Exam 4 - Sedative/Hypnotics/Anxiety (Watts/Ott) Flashcards
Definition of Sedative
calms anxiety
decreases excitement/activity
does NOT produce drowsiness or impair performance
Definition of Hypnotic
induces sleep!!
implies restful/refreshing sleep
Definition of Anxiolytic
Anti-anxiety
relieves anxiety w/out sleep or sedation
(*not all anxiolytics are sedatives….)
Definition of Narcotic
actually means “sleep producing”
noooow refers to opioids or illegal drugs
Reticular Formation:
regulates ________ and ___________
sleep-wake transitions
and
synchronization of EEG
Reticular Formation:
intricate system composed of __________ in what is otherwise _______
loosely clustered neurons
white matter
3 stages of Sleep
Wakefulness
Slow-wave sleep (NREM)
Paradoxic sleep (REM)
what are the stages of NREM Sleep
stage 1: dozing
stage 2: unequivocal sleeo
stage 3: voltage increase/frequency decrease
stage 4: delta waves
NREM Sleep Stages:
what is stage 1?
dozing
NREM Sleep Stages:
what is stage 2?
unequivocal sleep (asleep but easily awaken)
NREM Sleep Stages:
what is stage 3?
voltage increase/frequency decrease
NREM Sleep Stages:
what is stage 4?
delta waves
what are the GABA receptor subtypes
alpha 1
alpha 2
alpha 3
alpha 5
what GABA receptor subtype is most prevalent (~50%)
alpha 1
GABA alpha 1 receptors used to be known as _____ receptors
BZ1
GABA alpha 2, 3, 5 receptors used to be known as _____ receptors
BZ2
where are GABA alpha 1 receptors found
ubiquitous (anywhere in da brain)
where are GABA alpha 2 receptors found
cortex; limbic system; spinal cord
where are GABA alpha 3 receptors found
cortex; limbic system; spinal cord
where are GABA alpha 5 receptors found
Hippocampus
GABA alpha 1 receptor has roles in what?
sedation
anti-convulsion
amnesia
addiction
GABA alpha 2 receptor has roles in what?
anxiolytic
muscle relax
GABA alpha 3 receptor has roles in what?
muscle relaxation
GABA alpha 5 receptor has roles in what?
muscle relaxation
amnesia
T or F: GABA(A) receptor is pentameric
truuuue
GABA(A) receptor what are the subunits of it
2 alpha
2 beta
1 gamma
(5 total!!)
Does it bind on the orthosteric or allosteric site on GABA receptor?
GABA
orthosteric
Does it bind on the orthosteric or allosteric site on GABA receptor?
BZD
allosteric
Does it bind on the orthosteric or allosteric site on GABA receptor?
barbiturate
allosteric
Does it bind on the orthosteric or allosteric site on GABA receptor?
ethanol
allosteric
Does it bind on the orthosteric or allosteric site on GABA receptor?
glucocorticoid
allosteric
BZDs or Barbiturates have “internal safety system”
BZDs!! (why slightly safer than barbiturates)
what ligands act at the BZD receptor on GABA receptor…..
BZDs…
non-BZDs (zolpidem, zaleplon, eszopiclone)
BZD antagonist: flumazenil
BZD inverse agonist: B carboline
what drug is a GABA channel blocker
Picrotoxin
BZDs increase ______ of channel opening
vs
Barbiturates increase ______ of channel opening
BZD: frequency
Barbiturates: duration
how does alcohol work at the GABA receptor?
enhances actions of GABA at GABA(A) receptor
what are the 2 structure activity relationships we need to know for BZDs
1 Position alkylation leads to source of active metabolites
and
annealating the 1-2 bond with an electron rich ring yields high affinity and decrease half life
BZD and Structure activity
annealating the ___ bond with an electron rich ring yields ____ affinity and _____ half life
1-2 bond
HIGH affinity
DECREASE half life
BZDs with ______ elimination rates all have active metabolites
slow
what BZDs have slow elimination rates
Chlordiazepoxide Diazepam Flurazepam Clorazepate Quazepam Prazepam
what BZDs have intermediate elimination rates
alprazolam lorazepam clonazepam oxazepam temazepam
what BZDs have rapid elimiation rates
Midazolam
Triazolam
BZDs that are slowly or intermed./rapidly eliminated are useful in pts who “wake up”
slowly
BZDs that are slowly or intermed./rapidly eliminated are preferable in elderly pts?
intermed/rapid
BZDs that are slowly or intermed./rapidly eliminated are preferable in pts with hepatic problems?
interm/rapid
BZDs that are slowly or intermed./rapidly eliminated are known to have rapid tolerance
intermed/rapid
BZDs that are slowly or intermed./rapidly eliminated are known to cause rebound insomnia
intermed/rapid
BZDs that are slowly or intermed./rapidly eliminated are known to have active metabolites
slow
BZDs that are slowly or intermed./rapidly eliminated are known to have accumulation
slow
General Considerations for BZDs:
Readily absorbed or delayed absorption?
readily absorbed!
thus can be delayed by food!!
