Lecture 8.1

Question 1

What is the Inactivity Theory of sleep?

Answer 1

The Inactivity Theory of sleep is an evolutionary perspective suggesting that animals inactive at night were less likely to be targeted by predators in the dark.

Question 2

How does the Energy Conservation Theory explain the purpose of sleep?

Answer 2

The Energy Conservation Theory explains that sleep reduces energy demands during the night when it is the least efficient time to hunt for food.

Question 3

According to the Restorative Theory, what are the two main functions of sleep?

Answer 3

According to the Restorative Theory, sleep allows for the body to repair and replenish body systems that become depleted throughout the day, and it also gives the brain itself a rest from being active all day.

Question 4

What is the main idea behind the Brain Plasticity Theory of sleep?

Answer 4

The main idea behind the Brain Plasticity Theory of sleep is that sleep is essential for neural reorganization and the growth of the brain.

Question 5

What is the Reticular Activating System, and what is its function?

Answer 5

The Reticular Activating System is a neural network projecting from the mid-brain and pons to the cortex via the hypothalamus and thalamus. Its functions include modulating the signals that reach the cortex and how much attention you pay to stimuli, and it is involved in wakefulness, vigilance, and arousal. Additionally, it maintains sleep/wake cycles by modulating the speed of neuron firing and filtering out noise.

Question 6

What is Excessive Daytime Sleepiness (EDS)?

Answer 6

Excessive Daytime Sleepiness (EDS) is an overwhelming feeling of sleepiness even after adequate sleep at night, broken up by periods of normal levels of alertness.

Question 7

What is cataplexy?

Answer 7

Cataplexy is sudden muscle weakness triggered by emotion.

Question 8

What is sleep paralysis?

Answer 8

Sleep paralysis is a temporary inability to move or speak while falling asleep or waking up, and it involves hallucinations.

Question 9

What are the different presentations of insomnia?

Answer 9

The different presentations of insomnia include mixed presentation, which is difficulty staying asleep.

Question 10

What is the difference between primary and secondary insomnia?

Answer 10

Primary insomnia is not linked to a health condition, while secondary insomnia is due to a health condition, pain, medication, or substance use such as alcohol.

Question 11

How is acute insomnia different from chronic insomnia?

Answer 11

Acute insomnia lasts one night to a few weeks, whereas chronic insomnia happens three nights per week for three months or longer.

Question 12

What is sleep onset insomnia?

Answer 12

Sleep onset insomnia is difficulty falling asleep.

Question 13

What is postdormitional insomnia?

Answer 13

Postdormitional insomnia is waking too early and being unable to fall back asleep afterward.

Question 14

What are hypnotics?

Answer 14

Hypnotics are a class of psychoactive substances used to treat insomnia.

Question 15

How does allosteric modulation affect GABA-A receptors?

Answer 15

Allosteric modulation causes a conformational change to the central pore of GABA-A receptors when GABA binds, allowing more chloride ions to pass through.

Question 16

What is inverse agonism, and how do antihistamines utilize it?

Answer 16

Inverse agonism is when antihistamines bind to H1 receptors and stabilize the effects of histamine; this prevents histamine from stimulating neurons that promote wakefulness, reducing signaling activity.

Question 17

What are the key neurotransmitters involved in sleep and wakefulness?

Answer 17

The key neurotransmitters involved in sleep and wakefulness include histamine (HA), dopamine (DA), noradrenaline (NA), serotonin (5-HT), and acetylcholine (ACh).

Question 18

How does the reticular activating system modulate attention?

Answer 18

The reticular activating system modulates the signals that reach the cortex and how much attention you pay to stimuli.

Question 19

What is the role of the tuberomammillary nucleus (TMN) in the sleep/wake switch?

Answer 19

The tuberomammillary nucleus (TMN) is the ‘on switch’ and a wake promoter within the hypothalamus’s set of circuits.

Question 20

How does GABA from the VLPO affect wakefulness?

Answer 20

GABA from the ventrolateral preoptic nucleus (VLPO) is released when the sleep/wake switch is ‘off’ to inhibit arousal systems and the wake promoter.

Question 21

What are the two processes in the Two-Process Model of Sleep?

