Week 6 & 7 - Substance Use Disorder (SUD) Flashcards
Define SUD
SUD is where an indiviual uses substances in behaviour that becomes compulsive + they continue despite harmful consequences
- SUD causes a psyhcological + physical change in brain (from repeated exposure)
- its a treatable condition + recovery is possible
- use ICD-11 to diagnose disorder
- use DSM-5
- liekly to have some form of SUD if some criteria is met (not all)
Why does SUD occur
SUD caused by many factors e.g. genetic, social, environmental
- social ~ experiences with friends, to have fun
- environmental ~ help you fell better, alleivate stress, anxiety, fear etc.
- genetic ~ genes associated with alcohol breakdown
What symptoms are associated with SUD
- Euphoria (intesnse pleasurable feeling)
- feeling differs depending on type of drug, route (oral or IV)
- IV adminstration = feeling more intense as enters bloodstream then brain quicker
- High
- Buzz
- Period of sedation (drowsiness, relaxed)
Explain the role of the reward pathway (dopamine pathway)
Mesolimbic Pathway
- When take substance binds to receptors on dopamine cell bodies (in VTA) = cell bodies activated
- ↑ Dopamine relased into nucleus accumbens
- Release of dopamine drives pleasurable feeling
- Nucleus accumebns interacts with diff. area e.g. pre-frontal cortex, areas linked to forming memories (associated with substance), decisions, emotions etc.
NOTE: some substances may:
- act at synapse = prevents re-uptake of dopamine
- act at GABA receptors = removes inhibiton of dopamine neurones = ↑ dopamine released
- as GABA neurones feed onto dopamine neurones
List the substances that can cause addiction
- Alcohol
- Nicotine
- Drugs e.g. weed, cocaine
- Psychiatric meds i.e. benzodiazepines
- Caffeine
- Food
- Gambling
- Sex
- Harmful relationships
- Technology i.e. phone, devices
Anything that gives pleasure + is done excessively
How do changes in the brain occur during addiction
Neuroadaptation occurs
- Formation of drug related memories (hippocampus)
- causes cravings - Changes in VTA and nucleus accumbens (NA) after long-term exposure to drug
- Decision-making process is impaired = impulsivity = seek drug (due to frontol cortex changes)
- Amygdala is altered ~ relates to stress + craving
- part of brain that processes emotionaal response - Dissociation of dopamine circuits (after repeated exposure)
- mesolimbic (VTA to NA)
- nigrostriatal = get changes in behaviour
- ↓ activation of D2 recptors + ↑ activation of D1 and D3
List the 3 different stages of the addiction cycle
- Take drug
- could be inital (1st time) or continuous - Experience WITHDRAWALS
- once drug has left system
- experience low mood, physical effects
- if 1st time effects wont be as significant - Begin CRAVING drug
- feel anticipation to take drug again
- feel preoccupied
- leads to taking drug = stage 1 = leading to dependance
NOTE: don’t become addicted after first time
Explain the addiction cycle after inital (1st time) use
- TAKE drug
- gives a pleasurable feeling due to surge of D2 release into nucleus accumbens (NA)
- higher surge = more intense feeling
- Experience WITHDRAWAL
- effects begin to wear off as D2 levels decrease
- may get dip in D2 levels (below normal) = experience low moods
- Begin CRAVING drug
- become preoccupied with the intense feeling = want to do it again
- stronger the D2 dip is = stonger craving
Explain the addiction cycle after continued / repeated use
- TAKE drug MORE FREQUENTLY
- due to pleasurable feeling it gave BUT more drug is required to give effect the intial use gave (tolerance building)
- Experience WITHDRAWAL
- more often you take it = more likely to get withdrawal as becoming dependat on it - Stronger CRAVINGS
- may even feel anticipation when in environemnt usuallyy take drugs in
- happens sevral times a day
How does drug tolerance occur
- over time pharmcological effect of drug ↓ (NOT immediate)
- When tolerance begins = will need to take more of drug to feel same effects
MECHANISM:
1. Desensitisation of receptor occurs
- i.e. receptor becomes less responsive / no response to drug
- Fast change: conformational change occurs with receptor when drug binds BUT ligand channel doesnt open
- Slow change: intracellular regions of the receptor become phosphorylated leading to desensitisation (of ligand receptor) OR second messengers cant be activated (G-protein receptor)
- Translocation (movement) of receptor
- in substance misuse endocytosis of functional receptors (on membrane) occurs at greater rate = ↓ no. of receptors
- Mediators are used up
- substance prevents reuptake of monamines (MA) like dopamine = MA not recycled
- MA stores become depleted - Drug metabolised more quicker
- need to take more of substance to have the same effect
- as now when take same amount will have a ↓ plasma conc.
