Drug Dependency Flashcards
Define addiction
Chronic disease characterised by drug seeking
Compulsive and difficult to control despite harmful consequences
Define drug abuse
Pattern of drug use in which individual is using methods/amounts of substance which directly/indirectly harm themselves and/or others
Define drug dependence
Adaptive state that develops after repeated drug use (withdrawal symptoms)
Define psychological dependence
Dependence involving emotional/motivational withdrawal symptoms (e.g. depression/restlessness/dysphoria)
Define physical dependence
Dependence involving significant physical-somatic withdrawal symptoms (e.g. fatigue/nausea/seizures/pain)
Which drugs are the most harmful?
Alcohol
then heroin, crack cocaine, meth
What do opiates target?
Mu and delta opoid receptors
What does cocaine target?
DA (dopamine) , NAd (noradrenaline) and 5-HT uptake systems, inhibiting them
What does amphetamine target?
monoaminergic transmission amplifier: uptake systems, agonist of trace amine associated receptor 1
What does ethanol target?
GABA and NMDA receptors (glutamate) modulating both excitatory and inhibitory systems in the brain
What does nicotine target?
nicotinic receptors
What do cannabinoids target?
CB1 receptors
What do phencyclidine and ketamine target?
NMDA glutamate receptors
What do hallucinogens target?
5-HT2A receptors
What do barbiturates and benzodiazapines target?
- GABAa receptors
What 3 factors determine addiction development?
- environment
- drug induced effects (pleasant/unpleasant, in pleasure there is a decrease in the occupancy of dopamine receptors)
- genes (polymorphisms in the opoid MU, kappa and delta receptors)
What are the 3 stages of the addiction cycle?
- binge/intoxication (positive reinforcement)
- withdrawal/negative affect (negative reinforcement)
- preoccupation/anticipation (conditioned positive and negative)
What are the core clinical symptoms of addiction?
Intoxication
bingeing
withdrawal
craving
What is the withdrawal mechanism?
- acutely dopamine from the VTA stimulates the nucleus accumbens (reward system) causing pleasure
- nucleus accumbens projection neurons releasing transmitters on the VTA’s kappa opoid receptors and act as regulatory break
- drug abuse inhibits VTA = dopamine release reduced = dysphoria
What is the VTA?
ventral tegmental area
origin of dopaminergic cell bodies, mesocorticolimbic dopamine system and other dopamine pathways
natural reward circuitary of the brain
What is the mechanism of drug dependence?
- involves excitatory amino acids and dopamine
- when you crave the drug you know there are certain activities you need to get it so gives rise to planning of taking the drug making your a brain a slave to impulse
- also reduced availability of D2 receptors and reduced metabolism
What structures are involved in drug dependence?
- involved in craving/planning/taking:
VTA, nucleus accumbens, amygdala, insula, PFC, hippocampus
What is the mechanism of neuroplasticity in drug-seeking behaviour?
More dependent you become = more compulsive/uncontrolled you are to take it
- loss of control over various CNS structures
What changes are there to the prefrontal cortex in addiction?
impaired processes associated with PFC:
- self control and motivation
- emotional regulation
- attention and flexibility
- working memory
- decision making
- awareness and insight
- learning and memory
- salience attribution
How is chronic drug abuse related to gene regulation?
- addiction changes gene expression throughout the brain
- increased expression of FosB gene
What is the alcohol consumption indicative of abuse?
Regular consumption of:
M - 5 units a day
W - 3 units a day
What are signs of acute alcohol intoxication?
Euphoria followed by depressed mood, slurring of speech, ataxia, general incoordination, pupillary dilatation
Modulates the activity of pharmacological targets - depressed excitatory transmission and potentiates inhibitory transmission
What are the long term consequences of alcohol abuse?
- gastritis, peptic ulcer disease, oesophageal varices, pancreatitis
- shrinkage of grey matter in alcoholic patients
What does MDMA target?
5-HT uptake system dopamine uptake system 5-HT2 receptors H2 receptors Alpha2 adrenergic receptors
What mediates behavioural actions of MDMA?
5-HT release:
- psychomotor effects: repetitive movements, hyperlocomotion (mediated by 5-HT and 5-HT1B receptor)
- temperature effects
What are the effects of acute MDMA toxicity?
- temperature elevation
- hyponatremia
- cerebral oedema
- increased renal absorption of water
- rhabdomyolysis (muscles breaking down and blocking kidneys)
What is the main agonist of cannabis/
THC - tetrahydrocannabinol
What do cannabinoids bind to?
CB1 and CB2 receptors
What are the properties of CB1 receptors?
- concentrated in the CNS
- most abundant GPCR in mammalian brain
What are the properties of CB2 receptors?
- in peripheral organs
- associated with the immune system
What is the mode of action of cannabis?
Produce inhibitory effects by inhibiting glutamate and GABA pre-synaptically
What are the risks of cannabis?
- LT use = increased risk of schizophrenia and major depression
- acts as a gateway drug
- related to depression, memory problems and paranoiea
What are the forms of cannabis?
- inhaled
- THC/donabinol
- cannabidiol
- nabilone
- sativex and cannador
Which drugs target alcohol addiction?
- benzodiazapines
- AED (carbamazepine)
- accamprosate
- naltrexone
- disulfiram
- SSRIs
- thamine
- malmefene
What is the mechanism of benzodiazepines?
direct GABA agonist
What is the mechanism of carbamazepine?
GABA promoter
What is the mechanism of accamprosate?
Effect of glutamate receptors reducing withdrawal related neuronal excitation
What is the mechanism of naltrexone?
Opoid agonists
What is the mechanism of disulfiram?
Aldehyde dehydrogenase inhibitor allowing build up of aldehyde (makes people feel bad)
What are the indications for benzodiazepines?
withdrawal symptoms
seizures (prevention/treatment)
delirium (prevention/treatment)
What are the indications for carbamazepines?
withdrawal symptoms
seizure prevention
What is the indication for accamprosate?
Maintenance of abstinence
What is the indication for naltrexone?
Maintenance of abstinence
What is the indication for disulfiram?
Maintenance of abstinence
What is the indication for SSRIs?
Maintenance of abstinence
Treatment of co-morbid depression
What is the indication for thiamine?
Prevention of neurological symptoms
Treatment of Wernicke’s encephalopathy
What is the indication for nalmefene?
For reduction of alcohol consumption
Which drugs target nicotine addiction?
Nicotine replacement therapy - nicotine agonist
Bupropion
Varencicline
What is the mechanism of bupropion?
Monoamine (especially dopamine) reuptake inhibitor
What is the mechanism of varencicline?
Alpha-4-Beta-3 selective partial agonist of nicotinic receptors
What are the indications for nicotinic replacement therapy?
Smoking cessation
What are the indications for Bupropion?
Smoking cessation
What are the adverse effects of varencicline?
Nausea
Psychiatric disturbances
Which drugs target opoiate addiction?
Methadone opoid agonis
Buprenorphine
Clonidine and Lofexidine
Naltrexone
What is the mechanism of methadone?
opoid agonist
What is the mechanism of buprenorphine?
Opoid MU receptor partial agonist, kappa antagonist
What is the mechanism of clonidine and lofexidine?
Alpha 2 adrenoreceptor agonists
What are the indications of methadone opoid agonists
Withdrawal symptoms
What are the indications of buprenorphine?
Withdrawal symptoms
What are the indications of clonidine and lofexidine?
Withdrawal symptoms
What are the indications for naltrexone?
Relapse prevention in selected patients
