dysfunction,
evidence of physical dependence, and/or related
hardship.
16

17.  Characterized by the following:
• Craving: A strong need, or compulsion to drink.
• Loss of control: inability to limit one’s drinking
on any given occasion.
• Physical dependence: Withdrawal symptoms
• Tolerance: The need to drink greater amounts of
alcohol in order to “get high.”
17

18. WITHDRAWAL SIGNS AND SYMPTOMS
 Nausea
 Tremor
 Anxiety, Agitation
 Autonomic changes (BP, HR, Temp.), sweating
 Seizures
 Sensorium changes (eg, hallucinations, confusion) 18

19. WITHDRAWAL SYNDROME STAGE 1
 Begins within 24 hours
 Lasts up to 5 days
 90% of cases do not go beyond stage 1
 Other symptoms include depressed mood, anxiety,
diaphoresis, headache, nausea/vomiting, etc.
19

20. WITHDRAWAL SYNDROME STAGE 2
 Mostly untreated or undertreated in stage 1
 Same signs and symptoms as in stage 1 - more
severe
 Hallmark is hallucinations (generally perceived as
benign)
 Usually occurs 48 hours after last drink
20

21. WITHDRAWAL SYNDROME STAGE 3
 Usually occurs 72 hours after last drink
 Delirium Tremens (acute reversible organic
psychosis)
 Often disoriented and labile
 Seen in persons with severe alcoholism and/or
significant medical problems
21

22. 22

23. TREATMENT FOR ALCOHOL DEPENDENCE:
• Removal from drinking environment
• Mutual (self)-help groups
• Counseling
• Pharmacotherapy
• Rehabilitation
23

24. PHARMACOTHERAPY
Benzodiazepines --
 Diazepam
 Chlordiazepoxide
 Lorazepam
 Oxazepam
Anticonvulsants --
 Carbamazepine
 Valproic acid
 Phenytoin
 Gabapentin
 Baclofen 24

25. TO PREVENT RELAPSE
• Disulfiram
• Naltrexone
• Acamprosate
25

26. DISULFIRAM
 Alcohol ingestion-unpleasant reaction-patient
avoids alcohol to avoid the aversive experience.
26

27.  Dose 250-500mg/day
 contraindications:
 recent alcohol use
 Pregnancy
 cognitive impairment, risk of harm from disulfiram--
ethanol reaction, drug interactions
 side effects:
hepatitis, neuropathy
Antabuse reaction: flushing, throbbing headache,
dizziness, vomiting, mental confusion, circulatory
collapse
27

28. ACAMPROSATE
Mechanism of Action :
 Blockade of Glutamate NMDA receptors .
 Activation of GABA-A receptors.
 Acamprosate restores the imbalance in the
excitatory & inhibitory NTs, caused by alcohol.
(Littleton, 1995; Rammes et al, 2001)
28

29.  Dose: 666mg TID
 contraindication:
renal insufficiency
 side effect:
diarrhea; pregnancy
29

30. NALTREXONE
 µ Opioid receptor antagonist.
 Endogenous opioid system- neurological substrate
for drug reward, mediated through actions in the
dopamine system.
30

31. EFFECTIVE IN
 Early age of dependence (<25yrs)
 Family history of Alcohol dependence.
 High Craving.
 Co-morbid opioid and nicotine dependence
31

32. Dose: 12.5-50 mg/d
contraindication:
opiates, pregnancy
side effects:
nausea, dizziness
32

33. NEWER THERAPIES
 Nalmefene
 Dopaminergic drugs
 SSRI
 Serotonin receptor agonist and antagonist
33

34. NALMEFENE
 • opioid receptor antagonist similar to naltrexone.
 • A small pilot study in 21 alcohol-dependent
patients treated for 3 months showed this drug to
have some beneficial effect on relapse to heavy
drinking.
(Mason BJ, et al 2003)
34

35. DOPAMINERGIC DRUGS
 Tiapride
 Flupenthixol
Shown some promise but still experimental
35

36. SEROTONERGIC DRUGS
Selective serotonin reuptake inhibitors
 Fluoxetine
 Sertraline
 Citalopram
Drugs acting at serotonin receptors
 Buspirone
 Ondansetron
36

37.  Brain serotonin contributes to alcohol craving
through interaction with mesolimbic dopamine
neurotransmission.
 SSRIs reduce 5-HT levels, thereby reciprocally
enhancing DA function and substituting for alcohol’s
rewarding effects.
37

38. FLUOXETINE
 • Five studies investigated fluoxetine difference in
alcohol consumption between treatment groups: no
difference in alcohol consumption seen
 a reduction in craving reported in the fluoxetine
treated group.
(Gorelick and Paredes, 1992).
38

39. SERTRALINE
 Cohort study of 100 outpatients stratified for
presence or absence of a lifetime depressive
episode.
 beneficial effect of sertraline on alcohol
consumption in patients without a history of
depression, but not in those with previous
depressive episodes.
(Pettinati et al., 2001)
39

40. ONDANSETRON
 5-HT3 receptor antagonist.
 Two trials demonstrated some efficacy on
measures of drinking frequency and intake in
early-onset alcoholics
(Sellers et al., 1995; Johnson et al.,2000).
40

