L10 Benzodiazepines and Cannabinoids Flashcards
TF: there is conclusive evidence that cannabinoids have therapeutic effects for chronic pain in adults and chemotherapy-induced nausea/vomiting
true
what are the 2 major compounds in marijuana
THC (tetrahydrocannabinol)
CBD (cannabidiol)
What receptors do cannabinoids act on and where are they located
CB1 (GPCR): brain (psychotropic effects)
CB2: immune system/periphery
What is the action of cannabinoids on CNS? Which receptor is activated?
inhibition of GABA, glutamate, dopamine mainly presynaptically
CB1 receptors
what are the functions associated with the hippocampus?
stress, learning, memory
what functions are associated with the medulla
nausea/vomiting, CTZ
what functions are the basal ganglia and the cerebellum involved with
movement
TF: hypothalamus is associated with higher cognitive function
false
it is associated with appetite
what are the 3 families of compounds that act on cannabinoid receptors
1) endocannabinoids: made in the body
2) phytocannabinoids: plant-derived cannabinoids similar to endocannabinoids
3) synthetic cannabinoids: made in labs, mimics of THC and other plant-derived compounds
What are the major endocannabinoids? Which compound are they derived from and how are they produced?
anandamide, AEA (arachidonoylethanolamide)
2-AG (2-arachidonoylglycerol)
both are arachidonic acid derivatives (arachidonic acid is a constituent of the plasma membrane and a precursor of many compounds)
produced/synthesized by postsynaptic enzymes (thus in the postsynaptic neuron) so that they can act on presynaptic CB1 receptor to inhibit transmitter release (that is the role of CB1)
explain what the retrograde signaling system does in the context of cannabinoids
it involves the presynaptic inhibition of transmitter release
- AEA or 2-AG (endogenous cannabinoids) are synthesizes in the post-synaptic neuron and act pre-synaptically at the CB1 receptor
- activation of CB1 at pre-synaptic terminal decreases Ca2+ intake (blocks channels) into pre-synaptic neuron and increase K+ efflux into synaptic cleft (opens channels) - it also inhibits vesicle exocytosis
- decreased reuptake of calcium thus decreasing release of neurotransmitters (also cell hyperpolarization decreases excitability as well)
- less neurotransmitters = less stimulation
which compounds can act on CB1
endocannabinoids (AEA, 2-AG), THC, dronabinol, nabilone
*NOT CBD (low affinity)
activation of CB1 opens/blocks calcium channels and opens/blocks potassium channels
blocks calcium channels (decreasing synaptic transmission)
opens potassium channels (hyperpolarization
TF: cannabinoid receptors are on multiple types of cells
true
How can cannabinoids be absorbed?
smoking, ingesting/orally (readily absorbed by small intestine and colon), skin/topical (lipid soluble compounds)
how are cannabinoids distributed in the body
they are distributed to extracellular water since they are highly lipid soluble
they can also be stored in fat
some bind to serum proteins
rapidly cross the blood brain barrier
can also be passed to the fetus
where does cannabinoid metabolism occur? does it result in metabolites?
liver, yes
how are cannabinoids excreted
through saliva, sweat, urine (largely), feces, bile
where are the major sites of action for THC and CBD?
THC: CYP1A2 inducer
CBD: CYP3A4 inhibitor
both are involved in the metabolism of many other drugs
Why must you be cautious of THC and CBD use when consuming other drugs?
THC and CBD can modify the metabolism of other drugs
TF: Smoking weed isn’t harmful to lungs
false
there are carcinogens when smoking weed (similar to smoking cigarettes)
what are the main risks associated with smoking cannabis
cancer, heart attacks, strokes
TF: cannabinoids do not act on the reward pathway in the brain
false, they do act on the reward pathway
Can chronic use of cannabinoids change the properties of GABA and glutamate receptors?
yes (the details are still being researched)
what is the likely withdrawal reaction associated with chronic cannabinoid usage (CUD - cannabis use disorder)
withdrawal is likely excitatory since cannabinoids have inhibitory action
non-lethal (like nicotine)
TF: schizophrenia is more dependent on genetic factors rather than environmental factors
false, it is the opposite
how are dopamine levels in a schizophrenic patient?
dopamine levels are elevated
what is the name of the first effective neuroleptic (antipsychotic) drug
Chlorpromazine
TF: Amphetamines and cocaine (CNS stimulants) caused higher risks of schizophrenia
True, since these would block dopamine reuptake thus increasing dopamine levels
Which receptor does chlorpromazine act on and in what way
D2 receptor, blocks it thus preventing activation by dopamine
BUT not selective and will block other things
What is the effectiveness of antipsychotic drugs based on?
the blocking of D2 receptors
which pathways do antipsychotic drugs act on
mesolimbic and mesocortical
overactivation of the mesolimbic and mesocortical pathways due to incerased dopamine causes what effects respectively?
mesolimbic: delusion and hallucination
mesocorticol: impaired effect, intellectual impairment, defective cognitive abilities
TF: dopamine receptors can excite or inhibit
true
is D2 an excitatory or inhibitory dopamine receptor
inhibitory
Blocking D2 receptors can help reduce the overactivity of dopaminergic transmission, particularly in the mesolimbic pathway, which is thought to contribute to symptoms like hallucinations and delusions.
