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BB2 > Anxiety & Sleep > Flashcards

Anxiety & Sleep Flashcards

1
Q

What are some clinical uses of hypnotics and anxiolytics?

A
  • relief of anxiety states
  • induction of sleep and sedation
  • control of withdrawal states in addiction
  • muscle relaxation
  • severe behavioural disturbance
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2
Q

What is the sleep wake cycle mediated by?

A

Suprachiasmatic nucleus in the hypothalamus to control circadian rhythm

  • neurons increase activity during light phase
  • increase in melatonin in dark phase
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3
Q

What neural projections control wakefulness?

A

Cholinergic systems

Monoaminergic Projections

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4
Q

What parts of the cholinergic system control wakefulness?

A
  • pedunculopontine (Ach)

- laterodorsal tegmental nuclei (Ach)

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5
Q

Which parts of the monoaminergic projections control wakefulness?

A
  • locus coeruleus (noradrenaline)
  • raphe nuclei (serotonin)
  • tuberomammillary nucleus (histamine)
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6
Q

What neural projections affect sleep?

A

GABA and Galanin neurons

- ventrolateral preoptic nucleus

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7
Q

Which neurotransmitters maintain wakefulness?

A 
Noradrenaline
Dopamine
Histamine
Acetylcholine
Orexin
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8
Q

Which neurotransmitters promote sleep?

A

GABA
Galanin
Melatonin
Adenosine

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9
Q

Why does caffeine keep you awake?

A

Blocks adenosine which promotes sleep

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10
Q

How long does a sleep cycle last?

A
  • last 90 minutes
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11
Q

What are the phases in a normal sleep cycle?

A

REM - rapid eye movement phase
NREM - non-rapid eye movement phase
SWS - slow wave sleep (a type of NREM)

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12
Q

What is the relationship between sleep and memories?

A

Sleep consolidates memories through gene expression changes

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13
Q

What are the 3 types of insomnia? What are some examples?

A
  • transient (jet lag)
  • ST (associated with illness/bereavement stress)
  • chronic (lasts longer than 3 weeks)
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14
Q

What may sleep be an early sign of?

A

Neurodegeneration

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15
Q

What are the current treatments for insomnia?

A

Benzodiazapines (short acting) (end in pam) and Z drugs (longer acting)

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16
Q

Which drugs should be used to treat insomnia in the ST?

A

Lorazepam

Temazepam

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17
Q

Which drugs should be used to treat insomnia in the LT?

A
  • eszopiclone (Z drug)
  • Zolpidem (extended release

(still have short half life)

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18
Q

What do Z drugs target?

A

Alpha subunits

  • alpha 1 (hypnotic role)
  • alpha 3 (anxiolytic effects)
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19
Q

Which Z drugs target alpha-1?

A

Zaleplon/zolpidem

20
Q

What are some unwanted effects of benzodiazapines when used as hypnotics?

A
  • change in sleep patterns (suppresses deep and REM sleep which is needed for memory tracing)
  • daytime sedation (drowsy)
  • rebound insomnia
  • tolerance
  • dependence (withdrawal syndrome)
21
Q

What are the withdrawal symptoms of benzodiazapines when used as hypnotics?

A
  • anxiety
  • nausea
  • muscle cramps
  • seizures
22
Q

Why is excessive hypnotic use bad?

A

Can create a spiral of dependence

  • prolonged prescription needs to be avoided
  • can switch to non-pharmacological treatment (CBT)
23
Q

What drug has recently been used for insomnia?

A

Pregabalin - binds to alpha2delta subunit of voltage gated calcium channels, also used as anxiolytics, no disruption of sleep patterns, no tolerance

24
Q

What is the orexin system?

A
  • effects mediated by orexin OX1 and OX2 receptors
  • wide distribution of projections
  • regulates arousal, appeitie and wakefulness
25
Q

What is orexin?

A

Hypocretin
Peptide produced in the hypothalamus
2 types - A and B

26
Q

What does a deficiency of orexin entail?

