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Flashcards in Alcohol and Addiction Deck (41)
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Define dependence.

The physical and/or psychological effects produced by the habitual taking of certain drugs, characterised by a compulsion to continue taking the drug


Define physical dependence.

Dependence in which withdrawal of the drug causes specific symptoms, such as sweating, vomiting or tremors, that are reversed by further doses


Define psychological dependence.

Dependence in which repeated use of a drug induces reliance on it for a state of wellbeing and contentment, but there are no physical withdrawal symptoms if use of the drug is stopped


Define addiction.

A state of dependence produced either by the habitual taking of drugs or by regularly engaging in certain activities (e.g. gambling)


Define tolerance.

The reduction or loss of the normal response to a drug or other substance that usually provokes a reaction in the body


List the criteria needed to diagnose dependence/addiction.

1. Strong desire/compulsion to take the drug
2. Loss of control over substance-taking behaviour (e.g. onset, termination, levels of use)
3. Physiological withdrawal state
4. Tolerance
5. Progressive neglect of other pleasures/interests
6. Persistent use despite awareness of overt harmful effects
7. Narrowing of repertoire


Describe the causes of dependence/addiction to alcohol.

1. Excessive/long term use of drug

2. Genetics
a. If parents are alcoholics, child has x4 increased risk
b. Heritability of alcoholism: 0.3-0.6

3. Environmental factors
a. Socioeconomic status
b. Culture/customs relating to alcohol use
c. Peer behaviour
d. Religion
e. Employment status
f. Parental influence


Describe the signs and symptoms of dependence/addiction.

1. Not meeting obligations/responsibilities
2. Ceasing social/recreational activities
3. Increased criminality
4. Increased risk taking
5. Problems at school/work
6. Neglected appearance
7. Behavioural changes
8. Somatic problems, e.g.
a. Lack of energy
b. Lack of motivation
9. Drug specific signs and symptoms


Describe the features of withdrawal.

1. May be substance specific

2. Psychological disturbances, e.g.
a. Anxiety
b. Depression
c. Sleep disorders

3. Physical symptoms, e.g.
a. Tremor
b. Convulsions
c. Sweating

4. Symptoms are relieved by further substance use


What is the underlying mechanism of all types of addiction?

Neurophysiological reinforcement (reward) involving the mesolimbic pathway

Location: ventral tegmental area --> forebrain (especially nucleus accumbens)


How do stimulant drugs cause addiction?

Give 3 specific examples of the mechanisms by which this occurs.

Increased activation of the mesolimbic reward pathway

1. Inhibits monoamine reuptake
2. Therefore there is more dopamine in the synapse, so the reward pathway is constantly stimulated
3. Chronic use alters receptor sensitivity, making them less sensitive – this causes tolerance

1. Stimulates release of dopamine and NA
2. Blocks reuptake of dopamine and NA
3. Therefore there is more dopamine in the synapse, so the reward pathway is constantly stimulated

1. Binds and activates nicotinic acetylcholine receptors in reward pathway neurons
2. This causes opening of Na+ channels, which causes depolarisation
3. Therefore the reward pathway is stimulated


How do depressant drugs cause addiction?

Name one specific example.

Depressant drugs cause decreased activation of this pathway, BUT this causes:

1. Upregulation of excitatory (glutamate) receptors in the pathway
a. This means there is increased stimulation in absence of the drug (which then causes withdrawal symptoms)

2. Downregulation of inhibitory (GABA) receptors in the pathway
a. This means there is less inhibition, and the pathway is activated more



How does alcohol cause addiction?

1. Stimulates release of dopamine from the ventral tegmental area – this activates the reward pathway

2. Acute alcohol use inhibits glutamate receptors, and stimulates GABA receptors, causing an overall inhibitory effect
a. Alcohol acts on the GABA alpha receptor, which causes Ca2+ channels to open
b. This causes hyperpolarisation of neurons in the reward pathway
c. Therefore the pathway is not activated

3. Chronic alcohol use causes neuroplasticity
a. Upregulation of glutamate receptors increases the excitability of neurons
i. Therefore more glutamate receptors are stimulated and the pathway is activated
b. Downregulation of GABA receptors decreases the inhibition of neurons
i. Therefore neurons are no longer inhibited as much, and the pathway is activated
ii. NOTE: this causes tolerance


List the drugs which might be used to manage alcohol addiction.

Briefly describe the mechanism of action.

1. Disulfiram
a. Mechanism of action: blocks metabolism of alcohol by inhibiting the conversion of acetaldehyde into acetate (this leads to the build-up of acetaldehyde, which is toxic)
b. This results in many systemic effects, e.g.

2. Naltrexone
Mechanism of action: opioid antagonist (inhibits the reward pathway)
b. Can be started in patients who are still drinking

3. Nalmefene
a. Mechanism of action:
---Opioid antagonist (inhibits the reward pathway)
---Competitive antagonist at the mu opioid receptor (inhibits the reward pathway)
b. Should be administered on days where the patient thinks they are likely to consume alcohol

4. Acamprosate
a. Mechanism of action: stabilises glutamate and GABA systems

5. Benzodiazepines
a. Improve withdrawal effects


List recommended drinking levels for:

a) Men
b) Women
c) Pregnant women
d) Driving

Men: 14 units/week (3-4 units per day)

Women: 14 units/week (2-3 units per day)

Pregnant women: no safe amount - should avoid alcohol altogether

Legal driving limit: 50mg alcohol per 100ml blood (NOTE: in England/Wales, it's 80mg)


What is the definition of 1 unit of alcohol?

