Unit 6: Hypnotics Flashcards
Drugs for sleep: - benzos - barbiturates - ramelteon - zolpidem
Stages of Sleep
Stage 0: Awake
- irregular pattern of high frequency, low amplitude/”low power” electrical activity
- alpha activity predominates and beta activity occurs with focused thought and attention
Stage 1: N1 Sleep
- mental drifting, thoughts turn inwards, reduced attention to external stimuli
- normal breathing and heart rate
- few theta waves present in EEG
- can easily return to full wakefulness at the smallest disturbance
Stage 2: N2 Sleep
- unconscious to surroundings
- sleep spindles; K complexes (external sound, muscle twitching)
- some delta waves present on EEG
- slowed breathing and heart rate
- body temperature drops
Stage 3: N3/Deep/Slow Wave Sleep
- person is difficult to wake
- heart rate and breathing slow
- low body temp
- EEG shows synchronous waves of activity called delta waves
- dreams occur during deep sleep, but are difficult to recall
Stage 4: Rapid Eye Movement (REM) Sleep
- onset: roughly 90 mins after falling asleep
- transition from deep sleep to near consciousness; person can be more easily roused
- EEG pattern, breathing, heartbeat, body temp more similar to awake state
- dreams occur during REM sleep; easier to recall
- person will alternate between deep and REM sleep through the night; more time spent in REM as night progresses
What is sleep?
Sleep = cyclical process of reversible unconsciousness and immobility
- changes in the patterns of neuron activity; but brain is still very active
- all animals have circadian periods of activity and rest
- REM sleep observed in mammals and birds only (warm-blooded vertebrates)
Drugs and Sleep
Depressant = a drug that reduces neuron activity and arousal (wakefulness)
** Hypnotic** = a drug that induces sleep
Stimulant = a drug that promotes arousal (wakefulness)
REM Sleep
NREM = Non-REM Sleep (Stages N1, N2, N3)
REM = Rapid Eye Movement Sleep
- typical sleep cycle is approx. 90 mins—however, the length of time spent in NREM/REM varies throughout the night
- more NREM occurs initially, more REM sleep towards the morning
- we appear to require less REM sleep as we age
Age and REM Sleep
- newborns : 8hrs of REM; avg 16 hrs of sleep per day
- young adults (20+) : 2hrs of REM; avg 8 hrs of sleep per day
- elderly (80+) : 45 mins of REM; avg of 6.5 hrs of sleep per day
Sleep Distruptions/Lack of Sleep
Disrupted/Lack of Deep Sleep (N3)
- likely to feel unrested and highly fatigued the following day
- chronic lack of deep sleep is associated with longer lasting impairments:
- eg: neuron degradation; thought to preceed neurodegenerative disorders
- preventing NREM sleep causes a stronger “sleep pressure”; brain spends more time than usual in NREM
Disrupted/Lack of REM Sleep
- doesn’t create same sleep pressure
- impairs memory consolidation and retrieval—eg: likely to struggle with remembering the day before
Acute/Chronic Sleep Deprivation
Acute sleep deprivation:
- does not adversely affect organs; however, causes cognitive impairments (eg: memory) and increased emotionality (dysregulation)
Chronic sleep deprivation:
- classified as consistently sleeping fewer than 7 hours a night; associated with increased risk of:
- diabetes
- obesity
- cardiovascular disease
- cancer—shift work is considered a carcinogen
- Rechtshaffen experiment; rats deprived of sleep will die within 3-4 weeks after showing:
- increased appetite
- loss in weight
- inability to thermoregulate
Sleep Disorders:
Insomnia, Fatal Familial Insomnia, Narcolepsy
Insomnia : difficulty falling asleep, staying asleep, or causes premature arousal (woken up too early)—preventing good quality sleep; many causes:
- stress
- irregular sleep schedule
- lifestyle
- medications
- neurological disorder, etc
Fatal Familial Insomnia: very rare neurodegenerative disease caused by a mutation in the PRNP gene resulting in a progressive inability to sleep
- affects the thalamus; observed lack of sleep spindles
- midlife onset
- use of hypnotics does not change the course of the illness
- fatal; death occurs 6-36 months after onset
Narcolepsy: a sleep disorder where disruptions in sleep architecture prevent quality sleep, resulting in extreme sleepiness during the day
- also causes muscle paralysis (like that of REM sleep)
Why do we dream?
