addictions Flashcards
define tolerance
reduced responsiveness to a drug caused by previous administration
an example of homeostasis - body likes things the way they were
underlying mechanisms vary
when does tolerance develop
in response to many but not all drugs
e.g. opioids, ethanol, barbituates, benzodiazepines
mechanisms of tolerance
- drug metabolised faster (or if metabolite is the active form then it would be metabolised slower to produce a smaller effect)
what is dispositional tolerance
less drug reaches the active site:
- decreased rate of absorption
- increased rate of metabolism to inactive metabolites
- decreased rate of metabolism to active metabolites
- increased rate of excretion
what is pharmacodynamic tolerance
aka tissue/functional tolerance
site of action is less affected by the drug:
- down-regulation or internalisation of drug receptors
- reduced signalling down stream of drug receptors
- some other compensatory mechanism
how is tolerance linked to dependence
development of tolerance may also lead to withdrawal symptoms
e.g. drug effect - reduced transmitter release (unbalanced state)
adaptive response - increased sensitivity to transmitter (balanced state)
drug removed - unbalanced state again and now the adaptive response remains; the development of tolerance will cause dependence on the drug to achieve the normal state
withdrawal phenomena
the withdrawal effect of a drug is usually the reverse of the acute effect
development of tolerance may lead to physical dependence in order to avoid the (unwelcome) withdrawal effects
what is the reward pathway
neurones project from the ventral tegmental area to the nucleus accumbens and prefrontal cortex
when VTA neurones are stimulated dopamine is released
this causes a sensation of pleasure/reward
why has the reward pathway evolved
the reward pathway is normally activated by eating, drinking and sex
it therefore encourages those ‘healthy’ behaviours that lead to propagation of your genes
drugs and reward centres
some drugs of abuse tap into the reward pathway and increase dopamine levels e.g.
- heroin - increases firing rate of dopaminergic neurones
- amphetamine - increases dopamine release
- cocaine - inhibits dopamine uptake
- alcohol - inhibits inhibitory synapse (?)
produces the psychological component of addiction - craving
issues of risk re. drug use
type of drug and effect
purity, dose, strength, tolerance
route of administration + unsterile nature
legal status - different jurisdictions
comorbid health conditions
likelihood of dependency
method of purchase - legal, prescribed, OTC, black market, internet
drug related deaths - >1000 p/a in scotland and increasing
what substances have the biggest impact on local health services and communities
alcohol
heroin/opiate misuse
benzodiazepine misuse
cocaine/crack cocaine misuse
cannabis misuse - most widely abused but relatively lower risk profile than the above
examples of stimulant drugs
cocaine
amphetamine (speed)
methamphetamine - much more common in US/australia
methylphenidate (prescribed for ADHD, mild stimulant)
cocaine
- historical use
- forms
most potent natural stimulant historical indigenous use extracted from leaves of coca plant first isolated in 1880s formerly used in ENT surgery cocaine (powder), crack cocaine (smoked) crack produced by mixing cocaine w/ base (sodium bicarbonate) and purified
how does cocaine work
monoamine reuptake inhibitor - dopamine, serotonin, noradrenaline increase
issues with cocaine abuse
settings for drug use - financial wealth to poverty
image issues - crack cocaine vs powder
significant issue in NE Scotland
can use a large amount w/o overdosing (huge financial issues and associated problems)
rate of onset of effects of cocaine
depends on dose and rate of entry to the brain
smoking - almost immediate
injecting (high risk) - 13-30s
snorting - 3-5mins
effects of crack smoking are very intense but short lived (15 mins)
effects of cocaine
stimulant and euphoriant
anaesthetic effect
hypersensitive - noises, light
increased alertness and energy
increased confidence and impaired judgement
lessens appetite and desire for sleep
if mixed w/ alcohol –> cocaethylene (like cocaine but with longer 1/2 life)
medical problems w/ cocaine use
damage to nose and airways (from consistent vasoconstriction)
convulsions w/ resp failure
cardiac arrhythmias and MI - very cardiotoxic
HT and CVA
toxic confusion
paranoid psychosis
cocaine withdrawal effects
depression irritability agitation craving hyperphagia - want to eat lots hypersomnia - want to sleep lots
broadly opposite of drug effect
amphetamine
- route of administration
- effects
- problems
generally amphetamine sulphate
sniffed, swallowed or injected
effects similar to cocaine but longer lasting
toxic confusion occasionally w/ convulsions and death
amphetamine psychosis in heavy chronic use
how does amphetamine work
dopamine enhancer
examples of opiates
opium morphine heroin (diamorphine) methadone codeine and dihydrocodeine
heroin
- history and forms
first synthesised from morphine in 1874
addictive potential unrecognised for yrs - marketed as treatment for morphine addiction and cough
available as diamorphine or diamorphine hydrochloride
may be presented as powder or tar like substance
