Addiction Flashcards
Define addiction.
Relapsing-remitting disorder comprising behaviours that are performed in a compulsive manner in spite of the potential for self-harm
What is dependence?
Characterised by a state of withdrawal when the substance of abuse (e.g. drugs or gambling) is removed
What are the 3 types of behaviours associated with dependence?
- Drug-seeking/craving: anticipation of obtaining/taking a drug prior to use
- Binging/intoxication: taking substance, highs + issues of tolerance/dependence
- Withdrawal: -ve effects of removal of drug/not taking drug
What are the 2 types of dependence?
- Psychological: need to keep performing compulsive behaviours characterised by emotional distress on stopping
- Physical: need for functional effect of drug on body characterised by physical withdrawal symptoms
What is tolerance?
Requirement for increasing amount of drug/behaviour to elicit same level of +ve reinforcement (‘high’) as that experience during previous exposures to the substance/behaviour
What are the 3 different types of tolerance?
- Acute: repeated exposure to drug in short period of time e.g. cocaine high decreases in 1 night
- Chronic: constant exposure over prolonged period of time e.g. opioids
- Learned: frequent exposure to substance becomes integrated into normal behavioural routines e.g. alcohol
What is withdrawal?
Prolonged and painful process as an effect of removing substance/object of dependence but NOT the same as ‘crash’ when +ve effects wearing off and you get rebound dip in mood/behaviour - termed detoxification or detox when performed actively
Why does a crash occur?
Occurs before plasma drug levels drop so it not directly related to decreasing drug activity, it is due to changes in regional neuronal activation once the high occurring in striatum, thalamus, nucleus accumbens and cortical regions begins to subside, other areas (e.g. striatum + extended amygdala) involved in -ve aspects become more dominant
What are some common withdrawal symptoms?
Psychological: confusion, anhedonia, headache and fatigue
Physical: tachycardia, tachypnoea + tremor
What is Post-Acute Withdrawal Syndrome (PAWS)?
Symptoms experienced after prolonged period of withdrawal occurring a couple of months following initial withdrawal predominantly causing psychological effects rather than physical in acute stage e.g. insomnia, mood swings, anxiety + anhedonia
What brain areas are involved in dependency and their associated behaviours?
mPFC + orbitofrontal cortex + hippocampus: preoccupation, craving, conditioned cues + anticipation
Amygdala, BNST + ventral striatum (inc. n. accumbens): -ve emotions, dysphoria, malaise + withdrawal
Thalamus, dorsal striatum + GP: reward, binge, intoxication, euphoria + habit
What is the cycle of addiction/dependence?
- Binge occurs following a period of salience
- Anticipation then occurs followed by executive function
- Executive function causes neuroadaptation such as circuit, synaptic
+ molecular changes - Stress occurs followed by withdrawal after
What 3 key factors influence whether a person is more or less likely to become dependent?
- Genetics (polygenic inheritance)
- Environment e.g. in utero or personal choice
- Route of administration (injection > inhalation > snorting > ingestion)
What is nicotine?
A substance that acts both centrally in brain and peripherally in the autonomic ganglia via nicotinic cholinergic receptors acting as a stimulant and relaxant - PARASYMPATHOMIMETIC
What does nicotine do?
Stimulant effect: release of ACh, NA and A via ANS
+ve mood and addictive qualities: endorphins, DA + 5-HT - cognitive enhancement + increase in fine tuning of movement thought to provide +ve reinforcement underpinning addiction
What pharmacological interventions are used to increase smoking cessation adherence?
- NRT
- Bupropion: atypical AD
- Varenicline: partial agonist at nicotine receptor (some link to increases suicidal thoughts so requires monitoring)
What is thought to cause the general depressant effect of alcohol (reversed effects in chronic use)?
- Enhanced GABA activity
- Inhibition of glutamatergic NMDA receptors
- Inhibition of VDCC
What quick screening tool can be used for potential alcohol misuse?
Alcohol Use Disorder Identification Test (AUDIT) - a score of > 5 is +ve
What are the clinical features associated with fetal alcohol syndrome?
Low nasal bridge Epicanthal folds Short nose Ear abnormalities Flat mid face Absent philtrum Thin upper lip Growth/cognitive retardation Irritability Hyperactivity Poor impulse control/coordination Heart defects
What is opioid dependence associated with?
Decrease in µ-receptor and increase in κ-receptor (δ responsible for psychoactive effects)
What 2 opioids are licensed for use in maintenance therapy for opioid addiction?
- Methadone (T1/2 = 24hrs): µ-receptor agonist
- Buprenorphine (T1/2 = 12hrs): partial agonist at µ-receptor but antagonist/partial agonist at κ-receptor - less sedative
Which drug can be used to prevent relapse in both opioid and alcohol dependence?
Naltrexone - reduces ‘highs’ in both
How is caffeine (a methylxanthine) thought to work as a stimulant?
Mainly:
1. A2A adenosine receptor antagonist (neuroprotective)
Other:
- Increased NA transmission increasing arousal, vigilance + reducing fatigue
- Increased release of Ca from IC stores + subsequent 2nd messenger cascades
Why can you get a headache upon caffeine withdrawal?
Linked to changes in cerebral blood flow induced by caffeine used where caffeine usually will cause an increased cerebral activity associated with a REDUCED cerebral blood flow
What does the stimulant cocaine do?
Prevent reuptake of monoamine neurotransmitters via the MAT with indirect sympathomimetic properties due to effect of 5-HT/NA modulation of autonomic thermoregulation centres in hypothalamus and outflow to brainstem - 5-HT > DA > NA
How do the stimulant amphetamines (e.g. Ritalin) work?
Increase monoamine release by acting intracellularly on VMAT and reverse MAT to an extent increasing amount of monoamines in synaptic cleft - NA > DA > 5-HT
What tranquilisers are commonly drugs of abuse?
- BZDs: γ GABA receptor +ve allosteric modulator
2. Barbiturates: β GABA receptor +ve allosteric modulator
What are psychotomimetics?
Drugs that generally cause changes in perception and sensory distortion e.g. hallucination but do not cause physical dependence or addiction to extent of other drugs
What are the 2 groups of psychotomimetics?
- 5-HT acting e.g. LSD, mescaline + MDMA
2. NMDA glutamate receptor acting e.g. PCP + Ketamine
What does MDMA do?
Amphetamine analogue which acts as a psychostimulant blocking the 5-HT reuptake transporter and also DA and NA to a lesser extent
What does Phencyclidine (PCP) and ketamine do?
Anaesthetic and painkiller that has affects such as hallucinations, numbness, detachment, increased positivity (less so in Ket), panic or paranoia as a result of NMDA glutamate receptor blockade via PCP binding site inside channel preventing influx of Na and Ca
What is the UKs alcohol driving limit?
0.08%
Why can Loperamide (another opioid) be given to opioid dependent patients going through withdrawal?
Little effect on CNS as it crosses BBB but is rapidly transported back out making effects negligible