Why do we dream?
Dreams = thought to be a mental categorization of experiences for storage
- elements of dream often touch on aspects of events or thoughts from the day
- possibly so the brain can review and rehearse newly learned skills and facts
Nightmares = may serve a function of practicing one’s reaction to worst-case scenarios
Dreams and Sleep Stages
Dreams occur in both NREM and REM sleep, but the quality of the dreams are different
- REM dreams are more vivid, story-like and better recall upon waking
- NREM dreams are harder to recall/not recalled at all
Sleep/Wake System
1) Awake/arousal system
- activated by hunger, sunlight
- active orexinergic neurons/neurotransmitters firing from hypothalamus:
- acetylcholine : wakefulness, attention, parasympathetic nervous system functioning (rest & digest)
- histamine : regulating wakefulness, cognitive function
- dopamine : movement, memory, pleasurable reward/motivation
- serotonin : mood, digestion, sleep/arousal
- norepinephrine : attention, focus, fear, anxiety
- orexin : hunger signal, arousal
- increasing the firing of these neurons/increasing synaptic levels of neurotransmitters will promote wakefulness
2) Sleep system
- activated by satiety, adenosine
- during the day, the brain uses energy in the form of ATP; the byproduct of this energy is adenosine (accumulates when awake, cleared during sleep)
- adenosine binds to adenosine receptors in the sleep area of the brain; stimulates firing of sleep-on neurons
Pharmacological Methods of Promoting Sleep
Promoting Sleep:
1) Increase GABA transmission (eg: Benzos/Barbiturates; Zolpidem)
2) Activating sleep hormones (eg: Ramelteon)
Benzodiazepines:
Target, Mechanism of Action, Drugs Class
Target: Reticular Activation System; GABA receptors
Mechanism of Action: agonist of GABA receptors; benzos activate GABA ion channels, allowing (Cl-) flow in, enhancing inhibitory effects
- low doses : inhibition of inhibitors—disinhibition of dopamine neurons; burst firing of DA
- high doses : both the inhibitor and dopamine neurons are inhibited; arousal = low
- note: benzos don’t bind to the exact same site as GABA; they amplify the effects of GABA
Drug Class: depressant/hypnotic
Barbituartes:
Target, Mechanism of Action, Drug Class
Target: Reticular Activation System (reticular formation, cerebral cortex, thalamus); GABA receptors
Mechanism of Action: potent agonist of GABA receptors/ion channels
- prolongs opening of ion channel, allowing more (Cl-) in, enhancing inhibitory effects
- note: barbituartes don’t bind to the exact same site as GABA; they amplify the effects of GABA
Drug Class: depressant/hypnotic/sedative
Benzodiazepines and Barbiturates
Benzodiazepines: for anxiety; insomnia
- diazepam (Valium)
- clonazepam
- lorazepam,
- zopiclone
- zolpidem (Ambien)
Barbiturates: for seizures, surgical anaesthetics, capital punishment (death penalty), veterinary euthanization
- phenobarbital
- pentobarbital
note: HIGH potential for addiction and overdose; due to dopamine disinhibition and prolonged inhibitory effects
Dosage—use (elicits):
- lowest dose—anxiolytic (reduces anxiety by quieting neurons in the amygdala)
- low dose—sedative (relaxation, sleepiness)
- mid dose—hypnotic (sleep)
- mid-high—delirium (mental confusion); ataxia (uncoordinated movement)
- high dose—surgical anesthetia (benzos: prep for surgery; barbiturates: maintains anesthesia during surgey)
- overdose—coma, death (suppresses breathing, reducing oxygen to brain)
