Drugs of Dependence and Antidepressants Flashcards
What is drug dependence?
Drug taking becomes compulsive
Takes precedence over other needs
What is drug abuse?
Use of illicit substances or illicit use of legal substances
Recurrent and clinically significant adverse consequences
What contributes to psychological dependence?
Rewarding effect of psychoactive drug
What is the rewarding effect of the psychoactive drug?
Positive reinforcement > desire to continue experience
Does the rewarding effect only happen with drugs?
No, it can happen with any activity
What contributes to physical dependence?
Habituation/adaptation
What is habituation/adaptation?
Feeling normal/aversion of negative symptoms
Don’t take drug to feel good but not to feel bad
What are the reward and salience circuits involved in drug abuse and addiction?
Nucleus accumbens
Ventral pallidum
What are the memory and learning circuits involved in drug abuse and addiction?
Hippocampusw
Amygdala
What are the motivational drive circuits involved in drug abuse and addiction?
Orbitofrontal cortex
Subcallosal cortex
What are the inhibitory control circuits involved in drug abuse and addiction?
Prefrontal cortex
Anterior cingulate gyrus
What happens to the inhibitory control circuits in drug abuse and addiction?
Removed to elicit excitation
Which circuits have interplay between them in drug abuse and addiction?
Those for reward and salience, and memory and learning
Which neurotransmitter is implicated in reward pathways, and how?
Increased dopamine in nucleus accumbens
What are the key transmitters modulating dopaminergic transmission?
Atch Serotonin NA GABA Glutamate Opioids
Which neurotransmitters are targeted by most of the drugs that are used and abused?
Those that modulate dopaminergic transmission
Describe the dose-response curve in the CNS
Bell-shaped rather than sigmoid
What effects did cocaine have on people with high dopamine receptor levels?
Aversive effects
What effects did cocaine have on people with low dopamine receptor levels?
Pleasant effects
Do receptor levels change, and if so, what do they change in response to?
Yes, change in response to
- Time
- Disease
- Drug taking
How do some tolerance mechanisms work when receptors are involved?
Receptor levels are too high, so with extended drug use, they’ve been downregulated
What are two examples of opioids?
Morphine
Heroin
What are the CNS effects of opioids?
Euphoria
What are two examples of CNS depressants?
Alcohol
Diazepam
What are the CNS effects of CNS depressants?
Reduced anxiety
What are three examples of CNS stimulants?
Cocaine
Amphetamine
MDMA
What are the CNS effects of CNS stimulants?
Excitement
Euphoria
Reduce fatigue
What is an example of an hallucinogen?
LSD
What are the CNS effects of hallucinogens?
Altered perception
What is an example of a cannabinoid?
D-9-THC
What are the CNS effects of cannabinoids?
Altered perception
What is non-therapeutic drug use?
Consumption by choice not medical advice
What are the specific effects of CNS stimulants on CNS transmission>
NA, dopamine, and serotonin to various degrees
What does cocaine do at the synapse?
Block neuronal uptake of NA
What does amphetamine do at the synapse?
Utilises uptake carrier for NA to enter pre-synaptic terminal
Displaces NA from synaptic terminal
What effect do cocaine and amphetamine have on NA at the synapse?
Increase NA levels in synaptic cleft
Which neurotransmitters are predominantly affected in the CNS by cocaine and amphetamine?
Dopamine
Serotonin
Which neurotransmitters does amphetamine release in the CNS?
Predominantly NA and dopamine
Also serotonin
With what do the effects of amphetamine vary?
Mood
Personality
Environment
What are the CNS effects of amphetamine?
Mood elevation and euphoria
Increase locomotor activity
Stereotypic behaviour
What effects does amphetamine have on physical and mental performance?
Fatigue postponed
Confident and speedy performance, but less accurate
What is the possible mechanism for the appetite suppressant activity of amphetamine?
Serotonin effect
What is a medical application of amphetamine?
Analogues used for ADHD
Does amphetamine induce tolerance?
Yes, need larger dose for same effect with long term use
What is the mechanism by which amphetamine induces tolerance?
Downregulation of receptors over time
Does amphetamine cause psychological dependence?
Yes, but not as marked as cocaine
Which group of people are more susceptible to amphetamine dependence?
Depressives
Lonely people
What are the physical withdrawal symptoms of amphetamine?
Lethargy
Sleep
Desire for food
Depression
What does chronic use or an overdose with amphetamine cause?
Anxiety Nervousness Physically tension Tremors Confusion Dizziness Time passes quickly Hyperthermia Tachycardia Increased BP Vascular collapse > death Psychosis - hallucinations
Compared to amphetamines, what neurotransmitters do cocaine and MDMA targeet?
Target same ones but cocaine and MDMA have relative selectivity for dopamine, serotonin and NA
What are the cognitive effects of caffeine?