General Considerations for BZDs:
Increased ______ solubility will increase speed of delivery to brain
lipid
General Considerations for BZDs:
redistribution to highly perfused tissue may _______ duration of action
decrease (more high perfusion = less at brain!!)
General Considerations for BZDs:
T or F: cant cross placental barrier/is not detectable in breast milk
false!! it can cross placenta and get in breast milk
General Considerations for BZDs:
has _______ binding — NOT clinically relevant though
extensive protein
BZDs: Pharmacological Properties: For Sleep Physiology: \_\_\_\_\_ sleep latency \_\_\_\_\_\_ total sleep time \_\_\_\_\_\_ stage 2 \_\_\_\_\_ REM \_\_\_\_\_\_ stage 3 and 4
(increase or decrease in each blank?)
reduce latency
increase total time
increase stage 2
decrease REM
decrease stage 3 and 4
BZDs: Pharmacological Properties:
does it increase or decrease stage 2
increase
BZDs: Pharmacological Properties:
does it increase or decrease stages 3 and 4
decrease
BZDs: Pharmacological Properties:
does it increase or decrease REM
decrease
BZDs: Pharmacological Properties:
does it increase or decrease sleep latency
decrease
BZDs: Pharmacological Properties:
does it increase or decrease total sleep time
increase
what drug can be used for BZD overdose
Flumazenil
2 big side effects with Flumazenil
Induce convulsions
Panic Attacks
what drugs are “z-hypnotics”
zolpidem
Zaleplon
Eszopiclone
Z-Hypnotics act a ______ binding site/_____ receptor
BZD;
BZ1
what Z-hypnotic is approved for long term use
Eszopiclone
what Z-hypnotics is approved for short term use
zolpidem
zaleplon
how to treat overdose of Z-hypnotics
flumazenill! (same as BZD)
BZD or Z-hypnotics
which one cases less negative effects on sleep patterns
Z-hypnotics…why used for sleep more
ultra short acting, short/intermediate, or long acting barbiturates?
are used as anticonvulsants
long acting (Phenobarbitol, mephobarital)
ultra short acting, short/intermediate, or long acting barbiturates?
are used as sedative hypnotics?
short/intermediate
ultra short acting, short/intermediate, or long acting barbiturates?
are used as IV anesthetics?
ultra short acting
thiopental, methohexital, thiamylal
Barbiturates:
Has serious ADEs of ______ depression and ______ depression
cariodvascular; respiratory
PK of Barbiturates:
duration of action is _______ proportional to lipid solubility
directly
GABA(B) receptors:
is a G______ coupled receptor,
Gi/o
GABA(B) receptors:
Heterodimer or homodimer
heterodimer (two related seven transmembrane domain receptor subunits)
GABA(B) receptors: act inhibitory by.... Presynaptic ---> \_\_\_\_\_\_ conductance and Postsynaptic ---> \_\_\_\_\_\_ conductance
pre: decrease Ca2+
post: increase K+
(aka overall makes cell more negative = inhibitory)
what are some GABA(B) agonists
GHB
baclofen
what are the GABA(B) antagonists
phaclofen, saclofen, 2-hydroxysaclofen
what are the subtypes of GABA(B)
GABA(B)1
and
GABA(B)2
….
what is the name of the Rx drug of GHB
Sodium Oxybate
or
Xyrem
Concerns of using Xyrem/GHB
no antagonist available
use of other sedative-hypnotics
amnesia
date rape
MOA of Ramelteon?
high affinity of MT1 and MT2 melatonin receptors
receptors are in SCN (superchiasmatic nucleus)
what is known as the “master clock” of the body and is known to regulate circadian rhythms?
SCN (superchiasmatic nucleus)
metabolism of ramelteon?
CYP1A2
brand for ramelteon?