10ml of absolute alcohol OR 8g of absolute alcohol


How is the alcohol content of a drink calculated?

Alcohol content = % ABV x 0.78


How is the absolute alcohol content of a drink calculated?

Absolute alcohol = (% ABV x volume (ml)) / 1000


List the 3 pathways of alcohol metabolism.

1. Alcohol dehydrogenase (ADH) pathway
a. Location: cytosol
b. Function of ADH: catalyses the conversion of ethanol to acetaldehyde
c. There may also be some ADH in gastric mucosa (but the importance of this is debated)

2. Microsomal ethanol oxidising system (MEOS)
a. Location: smooth endoplasmic reticulum
b. Function of MEOS pathway: catalyses the conversion of ethanol to acetaldehyde via the action of CYP3E1
c. Small role when there are only low ethanol concentrations
d. Increased role in chronic alcohol abuse (up to 10%)

3. Catalase pathway
a. Location: peroxisomes


Describe the metabolism of alcohol.

1. Ethanol is converted to acetaldehyde via ADH
a. Aided by CYP2E1

2. Acetaldehyde is converted to acetate via ALDH (acetaldehyde dehydrogenase)
a. There are 2 isoforms of ALDH – mitochondrial ALDH2 is the most important

3. Acetate is converted to CO2 and H2O via the Krebs cycle etc., which is then excreted


What is the rate limiting step of alcohol oxidation?

Dissociation of the NADH-NAD enzyme complex (needed for ADH to oxidise ethanol)


What is the rate of alcohol elimination in the urine/breath?



Describe the social effects of alcohol.

1. Increased crime and antisocial behaviour
2. Single biggest risk factor for suicide
3. Breakdown of families
4. Loss of work
5. Health inequalities
6. Impaired interpersonal relationships
7. Domestic violence


When is the foetus most vulnerable to alcohol?

4-10 weeks


What are the risks of alcohol during pregnancy?

1. Spontaneous abortion
2. Foetal alcohol syndrome


Describe the features of foetal alcohol syndrome.

1. Pre- and post-natal growth retardation

2. CNS abnormalities
a. Microcephaly
b. Agenesis of corpus callosum
c. Cerebellar hypoplasia
d. Mental retardation
e. Irritability
f. Hypotonia
g. Incoordination
h. Hyperactivity

3. Craniofacial abnormalities
a. Short palpebral fissures
b. Epicanthic folds
c. Smooth philtrum
d. Thin upper lip
e. Mid-facial hypoplasia
f. Lower jaw hypoplasia
g. Short upturned nose
h. Minor ear abnormalities
i. Ptosis

4. Associated abnormalities, including congenital defects of:
a. Cardiovascular system
b. Skeletal system
c. Genitourinary tract
d. Ocular tract
e. Auditory system


Describe the effects of acute alcohol use on the body.

1. Social effects:
a. Elation
b. More talkative
c. Loss of social inhibition

2. Functional impairment:
a. Slurred speech
b. Unsteadiness
c. Drowsiness
d. Reduced motor function

3. Autonomic effects:
a. Flushing of skin
b. Pupil dilation
c. Tachycardia

4. Cognitive impairment:
a. Decreased reasoning
b. Impaired memory
c. Reduced perception
d. Easily distracted

5. Psychological effects:
a. Feelings of enhanced ability
b. Loss of emotional restraint – i.e. become more emotional


List some acute physical consequences of alcoholism.

1. Accidents
2. Aspiration pneumonia
3. Oesophagitis
4. Gastritis
5. Pancreatitis
6. Arrhythmias
7. Cerebrovascular accidents


List some chronic physical consequences of alcoholism.

1. Systemic:
a. Accidents
b. Systemic hypertension

2. GI system:
a. Malabsorption
b. Malnutrition
c. Pancreatitis

3. Liver:
a. Fatty liver
b. Hepatitis
c. Cirrhosis

4. Cardiovascular system:
a. Systemic hypertension
b. Cardiomyopathy
c. Coronary heart disease

5. Brain damage
a. Dementia
b. Wernicke-Korsakoff syndrome
c. Cerebellar atrophy
d. Central pontine myelinolysis

6. Musculoskeletal system:
a. Osteoporosis

7. Nerves:
a. Peripheral neuropathy

8. GU system:
a. Infertility
b. Sexual dysfunction


Briefly list the factors contributing to the pathophysiology of alcoholic liver disease.

1. Acetaldehyde production
2. Acetate production
3. Increased NADH/NAD ratio
4. Non-oxidative metabolism
5. Reactive oxygen species (ROS) production
6. Increased intestinal permeability
7. Production of IL-8 by hepatocytes