17. Drug dependance Flashcards
What is meant by ‘addiction’?
Chronic disease
Characterised by drug seeking and use that is compulsive or difficult to control, despite harmful consequences
Define ‘drug abuse’
Pattern of drug use in which the users consume the substance in amounts or use methods which are directly or indirectly harmful to themselves or others
Define ‘drug dependence’
An adaptive state that develops after repeated drug use - results in withdrawal symptoms upon cessation of drug use
Define ‘drug tolerance’
The diminishing effect of a drug which results after repeated administration at a set dose
Define ‘psychological dependence’
Dependence that involves emotional and motivational withdrawal symptoms e.g. depression, anhedonia, restlessness
Define ‘physical dependence’
Dependence that involves significant physical-somatic withdrawal symptoms e.g. fatigue, nausea, seizures, pain
What is the effect of drug use on public health?
Has a major impact on public health due to hospital admissions and mental illness diagnoses resulting from drug abuse
What are the different legal classifications of drugs (illegal drugs)?
Name some drugs that fall into each category
Classes A to B: A represent those that are deemed most dangerous and carry the harshest legal consequences and C represent those thought to have the least capacity for harm
Class A - heroin, methadone, cocaine, crack cocaine, ecstasy, LSD, magic mushrooms
Class B - amphetamnes, barbiturates, ketamine, cannabis, codeine
Class C - anabolic steroids, benzodiazepines
What receptors do opiates act on and how?
Agonists to mu and delta opioid receptors
What receptors does cocaine act on and how?
Antagonist to Da, NAd and 5-HT uptake systems
What receptors do amphetamines act on and how?
Monoaminergic transmission uptake systems
What receptors does ethanol on and how?
Modulator of GABAa and NMDA receptors
What receptors does nicotine act on and how?
Agonist to nicotinic receptors
What receptors do cannabinoids act on and how?
Agonist to CB1 receptors
What receptors do ketamine act on and how?
Antagonist to NMDA glutamate (excitatory) receptors
What receptors do hallucinogens act on and how?
5-HT receptors
What receptors do barbiturates and benzodiazepines act on and how?
Positive allosteric modulators of GABAa receptors
Which organ is affected and undergoes change in addiction?
The brain
Which factors determine the development of addiction?
Environment e.g. social circle smoking?
Drug-induce effects
Genetics - ability of becoming addicted to a drug and of getting over the addiction
What is the dopamine pathway in the brain important for?
Which specific region is involved in this?
Dopaminergic pathways are important for the reward system e.g. the nigra striatum pathway
The ventral tegmental area (VTA) is responsible for the linkage of the dopaminergic fibres to the nucleus accumbens
What is the ventral tegmental area?
Aka. The ventral tegmentum is a group of neurones located close to the midline on the floor of the midbrain
This is the origin of dopaminergic cell bodies
Describe and explain the addiction cycle
Addicts go through cycles and cycles - addiction is chronic
Stage 1 - Binge/Intoxication - exposure to the substance brings you pleasure - the positive reinforcement makes you feel good
Stage 2 - Withdrawal/negative affect - the substance stops and washes away from the system - you feel awful and there is a stage of withdrawal from the experience - negative reinforcement of not taking the drug
Stage 3 - Preoccupation and anticipation - become preoccupied with how you can start to feel the pleasurable experience again and this takes you back to stage 1
Give the cellular mechanisms that underlie why over time, people feel a need to increase their drug dosage
The drug results in dopaminergic release onto the dopamine receptors at the nucleus accumbens - neurones from here project straight back to the ventral tegmentum in a complete circle and they release GABA here
This results in a inhibition of the initial dopaminergic release to the accumbens neurones - simple mechanism of negative feedback
The GABA release will attempt to dampen down the activity of the dopaminergic cells and so the dosage required for the same hit will need to increase
Name all the regions of the brain that are affected by addiction
Ventral tegmental area Nucleus accumbens Amygdala Insula Prefrontal cortex Hippocampus
All these regions become dysfunctional in an addicted brain - the connectivity becomes distorted
What is the main region of the brain that is effected in addiction and what is it’s normal function?
Prefrontal cortex
Self-control !! Emotional regulation Motivation Attention and flexibility Working memory Decision making Awareness and insight Learning and memory Salience attribution
Chronic drug abuse and gene regulation
Get from mimi
What effect does alcohol have on the brain and why is this different to most other drugs?
Alters the excitability of NMDA (glutamate) receptors and also can change the influx of Cl- ions through GABAa receptors and SO it can modulation both excitatory and inhibitory conditions - makes it such a powerful drug
NB. alcohol abuse has both an acute effect spectrum and can also lead to long term consequences
What is the effect of alcohol on the size of the brain?
Alcohol abuse has also shown to lead to a shrinkage of the rain - leads to 12% less grey matter
What are the neuronal targets of ecstasy (MDMA)?
5-HT uptake system Dopamine uptake system 5-HT2 receptors H2 histamine receptors a2 adrenergic receptors
There is also a loss of serotonin fibres and an overall loss of serotonin innervation
Results in a pleasure sensation and an increased energy
Which receptors do cannabinoids bind to and where are they located?
CB1 (g-protein coupled receptor) and CB2 receptors
CB1 - CNS
CB2 - peripheral organs and are associated with the immune system
Cannabinoids are mainly inhibitory
What are the key stages in the management of addiction?
Detoxification of the drug from the body
Psychological support i.e. counselling
Medication when available e.g. for opioids, tobacco, alcohol
Evaluation and treatment for co-occuring mental health problems
Long term follow up
What medication can be used to treat alcohol addiction?
Opiate antagonist nalmefene
What medication can be used to treat nicotine addiction?
Varencline - a2B2 selective partial agonist at nicotine receptors
