lect 10 benzodiazepines and Cannabinoids Flashcards
major compund in marijuana
THC and CBD
cannabinoids therapeutic effects for?
chronic pain in adults and chemotherapy induced nausea
cannabinoids receptors and where
CB1 IN BRAIN CB2 IN IMMUNE SYSTEM
made in the body and natural ligand for cannabinoids receceptors
endocannabinoids
compounds of endocanna.
anandamine AEA, 2-AG
plant derived cannabinoid and coumpounds
phytocannabinoid, THC and CBD
made in lab cannabinoids and compound
synthetic cannabinoid, mimics of THC
pharmacodynamics of cannabinoids on transmitters
presynaptic inhibition of transmitters release
pharmacodynamics of AEA AND 2-AG at CB1 receptor
AEA AND 2-AG synthesized post synaptically, act presynaptically on CB1, increase potassium intake decreases calcium, hyperpolarization and inhibition of transmitters release pre synapt. less post synapt stimulation
Distribution cannabinoids
extracellular water, lipid soluble so stored in fat and bind serum proteins
Metabolism cannabinoids
Mainly in liver
excretion cannabinoids
Metabolites in saliva and sweat, largely in urine, some by liver to small intestine (feces)
cannabinoids act on which pathway for addiction
reward pathway in brain
schizophrenic brain has elevated levels of what
dopamine
first effective neuroleptic (antipsychotic) drug
chlorpromazine
amphetamine and cocaine users have more chances of developing what and why
have more chance of schizophrenia due to blockage of dopamine reuptake
How does chlorpromazine work
Block d2 receptors preventing activation by dopamine
pathways affected by antipsychotic drugs
mesolimbic and mesocortical pathway
increased dopamine effects on mesolimbic
dellusions, hallucinations
increased dopamine effects on mesocortical
intellectual impairement and defective cognitive abilities
downside of chlorpromazine
not very selective and had side effects, acted on histamine and 5-HT receptors
how does monoamine oxidase inhibitors work
inhibits the metabolism of neurotransm. by monoamine oxidase in presynapt and synapse. increases levels of excitory neurotransm. at synapse and post synapse
tricyclic antidepressants?
block 5-ht and noradrenalin reuptake transporter. so increase of neurotrans at synapse and post synapse
side effects of tricyclic antidepre.
block adrenergic, histamine and cholinergic receptors so affects vascular system (effects on SNS), produces sedation, affects GI tract and vision
selective serotonin reuptake inhibitors
interferes reuptake of serotonin by blocking 5-HT reuptake transporters. increase of neutrans at synapse and post synapse
how many 5-HT receptors and what type of receptor
15 and all over the place, GCPRS BUT 5-HT3 ligand gated ion channel
Most common SSRI and potency
Fluoxetine (Prozac) high potency of inhibiting reuptake 5-HT compared to other drugs blocking reuptake of NA
Atypical 5-Ht + NA reuptake inhibittor
they affect neurotransmitters in unique ways
seasonal depression treatment
exposure to a light source that emits the same wavelengths as sun
what are benzodiazepines used for
anxiety
true or false? anxiety is an adaptive system
True
what anxiety is not normal
anxiety that goes past an effective point and triggered by normal situations in life
what is anxiety states
combination of physical and mental manifestations. Are attacks or persisting state.
extreme state of anxiety disorder
Panic disorder
Core structure of benzodiazepines
1-4benzodiazepine
major effects of benzo. (6)
anti-anxiety(hippocampus amygdalla), induce sleep(celebral cortex), anticonvulsant(cerebellum hippocampus), muscle relaxant(spinal cord cerebellum), impair memory formation(amnesia hippocampus cerebral cortex), abuse potential(midbrain dopamine)
lethal to therapeutic window ratio of benzo
1000 so safe
first benzo drug widely used
Diazepam
what do stage fright people use instead
beta receptors blockers in ANS to prevent palpitations
benzo drugs acts on which receptors
GABA A receptors
first benzo in 1960
chlordiazepoxide
pharmacodynamic of GABA neurotrans.
bind to its 2 binding sites on receptor (2 gaba). Channel opens and influx of Cl- ions. hyperpolarization and inhibitory post synaptic potential. inhibits many neurotrans like 5-HT, dopamine, noradrenaline which leads to effects of benzo like antianxiety and sedation
pharmacodynamic of benzo
allosteric binding site (BDZ) on receptors different to gaba binding site. Facilitates binding of gaba to its site creating greater influx of chloride. so increases gaba activity gabaergic inhibition. binding by itself does nothing.
true or false? different drugs act on same location of gaba receptor
False.
GABA A subtypes and subunit
5 alpha subunits, each account for different effects of benzo and two subunits (synaptic and extrasynaptic)
two main categories of subunit of gaba a receptors
synaptic (subsynaptic) alpha 1-3 and extrasynaptic alpha 4-6
Gaba A receptor responsible for phasic inhibition
subsynaptic (synaptic) response
true or false? Major site of action of benzo happens on extrasynaptic receptors
False. its synaptic
tonic inhibition occurs where
Extrasynaptic receptor
benzo effect on dose response curve
shifts curve to the left, use of benzo leads to higher effects with lower dose of gaba
barbiturates effect on gaba
channel is open longer. Can open channel by itself so more powerful but more dangerous than benzo
diffence between benzo and barb.
benzo: affects frequency, no direct action, safer and selective
barb: affect duration, direct action, not selective not safe
which is easier to overdose benzo or barb
barb, benzo level off as concentration gets higher, barb is straight line so very lethal
alpha unit of gaba a for sedation
alpha 1
alpha unit of gaba a for anxiety
alpha 2
dose response curve for agonist and antigonist of benzo binding site BDZ
agonist shifts to left and antagonist to right
type of inverse agonists
beta-carbolines
which will shift dose response curve more to right for benzo effects
inverse agonists
GABA + benzo antagonist = ?
no effect normal curve, only block BDZ but not gaba
GABA + benzo inverse agonist =?
reduced effects of gaba
gaba + benzo agonist = ?
more effects of gaba
new drugs acting on GABAergic transmition and act on different sites than benzo
Zolpidem
drugs that act on GABA B receptor
presynaptic, G-coupled K channel in spinal cord for muscle relaxation
absorption of benzo
highly absorbed orally, highly lipid soluble, goes quick to brain and peak in 1 hour
metabolism of benzo
metabolized by CYP3A AND CYP2C19, have active intermediate with long half lives.
ex: diazepam or chlodiazepoxide metabolized into nordiazepam and the oxazepam
half lives of benzo
very long because are converted to multiple intermediates
old people and benzo dose
since low metabolism, careful doses to not overdose
toxicity of benzo
low when alone, but high if combined with cns depressants
name of benzo antagonist
flumazenil
how does tolerance to benzo have an effect on tthee body
tolerance will cause changes reuptake of neurotrans, uptake of gaba
withdrawal symptomps of benzo and duration (5)
anxiety, hallucinations, loss of coordination, restless leg syndrome, (seizures,coma, death). last a week
withdrawal on REM sleep
benzo suppressed REM but withdrawal causes REM rebound so many nightmares
insomnia treatment
short half life benzo
non benzo drug for sedation
zolpidem
How does Zolpidem work
only binds to a1, treats insomnia without changing REM sleep. binds next to BDZ site
