Sleep Aids Flashcards
What class of drugs are used to treat insomnia in the short-term?
Sleep aids
What is the name for the subjective complaint of difficulty falling asleep, staying asleep, and/or experiencing restorative sleep that results in daytime impairment?
Insomnia
What are the four main classes of FDA-approved medications for the treatment of insomnia?
Benzodiazepine receptor agonists
Non-benzodiazepine receptor agonist
Tricyclic antidepressant
Melatonin receptor agonists
What about the use of over-the-counter products such as antihistamines, Valerian, and melatonin and off label use of antidepressants, antipsychotics, and anticonvulsant drugs for the treatment of insomnia?
There is limited data to support the use of these medications in insomnia
What is the mechanism of action for benzodiazepine receptor agonists?
They nonselectively bind to the alpha subunits on the gamma-aminobutyric acid type A (GABA–A) receptor complex
This results in the enhancement of GABAs inhibitory effects
Similar to benzodiazepine receptor agonists, what is the mechanism of action for non-benzodiazepine receptor agonists?
They also bind to the GABA–A receptor, but have a higher selectivity for alpha receptor subunits
What is the mechanism of action for zolpidem and zaleplon?
They also bind to the GABA–A receptor, but have a greater affinity for the alpha-1 subtype
What is the mechanism of action for eszipclone?
They also bind to the GABA–A receptor, but has a greater affinity for the alpha-2 and 3 subtypes
What advantage does the selectivity demonstrated by these medications result in?
They end up being more sedation-specific, with fewer adverse effects
Melatonin is an endogenous hormone released from which gland? What is it released in response to? From what nucleus?
The pineal gland
In response to light and dark signals
From the suprachiasmatic nucleus (SCN)
What are the three melatonin receptors in the body?
MT1, MT2, and MT3
Which two melatonin receptors regulate the wake-sleep cycle?
MT1 and MT2
What is the mechanism of action (receptor binding) for the medication Ramelteon? What endogenous hormone does it mimic?
It is a melatonin receptor agonist that binds to MT1 and MT2 receptors and;
Mimics melatonin’s sleep-promoting properties
At low doses, which tricyclic antidepressant is a selective histamine-1 antagonist that produces sedating effects?
Doxepin
What happens to doxepin, with regard to sedating effects, at higher doses? Which 3 effects does it show at higher doses?
It loses its sedating effects at higher doses
At higher doses it becomes anti-cholinergic, anti-serotonergic, and anti-adrenergic
When appropriate, what should be utilized as an initial Non-pharmacologic intervention, and is considered effective, for the management of insomnia?
Psychological and behavioral therapies
Under what 3 conditions is pharmacologic intervention indicated for insomnia?
When a patient prefers the use of a medication
When immediate symptom relief is required
When the sleep disturbance produces significant distress or impairment
Whenever possible, what should the therapeutic approach to insomnia be?
Medications should be utilized short-term in combination with non-pharmacologic strategies whenever possible
The number 3 most common adverse effects of benzodiazepine receptor agonists are?
Drowsiness, dizziness, and headache
What common adverse effect is associated with benzodiazepines with long durations of action?
Residual daytime sedation
If a benzodiazepine with a long duration of action is causing residual daytime sedation, what should be done?
Switch to a medication with an intermediate or short duration of action; this will decrease daytime drowsiness
Which adverse effect of benzodiazepine receptor agonists is considered to be dose-dependent?
What should be done if a patient complains of this specific adverse effect?
Anterograde amnesia
The dose should be lowered and the patient instructed to take the medication only at bedtime
Benzodiazepines with short durations of action tend to cause what specific type of adverse effect?
Rebound insomnia
What is rebound insomnia?
This refers to a rapid return of difficulty with sleep initiation and/or maintenance
It may be worse than before treatment
How do you prevent rebound insomnia?
Gradually taper the benzodiazepine by 10% or less at 5-to-7 day intervals
Can benzodiazepine receptor agonists cause withdrawal symptoms on discontinuation?
Yes
Why are the adverse effects associated with benzodiazepines a concern in the elderly?
Because they may metabolize these medications more slowly and are at higher risk for falls
What are the 4 most common adverse effects of non-benzodiazepine receptor agonists?
Headache, drowsiness, fatigue, and dizziness
Eszopiclone, a non-benzodiazepine receptor agonist, can cause what adverse effect at higher doses?
Metallic aftertaste
What are two generic benzodiazepine receptor agonists?
Estazolam
Flurazepam
Benzodiazepine receptor agonist
Dural
Quazepam
Benzodiazepine receptor agonist
Restoril
Temazopam
Benzodiazepine receptor agonist
Halcion
Triazolam
What 3 indications are estazolam, flurazepam, and quazepam (Dural) used for?
Difficulty falling asleep
Frequent nocturnal awakening
Early-morning awakening
Benzodiazepine receptor agonists, Temazepam (Restoril) and Triazolam (Halcion) are used for what FDA approved indication?
