mark (L13) Flashcards
define substance abuse
Substance abuse (WHO) refers to the harmful or hazardous use of psychoactive substances, including alcohol and illicit drugs
define drug dependence
Drug dependence is the body’s physical need, or addiction, to a specific agent
economic cost of drug addiction
Drug addiction —places an enormous burden on society
through its repercussions on crime rate and healthcare.
The economic costs of addiction have been estimated
at 80 billion dollars in the United States alone (1999).
COST OF ILLICIT DRUG USE IS £10.7bn / YEAR
8% health service use
10% enforcement
28% deaths linked to eight illicit substances
54% drug related crime
why are certain drugs addictive?
Hypothesis: they intervene with reward behaviours
Nuclei release dopamine (VTA is the main area that releases reward signals and pleasure signals)
Frontal cortex - decision making
VTA - ventral tegmental area
why do we need reward pathways?
Drugs “kidnap” brain reward circuits
Why do we need reward pathways? To rewards us for signals that promote survival: Food consumption Drinking water Procreation Child nurturing/rearing They reinforce behaviour for repetition So called natural re-inforcers
Most addictive drugs increase dopamine release
dopamine pathways functions
reward and otivation pleasure and euphoria motor function and fine tuning compulsion perseveration
serotonin pathways functions
mood
memory processing
sleep
cognition
effect of drugs on everyday mood (also define salience)
The drugs release high levels of dopamine so that the normal levels of everyday life become too low in comparison
Salience - the feeling of wanting more
(drugs can override the self regulation, if there is strong memories of enjoyment last time they took the drugs, so salience is overcome and increases, drive increases, they take more)
define incentive salience
Incentive salience: cognitive process which confers a “desire”
or “want” attribute, including a motivational component,
to a rewarding stimulus. This is hi-jacked by drugs
Drugs over-ride top-down control
Drive is compulsion
skinner’s box study
Skinner’s box - give the rodent either a drug or a sweet substance
Measure the prevalence score - does it prefer to take the drug or the sweets
Increase the number of times the animal has to activate the lever to get the drug to see how committed they are to getting that drug
You can keep increasing the number of times they have to push the lever to see when the rodents decide that the drug isn’t worth it anymore
You can show the difference between the addictions of different drugs
For example study addiction of heroin VS tobacco
They will be more motivated to push the lever more times for heroin than for tobacco
the 2 types of dependence
- Physical dependence
- Results from adaptation by resetting homeostatic mechanisms in response to repeated drug use
- Withdrawal syndrome: direct evidence of physical dependence
- Withdrawal arises due to abrupt termination of drug use
- Appearance of signs and symptoms during withdrawal are characteristic of the drug category - Psychological Dependence
- Motivational component, craving for the drug
- Not always associated with physical dependence
- Some drugs (cocaine) psychological dependence can persist for very long periods
types of tolerance
Reduction in response to the drug after repeated administrations. Thus need increasing concentrations of
drug to get the same effect.
- Innate tolerance
Genetically determined sensitivity i.e. occurs after first dose - Acquire tolerance
Pharmacokinetic
Changes in metabolism and absorption reduce systemic blood concentration
Pharmacodynamic
Adaptive changes within the system resulting in altered response to the drug i.e. receptor desensitisation
- Cross tolerance
cocaine and amphetamines
benzodiazepines and barbiturates
Pharmacodynamic tolerance and G coupled proteins
Dopamine - works for a G protein coupled receptor
It has 7 transmembrane regions, an alpha subunit and a beta gamma subunit
the agonist binds and when you activate gpcr are the G protein dissociates to the alpha and beta gamma which can both signal
the receptors can be phosphorylated by these GRKs or by B arrestins
arrestins can become desensitised - don’t work anymore
disconnect as a signal so that the receptors can be internalised through endocytosis
the effect of the receptors are very rapid
early desensitisation within a minute or so
this effect on the receptor numbers on the surface and can still happen after an hour but ? can last for many weeks
receptors can be recycled back onto the membrane
there are short term tolerance effects of desensitisation or longer affects where there are less receptors on the cell surface which reduces the effect of the receptors
Principles for the effective treatment of drug addiction
Criteria for effective treatment:
1) Quick and easy access to treatment.
2) Addresses all of the patient’s needs, not just their drug use (including mental health problems etc)
3) Patient must stay long enough in treatment.
5) Requirement for counseling and other behavioral therapies.
6) Medication is often an important part of treatment in combination with behavioral therapies.
7) Drug use during treatment must be monitored continuously.
8) Treatment programs should test patients for HIV/AIDS, hepatitis B and C, tuberculosis, and other infectious diseases as well as teach them about steps they can take to reduce their risk of these illnesses
Pharmacological approaches to treating drug dependence
- Alleviate withdrawal symptoms
methadone to blunt opioid withdrawal - Long term drug substitution
Methadone, buprenorphine, or legal heroin - Blocking response to the drug
Naltrexone to block opioid effects - Aversive therapies
Disulfiram to induce unpleasant response to ethanol - Reducing continued drug use (treat underlying mental health problems)
Benzodiazepines to treat anxiety, anti-depressants etc.
