Lecture 17: Alcohol Dependence

Question 1

What is alcohol?

Answer 1

A by product of the fermentation of various fruits and grains.

Fat and water soluble, readily diffuses across all cell membarines, peak blood levels are within 30-60mind

> 0.15% - significant impairment of balance, slurred speech, nausea, vomiting

> 0.30% = loss of consciousness, anaesthesia

Easier to measure alcohol expired through respiration brreathalyzer (estimates blood alcohol concentration by analysing a sample of the breath which contains alcohol passed from blood stream into the lungs

Question 2

What is alcohols mechanism of action?

Answer 2

Agonist effect on GABA receptor - increased bindiong or influx of chlorine - a CNS depressant

GABA synapses control activity of different neuronal systems - glutamate, dopamine, opiods

Very low concnetrations <0.1nM = inhibit GABA receptor, impaired neuronal transmission so impaired brain function

Concentration > 1mM = activation of GABA receptor, inhibits glutamate/ NMDA receptor, leads to impaired neuronal transmission and impaired brain function

Question 3

What does sustained/ chronic use of alcohol lead to?

Answer 3

Peripheral neuropathy and dementia caused by alcohol toxicity and vitamin B6 (thiamine) deficiency (specific midbrain)

Alcohol prevents conversion of thiamine to TPP in small intestine and interferes with its storage in the liver.

This leads to sleep disdurbance, depression or anxiety, and overall malnourishment.

Question 4

What is thiamine?

Answer 4

Thiamine is stored in the liver and absorbed in the duodenum, where it moves through the body. It is involved in multiple cellular processes.

Thiamine is converted to thiamine pyrophosphate (TPP) - the metabollically active form.

Question 5

What is wernickes encephalopathy?

Answer 5

Confusion
Ophthalmoplegia
Ataxia
Thiamine deficiency

Question 6

What is Korsakoff syndrome?

Answer 6

Retrogade amnesia
Anterograde amneisia
Confabulation
Korsakoff syndrome

Question 7

What are the risks of further harm from alcohol?

Answer 7

• Accidental injury
• Sexual misdemeanours
• Violence
• CV disease
• Liver disease
• Cancers

Question 8

What is the alcohol withdrawal timeline?

Answer 8

Stage 1 - 8 hours - anxiety, insomnia, nausea, abdominal pain

Stage 2 - 1-3 days - high blood pressure, increased body temperature

Stage 3: 1 week - hallucinations, fever, seizures and agitation

Question 9

What is the Treatment of alcohol withdrawal?

Answer 9

• BDZs : similar mechanism of action to alcohol, diminish the severity of the symptoms as neuronal systems begin to revert back to pre alcohol states
• Chlordiazepoxide (CDP) used- long acting, prescribed on a reducing dosage regime over 5-7 days. Starting dose based on symptom severity i.e 60-100mg/day.
• Diazepam most often used- reduce by 1/6 of total dose per week – Usually by specialist services (might have patient in general medicine ward/community detox).

Question 10

What is used to Maintain abstinence?

Answer 10

acamprosate, disulfiram, naltrexone, nalmefene - BUT also high placebo effect if engaging with any health professional and joining support groups (AA).

Disulfiram has limited efficacy but thrice weekly supervised consumption may be superior to unsupervised daily acamprosate

Acamprosate and naltrexone both reduce the risk of returning to drinking but high Numbers Needed to Treat

Question 11

What is disulfiram?

Answer 11

Irreversibly inhibits aldehyde dehydrogenase causing accumulation of acetaldehyde – sweating, nausea, facial flushing, tachycardia, hypotension.