Anxiety Flashcards
name some of the clinical uses of hypnotics and anxiolytics
- Relief of anxiety states
- Induction of sleep (relief of insomnia)
- Sedation and amnesia before medical procedures
- Control of withdrawal states in addiction such as delirium tremens
- Muscle relaxation
- Severe behaviour disturbance
- Benzodiazepines ca also be used for the treatment of epilepsy
what controls the sleep wake cycle (circadian rhythm)
- SCN = suprachiasmatic nucleus in the hypothalamus
- The SCN controls 24 hour circadian rhythm
what happens to the SCN in the light phase of the sleep wake cycle
the SCN has increased activity in the light phase and decreased activity in the dark phase
what happens to melatonin in the dark phase of the sleep wake cycle
there is an increase in melatonin in the dark phase and decrease in the light phase
what are the neurone projections that cause wakefulness
o Cholinergic Systems:
Pedunculopontine (acetylcholine)
Laterodorsal tegmental nuclei (acetylcholine).
o Monoaminergic Projections:
Locus Coeruleus (noradrenaline)
Raphe nuclei (serotonin)
Tuberomamillary nucleus (histamine).
what are the neurones that promote sleep
o GABA and Galanin Neurons
Ventrolateral preoptic nucleus.
what are the neurotransmitters that maintain wakefulness
- noradrenaline,
- dopamine
- histamine
- acetylcholine
- orexin.
what are the neurotransmitters that promote sleep
- GABA
- Galanin
- melatonin
- adenosine (caffeine is an adenosine blocker).
what can block adenosine
caffeine
what controls nocturnal/diurnal rhythms
superchiasmatic nucleus of the hypothalamus
How long does each sleep cycle last
90 minutes
what are the different types of sleep
- REM = rapid eye movement phase
- NREM = no rapid eye movement phase
- SWS – slow wave deep sleep (NREM-3 and NREM-4)
what two sleep phases make up slow wave sleep
– slow wave deep sleep (NREM-3 and NREM-4)
what phase of sleep is lose to waking us up
- REM phase sleep is close to waking up
- as we get closer to the morning we have more dreams and sleep more lightly
what waves are used in normal wakefulness
beta waves (13-30hz)
what waves are used when you are awake and relaxed
alpha waves (8-12hz)
name the waves used in - stage 1 - stage 2 - stage 3 - stage 4 of sleep
- stage 1 = theta waves (35-75hz)
- stage 2 = theta waves with sleep spindles and K complex
- stage 3 = delta waves (less than 35hz) less than 50%
- stage 4= delta waves (less than 35hz) more than 50%
what does hz mean
this is the number of waves per second
what happens during sleep to memory
- The brain is active and sleep may consolidate memories through gene expression changes
what are the types of insomnia
- Transient (e.g. jet lag)
- Short-Term (associated with illness/bereavement stress)
- Chronic (lasts longer than 3 weeks).
what can be the cause of a sleep disorder
- can be trivial e.g. due to stress or it can be due to something more serious such as a psychiatric disorder or early stage of neurodegeneration
what is currently used to treat insomnia
Benzodiazepines (short acting) and Z drugs are used to treat insomnia
what is used for short term use in insomnia
lorazepam
temazepam
what do benzodiazepines end in
pam
what drugs are used long term in insomnia treatment
- Eszopiclone (z-drugs)
* Zolpidem (extended release).
what are the targets of Z drugs
alpha subunits
• Alpha-1: hypnotic role
o Zaleplon/zolpidem.