What are the 4 major categories of antidepressants and what do they act on?
they mainly act on the metabolism and uptake of transmitters
1) MAOIs (monoamine oxidase inhibitors)
2) Tricyclic antidepressants
3) SSRIs (selective serotonin reuptake inhibitors)
4) Atypical NA + 5-HT reuptake inhibitors
Where are MAOs found and what do they do
in the presynaptic terminal and in the synaptic cleft, they breakdown neurotransmitters (NA, DA, 5-HT)
How do tricyclic antidepressants help with depression
they interfere with neurotransmitter reuptake by blocking 5-HT and NA transporter
though this has many side effects due to blocking other receptors (adrenergic, histamine, cholinergic)
Why do tricyclic antidepressants cause so many side effects
NA blockage affects vascular system (sympathetic nervous system)
histamine receptor blockage causes sedation
ACh receptor blockage affects GI tract and vision
What distinguishes SSRIs from other antidepressants
they are more specific as they only block 5-HT reuptake transporters without inhibiting reuptake of other neurotransmitters
TF: 5-HT receptors are only found in the CNS
false,
found in smooth muscles, platelets, CNS, PNS, GIT, blood vessels, etc.
TF: 5-HT3 is a GPCR 5-HT receptor
false, it is an ion-gated ion channel
though most 5-HT receptors are GPCRs
what is commonly administered SSRI
fluoxetine (prozac)
most effective at inhibiting 5-HT reuptake with lower side affects due to being more selective
which type of antidepressant is most used nowadays
SSRIs
Why is the brain so difficult to study in terms of drug action and effect
neurons follow a diffused patterns making it difficult to pinpoint the order of transmission
What are benzodiazepines used to treat
anxiety
what are the major effects of benzodiazepines
antianxiety (hippocampus and amygdala)
sedative/hypnotic (cerebral cortex)
anticonvulsant (cerebellum, hippocampus)
muscle relaxant (spinal cord, cerebellum, brainstem)
amnesia (cerebral cortex, hippocampus)
antiepileptic (cerebellum, hippocampus)
why do benzodiazepines have abuse potential
they can act on the midbrain which is involved in dopamine pathways
what does it mean when the lethal to therapeutic dose is a small number
it means the lethal dose is very close to the therapeutic dose
what is the first benzodiazepine drug to be widely used
diazepam (valium)
TF: benzodiazepines act as antagonists to GABAA receptors
false, they act allosterically
which was the first benzodiazepine
chlordiazepoxide (librium)
describe the action of GABA receptors
2 neurotransmitters must bind, allowing Cl- influx into cell
this leads to hyperpolarization (inhibitory effect)
GABA thus has an inhibitory effect on many neurotransmitter systems
This results in antianxiety/sedative/anticonvulsant/etc. effects
when benzodiazepine binds to the BDZ (benzodiazepine binding site), what happens?
the binding facilitates the 2 GABA neurotransmitters to bind thus increasing GABA activity and facilitates GABAergic inhibition
TF: benzodiazepines and ethanol both act at the same location of the GABA receptor
false
benzodiazepines, ethanol, barbiturates, steroids, anesthetics all act on different locations of the same receptor
what are the subsynaptic GABA_A receptors responsible for
phasic inhibition and major site of action of benzodiazepines
what are the extrasynaptic GABA_A receptors responsible for
tonic inhibition
TF: benzodiazepines will shift the dose-response curve to the right
false, it will shift to the LEFT
(increase chloride flow i.e. action of the GABA_A receptor)
What is the difference between benzodiazepines and barbiturates
benzodiazepines affect frequency of opening (safer and more selective)
barbiturates increase the duration of channel opening and act directly to increase chloride passage through channel (affect many sites, not as safe)
TF: it is easy to overdose on barbiturates
false
why would one need to use a benzodiazepine antagonist? give an example of a benzodiazepine antagonist
to reverse the effects of benzodiazepines
flumazenil
what is an inverse agonist of benzodiazepine? example and what it does
beta-carbolines
increase anxiety (opposite to benzodiazepines)
inverse agonists of benzodiazepine shift the dose-response curve to the left/right
right
TF: benzodiazepine inverse agonists bind to the same site as benzodiazepines
true
What is Zolpidem
a nonbenzodiazepine that only binds to alpha 1 of GABAA receptor to treat insomnia without altering REM sleep (binds next to BDZ site)
GABA + benzodiazepine agonist = ? (effect of GABA)
increased effect of GABA
GABA + benzodiazepine inverse agonist = ? (effect of GABA)
decreased effect of GABA
GABA + benzodiazepine antagonist = ? (effect of GABA)
no effect of GABA (GABA somewhat normal function depending on whether the antagonist is competitive or not, since BDZ is an allosterically binding molecule, i believe there would be no competition thus normal GABA function)
what is Zolpidem
it is a newer drug that acts on GABAergic transmission, binds close (but not at) DBZ and has a range of side effects
what effect do GABA_B agonists have?
they cause muscle relaxation
