Drug Abuse, Addiction + Dependence Flashcards
What is drug abuse?
Use of drugs for non-therapeutic use
What is substance misuse disorder?
Persistent use of drugs despite substantial harm + adverse consequences
What is addiction?
Compulsion to engage in a behaviour despite substantial harm + adverse consequences
What is dependence?
Physiological state in which the person can only function normally in the presence of the drug
What is withdrawal?
Removal of the drug produces a physiological disturbance
What are examples of amphetamines?
Speed
Ecstasy
Crystal meth
MDMA
What are amphetamines used for?
ADHD
Narcolepsy
What does amphetamine-like drugs do?
Increase synaptic levels of monoamines by causing non-impulse dependent release
= release of neurotransmitters without release
What does the release of excess monoamine neurotransmitters induce?
Amphetamines
“High”
Reward
Locomotor activation
What transporters does monoamine neuronal terminals have?
Amphetamines
Dopamine transporter (DAT)
Noradrenaline transporter (NAT)
Serotonin transporter (SERT) 5-HTT
What is the selectivity of amphetamines dependent on?
Affinity for each transporter
What does methamphetamine have the highest affinity for?
DAT
What does d-amphetamine have affinity for?
DAT + NAT
What does ecstasy have affinity for?
DAT, NAT + SERT
Describe the mechanism of action for amphetamines
Amphetamines enter nerve terminal via plasma membrane transporter
Different affinities for transporters
Amphetamines are transported into vesicles by VMAT2
Cause release of neurotransmitters into cytosol
Membrane transporter reverses release of neurotransmitters
Reuptake of neurotransmitters BLOCKED
Describe how amphetamines activate the reward pathway
Increase dopamine release + increase stimulation of D2 + D1 receptors in nucleus accumbens
What is the mechanism of action of cocaine?
Binds to DAT
Reuptake of DA is blocked
Level of DA increased in synaptic cleft
How does cocaine activate the reward pathway?
Blocks DA reuptake + increases stimulation of D2 + D1 in nucleus accumbens
What are examples of exogenous opioids (synthetics/natural)?
Codeine
Pethidine = childbirth
Morphine
Diamorphine (heroin)
Fentanyl
Oxycontin
What is the effects of opioids?
Analgesia
Sedation
Anaesthetic
Anti-tussive = stop coughing
Reduce GI motility
Depress respiration
Constrict pupils
What is tolerance?
Response to given concentration of drug is reduced
More drug must be given to achieve same response
How does opioids activate the reward pathway?
Activate μ receptors
= decrease GABA release
= DA neurones are disinhibited
= fire more
Describe the dependence of heroin
Produces “high”
Repeat
Addiction
Tolerance develops
More drug
Physical dependence
Relieve withdrawal + psychological dependence
Describe the dependence of codeine
Therapeutic use
Tolerance develops
More drug needed
Physical withdrawal
Addiction
How do you manage opioid withdrawal?
Gradual dose reduction
Substitution of longer acting opioid
Change route of administration
Substitution of non-euphoric opioid
Treatment of withdrawal effects (anxiety, diarrhoea)
What can reverse opioid overdose?
Naloxone = nasal spray
Describe the nicotine receptor
Pentamer
Open receptor is permeable to Na+ + K+
How does nicotine activate the reward pathway?
Activates DA neurones directly + indirectly via Glu inputs
What is an example of dependence on a non-rewarding substances?
Benzodiazepines
What can benzodiazepines be used for?
Insomnia
Anxiolytic
Muscle relaxant
Describe GABA
Important neurotransmitter
Actions mediated by GABAa + GABAb
BOTH inhibitory
Describe the GABAa receptor complex
Pentamer
GABA binds = open
Lets Cl- through = inhibitory
Benzodiazepine bind = enhance function of GABA
What must you do with GABA + Benzodiazepines?
Limit prescription to 3 days
Reduce dose gradually
Switch to longer half-life drugs
= decreased dependence
