Anxiolytics and Sleep Flashcards
Describe the mechanism of action of benzodiazepines (BZDs).
Bind to and stimulate GABA receptors –> GABA is an inhibitory NT. They cause an influx of chloride into the cells causing hyperpolarization and a decreased ability to depolarize and activate.
Differentiate barbiturates from benzodiazepines.
Barbiturates are C-3 (BZDs are C-4) and are more toxic because they prolong, rather than potentiate GABA stimulation.
T/F: Death from BZD overdose is common.
False: Death from BZD overdose is rare unless combined with another sedative –> alcohol most common
What is the antidote for BZD overdose and what is the problem with its use?
Flumazenil –> decreases seizure threshold so should only be used when isolated BZD overdose can be confirmed
Describe the pharmacokinetics of BZDs.
They all differ in their onset, duration of action, and metabolism
State the clinical uses of BZDs.
Anxiety, agitation, antiemetic (especially in chemo), insomnia, seizures, anesthetic induction, alcohol withdrawal, muscle relaxation
Describe the process of discontinuing long-term use of BZDs.
They must be tapered over time to avoid severe withdrawal
Describe the AEs associated with BZDs and state one that can sometimes be beneficial.
Drowsiness, confusion, sluggishness, retrograde amnesia. Retrograde amnesia is beneficial in anesthesia.
Which two BZDs used for anxiety have the shortest duration of action (quick on and quick off)?
Lorazepam and Oxazepam –> these drugs are the final metabolites of other BZDs
By what routes and rough dosing are the short-acting BZDs administered?
Lorazepam - IV or PO (dosed in micro doses)
Oxazepam - PO (dosed in milligrams)
For what patients are the short-acting BZDs preferred?
Elderly and liver failure –> BZDs are lipophilic, short acting agents less toxic to liver
What is the dose limiting AE of BZDs?
Respiratory depression
Where are you likely to find agitated patients that would benefit from BZDs?
ICUs and nursing homes
What is the primary use of Alprazolam?
Panic attacks
State the father of all BZDs and describe its pharmacokinetics?
Diazepam –> longest half-life of all BZDs
What is the primary use of Temazepam and why isn’t it used much anymore?
Insomnia –> been replaced by Ambien, etc.
Describe the mechanism of action of buspirone?
Not a BZD –> serotonin antagonist. It is unknown exactly how it decreases anxiety.
What is the C schedule of buspirone?
It is not a controlled substance
What is the advantage of buspirone and what patients most benefit from its use?
No sedative effects –> can be used by bus drivers and other workers that operate machinery
Compare buspirone to BZDs regarding their efficacy as an anxiolytic.
They are as effective as BZDs but they take 3 weeks to have effect. Buspirone cannot be used acutely.
How is buspirone dosed?
TID
Describe the general treatment ladder in attempting to manage insomnia.
Improve sleep hygiene
OTC meds: diphenhydramine or melatonin
Prescription meds: non-controlled, then controlled
What medications that we have previously discussed in class can be used to treat insomnia?
Trazadone (atypical antidepressant), TCAs, Diphenhydramine
T/F: Patients are often on insomnia medications for life once they start them.
False: Patients should not be on insomnia meds for life –> treat the underlying cause (anxiety for ex)
What is meant by a drug being a “non-benzo benzo” and what three drugs are in this classification?
These drugs bind and stimulate BZD receptors but, structurally, they are not BZDs.
Zolpidem, Zaleplon, Eszopiclone
What is the indication for use of zolpidem?
Short term treatment of insomnia
T/F: Zolpidem has muscle relaxant and anti-seizure effects.
False
What is the maximum duration of use of zolpidem?
7 - 10 days
What is the difference between regular zolpidem and CR zolpidem
CR (controlled release) gives an initial dump of the medication followed by gradual drug release through the night.
What is the advantage of taking zaleplon over zolpidem?
Zaleplon has a shorter half-life so it can be taken later at night with less risk of a hang-over the next day
What differentiates Eszopiclone from the other non-benzo benzos?
It has a longer half-life and is indicated for chronic insomnia (still should not be prescribed for life)
What is the most significant AE of the non benzo benzos?
Sleep walking
What is the mechanism of action of ramelteon?
It is a specific MT1 and MT2 melatonin receptor agonist
T/F: Ramelteon is a schedule drug.
False: it is not a benzo and has very low abuse potential
T/F: Sleep medications increase the amount of time in REM sleep.
True: REM sleep is the most refreshing type of sleep
What drug induces more overall sleep but is very disruptive to REM sleep.
Ethanol
What is the mechanism of action of suvorexant.
Selective orexin receptor antagonist –> orexin keeps people awake in the sleep-wake cycle
T/F: Suvorexant is a schedule drug?
True: C4
What disorder is a problem with orexin?
Narcolepsy
What is the most expensive sleep medication?
Suvorexant
What are the AEs associated with suvorexant?
Sleep walking and significant hang-over
What is an alcohol dehydrogenase inhibitor that was previously used as a sleep aid?
Chloral hydrate
What is the criminal use of chloral hydrate?
Date rape drug –> significant interaction with ethanol
