Neurobiology of Addiction and Opiates Flashcards
outline the dopaminergic reward pathway
which 2 drugs cause the most significant increase in dopamine release
ampethamines and cocaine
what is the reward pathway involved in
it acts as a motivating signal, incentivises behaviour
it is involved in normal pleasurable experiences
what happens when you over stimulate the reward pathway, eg take too many drugs
the dopamine receptors downregulate, so a tolerance to reward is developed
this means the theshold for all rewards is increased - normal experiences arent pleasurable and more drug is reuqired for same effect
is downregulation of the dopamine receptors in reward pathway reversible?
yes?? over time, but the changes persist despite prolonged abstinence - this is a trigger for relapse
what is positive reinforcement
reinforcing stimulus, eg money for doing homework
what is negative reinforcement
an annoying stimulus is removed after a particular behavour, eg nagging stopped after dishes done
is drug addiction drive by positive or negative reinforcement
positive in the initial stages
negative in the later (eg to get rid of withdrawals, life seems dull)
what is the role of the prefrontal cortex
planning complex cognitive behaviour, personality expression, decision making and social behaviour
keeps emotions and impulses under control to achieve long term goals –> puts the breaks on the reward pathway
where does cortical maturation begin and end
back to front, from Mi to frontal gyri, prefontal cortex develops last
what is the significance of the late development of the pre frontal cortex
it is not fully developed till 20s (marshmallow test)
this means that the parts of the brain that control exectuive functioning mature later than limbic (emotional) systems –> teens show strong stimuls reward, minimal judgement and impulse control
what is the significance of starting addictions early
the PFC is vulnerable during development
synpatic plasticity - the earlier drugs start the longer the relatonship is
what effect can learned drug associations have
can cue internal states of craving eg opening a fag packet
what is the role of the orbito frontal cortex in addiction
provides an internal representation of the saliency of events and assigns a value to them –> creates a motivation to act
in addicts, this area is activated a lot when they are presented with a drug cue –> craving
how is the PFC affected by addiction
PFC is dysfunctional - no longer putting breaks on reward pathway or OFC
too much dopamine going around
do genetics have an influence on addiction?
Yes! large
They may affect: the way we respond to drugs metabolically; behavioural traits that predispose us to take drugs; how rewarding we find drug taking. Influence receptor levels, e.g. if there are low dopamine receptors there is a higher risk.
what does acute and chronic stress do in the reward pathway
acute triggers the release of dopamine in the reward pathway –> motivate dependent to take drugs
chronic causes downregulation of dopamine receptors - reduces sensitivity to normal rewards and encourages exposure to highly rewarding behaviours.
what pharmacodynamic features make heroin so addictive
it reaches peak plasma levels very quickly in blood stream - euphoria
short half life so plasma levels drop quickly - physiological withdrawal
what is another name for heroin
diamorphine
how is diamorphine made from morphine
add 2 acetyl rings
metabolism of heroin
diacetylmorphine (heroin) - 6 mono acetyl morphine - morphine
detection of which substance is indicative of heroin use
6MAM
where would you detect 6MAM
in urine, present for 6 hours after use
what does detection of morphine in urine indicate
could be heroine or codeine (the active metabolite of codeine is morphine)
what do opiate users teeth look like
bad - may be due to analgesia stopping them feeling dental pain
also, suppression of salivary production causes stomach acid to rot teet
when do withdrawal symptoms tend to occur
6-8 hours after
symptoms of opioid withdrawal
- Dysphoria and cravings
- Agitation
- Tachycardia and hypertension
- Piloerection – hairs on arms stand on end
- Diarrhoea, nausea and vomiting
- Joint pains
- Yawning
- Rhinorrhea and lacrimation
sympathetic overactivity
what drug can be used for withdrawal symptoms
Lofexidine - inhibits the release of norepinephrine in the CNS and PNS
has no effect on opioid cravings
local complications of IV use
cellulitis, abscess, thrombophelbitis, necrotizing fasciitis
endocarditis in IV drug users - which valve and bacteria
tricuspid valve - right sided
S Aureus (flucloxacillin)
systemic complications of IV use
Hep B, Hep C, HIV
which other drugs are implicated in opioid related death
gabapentin and pregabalin are used to enhance the effects of opioids (anticonvulsants)
diazepam and etilzopam are implicated too
which drug is used in an opioid overdose
Naloxone
- opioid antagonist
does heroin cause psychosis or delirium
no
what is the basic principle in opiate substitution therapy
replace a short acting opioid with a long acting one - buprenorphine or methadone
dosing of Buprenorphine/Methadone
once daily under supervision
is Buprenorphine or Methadone usually used
Methadone can be given in liquid form which is preferable - harder to divert. is a full agonist
Buprenorphine is a partial agonist and is only available as a tablet
what is opidate detoxification
achieving complete abstinence from all opiates
what is the main risk of opioid detoxification
death with relapse - physical tolerance levels lower but psycholoigcally the patient is still dependent and will often relapse and take the same high dose they did when they had a tolerance
rate of relapse within 1 year
70-80%
what is contingency management
Rewarding positive behaviours to reduce illicit drug use and/or promote engagement with services receiving methadone maintenance treatment, and to improve physical health care.
