Week 3- Neurobiology of addiction and alcohol misuse Flashcards
Describe the ICD-10 criteria of dependence?
A strong desire to take the substance Difficulties in controlling substance use A physiological withdrawal state Tolerance Neglect of alternative pleasures Persistence despite evidence of harm
What acronym is used for diagnosing addiction? What does it mean?
CAGE
C- cut down- have you ever felt you should cut down your drinking/whatever?
A- annoyed-have people annoyed you by criticising your drinking?
G- guilty-have you ever felt guilty about your drinking?
E-eye opener-have you ever had an eye opener (e.g. a drink in the morning to get you to wake up)
When you experience a rewarding stimulus, what occurs in the brain?
Information travels from the ventral tegmental area and travels through the nucleus accumbens to the prefrontal cortex.
Which pathway is involved in normal pleasurable experiences? Which neurotransmitter is involved?
Mesolimbic pathway.
Dopamine
What effect does the mesolimbic pathway have on behaviour?
A motivating signal and it incentivises behaviour (gives you incentive to do it).
Can you develop a tolerance to reward?
Yes- proven by gambling addicts vs non-gambling addicts
Non-gambling addicts received more blood flow to the striatum when they won than gambling addicts showing a build up of tolerance.
what happens to dopamine receptors in the brain during addiction?
Dopamine D2 receptors decrease during addiction. This is due to repeated dopamine release causing them to down-regulate.
What is positive reinforcement and negative reinforcement?
In the initial stages of taking the drug- you feel great- positively reinforcing the decision you’ve made.
However after the initial stages have worn off, you feel pretty crap and you need the drug again- negative reinforcement.
What is the role of the prefrontal cortex in addiction?
Helps intention guide behaviour
Modulates the effects of the reward pathway
Sets goals and focuses attention
Makes sound decisions
Keeps emotions and impulses under control to achieve long term goals.
How does the cortex mature?
Cortical maturation occurs in a back to front direction- starting in the primary motor cortex and then working its way to the prefrontal cortex.
Frontal lobe areas that mediate executive functioning mature later than limbic (emotional) systems.
What does dopamine release effect in the prefrontal cortex?
The ability to update information in the PFC
Ability to set new goals
Ability to avoid compulsive repetition of a behaviour.
The earlier the age the drug experimentation starts, the longer the relationship with drugs. True or false?
True.
What is the striatums role in addiction?
Habit-learning
What is the hippocampus’s role in addiction?
Declarative learning
What does the orbitofrontal cortex do?
Decides the importance of events and attaches a value to it. Its the key creator of motivation.
Describe the orbitofrontal cortex in addiction?
Addicts have increased activation of the orbitofrontal cortex when presented with drug cues. Hyperactivity of the OFC correlates with craving the drugs.
How can stress affect addiction?
Stress triggers dopamine pathways.
Rapid increase in these can motivate drug seeking in dependent individuals
Chronic stress can lead to dampening of dopaminergic activity through down regulation of D receptors
This reduces the sensitivity to normal rewards
Encourages exposure to highly rewarding behaviours.
SUMMARY NOTE
- Reward pathway involved in incentive salience
- Overstimulation leads to desensitization
- Pre frontal cortex puts the brakes on the reward pathway
- Pre frontal cortex matures late and is vulnerable whilst developing
- Pre frontal cortex dysfunctional in addicted people
- Hippocampus/amygdala/HPA axis also implicated in the development of addiction
How can you calculate units in alcohol?
10
e.g. 750ml of 40% =
750 x 0.4 divided by 10=30 units
When are you at high risk (in terms of units of alcohol consumed per week)?
Over 35 units per week.
When are you at increased risk (in terms of units of alcohol consumed per week)?
Regularly consuming between 15 and 35 units a week.
Define harmful use of alcohol?
A pattern of psychoactive substance use that is causing damage to health. The damage may be physical or mental.
What is alcohol dependence syndrome?
A strong desire or sense of compulsion to take a drug. Difficulty controlling use of substance in terms of onset, termination and level of use.
Physiological withdrawal state
Evidence of tolerance
Progressive neglect of other pleasures/interests because of the use of the substance
Persistence of use despite evidence of harmful consequences
What role do laboratory tests have in the detection of alcohol misuse and which tests are there?