Whats the difference between physcial and psychological dependance
Physical:
- get physical symptoms when stop taking substance (withdrawal)
- can last for days, weeks or longer (depends on drug, length of use, severity)
Psychological:
- drive to take substance again to get pleasurable feeling / avoid withdrawal effects (craving)
Both are linked + have role in addiction cycle
What are the specifc symptoms for AUD addiction
AUD - Alcohol Use Disorder | Initial and withdrawal symp.
INITIAL:
- Self-control impaired
- Sedation, sleepy (seen in mild intoxication)
- Memory and judgement affected
- Acute alcohol posioning if consume ↑ amount
- Binge drinking
- Chronic relapse i.e. occurs over long period of time
WITHDRAWAL:
- ↑ heart rate, BP
- tremor
- ↑ sweating
- anxiety + agitation
- due to nueroadaptations in stress system
- delirium tremens (DTs) and seizures
- = have high levels of alcohol
- may have hallucinations
The CIWA-m Score for Alcohol Withdrawal
Points awarded for:
- N&V
- Agitation
- Anxiety
- Tremors
- Sweating
- Auditory disturbances
- Visual disturbances
- Tactile disturbaces
- e.g. itching, pins & needles, burning, tingling etc,
- Headache
- Disorientation
- ↑ RR, HR, BP
SCORES:
- ≤ 8 = does not require medication for withdrawal
WITHIN First 24hrs (monitor 1hr)
- < 10 = no treatment / monitor
- 10 to 21 = 30mg Chlordiazepoxide
- >21 = 40mg Chlordiazepoxide
AFTER 24hrs (monitor every 2hrs)
- <16 = no treatment
- 16 to 21 = 20mg Chlordiazepoxide
- >21= 30mg Chlordiazepoxide
How does Ethanol (Alcohol) cause addiction
NOTE: most addictive substance: cheap, easily accessible, legal, social
Ethanol interacts with ligand and voltage -gated ion channels
- mainly NMDA and GABA A receptors
- more alcohol consumed = more changes in receptor
- changes in how alcohol is metabolised
Need to maintain alcohol intake to prevent withdrawal (i.e. hangover)
CAUSES:
- Upregulation of NMDA receptor
- Change in GABA A sub-units = functionality ↓ = need ↑ alcohol to have good effects
- ↑ excitation when GABA inhibition is lost
What is the 1st line for AUD
- Offer psyhchological intervention e.g. CBT
- If refuse pschological / not responsive or want meds. then use pharmacological
List the 3 pharmocotherapies for AUD
AUD - Alcohol Use Disorder
- Disulfiram
- Inhibits ALDH (enzyme) = prevents the conversion of acetylaldehyde into acetate
- if get build up of acetylaldehyde = feel sick = wont want to drink
- its a product formed when ethanol is broken down - MoA diagram in notes
- Acamprosate
- an NMDA receptor antagonist (competes with glutamate)
- Dampens Ca2+ activity by inhibiting Ca2+ channels + GABA A receptors
- manages withdrawal effects by balancing GABA + glutamate
- Naltrexone
- Mu opioid receptor antagonist
- Acts at receptor preventing endogenous opioids / B-endorphins released in response to alcohol consumption from binding (= ↓ consumption + craving)
OTHER: BZDs for short term AUD withdrawal
How does Benzodiazepines (BZDs) & Z drugs cause addiction
OR Affect reward pathway
BZDs are allosteric modulators of GABA A receptors
- bind to GABA A receptors = disinhibition = ↓ inhibition of dopamine neurone (in VTA) = ↑ dopamine released into nucleus accumbens
- effects are MINIMAL comapred to other substances BUT should NOT be prescibed >1 month
- longer term use = ↑ risk of addiction as tolerance can develop within 6 weeks
What are the specifc symptoms for BDZs and Z drug overdose and misuse
OVERDOSE:
- tremors
- blurred vision
- confusion, disorientation
- dizzoness
MISUSE
- Anorexia
- Anxiety, insomnia (NOTE also treats these conditions)
- Headache, palipitation, swetaing
- symptoms of withdrawal
- Memory impirment
- Hallucinations
- Seziures
- SE if stop abruptly, need to taper dose down slowly
- Suicidal thoughts
How does cannabis cause addiction
Cannabis contains cannabinoids (CB) that bind to CB1 receptors
- in cannabonoids have delta 9 (the component that produces high)
- causes inhibiton of neurone = downstream excitation
How does stimulants produce a high
i.e. cocaine and amphetamine
They inhibit dopamine reuptake
- they act at pre-synaptic neurone + inhibit dopamine trnasporters (on membrane)
How does opioids cause addiction
Opioids are used for pain relief
