Chapter 17: Drugs of Abuse Flashcards
what causes tolerance/decreased response to drug?
neuronal changes and changes in receptors/metabolism
physiological dependence is characterized by ___or ___ effect when the drug is removed
withdrawal symptoms; rebound
why cant beta blockers be abruptly stopped?
the body has become used to their BP lowering effects , causing rebound hypertension
what is psychologic dependence?
drug-seeking behaviour
prescription drugs that have either ___ or ___ effects are often misused
sedative or stimulant
does LSD have a therapeutic use?
no
can LSD be addictive?
no evidence to say it is addictive
t/f not all drugs that are misused are addictive
true
t/f all recreational drugs are addictive
no
there is a link between the activation of ___ pathways in the brain and the development of addiction
dopamine
activation of the mesolimbic dopamine pathways promotes ___ and ___ leading to addiction
reinforcement and reward
t/f different brain regions communicate to determine how we respond to a situation
true
the dopaminergic neurons that are linked to addiction are found in the mesolimbic pathways that runs from the ___ to the nucleus accumbens
ventral tegmental area (VTA)
drugs that cause addictive typically release ___ from the VTA neurons in the nucleus accumbens
dopamine
what happens in terms of addiction and aversion when dopamine is blocked from entering the nucleus accumbens?
has an avoidance effect in animal studies
t/f just blocking the release of dopamine from the VTA will 100% cure addiction
false, not that simple
the dopamine hypothesis of addiction states that all addictive drugs cause an increase in the release of dopamine from the ___ into the ___
VTA into nucleus accumbens
opioids, THC and GHB affect the dopamine release from the VTA by targeting ____ receptors
GPCR
benzodiazepines, nicotine, and ethanol affect the dopamine release from the VTA by targeting ___ receptors
ion channel
cocaine, amphetamine, ecstasy affect dopamine release from the VTA by targeting ___
transporters
drugs may act upstream of the VTA on ___ neurons to cause disinhibition of the dopaminergic neurons
GABAergic
opioids act on ___ receptors of the GABA neuron to reduce the amount of GABA onto VTA
mu opiod
cannabinoids act on ____ receptors of the GABA neuron to reduce GABA release on VTA
CB1
dopaminergic VTA neurons are influenced by inhibitory ___ neurons
inhibitory GABA
where are mu opioid receptors found on GABA and dopaminergic neurons?
GABA= dendrites of cell body dopa= presynaptic terminals
where are CB1 receptors found on GABA neurons?
presynaptic terminals
the mu opioid and CB1 receptors are coupled to a ___ G protein
GI/GO
the GI/GO pathway in GABA neurons stimulated by opioids and cannabinoids is mediated by ____ subunits
G beta-gamma
in cell body dendrites, when the mu opioid receptors are stimulated, the Gbeta-gamma subunit increases ___ efflux leading to ____that reduces the excitability of the neuron
K+; hyperpolaization
in the presynaptic terminals, when Gbeta-gamma subunits are activated they have an inhibitory impact on ___channels preventing the release of ____ which results in disinhibition of VTA dopaminergic neuron
Ca; NT
t/f drugs can act directly on VTA dopaminergic neuron
t
nicotine acts on nicotinic Ach receptors on the VTA dopaminergic neuron, causing influx of ___ ions leading to membrane ____.
Na; depolarization
nicotine on the VTA dopaminergic neuron has what effect?
increases excitability; releasing more DA into the nuclei accumbens
nicotine stimulates ___ nicotinic Ach receptors
NN
nicotine is ___ agonist of the NN receptor and varenicline is a ___agonist of the NN receptor
full; partial
which has a higher binding affinity for nicotine receptor? varenicline or nicotine?
varenicline
cocaine increases DA signalling by preventing ___
DA re-uptake
amphetamines increase DA signalling by increasing ___
DA release into synapse
amphetamines and cocaine influence the storage and re-uptake of ___ in presynaptic neurons
NE
how do amphetamines make NE be released from neurons?
bind to catecholamine transporters to be brought into NE vesicles until there is no room for NE and it gets pushed out into the cytoplasm, reaches such high levels that the NET lets it out into the synapse w/o energy required
how does cocaine increase NE levels?
blocks the NET so NE cant be taken back up into the presynaptic neuron, so it has a longer duration of action
t/f what amphetamines and cocaine do to NE, they also do to DA
treu
cociane acts on ___ tp prevent DA re-uptake by presynaptic neuron
DAT
t/f derivatives of amphetamines can be used to treat ADHD
t
ADHD is thought to involve reduced levels of __ and ___
DA and NE
t/f effects of amphetamines are opposite in patients with ADHD
t
cocaine is used as an anesthetic in some parts of the world bc of its ability to block ___channels
Na
if cociane is more pure, it will make the gums ___
tingle and possibly go numb
the intoxicating effects of drugs are based on what 2 factors?
how much and how fast the drug gets into the CNS
compare snorted and smoked (crack) cocaine in terms of peak blood concentration and onset time
crack has faster onset with lower peak concentration compared to nasal
the white fluffy powder form of coccaineis the ___ form
hydrochloride salt
what type of cocaine can be injected? how?
the white fluffy hydrochloride salt form which is ionized and can be dissolved in water to be injected
what is the “downside” of snorting the ionized form of cocaine?
ionized form has less optimal absorption across membrane
the free base form of cocaine is more known as ___
crack
which is better absorbed across membranes, crack or fluffy cocaine?
crack b/c its more neutral and not ionized
heroin has a much higher ability to accumulate in the CNS compared to morphine due to a small change in the ___
chemical structure
heroin is a ___opiod also known as diacetylmorphine
semi-synthetic
what is the structural change between heroin and morphine that makes heroine better absorbed across the BBB?
heroin has acetyl groups added to the hydroxyl groups, making it less polar so it dissolves across the lipphillic BBB better
once in the CNS, heroin is ___ to exert its effect
deacetylated
t/f heroin can be metabolized to morphine in the periphery which reduces its crossing of BBB when given orally
t
Fentanyl is a ____ opioid with a very different structure from heroin and morphine
fully synthetic
Fentanyl has a much higher LogP values, therefore its crossing of the BBB is much ___ (higher/lower) than heroin and morphine
higher
fentanyl has a much higher affinity for the ___receptor, making it much more likely to experience an overdose
mu opioid
t/f fentanyl is very cheap to produce and many people have overdose bc their drugs have been laced with fentanyl
true
Naltrexone MOA
opioid antagonist that quickly reverse life threatening respiratory suppression during an acute opioid overdose
why cant opioid antagonists like Naltrexone be used to help patients with chronic opioid use?
worsen withdrawal effects that will go away as soon as an opioid is used, so could make patients want to use opioid more that if they quit cold turkey
what are the withdrawal symptoms for opioids?
chills, muscle aches, vomiting, diarrhea, anxiety, hostility
what is a good treatment for helping patients stop opioid use?
a long acting opioid agonists with a slow onset so there is less addictive rush
Methadoen MOA
long-acting opioid agonist commonly used in treatment of opioid use disorder
Buprenorphine MOA
partial agonist of Mu opioid receptor that has slow action and also competes out full opioid agonists