Answer 21

The two processes in the Two-Process Model of Sleep are circadian wake drive and homeostatic sleep drive.

Question 22

How do circadian wake drive and homeostatic sleep drive change throughout the day?

Answer 22

As the day progresses, circadian wake drive diminishes, and homeostatic sleep drive increases until a tipping point is reached.

Question 23

What is melatonin’s function in regulating sleep?

Answer 23

Melatonin functions in regulating the circadian rhythm for sleep.

Question 24

What are the functions of orexin?

Answer 24

The functions of orexin are to regulate sleep/wake states, arousal, and vigilance. Orexin also receives information from the VTA and dorsal raphe, and projects to the basal forebrain and hypothalamus. It maintains wakefulness and suppresses sleep states, and it stops sleep from happening at inappropriate times (which underlies narcolepsy).

Question 25

What are the characteristics of disorders related to excessive daytime sleepiness?

Answer 25

Disorders characterized by excessive daytime sleepiness involve the sleep/wake switch being off during the daytime.

Question 26

What are the symptoms of narcolepsy?

Answer 26

The symptoms of narcolepsy include excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, insomnia, and REM sleep behavior disorder. REM sleep behavior disorder involves physical movement during REM sleep, such as punching or kicking.

Question 27

What are the two types of narcolepsy?

Answer 27

The two types of narcolepsy are Type 1, which involves low levels of orexin or cataplexy with EDS, and Type 2, which involves EDS without cataplexy and normal levels of orexin.

Question 28

What are the potential causes of narcolepsy?

Answer 28

Potential causes of narcolepsy include loss of orexin-producing neurons, possibly due to an autoimmune response, genetic predisposition, mental health conditions like depression or anxiety, hormone changes such as puberty or menopause, infections with some links to influenza, and brain injuries and tumors in the hypothalamus.

Question 29

What are the consequences of narcolepsy?

Answer 29

The consequences of narcolepsy include feeling run down or fatigued, slower reflexes, difficulty concentrating or remembering things, risk of physical harm such as while driving, and irritability, isolation, depression, and/or anxiety.

Question 30

What is the two-fold process in the pharmacological treatment of narcolepsy?

Answer 30

The pharmacological treatment of narcolepsy is a two-fold process: the use of stimulants to increase wakefulness and maintain waking during the day, and the use of antidepressants to help with cataplexy.

Question 31

What medications are used to treat narcolepsy?

Answer 31

Medications used to treat narcolepsy include modafinil and armodafinil to increase wakefulness and maintain waking during the day. While methylphenidate or amphetamines are options, they are not typically relied upon. Antidepressants, most commonly SSRIs and SNRIs like venlafaxine, fluoxetine, and duloxetine, are used to help with cataplexy.

Question 32

How does modafinil work?

Answer 32

Modafinil's mechanism of action is chemically and pharmacologically distinct from other CNS stimulants, and its precise mechanism is unknown. It enhances glutamate, inhibits GABA, blocks the dopamine reuptake pump weakly, and indirectly inhibits norepinephrine in the VLPO.

Question 33

What are the common side effects of modafinil?

Answer 33

Common side effects of modafinil include gastrointestinal upset, headache, flushing, loss of appetite, depression, nervousness/anxiety, blurred vision, confusion, numbness, and tingling sensations.

Question 34

According to Golicki et al. (2010), what is the efficacy of Modafinil?

Answer 34

According to Golicki et al. (2010), compared to placebo, Modafinil decreased EDS, decreased the number and duration of somnolence, sleep attacks and naps per day, and increased patient quality of life. However, it has equal efficacy at reducing the number of cataplexy attacks and is associated with more nausea.

Question 35

What are the three types of insomnia based on the timing of sleep disruption?

Answer 35

The three types of insomnia based on the timing of sleep disruption are sleep onset, which is difficulty falling asleep; postdormitional, which is waking too early and being unable to fall back asleep afterward; and mixed, which is difficulty staying asleep and frequent waking.

Question 36

What are the common causes of insomnia?

Answer 36

Common causes of insomnia include stress related to life events, sleep environment and/or poor sleep hygiene, mental health conditions like depression or anxiety, physical health conditions like chronic pain, hormone changes such as pregnancy or menstruation, prescription/OTC medications like pseudoephedrine, and disruptions to sleep patterns such as shift work.