- formed from a poppy that produce opium latex
Opioid Action in VTA
- act on Mu opiod receptors (found on GABA neurones)
- GABA neurones synapse with dopamine neurones
- Opioids inhibit GABA neurone = loss of dopamine inhibiton = ↑ dopamine released into nucleus accumbens (NAc)
Opioid Action in NAc
- acts on Mu opiod receptor on GABA neurones in NAc
- ↓ GABA release at synapse = ↓ inhibitory responses elsewhere
- ↑ excitation due to loss of inhibition
NOTE: morphine can be converted to heroin
- heroin (prodrug) is 2x more potent
- fentanyl (synthetic opiod) = 100x more potent than morphine = easy to overdose on
What are the specifc symptoms for opioid misuse
- Drowsiness
- Slowed respiration
- ↓ BP
Cause of symptoms = opioids acting on Mu opiod receptors in locus coernuleus (LC) = noradrenaline (NA) release blocked
- LC involved in keeping us awake, controlling resp. rate
- LC neurones adapt to overcome GABA inhibition quickly
- = when remove opioids = excess NA release = withdrawal
Explain how opioid tolerance occurs
Tolerance occurs when:
1. Get desensitisation of functional opioid receptors WITH ↑ or ↓ internilisation of receptor
- G-proteins become phosphorylated = uncouple = binding changes = deasensitisation
2. Get desensitisation with NO internilsiation
- results in sustained / abnormal signalling
NOTE: longer use opiod the greater tolerant you become to the symptoms
- tolerance occurs rapidly (within days) = why people begin ↑ dose / frequency to prevent withdrawal
Explain Opioid withdrawal
Occurs due to opioid dependace / addiction
- tolerance occurs rapidly (within days) + effects can last long time / be severe
- withdrawl symptoms can last from a few days, weeks, months to years
- compulsion is very strong = easy to fall back into taking them
Factors affecting withdrawal severity:
- dose / frequency
- how long youve been taking it
- strength
COWS - Clinical Opioid Withdrawal Scale
- used to measure withdrawal
- helps determine treatment + how to reduce withdrawal
What are the 3 treatments for opioid addiction
- Methadone
- synthetic opioid, is an agonist at Mu receptor (what it acts on)
- ↓ withdrawal over time due to long half life AND delays + prolongs abstinence
- ↓ tolerance and dependance
- slowly taper dose until patient comes off methadone, if stopped abruptly = withdrawal
- taken orally (may need to be supervised in pharmacy)
- Buprenorphine
- synthetic opioid, is a partial agonist at Mu receptor = gives some stimulation but not full response like heroin / morphine
- partial = dont get a high = weaker withdrawals
- long acting
- Naltrexone
- acts on Mu receptor + blocks effects of ANY OPIODS = ↓ cravings
- if take opiods whilst on naltrexone opiods wont do anything (as drug blocked receptors)
- DO NOT take both at same time = withdrawal - injection formulation
How does nicotine cause addiction
- Nicotine stimualtes the release of endogenous (naturally made in body) opiods
- opiods act on Mu receptors on GABA neurones in VTA and NAc
- Nicotine acts on nAChRs in VTA = more dopamine neurones fire dopamine
- Nictoine acts on glutamate recpetors = further dopamine neuorne stimulation in NAc
Explain Nicotine tolerance
nAChRs = nicotine acetylcholine receptors
Tolerance occurs rapidly due to rapid desnsitisation of nAChRs (α7 and α4β2)
- β2 subunit desnsitises rapidly
- α7 subunit doesnt desensitis easily
Nicotine gets into bloodstream quickly as its inhaled
- activates nicotine spike = nAChRs are activated
- has a short half life (2hrs) = tend to smoke more often = nictoine buildup = nAChRs are affected
What are the withdrawal symptoms of nicotine dependance
- Cravings
- Restlessness
- Increased irritability
- Anxiety
- Increase appetite + weight
What are the 2 NRT / treatments for nicotine addiction
- Bupropion (sustained release)
- an anti-depressant
- ↓ cravings, weigth gain, depressed mood (from withdrawal)
- inhibits dopamine + noradrenaline reuptake
- acts as an antagonsit at nAChRs = wont have any eefcet if still smoke (no ↑ dopamine release)
- begin treatment before stop smoking, used for up to 10 weeks
- Varencline
- selective partial agonist at α4β2 = dont get full nicotine effect = ↓ withdrawal effects
- ↓ nicotine induced dopamine release
- helps body overcome tolerance + dependance