Not really a big role.
Test GGT- for indication of liver injury
Carbohydrate deficient transferin- identifies men who drink greater than 5 units a day for two weeks
Mean corpuscular volume- alcoholism is the most common cause of raised MCV.
What does FRAMES stand for?
F- feedback- review problems experienced because of alcohol
R- responsibility- its the patients responsibility to change
A- advice- advise reduction or abstinence
M-menu- provide options for changing behaviour
E-empathy-use empathetic approach
S-self efficacy- encourage optimism about changing behaviour.
How long should brief interventions in alcoholism last?
5-15 minutes.
When should you consider referral for specialist treatment in alcohol abuse?
Show signs of moderate or severe alcohol dependence
Have failed to benefit from structured, brief advice and an extended intervention. They must wish to tackle the issue.
Show signs of severe alcohol-related impairment or co-morbid condition.
What is detoxification?
The process by which patients become alcohol free
What is relapse prevention?
A combination of psychosocial and pharmacological interventions aimed at maintaining abstinence or problem free drinking without detoxification.
What effects does alcohol have on the body (in terms of receptors and pathways)?
It exhibits the action of excitatory NMDA-glutamate controlled ion channels
It potentiates the action of inhibitory GABA type A controlled ion channels.
What effect does alcohol withdrawal have on the body (in terms of receptors and pathways)? What does this cause?
Leads to excess glutamate activity and reduced GABA activity.
Excess glutamate activity is toxic to the nerve cells. Withdrawal of alcohol too quickly leads to CNS excitability and neurotoxicity.
How does alcohol withdrawal syndrome present?
Restlessness, tremor, sweating, anxiety, nausea, vomiting, loss of appetite and insomnia.
Also tachycardia and systolic hypertension present.
Generalised seizures and delirium can occur in the first 24 hours.
When do the symptoms of alcohol withdrawal syndrome present?
usually start in the first few hours and resolve after 5-7 days.
Symptoms are at their worst at 24-48 hours.
What is delirium tremens?
Often presents insidiously with night time confusion.
You get confusion, disorientation, agitation, hypertension, fever, visual and auditory hallucinations, paranoid ideation.
When does delirium tremens present?
Peak onset is within 2 days of abstinence.
How do you manage alcohol withdrawal?
General support- give the patient reassurance and advice
Benzodiazepines- cross tolerant with alcohol (work on GABA A receptors). Need to titrate against severity of withdrawal symptoms. Reduce gradually over 7 days or more.
Vitamin supplementation- thiamine as prophylaxis against Wernickes encephalopathy (must be parenteral). Increase dose if wernickes is suspected.
NOTE- additional measures in managing alcohol withdrawal?
Adequate hydration
Analgesia
Treat intercurrent infections and other physical conditions
Environmental factors
Where do patients undergo detoxification?
Majority are done in the community.
When would you have someone as an inpatient undergoing detoxification?
Severe dependence A history of delirium tremens or alcohol withdrawal seizures History of failed community detoxification Poor social support Cognitive impairment Psychiatric co-morbidity Poor physical health madeleine pitcathley
What psychosocial interventions can stop relapse into alcohol addiction?
CBT Motivational enhancement therapy 12 step facilitation therapy Behavioural self control training Family and couple therapy
What pharmacological therapy can stop relapse in alcohol addiction?
Disulfiram (Antabuse)
Acamprosate
Naltrexone
How does disulfiram work?
It inhibits acetaldehyde dehydrogenase leading to accumulation of acetaldehyde if alcohol is ingested.
It leads to flushed skin, tachycardia, nausea and vomiting, arrhythmia and hypotension depending on the volume of alcohol consumed.
However efficacy requires compliance.
How does acamprosate work?
Acts centrally on glutamate and GABA systems and reduces cravings.
Should be started as soon as detoxification is complete.
Side effects of acamprosate?
Headache, diarrhoea, nausea
How does naltrexone work?
Opioid antagonist sna reduces reward from alcohol
What is the first line agent in relapse prevention for alcohol?
Naltrexone.
