Exam 4 - Lec 58-59 Anxiety and Sleep Yang Flashcards
main NT target for current meds for sleep
a. serotonin
b. GABA
c. adenosine
d. histamine
e. catecholamines (NE, epi, dopamine)
b. GABA
two allosteric sites for BZDs
alpha 1, gamma 2
BZDs inc ______ of calcium channel opening
a. frequency
b. duration
a. frequency
barbiturates inc _______ of calcium channel opening
a. frequency
b. duration
b. duration
where do Z-hypnotics act at the BZD receptor?
BZ1 receptors of alpha 1
drug that is a BZD antagonist and is used for overdose
flumazenil
T or F: barbiturates inc duration of calcium channel opening and has direct effects on GABA-A at high doses
T
SAR of BZDs: 2 things to know (slide 18)
-1 position alkylation is source of active metabolites
-annealating the 1-2 bond with an “electron rich” ring (triazole or imidazole) yields high affinity and dec half-life
T or F: diazepam has a short half-life
F
slow elimination rate BZDs have what in common?
they all have active metabolites
which of the following is a slow elimination rate BZD?
a. diazepam
b. clonazepam
c. midazolam
a. diazepam
slow elimination rate BZD used as an anxiolytic, for alcohol withdrawal, and tx of seizures; metabolites accumulate
a. chlordiazepoxide
b. diazepam
c. flurazepam
d. clorazepate
e. quazepam
f. prazepam
b. diazepam
what are the two rapid elimination rate BZDs?
midazolam, triazolam
intermed elimination rate BZD used as an anticonvulsant
a. alprazolam
b. lorazepam
c. clonazepam
d. oxazepam
e. temazepam
c. clonazepam
(tolerance may develop with prolonged use)
what is midazolam used for? (slide 22)
rapid anesthesia
which drug class is most likely to cause toxicity on a dose-response curve?
a. barbiturates
b. BZDs
a. barbiturates
BZDs dec what stages of sleep? (3 of them)
REM, stage 3 and 4
T or F: flumazenil can treat a barbiturate overdose
F (BZD or Z-hypnotic overdose)
which Z-hypnotic(s) are used for short-term tx of insomnia? SELECT ALL THAT APPLY
a. zolpidem
b. zaleplon
c. eszopiclone
a. zolpidem
b. zaleplon
which Z-hypnotic(s) are used for long-term tx of insomnia? SELECT ALL THAT APPLY
a. zolpidem
b. zaleplon
c. eszopiclone
c. eszopiclone
how long can zaleplon be used for insomnia? (range)
7-10 days
T or F: Z-hypnotics cause more negative effects on sleep patterns vs BZDs
F (less negative effects)
what SE of Z-hypnotics should we warn pts about?
nocturnal activity, so doing things while they are asleep such as driving, cooking, eating, etc
which of the following is a long-acting barbiturate and anticonvulsant?
a. phenobarbital
b. pentobarbital
c. secobarbital
d. thiopental
a. phenobarbital
which of the following is a short-to-intermediate acting sedative-hypnotic barbiturate?
a. phenobarbital
b. pentobarbital
c. secobarbital
d. thiopental
b. pentobarbital
which SE of barbiturates can lead to death?
respiratory depression
barbiturates and BZDs bind to which GABA-A receptors subunits?
alpha 1-5
Z-hypnotics bind to GABA-A ____ receptors of ___ and inc _______ of GABA-A channel opening
BZ1; alpha 1; frequency
which of the following does NOT increase frequency of GABA-A channel opening?
a. barbiturates
b. BZDs
c. Z-hypnotics
a. barbiturates
the GABA-B receptor is what kind of receptor?
Gi/o-coupled (metabotropic; inhibitory)
which of the following is FALSE about the GABA-B receptor?
a. it is Gi/o-coupled
b. located in brain and limbic system
c. presynaptic GABA-B activation leads to decreased calcium conductance
d. postsynaptic GABA-B activation leads to decreased potassium conductance
e. baclofen and GHB are agonists
d. postsynaptic GABA-B activation leads to decreased potassium conductance
(increased potassium conductance)
antagonist of GHB
there is none (meaning no reversal drug in the case of toxicity)
ramelteon is a melatonin _______
a. antagonist
b. agonist
b. agonist
ramelteon MOA
-has high affin for MT1 and MT2 melatonin receptors in the SCN
-serves as “master clock” by regulating circadian rhythm
T or F: there is no abuse, withdrawal, or dependency with ramelteon
T
which drug is considered an orphan product?
a. melatonin
b. ramelteon
c. tasimelteon
d. suvorexant
c. tasimelteon
(only approved in a specific population i.e. blind pts)
what is orexin? how do orexin receptor antagonists work for insomnia?
Orexin neurons in the hypothalamus produce orexin, which regulates sleep-wake cycles and helps drive arousal and attention (basically helps you stay awake). Blocking these receptors promotes sleep (reducing arousal) and decreases wakefulness
drug that is an orexin receptor antagonist
suvorexant (Belsomra)
suvorexant MOA:
receptors located in the _________; decreases arousal and attention; reduces ______ stimuli (DA release) via receptors that modulate the mesolimbic projections between the _____ and the _____ _____
hypothalamus; rewarding; VTA; nucleus accumbens
indication for suvorexant
tx of insomnia
two drugs/drug classes that can be used as a sedative/hypnotic (slide 14; lec 59)
trazodone
antihistamines (OTC)
what drug class are diphenhydramine, doxylamine, and pyrilamine?
antihistamines
which herbal/natural sedative-hypnotic can be used for jet lag and for night shift workers?
a. tryptophan
b. melatonin
c. valerian
d. chamomile
b. melatonin
AE of valerian
hepatotoxicity
how can too much NE lead to anxiety?
too much NE stimulates ANS (fight or flight), and enhances sensitivity to the amygdala (fear center) leading to anxiety
glutamate is converted to GABA by which enzyme in the CNS?
glutamic acid decarboxylase
which drug tx for anxiety is quick acting and effective?
a. BZDs
b. SSRIs
c. SNRIs
d. TCAs
e. buspirone
a. BZDs
new breakthrough nasal spray antidepressant
esketamine
which of the following is TRUE about buspirone?
a. full agonist on brain 5HT1A receptors
b. longer onset of action than BZD (adaptive response)
c. high abuse potential
d. good for panic disorders
b. longer onset of action than BZD (adaptive response)
(a is partial agonist; c is low abuse potential; d is not good for panic disorders, BZD is much faster)
why does propranolol’s dose need to tested and titrated initially when used for social anxiety?
it is sedating, so they might go to sleep if dose is too high
propranolol decreases _______ sx of anxiety
peripheral
uses of clonidine for anxiety (2 of them)
panic attacks; anxiety assoc with withdrawal
4 glutamatergic agents that are investigational anxiolytics
d-cycloserine
memantine
fenobam
LY354740
d-cycloserine and memantine fall under which class?
a. NMDA receptor modulators
b. mGluR5 antagonist
c. mGluR2/3 agonist
a. NMDA receptor modulators
fenobam is a glutamatergic agent that falls under which class?
a. NMDA receptor modulators
b. mGluR5 antagonist
c. mGluR2/3 agonist
b. mGluR5 antagonist
LY354740 is a glutamatergic agent that falls under which class?
a. NMDA receptor modulators
b. mGluR5 antagonist
c. mGluR2/3 agonist
c. mGluR2/3 agonist
