Sleep and hypnotics second half 1.0 Flashcards
Changes in NREM sleep?
muscle tension reduced, temp lowered, energy consumption lowered, more parasympathetic activity
What area of the brain is important for control of sleep?
Reticular activating system
What are thalamo-cortical inputs used for?
controlling sleep
What happens if you stimulate the reticular activating system in the brainstem?
wake up an animal
Which brain areas make up the reticular activating system?
Locus coeruleus, raphe nuclei, brainstem/forebrain, midbrain
What are all the areas that are part of the RAS involved in?
Amine NT secretion
Increased firing of the RAS neurons is associated with?
waking up
Decreased firing of the RAS neurons is associated with?
falling asleep
Amine NT associated with locus coeruleus?
noradrenaline
Amine NT associated with raphe nuclei?
serotonin
Amine NT associated with brianstem/forebrain?
ACh
Amine NT associated with midbrain?
histamine
What is the activity of the RAS regulated by?
Hypothalamus
Which neuropeptide is expressed in the hypothalamus that helps regulate the RAS?
orexin
What does orexin do?
Stimulates RAS activity
What causes decreased firing of RAS neurons
GABA
What are “REM on” neurons?
cholinergic neurons in the brainstem
What are “REM off” neurons?
Serotonergic and noradrenergic neurons in the brainstem
RAS-thalamus-cortical interactions of an awake brain?
Awake–> RAS activates thalamus–> thalamus generates non-rhythmic activity–> cortex entrained into fast waking activity
RAS thalamus cortical interactions of an asleep brain?
Asleep–> RAS activity switched off–> thalamus generates rhythmic activity–> coretex entrained into slow sleep rhythms
Symptoms of insomnia?
Difficulty getting to sleep, difficulty staying asleep or feeling sleepy when having had sleep
Which NT do drugs that can help you sleep target?
GABA
Why is GABA targeted by sleepy drugs?
GABA can inhibit the RAS,
What is decreased activity of RAS associated with?
Falling asleep
What kind of modulators of GABAa are benzodiazepines?
allosteric
Nitrazepam and flurazepam are?
Long acting benzodiazepines
Loprazelam and temazepam are?
Short acting benzodiazepines
What differentiates the acting time of benzodiazepines used to treat sleep issues?
The metabolism time of them (short acting are metabolized quickly)
What are the Z drugs?
Zolpidem, zolpiclone, zalpeon
Action of z drugs?
bind at GABA and enhance endogenous activity of GABA
What are orexin antagonists used for?
hypnotics
Where is melatonin secreted from?
pineal gland
What does melatonin regulate?
circadian rhythms
Rising melatonin levels means?
Need to go to sleep
Narcolepsy?
Pathological increase in sleep, sudden onset of sleep and sudden loss of motor control
What may cause narcolepsy?
Reduced numbers of orexin neurons, loss of RAS activation
