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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
What is orexin?
Hypocretin Peptide produced in the hypothalamus 2 types - A and B
26
What does a deficiency of orexin entail?
- narcolepsy (excessive sleepiness)
27
What are some orexin antagonists?
Suvorexant | decreases wakefulness
28
What are the effects of suvorexant?
- morning sedation - sleep paralysis - decreased amnesia - decreased confusion
29
What are some anxiety disorders?
``` Panic disorder Social phobia Agoraphobia - fear of open spaces OCD Post-traumatic stress disorder Simple phobia - spiders/blood/needles ```
30
Which structures are involved in anxiety disorders?
Limbic - amygdala, insula, anterior cingulate, prefrontal cortex, thalamus, HPA axis
31
What neurotransmitters are involved in anxiety disorders?
Monoaminergic systems | GABAergic systems
32
How is the amygdala involved with anxiety?
Hyperactivity of amygdala and limbic structures = fear/anxiety
33
Which genes are associated with panic disorders?
``` COMT CCK CCKb (CCK receptors) 5-HT2 receptor MOAa Adenosine A2 receptors ```
34
What are the classes of anxiolytics?
``` Benzodiazepines 5-HT1a agonists (partial agonists) SSRIs SNRIs Beta adrenoreceptor antagonists ```
35
Which drugs are benzodiazepines?
Clonazepam Alprazolam Lorazepam Diazepam
36
Which drugs are 5-HT1a partial agonists?
Buspirone | Ipsapirone
37
Which drugs are SSRIs?
Fluoxetine Escitalopram Paroxetine
38
Which drugs are SNRIs?
Venlafaxine | Duloextine
39
Which drugs are beta-adrenoreceptor antagonists?
Propanolol
40
What are the properties of the GABAa receptor?
- 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
What is the effect of benzodiazapines on GABA receptors?
- positive allosteric modulators - potentiates hyperpolarisation = open state frequency and duration increases - barbiturates also do this to GABAa channel
42
What is flumazenil used for?
Overdose of benzodiazepines - antagonists of benzodiazepine binding sites - but has short half life so need to keep injecting until patient is safe
43
What is the treatment for generalised anxiety disorder?
- buspirone - SNRI (venlafaxine, duloxetine) - SSRI (fluoxetine, escitalopram) - anti-psychotic drugs (risperidone, quetiapine, olanzapine)
44
Why have barbiturates become obsolete in treating anxiety?
- 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
What are the unmet clinical needs in generalised anxiety disorder?
- 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
What are some complications of benzodiazepines for the elderly?
- psychomotor impairment - risk of falls - daytime drowsiness - intoxication - amnesia - depression - respiratory problems - abuse and dependence
47
How can we make Z drugs more selective in the future?
- those targeting alpha1 subunit have hypnotic role | - targeting alpha3 subunit have more anxiolytic effects

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