Flashcards in CPTP 3.5 Neuropharmacology 3 (Hypnotics and Anxiolytics) Deck (45)
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1
What are the stages of sleep?
First 3 hours --> 'slow wave' sleep
After that --> REM sleep
2
What happens during each stage of sleep, and what brain region is responsible for the activity?
Slow wave sleep:
• Hippocampus and neocortex
• Reactivation of memories from the day
REM sleep:
• Cortex
• Consolidation of memory into long-term stores
3
Recall the mechanisms of arousal
• Suprachiasmatic nucleus receives messages from the retina
• This activates the dorsomedial hypothalamic nucleus
• This activates the arousal pathways
4
Recall the ascending arousal pathways (which are activated by the dorsomedial hypothalamic nucleus)
What do they all do?
• Raphe nucleus (5-HT)
• Locus coeruleus (noradrenaline)
• Tuberomammillary nucleus (histamine)
These project to the cortex and keep it alert by "washing over" the synapses
5
What structures inhibit the ascending arousal pathways?
Ventrolateral preoptic nucleus
• GABA
• Galanine
Pineal gland
• Melatonin
6
What are the arousal and sleep-inducing neurotransmitters?
Sleep inducing:
• GABA
• Galanine
• Melatonin
Arousal:
• Histamine
• Noradrenaline
• Serotonin
7
What happens to sleep as you age? Why?
Much reduced duration of sleep. You produce less melatonin as you age
8
What are the types of insomnia?
• Initial (cant get to sleep)
• Middle (wake up in the middle of the night)
• Early waking
9
What are the causes of insomnia?
>Stress
>Psychiatric disorders:
• Anxiety
• Depression
• Bipolar
• PTSD
>Illness
• Alzheimers
• Rheumatoid arthritis
• Asthma
>Medication
• Stimulants
• Antidepressants
10
Why does stress cause insomnia?
Increased HPA axis activity causes arousal pathways to be more active
11
What cause of insomnia gives rise to:
1) initial insomnia?
2) terminal insomnia?
1) Anxiety
2) Depression
12
What effect do bipolar disorder and PTSD have on sleep?
Bipolar disorder:
• Less SWS
PTSD:
• Less REM
13
What properties must a hypnotic have?
• Short half-life
• Inhibits ascending arousal pathways
• Does not affect REM or SWS brain areas
14
What physiological effect does anxiety have?
Sympathetic NS activation:
• CV
• Hyperventilation
• Sweating
• GI (butterflies)
15
What 'theme' of core symptoms fo anxiety disorders share?
Fear, escape, avoidance
16
Name the anxiety disorders
• OCD
• PTSD
• GAD
• Panic disorder
• Agoraphobia
• Social anxiety
17
What three main neurotransmitters are associated with anxiety disorders?
Serotonin and noradrenaline - Increased
• Increased release
GABA - Decreased
• Decreased amounts of GABA-A receptor function, so less binding
18
What effect do SSRIs have on 5-HT levels and anxiety?
Increases 5-HT in synaptic cleft, and increases anxiety
19
How are hypnotics and anxiolytics linked?
They both are non-specific CNS depressants that reduce levels of arousal, the difference is the dose.
(To induce sleep, a higher dose is needed than for anxiolytic effects.)
20
How should hypnotics and anxiolytics half lives differ?
Anxiolytics - Long half life
Hypnotics - Short half life
21
What are the classes of hypnotics and anxiolytics? What separates these?
• Barbituates
• Benzodiazapines
• (Alcohol)
HYPNOTIC ONLY:
• Z-hypnotics
• Antihistamines
Therapeutic windows and pharmacokinetics
22
Why are barbituates not used any more?
• Interact with alcohol
• Very small therapeutic window
23
Name the formulary benzodiazepines. What is the half-life and use of each?
Name the formulary Z-hypnotic
• Temazepam, 10hrs, hypnotic
• Lorazepam, 15 hrs, anxiolytic
• Chlorodiazepoxide, 20hrs, anxiolytic
• Diazepam, 40hrs, anxiolytic
Z-hypnotic:
• Zopiclone, 6 hours
24
What other use can hypnotics and anxiolytics have?
• Reduce muscle tone (i.e. in tension headaches)
• Anticonvulsant
• Surgical sedative
25
What drug is used as a surgical sedative, what is its half life and drug class?
Midazolam
• t(1/2) = 1-4 hours
• benzodiazapine
26
Why do chlorodiezepoxide and diezepam have such long half-lives?
Their metabolites are biologically active
27
What are the adverse effects associated with hypnotics and anxiolytics?
What causes many of these?
• Interaction with alcohol
• Poor motor co-ordination
• Poor memory (this is why roofies, a benzo, causes the victim to not remember)
• Decreased REM sleep
• Tolerance, dependence and withdrawal syndrome
Neurological side effects caused by non-selective CNS suppression
28
What are the modes of action of the hypnotics and anxiolytics classes?
Barbituates:
• Non-selective depressant activity, reduces Na+ channels preventing action potentials
• GABA-A receptor has barbiturate site which can activate it in absence of GABA, by opening the Cl- channel
Alcohol:
• Allosteric modulator of GABA-A receptor (enhance effect of GABA)
Benzodiazepines:
• Allosteric modulator of GABA-A receptor (enhance effect of GABA)
Z-hypnotics:
• Allosteric modulator of GABA-A receptor (enhance effect of GABA)
29
Why do barbiturates have a smaller therapeutic window and less safe in overdose?
They activate GABA-A, rather than modulate it, thus GABA does not need to be present, making it much more potent. (endogenous GABA cannot act as a rate-limiting step)
30
