CPTP 3.5 Neuropharmacology 3 (Hypnotics and Anxiolytics) Flashcards Preview

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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

What is the nature of the interaction between alcohol and the hypnotic/anxiolytic drug classes?

They potentiate each other.