Sleep and Pharm of Sleeping Meds Flashcards
What are the two major categories of sleep?
• REM and nonREM
what are the 3 stages of nonREM sleep?
*remember, sleep is either REM or nonREM
§ Stage 1: Transition phase from being awake to falling asleep. EEG like wakefulness (α rhythm), then begins to slow down along with muscle activity. People in stage 1 may experience falling sensations, followed by sudden muscle jerks.
§ Stage 2: Light sleep; short, fragmented thoughts, EEG slower with bursts of rapid waves (sleep spindles); 50% of total.
*Slow Wave Sleep (SWS - formerly stages 3 and 4): EEG very slow (delta sleep). Deepest level of sleep (described as “best”) - most difficult stage to arouse person from and people are often groggy several minutes after awakening. Stage where somnambulism, night terrors, and nocturnal enuresis can occur.
What characterizes REM sleep?
§ REM: Active period of sleep with intense brain activity - EEG rapid and desynchronized similar to waking state. Occurrence of rapid eye movements, decreased muscle tone, increased blood pressure, pulse, and respiration. Stage of most recallable dreams.
What is sleep architecture? How does it change throughout the night?
Sleep architecture refers to the predictable alteration (right mix) of REM and NREM throughout the night.
- NREM (70-75%) and REM (25-30%) occur cyclically over 90-110 minutes (4-5 times per night).
- The first cycles each night contain short periods of REM and larger amounts of slow wave sleep. REM sleep increases throughout the night and by morning nearly all sleep is stages 1-2 and REM.
The three Z drugs are closest to the ideal hypnotic. But what would that perfect drug do?
· Should rapidly induce sleep (influenced by drug absorption)
· Duration sufficient to maintain sleep during night, but no morning “hangover” (influenced by half-life)
· Repeated use should not result in dependence or tolerance
· Abrupt discontinuation should not lead to rebound insomnia (influenced by duration of action [t1/2])
· High therapeutic index
Should normalize disturbed sleep without disturbing normal sleep
Sedative-Hypnotics can be used as therapy for sleep. However, they are nowhere near ideal. Why is that?
· Decrease latency of sleep onset (useful effect to promote onset)
· Increase duration of stage 2 sleep (useful effect for maintenance of sleep state)
· Decrease of delta sleep (deleterious effect), esp. barbiturates. (Less with flurazepam or zolpidem / zaleplon).
· Decrease duration of REM sleep (cause of REM rebound on withdrawal leading to increases in nightmares) (deleterious effect), esp. barbiturates. (Less with flurazepam, temazepam, minimal with zolpidem / zaleplon / eszoplicone).
Use for longer than 1 week generally leads to tolerance, esp. barbiturates. (Less with flurazepam, minimal with eszopiclone / zolpidem / zaleplon).
Why might antimuscarinics have an effect on sleep?
- They have effects on the pedunculopontine tegmental area cholinergic neurons
- These are active during REM and awake states
- Thus anti-muscarinics would end up suppressing REM sleep
- Muscarinic agonists activate REM
The dorsal Raphe nuclei are important for sleep how?
• these are serotonergic neurons • active in awake • reduced in NREM • decrease REM on Thus antidepressant SSRI, SNRI, TCA will increase 5HT and decrease REM
The locus ceruleus is important for sleep how?
- • Super similar to the dorsal raphe nuclei in sleep function
- these are norepinephrine using neurons
- • active in awake
- • reduced in NREM
- • decrease REM on
- Thus antidepressant SSRI, SNRI, TCA will increase 5HT and decrease REM
The ventral tegmental area (VTA) is important for sleep how?
- These are dopaminergic neurons
- Active in awake
- Increase REM off
- Thus amphetamines or methylphenidate will increase DA release and promote wakefulness
- Whereas antipsychotics will block DA and result in sedation
What is the VLPO in the brain and why is it important for sleep?
- it is part of the circadian rhythm generator
- The ventrolateral preoptic nucleus (VLPO), also known as the intermediate nucleus of the preoptic area (IPA), is a small cluster of neurons situated in the anterior hypothalamus, sitting just above and to the side of the optic chiasm in the brain of humans and other animal
- The VLPO, together with the reticular activating system and the widely projecting orexin neuronal system that originates in the lateral hypothalamus, are the interconnected neural systems which control states of arousal, sleep, and transitions between these two states
The posterior hypothalamus is involved in sleep how?
- These are histamine neurons
- Active in awake
- Decreased when the VLPO releases GABA on them)
- They are reduced during NREM
- They are OFF during REM
- Thus antihistamines will promote drowsiness and sleep
The lateral hypothalamus is involved in sleep how?
- These neurons use the NT orexin
- Active in awake
- During awake they excite NE/5HT REM off neurons
- They are OFF during nREM
- Unknown REM activity
- Orexin antagonists like suvorexant will promote sleep by blocking excitatory actions of orexin on NE-5HT neurons
The anterior hypothalamus is involved in sleep how?
- These are GABAergic neurons
- OFF in awake
- Active in NREM
- Decreased by histamine
- Decreased by orixin
- Reduced activity in REM
- Thus, benzodiazepines enhance GABA and promote sleep onset/continuity
The basal forebrain is involved in sleep how?
- These neurons use adenosine
- Decreased cholinergic arousal centers during awake
- Thus caffeine, which is an adenosine agonist, increases alertness