A
  • narcolepsy (excessive sleepiness)
27
Q

What are some orexin antagonists?

A

Suvorexant

decreases wakefulness

28
Q

What are the effects of suvorexant?

A
  • morning sedation
  • sleep paralysis
  • decreased amnesia
  • decreased confusion
29
Q

What are some anxiety disorders?

A 
Panic disorder
Social phobia
Agoraphobia - fear of open spaces
OCD
Post-traumatic stress disorder
Simple phobia - spiders/blood/needles
30
Q

Which structures are involved in anxiety disorders?

A

Limbic - amygdala, insula, anterior cingulate, prefrontal cortex, thalamus, HPA axis

31
Q

What neurotransmitters are involved in anxiety disorders?

A

Monoaminergic systems

GABAergic systems

32
Q

How is the amygdala involved with anxiety?

A

Hyperactivity of amygdala and limbic structures = fear/anxiety

33
Q

Which genes are associated with panic disorders?

A 
COMT
CCK
CCKb (CCK receptors)
5-HT2 receptor
MOAa
Adenosine A2 receptors
34
Q

What are the classes of anxiolytics?

A 
Benzodiazepines
5-HT1a agonists (partial agonists)
SSRIs
SNRIs
Beta adrenoreceptor antagonists
35
Q

Which drugs are benzodiazepines?

A

Clonazepam
Alprazolam
Lorazepam
Diazepam

36
Q

Which drugs are 5-HT1a partial agonists?

A

Buspirone

Ipsapirone

37
Q

Which drugs are SSRIs?

A

Fluoxetine
Escitalopram
Paroxetine

38
Q

Which drugs are SNRIs?

A

Venlafaxine

Duloextine

39
Q

Which drugs are beta-adrenoreceptor antagonists?

A

Propanolol

40
Q

What are the properties of the GABAa receptor?

A
  • post synaptic
  • fast inhibitory transmission = hyperpolarisation through Cl- influx which is higher extracellular than IC
  • stops propagation of electrical activity in the cerebral cortex
  • extreme heterogeneity = multiple subunit combinations
  • binding site for benzodiazepine (positive allosteric modulator)
41
Q

What is the effect of benzodiazapines on GABA receptors?

A
  • positive allosteric modulators
  • potentiates hyperpolarisation = open state frequency and duration increases
  • barbiturates also do this to GABAa channel
42
Q

What is flumazenil used for?

A

Overdose of benzodiazepines

  • antagonists of benzodiazepine binding sites
  • but has short half life so need to keep injecting until patient is safe
43
Q

What is the treatment for generalised anxiety disorder?

A
  • buspirone
  • SNRI (venlafaxine, duloxetine)
  • SSRI (fluoxetine, escitalopram)
  • anti-psychotic drugs (risperidone, quetiapine, olanzapine)
44
Q

Why have barbiturates become obsolete in treating anxiety?

A
  • major risk of drug dependence
  • tolerance dev.
  • induction of liver microsomal enzymes (drug interaction risk)
  • if overdose = fatal toxicity (respiratory depression)
  • accumulation = drowsiness, disorientation, ataxia, slurred speech
  • withdrawal syndrome = agitation, insomnia, depression, tension, seizures
45
Q

What are the unmet clinical needs in generalised anxiety disorder?

A
  • drugs with fast mechanism of action/efficacy
  • drugs with broad spectrum of benefits
  • drugs leading to improved rates of remission
  • devoid of withdrawal symptoms
  • fewer adverse drug interactions
  • safe for elderly
46
Q

What are some complications of benzodiazepines for the elderly?

A
  • psychomotor impairment
  • risk of falls
  • daytime drowsiness
  • intoxication
  • amnesia
  • depression
  • respiratory problems
  • abuse and dependence
47
Q

How can we make Z drugs more selective in the future?

A
  • those targeting alpha1 subunit have hypnotic role

- targeting alpha3 subunit have more anxiolytic effects

BB2 (31 decks)

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