SM_90b: Sedatives and Hypnotics Flashcards
Sedative reduces ___ and produces a ___ effect
Sedative reduces excitatory response to external stimuli and produces a calming effect
Hypnotic causes ____ and ____
Hypnotic causes drowsiness and sleep
Sedative hypnotics cause ____ in lower doses and ____ in higher doses
Sedative hypnotics cause sedation in lower doses and sleep in higher doses
Most sedative-hypnotics act on the ____ receptor
Most sedative-hypnotics act on the GABAA receptor
- Ligand gated Cl- channel
- Bind between alpha and gamma subunits
Benzodiazepines bind between the ____ and ____ subunits of the GABAA receptor at the ____ site
Benzodiazepines bind between the alpha and gamma subunits of the GABAA receptor at the BDZ site
Benzodiazepines ____ GABA channel openings and ____
Benzodiazepines increase the frequency of GABAA channel openings and require GABA to open channels before acting
General anesthetics (propofol, etomidate) act by ____
General anesthetics (propofol, etomidate) act by increasing the duration of GABAA channel openings
- Act on beta subunit
- Higher doses can open channel without GABA
Barbiturates act by ____
Barbiturates act by increasing the duration of GABAA channel opening
- Act on alpha subunit
- Higher doses can open channel without GABA
Picrotoxin is a ____
Picrotoxin is a non-competitive GABAA antagonist that binds to the channel part of all subunits
Convulsant
Bicuculline is a ___
Bicuculline is a competitive GABAA antagonist that binds to GABA binding site
Convulsant
Penicillin is an ____
Penicillin is an uncompetitive GABAA antagonist
Convulsant
(blocks open channels, so needs agonist to work)
Benzodiazepines max out at causing ____ due to a ____
Benzodiazepines max out at causing anesthesia due to a ceiling effect
-azepams and -azolams are ____
-azepams and -azolams are benzodiazepines
____ is used for immediate relief of anxiety or aggression
Diazepam is used for immediate relief of anxiety or aggression
____ or ____ are used for immediate relief of panic
Alprazolam or clonazepam are used for immediate relief of panic
(severe anxiety with strong autonomic overactivity)
____ is used to treat REM sleep behavior disorder in which muscle atonia is absent
Clonazepam is used to treat REM sleep behavior disorder in which muscle atonia is absent
____ or ____ are used for sedation/amnesia during medical procedures and in balanced anesthesia
Midazolam or diazepam are used for sedation/amnesia during medical procedures and in balanced anesthesia
____, ____, or ____ are used as anticonvulsants
Diazepam, lorazepam, and clonazepam are used as anticonvulsants
____ are ____ used for muscle spasms
Diazepam and clonazepam are used for muscle spasms
____ are used to treat ethanol withdrawal
Benzodiazepines are used to treat ethanol withdrawal
____ can create anterograde amnesia
All benzodiazepines can create anterograde amnesia
____ may cause breakthrough panic attacks, while ____ may prevent breakthrough panic attacks
Short-acting agents such as alprazolam may cause breakthrough panic attacks, while long-acting agents such as clonazepam may prevent breakthrough panic attacks
After several months, stopping benzodiazepines will cause ___
After several months, stopping benzodiazepines will cause withdrawal symptoms
- Low to moderate dose: anxiety, agitation, muscle cramps (myoclonic jerks), sleep disturbances, dizziness, increased sensitivity to light and sound, paresthesias and strange sensatiosn
- High dose: seizure and delirium
Benzodiazepines are well-absorbed ___
Benzodiazepines are well-absorbed orally
(peak plasma concentrations generally achieved in 1 hour)
Majority of benzodiazepines are metabolized by ____ in Phase I and all are ____ in Phase II
Majority of benzodiazepines are metabolized by CYP3A4 in Phase I and all are glurcuronidated in Phase II
(excreted in urine)
____, ____, and ____ are benzodiazepines without active metabolites and do NOT need to be metabolized by CYPs
Lorazepam, oxazepam, and temazepam (LOTs) are benzodiazepines without active metabolites and do NOT need to be metabolized by CYPs