Difficulty falling asleep
Non-benzodiazepine receptor agonist
Ambien
Zolpidem
Non-benzodiazepine receptor agonist
Ambien CR
Zolpidem CR
Non-benzodiazepine receptor agonist
Edluar
Zolpidem sublingual
Non-benzodiazepine receptor agonist
Intermezzo
Zolpidem sublingual
Non-benzodiazepine receptor agonist
Zolpimist
Zolpidem oral spray
Non-benzodiazepine receptor agonist
Lunesta
Eszopiclone
Non-benzodiazepine receptor agonist
Sonata
Zaleplon
Zolpidem (Ambien), zolpidem sublingual (Edluar), Zolpidem oral spray (Zolpimist), and Zaleplon (Sonata) are all used for what single indication?
Difficulty falling asleep
Which 2 non-benzodiazepine receptor agonists are used for both difficulty with sleep onset and/or sleep maintenance?
Zolpidem CR (Ambien CR)
Eszopiclone (Lunesta)
When should the non-benzodiazepine receptor agonist zolpidem sublingual (intermezzo) be used?
It should be used for middle-of-the-night waking followed by difficulty returning to sleep
It is not indicated if the patient has less than four hours of bedtime remaining before the planned waking time
Tricyclic antidepressant
Silenor
Doxepin
Which tricyclic antidepressant is used for difficulty with sleep maintenance?
Doxepin (Silenor)
Melatonin (MT1 and MT2) receptor agonist
Rozerem
Ramelteon
At higher doses, what can the non-benzodiazepine receptor agonist Zaleplon cause?
Rebound insomnia
What unique adverse effect has zolpidem been associated with?
Parasomnias, including sleepwalking and sleep-eating
It is recommended by the manufacturers of zolpidem (Ambien) that women begin treatment with lower starting doses. What is this based on?
This is based on data regarding the relationship between psychomotor performance and drug blood levels
What are the most common adverse effects reported in clinical trials for doxepin?
Somnolent/sedation
nausea
increased upper respiratory tract infections
At higher doses, what are the adverse effects associated with doxepin (3)?
Orthostatic hypotension
anti-cholinergic effects
cardiac conduction delay
Is there any abuse potential associated with doxepin? Are there any withdrawal symptoms on discontinuation?
No; No
True or false: Ramelteon is generally well tolerated
True
What are the most common adverse effects reported in clinical trials for Ramelteon?
Headache
somnolence
dizziness
nausea
Should a patient be concerned about abuse potential or withdrawal symptoms upon discontinuation with the use of Ramelteon?
No
What drug-to-drug interaction is exhibited when CNS depressants (e.g. opioids) are combined with the use of benzodiazepine receptor agonists, non-benzodiazepine receptor agonists, doxepin, and Ramelteon?
There is a potentiation of impaired cognitive and motor effects
Therefore, it is recommended that sleep aid be initiated at a low dose and titrated based on the patient’s response
What drug-to-drug interaction is exhibited when alcohol is combined with the use of benzodiazepine receptor agonists, non-benzodiazepine receptor agonists, doxepin, and Ramelteon?
There is a potentiation of impaired cognitive and motor effects
Therefore, patients should be educated to avoid alcohol while taking these medications
What is the drug-to-drug interaction of food with zolpidem, doxepin, eszopiclone, zaleplon?
If taken with or immediately after a meal, can delay onset of sleep
Therefore, patients should take these medications on an empty stomach
What happens when you use a strong CYP3A4 inhibitors (such as azole antifungals and HIV protease inhibitors) with medication such as zolpidem, triazolam, estazolam, eszopiclone and Ramelteon?
Increased plasma concentration of the sleep aid
Therefore, avoid using these medications with triazolam or estazolam
In the case of zolpidem, eszopiclone, or ramelteon, initiate treatment at a low dose and monitor for side effects
How does the use of fluvoxamine influence the simultaneous use of ramelteon?
It increases the plasma concentration of the sleep aid
Therefore, avoid the use of ramelteon
Which medications can be used to treat not only their respective primary disorders, but also insomnia?
Trazodone, mirtazapine, and neuroleptics
In certain cases, can treating the patient’s psychiatric illness improve insomnia?
Yes, for example, a common symptom of depression is insomnia, and, as the patient’s depression improves, sleep often improves.
Why should one use caution when treating a patient with benzodiazepines and non-benzodiazepine receptor agonists?
Patients can become tolerant and require higher doses
Therefore, monitor for withdrawal symptoms after discontinuing the medication
What have studies shown regarding melatonin?
Studies have shown that melatonin does not help with insomnia, but is useful for resetting the sleep cycle after sleep disruptions such as shiftwork or jetlag
Liira J et al.: pharmacological interventions for sleepiness and sleep disturbances caused by shift work. Cochran database syst. Rev. 8:, 2014.
