59 - Pharmacology of anxiolytics and sedative/hypnotics Flashcards
GABA B receptor
G ___ coupled (inhibitory)
heterodimers
- two related 7 transmembrane domain receptor subunits
- GABA B1, GABA B2
located in brain and limbic system
inhibitory
presynaptic: decrease ___ conductance
postsynaptoc: increase ___ conductance
agonist
- ___ - skeletal muscle relaxant (and treatment of alcoholism)
- gamma-hydroxybutyric acid (GHB) - CNS ___
antagonist (reaserch use)
- phaclofen, saclofen, 2-hydroxysaclofen
i/o
- Ca
- K
- baclofen
- depressant
sodium oxybate, ___ (Xyrem)
- C-I, illicit use and C-III, medical use (liquid)
- available only to prescribers enrolled in Xyrem Patient Success Program
Actions
- with concomitant stimulant use: decreased excessive ___ sleepiness, increase daytime ___
- decreased ___
Pharmacology
- GABA B, GABA B, and GHB (?) receptors
Concerns
- MOA
- combined with other agents
- red tape
- abuse and misuse
GHB
- daytime
- wakefulness
- cataplexy
GHB
street names
- liquid ecstasy, liquid X, juice, grievous bodily harm, scoops, georgia home boy
background
- 1960s to today: anesthetic, fat burner, ___ hormone promoter, raves, date rape, bodybuilding
PCOL
CNS ___ ; dose ___
- dizziness
- drowsiness
- coma
patients often ___ spontaneously
prodrugs
- gamma-butyrolactone (GBL)
- 1,4 - butanediol
growth
depression, dependent
awaken
GHB
Acute Effect
- loss of ___ and reflexes
- amnesia
- N/V
- headache
- ___
- death
Concerns
- supportive treatment - no ___
- other sedative-hypnotics - including ___
- ___
- date rape
- consciousness
- seizures
- antagonist
- alcohol
- amnesia
circadian rhythm of melatonin
fluctuation in melatonin levels over a 24 hour period
- pineal gland begins producing melatonin in the evening at ___ pm
- melatonin levels peak in the ___ of the night
- melatonin levels decline to low daytime amounts at aronud ___ am
8 pm
middle
7 am
___ (Rozerem): melatonin agonist
- MOA: high affinity for MT1 and MT2 melatonin receptors
- receptors located in the ___ nucleus (SCN) - serves as the master ___ by regulating circadian rhythms - loss of melatonin in ___ and alzheimers
Metabolism
- CYP ___ substrate
- treatment of insomnia characterized by difficulty with sleep ___
- non-controlled substance sleep aid
- ___ abuse, withdrawal, or dependency
- ___ risk for next-day “hangover” effects
remelteon, agonist
- suprachiasmatic, clock
- aging
- 1A2
- onset
- no
- negligible
___ (Hetlioz): melatonin agonist
MOA
- high affinity for MT1 and MT2 melatonin receptors
Treatment of Non-24hr sleep wake disorder (non-24) in ___ individuals
orphan product registration
tasimelteon
blind
oxerin/hypocretin system
___ (Belsomra): ___ receptor antagonist
MOA
- high affinity antagonst for OX1 and OX2 receptors
- receptors located in the ___
- decrease arousal and attention via receptors in locus coeruleus and the raphe
- reduce ___ stimuli (DA release) via receptors that modulate the mesolimbic projections between the ___ and the nucleus ___
- treatement of ___
- ___ impairment likely/possible (use the lowest dose possile)
- scheduled C-IV
suvorexant, orexin
- hypothalamus
- rewarding, VTA, accumbens
- insomnia
- morning
FDA Requests Label Change for All Sleep Disorder Drug Products
including newer non-BZDs drugs (eszopiclone, ramelteon, zaleplon, zolpidem)
FDA required labeling needs to include information about sleep-related ___
- sleep driving
- cooking
- phone calls
behaviors
more sedative-hypnotics
trazodone
- ___ (lots of targets)
- hypnotic-unlabeled investigational use
___ (OTC drugs)
- biphenhydramine
- doxylamine
- pyrilamine
- antidepressant
- antihistamines
Herbal/natural sedative hypnotics
melatonin - nutraceutical, traveler’s ___, ___ shifts - insomnia, sleep disturbances
- overdose: ataxia, drowsiness
valerian (Valeriana officinalis) - insomnia, ___ has been noted\
chamomie
- mild sedatice, avoid use in patients with ___ allergy
- use caution in patients using ___ substrates
tryptophan, lemon balm, kava kava
- jet-lag, work
- hepatotoxicity
sedative-hypnotic overdose
s/s
- depressed ___
- BP
- reflexes
- hypo ___
treatment
- supportive treatment
- maintain respiartion
- maintain CV function
- ___ for benzodiazepines or Z-hypnotics
- respiration
- hypothermia
- flumazenil
types of anxiety
- GAD
- panic disorder
- social anxiety or social phobia
- OCD
- PTSD
- anxiety associated with other medical issues (autism, depression)
drug and disease induced anxiety
drugs
- cocaine
- beta agonist
- psychostimulants ( ___ )
- corticosteroids
disease
- CHF
- COPD
- ___ diseases
withdrawal
- antidepressants
- anxiolytics
- drugs of abuse
- cell phone/social media (?)
caffeine
terminal
neurotransmitters and anxiety - NE
NE
- overactive locus ___ - release NE
- stimulate ___
- dysregulated in GAD and other types of anxiety
- projects to the ___ (fear center)
- coeruleus
- ANS
- amygdala
neurotransmitters and anxiety
GABAergic system - normally counteracts/balances stimulatory effects of excess __
hypothesis proposes reduced GABAergic signaling. Agents that ___ GABA signaling are anxiolytic
GABA/glutamate (I/E) balance
- glutamate is converted to GABA by ___ in the CNS
involved in GAD and panic disorder
- NE
- increase
- glutamic acid decarboxylase (GAD)
___ (BuSpar)
- ___ agonist on brain ___ receptors
- moderate affinity for brain D2 receptors
- longer onset of action than BZD ( ___ response)
- low abuse potential, no or little withdrawal
uses
- GAD, social anxiety, comorbid depression
- adjunct use with OCD, PTSD
- not good for ___ disorders (BZD much ___ )
buspirone
- partial, 5HT1A
- adaptive
- panic
- faster
___ (Inderal)
uses - may need ___ dose initially
- social anxiety
- PTSD - ___
CNS penetration - ___ philic
decreased ___ symptoms of anxiety
monitor CV effects: HR and BP
SE
- hallucinations
- vivid dreams
- lethargy
- impotence
propranolol
- test
- nightmares
- lipophilic
- peripheral