• Alpha-2 subunits: anxiolytic effects
what are the side effects that benzodiazepines can give you
- Change in sleep patterns (suppress deep sleep and REM sleep)
- Daytime sedation
- Rebound insomnia – start becoming tolerant and need them all the time to induce sleep and if you stop then you wont be able to sleep, can lead to hyperanxiety
- Tolerance
- Dependence (withdrawal syndrome characterised by anxiety, nausea, muscle cramps, seizures)
what is the withdrawal symptoms of benzodiazepines characterised by
withdrawal syndrome characterised by anxiety, nausea, muscle cramps, seizures
what has been recently used for insomnia and why
- pregabalin
positive effects; - no disruption of sleep architecture
- no tolerance
what can pregabalin also be used as
anxiolytic
what can excessive use of hypnotics such as benzodiazepines and Z drugs lead to
- creates a spiral of dependence
how can you avoid the spiral of dependence
- avoid prolonged prescription of hypnotics
- non pharmacological intervention for the control of chronic insomnia such as CBT
where is orexin produced
- it is a peptide that is produced in the hypothalamus
what are the two forms of orexin
• Two forms: orexin A and orexin B (also known as hypocretin 1 and hypocretin 2)
what receptors does orexin bind to
• orexin OX1 and OX2 receptors
what does orexin do
• Regulates arousal, appetite, wakefulness
what results if you have a deficiency in orexin
narcolepsy
what is narcolepsy
this is a condition characterised by excessive sleepiness, increased frequency of falling alsleep in daytime
what does an orexin antagonist do
decrease wakefulness
- therefore it can be used in the treatment of insomnia
name an orexin antagonist
Suvroextant - this is an orexin receptor antagonist that an be used for insomnia treatment
what does suvroextant result in
o Morning sedation
o Sleep paralysis
o Decreased amnesia
o Decreased confusion
name some anxiety disorders
- Panic disorder
- Agoraphobia – fear of open spaces
- Social phobia (social anxiety disorder) – e.g. fear of speaking in public
- Simple phobia
- Obsessive compulsive disorder
- Post-traumatic stress disorder
- Generalized anxiety disorder
are anxiety disorders more common in males or females
females
what are the structures and neurotransmitters that are involved in anxiety disorders
- Limbic structures: amygdala, insula, anterior cingulate, prefrontal cortex, thalamus.
- abnormalities of the HPA axis.
- Monoaminergic systems.
- GABAergic systems.
is the amygdala hypoactive ir hyperactive in anxiety disorder
- hyperactive and part of the anxiety disorder results from the inability of higher cortical structures to control this hyperactivity
describe what each part of the amygdala results in which symptom of fear and panic
- lateral hypothalamus
- dorsal vagus nerve
- parabrachial nerve
- basal forebrain
- reticules ponis caudales
- central grey area
- paraventricular nucleus
- lateral hypothalamus - hear rate and blood pressure
- dorsal vagus nerve - bradycardia and ulcers
- parabrachial nerve - panting and respiratory distress
- basal forebrain - aroual, vigilance and attention
- reticules ponis caudales- increase startle response
- central grey area - freezings and social interaction
- paraventricular nucleus - corticosteroid release
what genes are linked to anxiety
- Catechol-O-methyl transferase (COMT)
- Cholecystokinin (CCK)
- CCKB receptor
- Adenosine A2 receptor
- Monoamine oxidase A (MAOA)
- 5-HT2 receptor
what are the types of anxiolytics used to treat anxiety
- Benzodiazepines
- 5-HT1A agonists
- SSRIs
- SNRIs
- β-adrenoceptor antagonists
- Barbiturates
name examples of benzodiazepines
- Clonazepam
- Alprazolam
- Lorazepam
- Diazepam
name examples of 5HT1A agonist
- buspirone
- ipsapirone
name examples of SSRIs
- Fluoxetine
- Escitalopram
- Paroxetine
name examples of SNRIs
- Venlafaxine
* Duloxetine
Name an example of a beta adrenoreceptor antagonists
• Propranolol.
what are there risks of using barbiturates
• Major risk of drug dependence
• Development of tolerance
• Induction of liver microsomal enzymes (risk of drug interactions).
• Fatal toxicity in overdose (respiratory depression).
• Withdrawal symptoms: agitation, insomnia, depression, tension.
- Accumulation causes drowsiness, disorientation, ataxia, slurred speech
What are the withdrawal symptoms of barbiturates
: agitation, insomnia, depression, tension.
What does the GABAa receptor do
Expressed post-synaptically, lead to fast inhibitory transmission (hyperpolarization) through influx of Cl-
- therefore this stops the transmission of electrical activity in the cerebral cortex
what part of the GABAa receptor does benzodipaeine binds to
alpha1 gamma 2 part of the channel
describe what benzodiazepines do to the GABA channel versus barbiturates
benzodiazepines increase frequency of opening whereas barbiturates increase the duration of opening
wha does diazepam do the GABAa channel
g. Diazepam potentiates GABA-induced hyperpolarization.
What is Flumazenil
- Flumazenil acts as an antagonist at the benzodiazepine binding sites but has a short half-life
name an antagonist of the benzodiazepine binding site
flumazenil
what is the treatment of generalised anxiety disorder
- buspirone
- venlafaxine, duloxetine (SNRI)
- fluoxetine, escitalopram (SSRI)
- risperidone, quetiapine, olanzapine (APD)
what are complications of benzodiazepine use in the elderly
- Psychomotor impairment
- Risk of falls
- Daytime drowsiness
- Intoxication
- Amnesia
- Depression
- Respiratory problems
- Abuse and dependence