Increases alertness and well being
No euphoria
Delays onset of sleep
In what ways does caffeine stimulate mental activity?
Postpones boredom, fatigue, and inattentiveness
Enhanced intellectual and motor performance
What do high doses of caffeine cause?
Anxiety
Tension
Tremors
What is the drug class of caffeine?
Methylxanthine
What are the targets of caffeine?
Predominantly an adenosine antagonist
Phosphodiesterase inhibitor > cAMP not broken down
By targeting 2nd messengers, it affects transmission beyond NA, DA and 5-HT
Does caffeine cause dependence?
Not strongly in animals or humans
Reinforcing behaviour linked with social aspect
What is a withdrawal symptom of caffeine dependence?
Headache
What sort of hallucinations does LSD cause?
Visual
Auditory
Tactile
- Sensory modalities get confused
What happens to your thought processes whilst on LSD?
Disturbed but aware drug-induced
Does LSD cause dependence?
Could be aversive rather than reinforcing some people - “bad trip”
How is tolerance to LSD mediated?
Receptor mediated
How fast does tolerance to LSD happen?
Quickly
What happens when you take LSD with other psychotomimetics?
Effects impaired by cross tolerance
What is the target of LSD?
In CNS agonist at 5-HT2 receptor
Causes inhibition of 5-HT neurons in Raphe
What neurotransmitters does MDMA/ecstacy release?
Dopamine and serotonin
What are the effects of MDMA?
Stimulant and hallucinogenic effects
Is MDMA as effective as amphetamine or LSD?
No
What cognitive effects does MDMA have?
Feeling of closeness
Empathy
Love
Heightened self-awareness
Does MDMA cause dependence?
Yes because of rewarding reinforcing effect
What are the effects of MDMA on the cardiovasular system?
Increases HR
Increases BP
What effect does MDMA have on thermoregulation?
Disrupts it - causes chills and sweating
What is the effect of the active metabolites of MDMA on the brain?
Potential degeneration of 5-HT and DA neurons Affects - Mood - Memory - Sleep - Appetite
What effect do CNS depressants have?
Relaxation
Sense of well being
What are two forms of cannabis that are often taken?
Marijuana - Dried leaves - Flower heads Hashish - Extracted resin
What is the active component in cannabis?
D9-THC
What are the cognitive effects of D9-THC?
Relaxation
Feeling of well being
Sharpened sensory awareness - increased intensity of sounds and sights
What influences the effects of D9-THC?
Characteristics of drug
Individual
What are the cannabinoid receptors to which D9-THC binds?
CNS - CB1
PNS - CB2
What type of receptors are CB1 and CB2, and what effect do they have when they’re activated?
GPCRs
Inhibition of adenylate cyclase > inhibition of transmission
Which other drug can possibly interact with D9-THC?
Caffeine
What is anandamide?
Endogenous cannabinoid receptor agonist
Unknown physiological role
What is nabilone?
Synthetic cannabinoid analogue
Being developed as anti-emetic
What is the effect of cannabinoids on neurotransmitters?
Increase dopamine neuronal firing by decreasing GABAergic inhibition of dopamine neural activity
What are the central effects of D9-THC?
Impaired short term memory Impaired motor coordination Catalepsy Analgesia Anti-emetic Increased appetite
What are the peripheral effects of D9-THC?
Tachycardia
Vasodilation
Reduced intraocular pressure
Bronchodilation
Does D9-THC cause dependence?
Some evidence of physical and psychological dependence in heavy users
What are the effects of ethanol on the neuron?
Inhibit Ca channel opening > stop exocytosis
Enhance GABA action and glycine mediated inhibition
- GABA-A receptors
- Reversal by Flumazenil
Opens some K channels > cell hyperpolarises
Inhibits glutamate receptors
- NMDA channel
How does ethanol bind to the GABA-A receptor?
Binds in lipid membrane
Changes shape of receptor
Increases GABA binding
What are the behavioural effects of ethanol?
Subjective
- Increased self confidence
- Euphoria
- Usually loud and outgoing
- Less often morose and withdrawn
- At higher doses aggression and mood swings
What are the motor effects of ethanol?
Loss of motor coordination
Slurred speech
What are the tissue effects of ethanol?
Liver damage
Neurodegeneration
Foetal impairment
What is the mechanism of tolerance of ethanol?
Pharmacokinetic mechanism - enhanced clearance
What are the behavioural signs of ethanol withdrawal?
Anxiety Insomnia Nausea Anorexia Delusions Hallucinations
What are the neurological signs of ethanol withdrawal?
Tremor Hyperactive reflexes Agitation Delirium Convulsions Status epilepticus
What are some physical signs of ethanol withdrawal?
Vomiting
Postural hypotension
Sweating
Hyperpyrexia