Question 37

What are the consequences of insomnia?

Answer 37

The consequences of insomnia include feeling run down or fatigued, slower reflexes, difficulty concentrating or remembering things, and irritability, depression, and/or anxiety. Typically, insomnia predates other psychiatric symptoms, especially depression.

Question 38

What are the two primary objectives in the pharmacological treatment of chronic insomnia?

Answer 38

The two primary objectives in the pharmacological treatment of chronic insomnia are to improve sleep quality and quantity and to improve daytime impairments.

Question 39

What classes of psychoactive substances are used to treat insomnia?

Answer 39

Classes of psychoactive substances used to treat insomnia include benzodiazepines, Z-drugs (non-benzodiazepines), melatonergic hypnotics, antidepressants, and antihistamines.

Question 40

How do benzodiazepines affect neural activity?

Answer 40

Benzodiazepines inhibit neural activity via positive allosteric modulation of GABA-A receptors. The binding of GABA to GABA-A receptors causes a conformational change to the central pore, allowing more chloride ions to pass through. When benzodiazepine binds to the allosteric site on the GABA-A receptor and GABA is present, it amplifies GABA activity to move more chloride ions through, hyperpolarizing membranes; however, if no GABA is present, nothing happens.

Question 41

According to Holbrook et al. (2000), what is the efficacy of Benzodiazepines?

Answer 41

According to Holbrook et al. (2000), compared to placebo, benzodiazepines decreased sleep latency by 4.2 minutes, which was non-significant, but significantly increased total sleep duration by 61.8 minutes.

Question 42

How do Z-drugs differ from benzodiazepines in their mechanism of action?

Answer 42

Z-drugs inhibit neural activity via positive allosteric modulation of GABA-A receptors, similar to benzodiazepines. However, Z-drugs preferentially bind to the alpha-1 subunit of GABA-A receptors, which, with GABA binding, opens chloride channels to increase neuronal inhibition. This difference results in less tolerance, dependence, or withdrawal compared to benzodiazepines, which bind to multiple subunits, resulting in broader inhibitory effects.

Question 43

What are the administration details and examples of Z-drugs?

Answer 43

Z-drugs are always administered orally as tablets, and Australian examples include Zolpidem (Stilnox) and Zopiclone (Imovane). Effects are seen within approximately 30 minutes of administration and last 6-8 hours.

Question 44

What are the common side effects of Z-drugs?

Answer 44

Common side effects of Z-drugs include adverse cognitive effects such as memory loss, psychomotor effects like falls, fractures, and road crashes, daytime fatigue, headache, gastrointestinal upset, dizziness, and tolerance, dependence, and withdrawal.

Question 45

According to Huedo-Medina et al. (2012), what is the efficacy of Z-drugs?

Answer 45

According to Huedo-Medina et al. (2012), compared to placebo, Z-drugs decreased polysomnographic sleep latency by 22 minutes, but there were no differences in wake after sleep onset, number of wakenings, total sleep time, or sleep efficiency.

Question 46

How do melatonergic hypnotics work?

Answer 46

Melatonergic hypnotics work as melatonin receptor (MT1 and MT2) agonists in the suprachiasmatic nucleus. They mimic the process of endogenous melatonin, which is released by the pineal gland and increases as sleep approaches, contributing to the onset of sleep and decline in wakefulness, by acting as an agonist at the same receptor sites. They have no significant affinity for GABA, negating the potential for abuse and are not associated with adverse cognitive or psychomotor effects.

Question 47

What are the administration details and examples of melatonergic hypnotics?

Answer 47

Melatonergic hypnotics are always administered orally as tablets, and Australian examples include Agomelatine and Melatonin (Circadin). Effects are seen within approximately 30 minutes of administration and last 4-5 hours.

Question 48

What are the common side effects of melatonergic hypnotics?

Answer 48

Common side effects of melatonergic hypnotics include daytime fatigue, gastrointestinal upset, dizziness, irritability, dry mouth, headache, and anxiety.

Question 49

According to Luthringer et al. (2009), what is the efficacy of melatonergic hypnotics?