41. METADOXINE
 Accelerates elimination of alcohol from blood and
tissues
 Helps to restore functional structure of liver
 Dose: 500mg- 1g OD
 SE: diarrhea, rashes
41

42. COMBINATION THERAPY
 NALTREXONE AND ACAMPROSATE
 Naltrexone decreases positive craving for alcohol,
acamprosate attenuates conditioned craving post-
drinking cessation.
 Acamprosate can increase blood levels of
naltrexone, thereby augmenting its neurochemical
effects.
42

43. DISULFIRAM AND NALTREXONE/ACAMPROSATE
 • Disulfiram and Naltrexone/Acamprosate
prescribed together to increase the efficacy of
treatment.
 • Naltrexone/Acamprosate reduce alcohol craving
and Disulfiram adds an additional deterrent to
drinking.
43

44. HERBS
 Milk thistle (Silymarin)
 Kudzu root
 Dandelion
44

45. TREATMENT OF ALCOHOL WITHDRAWAL
SYNDROME
General principles:
 Careful monitoring and supportive care
 Correction of electrolyte imbalance
 Parenteral Thiamine (100 mg ) daily
 Detoxification with BZD.
 Restrict access to addicting substances
 Benzodiazepines are the main stay-safe and all
have equal efficacy in alcohol withdrawal
45

46. ACUTE ALCOHOL INTOXICATION
 Gastric lavage
 Maintain patent airway and prevent aspiration
 Tracheal intubation & positive pressure ventilation
 Maintain fluid and electrolyte balance
 Glucose infusion with thiamine
 Recovery can be hastened by haemodialysis
46

47. ALCOHOL WITHDRAWAL SEIZURES
 Mostly Grand mal seizures
 Usually 24-48 hours after last drink but may be
within 8 hours
 Increased risk if prior seizure
 More common in untreated alcoholics
47

48.  Should hospitalize if first seizure
 Need to be evaluated for other causes (eg, head
injury, CVA, or CNS infection, etc.) if first seizure or
history not clear
 Work up includes brain imaging and EEG
 1 in 4 patients have a second seizure within 6-12
hours
48

49. METHANOL
 Only of toxicological importance
 Added to industrial rectified spirit to render it unfit for
drinking
Poisoning:
 Vomiting, epigastric pain
 Headache, uneasiness
 Tachypnoea, dyspnoea
 Bradycardia, hypotension
 Delirium and seizures
 Retinal damage
49

50. Treatment:
 Keep patient in a dark room
 Gastric lavage with sodium bicarbonate
 Maintain ventilation and BP
 Ethanol(10% in water) 0.7ml/kg bolus and 0.15ml/kg /hr
 Haemodialysis hastens methanol clearance and recovery
 Fomepizole:
15mg/kg loading dose
followed by 10mg/kg 12th hourly till methanol falls below
20mg/dl
50

51. CONCLUSION
 The combination of both pharmacological and
psychosocial therapy is effective in management of
alcohol dependence.
 Consider a multidimensional approach
 Treat patient as a component of the society as a
whole, and not as a individual.
51

52. BIBLIOGRAPHY
 Goodman & Gilman’s The Pharmacological Basis of Therapeutics
 Rang and Dale’s pharmacology.
 Textbook of medical pharmacology - Dr.Padmaja Udaykumar.
 Essentials of medical pharmacology -K D Tripathi
 Understanding Alcohol - Glossary [online]. 2003. [cited 2005 Jul 13].
Available from URL:
http://science.education.nih.gov/supplements/nih3/alcohol/other/glossary.htm.
 Alcohol Use: Chronic Drinking [online]. 1992. [cited 2005 Jul 13]. Available
from URL: http://www.indicators.ak.org/indicators/alcoholusechronic98F.htm
 Johnston LD, O'Malley PM, Bachman JG, Schulenberg JE. Overall teen use
continues gradual decline; but use of inhalants rises. Ann Arbor (MI):
University of Michigan News and Information Services; December 21, 2004.
Table 3. [cited 2005 Jul 7). Available from URL:
http://www.monitoringthefuture.org/data/04data.html#2004data-drugs.
 Substance Abuse and Mental Health Services Administration. Overview of
Findings from the 2003 National Survey on Drug Use and Health. Rockville
(MD): Office of Applied Studies; 2004. p. 14. [cited 7 July 2005].
52

53.  Short-Term Effects of Alcohol . [cited 2005 July 22]. Available
from URL: http://www.hsc.wvu.edu/som/cmed/alcohol/short-
term.htm.
 Understanding Alcohol - Information about Alcohol. Teacher’s
guide. [online]. [cited 20 June 2005]. Available from URL:
http://science.education.nih.gov/supplements/nih3/alcohol/guide/i
nfo-alcohol.htm.
 Neuroscience for Kids - Alcohol. Alcohol [online]. [cited 2005 Jun
20]. Available from URL:
http://faculty.washington.edu/chudler/alco.html.
 HowStuffWorks. How Alcohol Works [online]. [cited 2005 Jun
20]. Available from URL:
http://www.science.howstuffworks.com/alcohol5.htm.
53

54.  Liv 52 - p-methoxy benzoic acid,
Chicory (Kasani) It is also a potent antioxidant,
54