Rozerm
what other drug is known as a melatonin agonist? (not ramelteon)
Tasimelteon (Hetiloz)
why is ramelteon a good option
no abuse/withdrawal/dependency
negligible risk for hangover effect next day
Orexin is known to cause wakefullness or sleepiness?
wakefullness
what drug is an orexin receptor antagonist
Suvorexant (belsomra)
what is brand for suvorexant
belsomra
MOA for suorexant
antagonists for OX1 and OX2 orexin receptors
what drugs can cause anxiety
cocaine
beta agonists
psychostimulants (caffeine)
corticosteroids
what diseases can cause anxiety
CHF
COPD
diagnosis of terminal diseases
how is NE related to anxiety
NE stimulates autonomic nervous system
NE is seen to be dysregulated in GAD and other types of anxiety
how is serotonin related to anxiety?
involves amygdala(emotions) and NE
4 main tx options of ranxiety
BZDs
Antidepressants
Buspirone
Beta blockers
Buspirone is a partial agonist for _____ receptor s and has moderate affinity for _____ receptors`
5HT1A
D2
Diagnostic criteria for insomnia disorder
present for at least 3 mos
takes place at least 3 nights per week
primary complaint of unsatisfying sleep quantity or quality
difficulties with sleep initiation (latency); sleep maintenance, and/or early morning awakening
Duration of Insomnia Disorders:
Episodic: lasting _____?
1 month to less than 3 mos
Duration of Insomnia Disorders:
Persistent: lasting ______?
greater than 3 months
Duration of Insomnia Disorders:
Recurrent: experiencing?
2 or more episodes during 1 year
Diagnostic criteria for insomnia disorder:
present for at least _____
takes place at least ______ per week
3 mos
3 nights
1st line tx for insomnia?
non-pharm: behavioral therapies/sleep restriciton therapy/relaxation training
SLEEP HYGIENE!!!
what are the main options for insomnia?
z-hypnotics (most popular)
BZDs
Melatonin Agonists
Doxepin
BZDs and Insomnia:
longer acting agents can cause significant ______
daytime hangover
BZDs and Insomnia:
T or F: Any BZD can be used for insomnia
Truueeee
BZDs and Insomnia:
MUST consider tapering when discontinuing!!
to avoid ___________
tapering can take up to _______
avoid life threatening withdrawal/seizures
4 months
Melatonin Agonists are good for sleep ______
latency/initiation
per AASM Guidelines: (aka sleep medicine)
what drugs are used for sleep maintenance ONLY
suvorexant
doxepin
per AASM Guidelines: (aka sleep medicine)
use for sleep onset ONLY
zaleplon
triazolam
ramelteon
suvorexant is known to block the binding of wake promoting neuropeptides known as _______ and _____ which is thought to suppress the “______”
orexin a and orexin b
wake drive
how do you dose suvorexant?
10 mg 30 mins before bed — need at least 7 hours left to sleep!!
may increase to 20 mg
Big caution for suvorexant?
daytime somnolence risk
(10 mg: caution for impaired driving risk the next day
if 20mg: literally dont freakin drive)
can nacrolepsy pts use suvorexant?
hell nah!
could cause paralysis/hypnogogic/hypnopompic hallucinations and cateplexy
CYP interaction with suvorexant
3A4 substrate
Diagnostic criteria for sleep apnea
pts must have evidence of least 5 obstructive apneas per hour of sleep (confirmed by polysomnography)
plus nocturnal breathing disturbances OR daytime sleepiness
OR
evidence of 15 or more obstructive apneas per hous of sleep regardless of other symptoms (confirmed by polysomnography)
if apnea and insomnia - what do you treat first?
apnea; b/c they cant breathe,dawg
Tx of sleep apnea
weight loss
CPAP
tx excessive daytime sleepiness with modafinil or armodafinil (also review CPAP adherence)
surgery is an option
Diagnostic criteria for Narcolepsy
recurring episodes of irresistible need to sleep, fall asleep, or nap:
3 x per week over past 3 mos
AND at least one of the following:
- cataplexy episodes
- hypocretin deficiency
- REM sleep latency < 15 mins on night w/ polysomnography (and other things with lots a numbers that I dont want to learn yet :( )
mild narcolepsy = ?
infrequency cataplexy attacks (<1 per week)
moderate narcolepsy?
cataplexy attacks daily or every few days
and/or(?)
nocturnal sleep disturbances
severe narcolepsy?
cataplexy seen as drug resistant w/ multiple attacks per day
almost constant sleepines…
and
nocturnal sleep disturbances
what drug is used to treat cataplexy
Xyrem (sodium oxybate) GHB
how is sodium oxybate taken
dosed twice per night
first dose right before bed; second dose is 3 - 4 hours later
black box warning for sodium oxybate
respiratory depression and misuse risk
what drugs can be used for the excessive daytime sleepiness
methylphenidates/amphetamine stuff
modfainil/armodafinil
sodium oxybate
selegiline (gets metabolized to amphetamine)
how to pharmacologically treat shift sleep work disorder
take armodafinil/modafinil 1 hour before work period starts during “wake time”
Drug therapy options for RLS (restless leg syndrome)
dopamine agonists 1st line!! (pramipexole, ropinirole) maybe LD/CD horizant (gabapentin enacarbil) NO opiods!! iron supplement IF iron deficient maybe clonazepam
