PHAR 308: Flashcards 13 - Sleep Disorders

What are the two sleep stages in a sleep cycle?

1. Non REM (NREM) sleep which is light and deep sleep

2. REM sleep - a distinctive electrical brain state which replenishes ATP and clears the metabolic and lymphatic state while body is paralyzed and dreaming

What are some of the neurotransmitters whjich are associated with brain waking activity?

ACh

Orexin 

NE

5HT

Histamine 

DA 

What are some of the brain tiring neurotransmitters/states?

ADP

Light decrease

Melatonin

What are some of the Brain Sleep neurotransmitters 

GABA 

Galanin 

What are the tests to diagnose sleep disorders?

polysomnogram

What is the activity of Histamine on sleep patterns?

Diametric Effects

H1 receptor will increase the neuronal activity when bound with histamine - acts as an arousing neuropeptide

H3 receptor will decrease histamine release when bound to histamine by instigating a negative feedback loop

What is the action of Melatonin in the sleep cycle?

Pineal gland is responsible for the production of melatonin when the light levels decrease. This supports the circadian rhythm.   

What is a parasomnia?

A sleep disorder of irregular sleep pattern

What are the four types of parasmonias?

1. Non REM Arousal Disorder

2. Sleep wake transition disorder

3. Parasomnia related to REM sleep

4. Other parasomnia

What is are the four major manifestations of arousal disorders (NREM)

Confusional Arousal 

Sleep Walking 

Night Terror 

Sleep related Eating Disorder 

What is confusion arousal?

Partial waking from deep sleep leading to confusion and disorientation

Disruption of REM impacts the homestasis which is detrimental to health is occurs a lot

What is sleep walking

somnambulism

Individual arises during the night

movement away from the sleep location which can be damgerous

What are sleep terrors 

Mostly in children 

Abrubt sitting up and screaming during the night in a state of extreme terror 

What is sleep related eating disorder?

Eating when asleep

What are the treatments for Arousal disorders?

Removal of triggers

Practice good sleep hygiene

Hypnosis therapy to reduce stress and anxiety

Pharmacological intervention

• hypntoics

• sedatives

• antidepressants

What are the features of sleep hygiene 

1. Routine for sleep time and wake time 

2. Avoid napping

3. Avoid stimulants

4. Avoid eating a large meal before bedtime

5. Exercise but not before bedtime 

6. Expose to light during the day 

7. Have a bedtime routine 

8. Associate the bed only with sleeping 

What is REM behaviour disorder?

REM behavious disorder (RBD) is when the REM paralysis does not set in for an individual so they are able to move and enact dreams

early biomarker of PD

What are some non pharmacological treatments of RBD?

bedroom safety, remove dangers to the person and make it hard for then=m to leave the room

What are some pharmacological interventions for RBD?

• Clonazepam (benzodiazepines)

• Melatonin (Ensure good circadian rhythm)

• Rivastignine and Donezipil 

What are some other notable parasomnias?

Sleep Paralysis

Nightmares

Painful Sleep Related Erections

Sleep Related Sinus Arrest

What is Hypersomnia?

Excessive daytime sleepiness despite a long and restful night sleep and normal circadian rhythm

What is narcolepsy?

A neurological disorder which prevents the brain from controlling REM sleep patterns leading to sleep attacks.

What are the symptoms of narcolepsy?

1. Hypersomnolence

2. Fragmented Sleep

3. REM dysfunction

4. Fatigue and Cataplexy

What is cataplexy?

Paralysis occuring in the REM sleep resulting in a loss of muscle tone, can be related with a positive emotion

How does someone acquire narcolepsy?

Orexin/Hypocretin is a neuropeptide which activates the brainstem, forebrain and arousal regions making one feel awake. 

Narcolepsy is related to an autoimmune disease which leads to the destruction of these neurons. 

What are 6 treatments fro narcolepsy?

1. Improved sleep hygiene

2. Stimulants during the day to deter REm sleep

3. Antidepressants to suppress REM sleep

4. Modafil

5. Pitolosant

6. Sodium Oxybate

What is Modafinil

A orexin agonist to increase the secretion of orexin from neurons

decraeses the DA uptake and stops GABA to have more excitatory synapse

Has a long half life and good absorption so is well tolerated as an oral drug

What is Pitolisant?

A selective, competitive, high affinity inhibitor to act as an inverse agonist of H3 which prvents negative regulationn of Histamine 

Leads to more wakefulness 

Oral absorption and t1/2 is optimal 

What is Sodium Oxybate

A central nervous sysetm depressant which treats cataplexy and sleepiness in the daytime

MOA is unknown, maybe a GABA agonist

super fast acting 

What is Insomnia?

Difficulty falling asleep and staying asleep 

What is the diagnosis of insomnia?

3x a week there is difficulty falling asleep and that lasts for 3 consecutive months

What are the resulting effects of insomnia?

fatigue, difficulty focusing, difficulty concentrating, mood issues and decreased performance

What are some treatments?

CBT

GABA enhancers 

Melatonin receptor agonists 

Orexin receptor agonists 

other (antihistamines and antidepressants)

What are the GABA enhancer drugs and how do they treat insomnia?

Benzodiazepenes will acts as positive allosteric modulators of GABA to increase inhibitory synapse in the brain

this will decrease sleep latency and prolong to first stages of sleep

What are melatonin Receptor Agonists and how do they treat Insomnia?

mimic melatonin which is a neurohormone form the pineal gland that regulates the circadian rhythm

Rameteon and Tasimelteon to treat insomnia and non 24 hour sleep wake disorder

What are orexin receptor antagonists and how do they treat insomnia 

Blocking orexin signalling disrupts arousal NT in the brain 

Suvorexant is the main orexin antagonist to block OX1 and OX2 

What are antidepressants and how do they contribute to treating insomnia?

have sedative effects and antagonize the H1 receptos (prevent arousing histamine)

What are antihistamines and how do they treat insomnia?

Antagonize the H1 receptor and prevent the arousing effects of histamine