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Neuropharmacology > Sedatives and Hypnotics > Flashcards

Sedatives and Hypnotics Flashcards

1
Q

What is the optimum number of hours for a healthy sleep?

A

7-9 hours

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2
Q

What are the 2 main types of sleep?

A
  • rapid eye movement (REM)
  • non rapid eye movement (NRRM)
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3
Q

How long does each sleep cycle last?

A

90-120 minutes i.e. in a typical night there are 2-3 cycles

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4
Q

Describe the stages of the sleep cycle

A
  • stage 1 – drowsiness, small wave frequency ~5% of sleep time
  • stage 2 – asleep, theta waves with sleep spindles and K-complexes ~50% of sleep time
  • stage 3 – delta waves, less sleep spindle ~5% of sleep time
  • stage 4 – deepest stage of NREM, delta waves, hard to wake, GH released, slow wave sleep ~15% of sleep time
  • REM – fast desynchronised brain wave activity, body effectively paralysed, dreaming most likely to occur ~25% of sleep time
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5
Q

How can human brain activity be measured?

A

electroencephalogram (EEG)

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6
Q

When does REM duration increase?

A

towards the ends of the night

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7
Q

What is memory consolidation?

A

when short-term memory is converted to long-term memory

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8
Q

What can one night of bad sleep cause?

A

an accumulation of toxic beta amyloid in the brain

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9
Q

Give examples of sleep disorders

A
  • snoring
  • obstructive sleep apnoea
  • insomnia
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10
Q

What does GABA binding to its receptor cause?

A

hyperpolarisation

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11
Q

What does the GABA receptor consist of?

A

19 subunits

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12
Q

Where does GABA bind?

A

at the interface of the alpha and beta subunits

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13
Q

What are GABA α1 subunits involved in and where are they highly expressed?

A

sleep expressed in ventrolateral preoptic nucleus

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14
Q

What are GABA α2 and 3 subunits involved in and where are they highly expressed?

A

anxiety expressed in amygdala

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15
Q

What are sedatives and hypnotics?

A

a class of drugs used to induce and/or maintain sleep, e.g. benzodiazepines and non-benzodiazepines (Z-drugs)

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16
Q

What are the sleep and wake promoters in the hypothalamus?

A
  • sleep - VLPO
  • wake - TMN
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17
Q

What is the mechanism of action of benzodiazepines?

A

they enhance the action of GABA and bind at GABA receptors to increase the flow of chloride ions into the cell to slow or stop nerve impulses

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18
Q

What are therapeutic actions of benzodiazepines in short-term use?

A
  • anxiolytic
  • hypnotic
  • myorelaxant
  • anticonvulsant
  • amnesia
19
Q

What do benzodiazepines do?

A

increase frequency of channel opening and non-selectively bind to alpha subunits 1-6 to induce sedation, anxiolytic, muscle relaxation and alcohol potentiation actions

20
Q

Give examples of benzodiazepines in order of increasing lengths of action

A
  • midazolam (very short)
  • temazepam (short)
  • lorazepam (medium)
  • diazepam (long)
21
Q

What are side effects of benzodiazepines?

A
  • sedation
  • muscle relaxation
  • drowsiness
  • dizziness
  • decreased alertness and concentration
  • impairment of motor coordination
22
Q

What are the adverse side effects of benzodiazepines?

A
  • oversedation
  • memory impairments
  • depression
  • tolerance
  • dependence
23
Q

What does oversedation cause?

A

‘hangover’ effects due to a tolerance developing over 1-2 weeks and symptoms include drowsiness, poor concentration, incoordination, muscle weakness, dizziness and mental confusion

24
Q

What is memory impairment by benzodiazepines characterised by and when is it induced?

A

lack of coordination and attention used to relieve from the stress of catastrophic disasters

25
Q

How can prolonged use of benzodiazepines cause depression?

A

they can reduce the brain’s output of serotonin and noradrenaline and cause emotional anaesthesia due to the inhibitory effect on activity of brain emotional centres

26
Q

How can tolerance to benzodiazepines arise?

A

compensatory changes occur in the GABA and benzodiazepine receptors which become less responsive i.e. inhibitory actions of GABA and benzodiazepines are decreased and activity of excitatory neurotransmitters tends to be restored due to decreased GABA activity

27
Q

What can withdrawal symptoms of benzodiazepines cause?

A

rebound insomnia, restlessness, agitation and irritability

28
Q

What do Z-drugs do?

A

bind between the alpha and gamma subunits of the GABA receptor to have an anti-anxiety and sedative effect without altering REM sleep

29
Q

Give examples of Z-drugs in order of increasing lengths of action

A
  • zolpidem (very short)
  • zopiclone (short)
30
Q

What are side effects of Z drugs?

A

memory loss, daytime sedation and impairment of motor function

31
Q

What are the overall effects of benzodiazepines on sleep?

A
  • decreased sleep latency
  • increased time in stage 2
  • increased total sleep time
  • decreased REM
32
Q

What are the overall effects of Z drugs on sleep?

A
  • decreased sleep latency
  • increased time in stage 2
  • increased total sleep time
  • no effect on REM
33
Q

What do barbiturates do?

A

increase ion channel opening duration and at high doses, mimic GABA and directly activate the receptor

34
Q

What is meant by barbiturates having a low therapeutic index?

A

a small overdose can result in coma or death due to respiratory depression

35
Q

Give examples of barbiturates

A

pentobarbital, phenobarbital and secobarbital

36
Q

Why are barbiturates no longer used as sedatives?

A
  • they have a narrow therapeutic-to-toxic dosage range
  • they suppress REM sleep
  • tolerance develops relatively quick
  • they have a high potential for physical dependence and abuse
37
Q

How do melatonin levels fluctuate?

A

they rise and fall in circadian fashion in the suprachiasmatic nucleus

38
Q

What are the 2 GPCRs for melatonin and what do they do?

A
  • MT1 receptors promote the onset of sleep
  • MT2 receptors shift the timing of circadian system
39
Q

What is ramelteon?

A

a melatonin agonist that binds to both MT1 and MT2 receptors with high affinity

40
Q

What is melatonin used for?

A

to treat transient and chronic insomnia

41
Q

What are side effects of melatonin?

A

dizziness, fatigue, infertility and endocrine changes (e.g. decreases in testosterone and increases in prolactin)

42
Q

What is suvorexant?

A

an orexin receptor antagonist that blocks binding of wake-promoting orexin A and B neuropeptides

43
Q

How does suvorexant work?

A

by turning off wakefulness rather than by inducing sleep

44
Q

What do drugs with shorter half-lives in the body do?

A

reduce the incidence of hangover

Neuropharmacology (12 decks)

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