Answer 49

According to Luthringer et al. (2009), compared to placebo, Circadin decreased polysomnographic sleep latency by 9 minutes in a sample of 55+ year olds, and 50% reported substantial improvement in sleep quality compared to 15% in the placebo group.

Question 50

How does histamine regulate wakefulness?

Answer 50

Histamine, synthesized from histidine, is produced solely by cells in the tuberomammillary nucleus (TMN) of the hypothalamus. Projections from the TMN go to the prefrontal cortex (PFC), basal forebrain (BF), striatum (S), nucleus accumbens (NA), thalamus (T), amygdala (A), hippocampus (H), brainstem neurotransmitter centers (NT), and spinal cord (SC). Histamine is a key neurotransmitter that regulates wakefulness. Once synthesized, histamine is packaged into synaptic vesicles by vesicular monoamine transporter 2 (VMAT 2). Upon release, it can excite neurons via the H1 receptor, leading to wakefulness, or inhibit histaminergic/other neurons via H3 receptors. There is no reuptake mechanism; histamine is broken down into tele-methylhistamine by histamine N-methyltransferase (HNMT) in the synaptic cleft and in glial cells, and tele-methylhistamine is further metabolized by monoamine oxidase B (MAO-B) to tele-methylimidazoleacetic acid (t-MIAA).

Question 51

How do antihistamines work as inverse agonists?

Answer 51

Antihistamines work as non-selective H1 inverse agonists. Inverse agonism is when antihistamines bind to H1 receptors and stabilize the effects of histamine. This prevents histamine from stimulating neurons that promote wakefulness, reducing signaling activity, which leads to increased drowsiness and sedation.

Question 52

What are the differences between 1st and 2nd generation antihistamines?

Answer 52

1st generation antihistamines easily cross the blood-brain barrier and have strong effects, while 2nd generation antihistamines do not cross the blood-brain barrier as easily and are less sedating.

Question 53

What are the administration details and examples of antihistamines?

Answer 53

Antihistamines are always administered orally as tablets, and Australian examples include Doxepin (Deptran) and Doxylamine (Restavit). Effects are seen within approximately 15-30 minutes of administration and last 6-8 hours.

Question 54

What are the common side effects of antihistamines?

Answer 54

Common side effects of antihistamines include daytime fatigue, dizziness, irritability, dry mouth, nose, or throat, headache, facial flushes, and rapid onset of tolerance.

Question 55

According to Rojas-Fernandez & Chen (2014), what is the efficacy of doxepin?

Answer 55

According to Rojas-Fernandez & Chen (2014), compared to placebo, doxepin significantly reduced waking after sleep onset and increased total sleep time into the last third of the night. However, it did not significantly affect sleep onset, and there was no significant difference between 3mg and 6mg doses. The efficacy of antihistamines depends on the drug, having greater effects on sleep maintenance than on sleep onset.

Question 56

What does CBT for insomnia involve?

Answer 56

CBT for insomnia involves cognitive techniques such as restructuring and at least one or more behavioral interventions. These interventions include sleep hygiene, which is establishing an appropriate bedroom environment and avoiding screen-based devices before bedtime and coffee or alcohol consumption; stimulus control, which is using the bedroom only to sleep and leaving the bedroom when unable to fall asleep; sleep restriction, which is restricting sleep times and increasing in-bed sleep times; relaxation, which is taking short and long relaxations during the day; cognitive restructuring, which is restructuring undesired thinking patterns; and a wrap-up, which is going over each component to prevent the relapse of insomnia.

Question 57

According to Smith et al. (2002), how does the efficacy of CBT compare to benzodiazepines for insomnia treatment?

Answer 57

According to Smith et al. (2002), a meta-analysis of benzodiazepines versus CBT for the treatment of insomnia showed that the overall mean effect size averaged across all sleep variables was comparable (0.79 v 0.80). However, sleep latency was more reliably reduced with psychological interventions.

Question 58

According to Morin et al. (1999), how does the long-term efficacy of CBT compare to benzodiazepines for insomnia treatment?

Answer 58

According to Morin et al. (1999), a meta-analysis of benzodiazepines versus CBT for the treatment of insomnia showed that pre-post therapy total sleep time improvements were comparable for both groups. But follow-up data showed that only the CBT group maintained their improvement.