____ is important for Phase I metabolism of the -azepams
CYP2C19 is important for Phase I metabolism of the -azepams
(in addition to CYP3A4)
Benzodiazepine syngergy with ____ or ____ can be deadly via respiratory depression
Benzodiazepine syngergy with opioids or propofol can be deadly via respiratory depression
____, ____, and ____ are benzodiazepines prescribed to the elderly because they have no active metabolites
Lorazepam, oxazepam, and temazepam (LOTs) are benzodiazepines prescribed to the elderly because they have no active metabolites
____, ____, and ____ are benzodiazepines useful in Asian patients because they have no active metabolites
Lorazepam, oxazepam, and temazepam (LOTs) are benzodiazepines useful in Asian patients because they have no active metabolites
_____ is a benzodiazepine antagonist
Flumazenil is a benzodiazepine antagonist
____ is both used to isolate the GABAA receptor and a drug of abuse
Flunitrazepam is both used to isolate the GABAA receptor and a drug of abuse
(Rohypnol / roofies)
_____ acting on benzodiazepine sites are drugs of choice for sleep because they produce little dependence, reduce the number of awakenings, and restore sleep architecture
Zazoles acting on benzodiazepine sites are drugs of choice for sleep because they produce little dependence, reduce the number of awakenings, and restore sleep architecture
- Zaleplon
- Zolpidem
- Eszoplicone
Zazoles (zaleplon, zoplidem, eszopliclone) are selective for omega-1 (BZ-1) sites on GABAA receptor, which only exist when the gamma subunits are next to the a1 subunits
- Induce sleep sooner
- Reduce number of awakenings
- Do NOT suppress slow wave or REM sleep
Acute ethanol exposure causes ____
Acute ethanol exposure causes increases in GABAA receptor currents
Combining ethanol and benzodiazepines may cause ____ due to pharmacological principle of ____
Combining ethanol and benzodiazepines may cause severe life-threatening depression of the medullary respiratory center due to pharmacological principle of synergy
Treat ethanol withdrawal with ___
Treat ethanol withdrawal with benzodiazepines
- Need long-acting benzodiazepine (diazepam) for severe cases
- Need shorter-acting drugs such as lorazepam and oxazepam for alcoholics with liver disease and the elderly
Generally, waveforms become progressively ____ and ____
Generally, waveforms become progressively bigger and slower
Describe EEG patterns in sleep
EEG patterns in sleep
- Awake: beta waves (desychronized), alpha (relaxed), no theta
- No REM in first cycle
- N1: theta (light sleep)
- N2: theta, spindles, K complexes (parasympathetics kick in)
- N3-4: delta waves (slow wave, deep sleep, restorative, lot of parasympathetics, important for factual memory)
REM is called ____ because the EEG pattern looks like an awake patient
REM is called stage 5 / paradoxical sleep because the EEG pattern looks like an awake patient
Insomnia is ____, ____, ____, and ____
Insomnia is longer awake latency, reduced REM, reduced slow wave sleep, and decreased total sleep time
Benzodiazepines ____ sleep quality by causing ____, ____, and ____
Benzodiazepines improve sleep quality by shortening awake latency, increasing N1 and N2 duration, and decreasing slow wave sleep and REM duration
Zazoles (zaleplon, zolpidem, eszopiclone) are ____ that bind selectively at ____ and cause ____ and ____ but do not ____
Zazoles (zaleplon, zolpidem, eszopiclone) are omega-1 (BZ-1) agonists that bind selectively at the junction of a1 and gamma subunits and cause quicker sleep induction and reduced number of awakenings but do not suppress slow wave sleep or REM sleep
(normalize sleep)
Zazoles (zaleplon, zolpidem, and eszopliclone) are metabolized by ____ and cause NO ____
Zazoles (zaleplon, zolpidem, and eszopliclone) are metabolized by CYP3A4 and cause NO rebound insomnia
Zaleplon has a ____ half life and is good for treating ____
Zaleplon has a short half life and is good for treating sleep onset insomnia
