drug habituation, tolerance and dependence Flashcards
What makes drugs of abuse psychoactive?
They can cross the blood brain barrier
In which 4 ways do drugs of abuse affect brain function?
- Mood
- Perception
- Behaviour
- Cognition
What is the key feature of drugs of abuse that makes them addictive?
The user finds it rewarding and pleasant
Withdrawal= bad feeling
What two processes occur once you have been taking a drug repeatedly fro long periods of time?
Tolerance
Dependence
Why does dependence occur?
Long term adaptive changes occur in receptors, transporters and second messengers etc.
What is withdrawal syndrome?
The unpleasant physical symptoms when an addicted person stops taking a drug of abuse
(means they want to take it again even more!)
How long after a person stops taking a drug of abuse can craving last for?
Many years!!
Why does withdrawal occur?
Uncompensated adaptive changes
(e.g. decrease in dopamine and increase glutamate levels)
What can cause dependence to occur?
Taking larger amounts for longer periods than origionally intended
(e.g. carry on taking opioids e.g. Morphine without pain)
Which characteristics of an individual who is dependant on a drug (7)?
- Express persistant desire to reduce substance use
- Spend a lot of time obtaining substance, using it and recovering from using
- Intense desire for substance (environmental cues)
- Impaired social performance (withdrawal from society & decreased ability to perform well at work)
- Risky use of substance (more likely to get caught)
- Tolerance
- Withdrawal effects
N.B. wont see all in those who are addicted
What is habituation?
A reduction in response to a drug when the usual dose is taken (following continued presence of stimuli)
How does habituation lead to tolerance?
Individual must markedly increase dose to achieve the desired effect = keep taking more
How long does it take to start to build up tolerance?
4 days (less than a 50% response)
What is another name for metabolic tolerance?
Pharmacokinetic tolerance
How does metabolic tolerance work?
Alters the metabolism of a drug
(increases break down = lower concentrations left in body = less of an effect)
Which enzyme expression is up-regulated in repeated alcohol exposure (metabolic tolerance)?
Alcohol dehydrogenase
= ethanol broken down faster = doesn’t reach same levels in blood so less intoxication
What is another name for functional tolerance?
Pharmacodynamic tolerance
What happens in functional tolerance?
There is a change in drug target expression or sensitivity on the target cells
Give an example of functional tolerance
Excess use of opioid receptor agonists
= phosphorylation of opioid receptor = internalisation of receptor or uncoupling of G protein = presence of opioid has no effect as cannot bind or doesn’t start cascade
How are receptors internalised?
It is held inside the cell in a vesicle membrane
By which process are receptors internalised?
Dynamin dependent endocytosis
What 3 things cause the type and intensity of withdrawal symptoms to vary?
- Drug
- Amount of drug
- Time
What are the 7 main symptoms of withdrawal?
- Tachycardia
- Hypertension
- Sweating
- Tremors
- Confusion
- Seizures
- Hallucinations
What is craving based on?
Psychological dependence
-> drug produces Euphoria and you want to feel the same way again= known as “substance dependant”
In which three ways does addiction cause problems?
- Drug harm (direct effects e.g. opiate respiratory depression & route of administration e.g. risk of HIV with IV use)
- Reduction in users ability to function normally (e.g. in social situations, problems at work = job loss = steal money)
- Cost to society!
Which drug causes the most harm to users and others?
Alcohol
Give 4 examples of opioid drugs that are drugs of abuse:
- Morphine
- Diamorphine (heroin)
- Methadone
- Oxyxodone
Give 4 examples of CNS depressants that are drugs of abuse:
- Ethanol
- Barbituates
- Solvents
- Ketamine
Still activate reward pathway
Give two examples of anxiolytics and hypnotics that are drugs of abuse:
- Benzodiazpeines
- Gamma-hydroxybutyrate (GHB)
N.B. both are moderate drugs of abuse… moderate dependency liability
Give 4 examples of Psychomotor stimulants (CNS stimulants) that are drugs of abuse:
- Amphetamines
- Cocaine
- Nicotine
- MDMA (ecstasy)
- > n.b. not psycologically or physically dependent
Give two examples of Psychomimetic agents that are drugs of abuse:
- Lysergic acid (LSD)
- Cannabis
What is dependence liability?
Includes all the properties of a drug:
- acute and chronic tolerance,
- physical dependence and withdrawal,
- psychologic dependence
In which 5 ways do we treat drug dependence?
- Alleviate withdrawal symptoms (e.g. methadone to reduce opioid withdrawal)
- Long-term substitution (e.g. methadone = bit of a buzz = reduce withdrawal)
- Blocking response (e.g. naloxone)
- Aversive therapy (e.g. disulfram = used for alcoholics = gives individual severe immediate hangover so dont want to drink it anymore)
- Reduce drug craving (e.g. Baclofen = GABA B receptor agonist = reduces craving for alcohol, opioid and stimulant craving)
Which two factors affect drug use and addiction?(not everyone gets addicted and not everyone to the same degree)
Genetics
- mutations in dopamine/serotonin receptors e.g. some people feel sick after a small amount of alcohol = less likely to get addicted
Environment
- availability of drug (if cant get hold of it cant get addicted!)
- Socio-economic factors (more money = more likely to take but also more likely to take if feel bad/deprived)