(or sleep maintenance)
____ is the most effective of the zazoles in normalizing sleep without residual effects
Zolpidem is the most effective of the zazoles in normalizing sleep without residual effects
(insomnia characterized by waking up in the middle of the night)
Eszopliclone is used for ____
Eszopliclone is used for sleep maintenance insomnia
(longest half life of the zazoles)
Zazoles can cause side effects of ___, ___, and ___
Zazoles can cause side effects of sleep-related eating, driving, and amnesia
____, ____, and ____ are other agents used to treat insomnia and resemble ____
Scopolamine / other antimuscarinics, sedating antihistamines, and ethanol are other agents used to treat insomnia and resemble scopolamine
- Decrease sleep latency
- Decrease number of awakenings
- Increase slow wave sleep
- Decrease REM sleep
____ is a helpful hypnotic for sleep
Ethanol is a helpful hypnotic for sleep
(suppression of REM sleep, increases in slow wave sleep)
____ is a melatonin MT1 / MT2 agonist used to treat insomnia
Ramelteon is a melatonin MT1 / MT2 agonist used to treat insomnia
____ undergoes circadian rhythms controlled by the clock genes
Suprachiasmatic nucleus undergoes circadian rhythms controlled by the clock genes
- Receives info from retina about daily pattern of light and darkness
- Provides alerting signal
Suprachiasmatic nucleus is reset by ____ inputs during the day and ____ at night
Suprachiasmatic nucleus is reset by light inputs during the day and melatonin at night
Melatonin is produced in the ____
Melatonin is produced in the pineal gland
Light inhibits melatonin production in the pineal gland via the ____
Light inhibits melatonin production in the pineal gland via the suprachiasmatic nucleus
(inhibitory GABAA synapse)
Melatonin production in the pineal gland is facilitated by darkness as elminiation of the light signal to the suprachiasmatic nucleus ____
Melatonin production in the pineal gland is facilitated by darkness as elminiation of the light signal to the suprachiasmatic nucleus decreases GABA inhibition of the PVN
Melatonin released from the pineal gland acts on the suprachiasmatic nucleus via specific ____ receptors to inhibit neurons in the suprachiasmatic nucleus, inducing sleep
Melatonin released from the pineal gland acts on the suprachiasmatic nucleus via specific MT1 receptors to inhibit neurons in the suprachiasmatic nucleus, inducing sleep
MT1 receptor activation ____ via beta-gamma subunits
MT1 receptor activation opens suprachiasmatic nucleus K+ channels via beta-gamma subunits
Ramelteon is good for ____ as ____ receptors control sleep onset
Ramelteon is good for sleep onset insomnia as MT1 receptors receptors control sleep onset
(no effect on number of awakenings)
Ramelteon is metabolized primarily by ____ and should not be used in ____ due to side effect of ____
Ramelteon is metabolized primarily by CYP1A2 and should not be used in children due to side effect of endocrine disorders
____ has affinity for the ____ receptor (phase synchronizing)
Tasimelteon has affinity for the MT2 receptor (phase synchronizing)
Suvorexant is an ____ used to treat insomnia
Suvorexant is an orexin receptor antagonist used to treat insomnia
(orexins are wakefulness neuropeptides so orexin receptor antagonists inactivate wakefulness)
(OX1 and OX2 are GPCRs)
Suvorexant is metabolized by ___ and has a ___ half life
Suvorexant is metabolized by CYP3A4 and has a long half life
Benzodiazepines have a _____ effect on CNS depression due to GABAA receptor channel kinetics
Benzodiazepines have a ceiling effect on CNS depression due to GABAA receptor channel kinetics
VLPO ____ arousal amines and orexin neurons via ____ receptors
VLPO inhibits arousal amines and orexin neurons via GABAA receptors
Suprachiasmatic nucleus ____ the VLPO (sleep switch)
Suprachiasmatic nucleus inhibits the VLPO (sleep switch)
Diazepam is dealkylated by _____
Diazepam is dealkylated by CYP2C19
(to nordazepam which is glucuronidated by CYP3A4)
