Anxiety Flashcards
What are the clinical uses of hypnotics and anxiolytics?
Relief of anxiety states
Induction of sleep
Sedation and amnesia before medical procedures
Control of withdrawal states in addiction (e.g. delirium tremens)
Muscle relaxation
Severe behavioural disturbance
What may benzodiazepines also be used for?
Epilepsy
What controls the 24 hour rhythm?
Suprachiasmatic nucleus in the hypothalamus
What are the two main factors that regulate the sleep wake cycle?
Homeostatic sleep drive – low in the morning, increases during the day
Circadian alerting signal – increases during the day until about 9pm, then starts to decrease
What are the neuronal projections involved in the control of wakefulness?
Cholinergic systems (pedunculopontine and laterodorsal tegmental nuclei)
Monoaminergic projections (locus coeruleus, raphe nuclei, tuberomamillary nucleus)
These project to the cortex.
What are the neuronal projections involved in the control of sleep?
GABA and galanin neurons (ventrolateral preoptic nucleus)
Which transmitters promote sleep? (3)
GABA
Melatonin
Adenosine
Which transmitters maintain wakefulness? (6)
Noradrenaline Dopamine Serotonin Histamine Acetylcholine Orexin
Which agents promote wakefulness? (6)
GABA antagonists Adenosine antagonist NA uptake blockers Dopamine stimulants Serotonin uptake blockers H3 antagonists
Which agents promote sleep? (6)
GABA agonists M1 and M2 agonists Dopamine agonists 5-HT2 antagonists H1 antagonists OR1/2 antagonists
Which agents cause sedation? (4)
GABA agonists
Alpha-1 noradrenergic antagonists
H1 antagonists
Muscarinic antagonists
How long does each sleep cycle last?
90 minutes
What do REM, NREM and SWS stand for?
Rapid eye movement phase
Non-rapid eye movement phase
Slow wave sleep
The sleep cycles are identical in the ratio NREM/REM sleep. True or false?
False
How are sleep stages assessed?
Polysomnography
How many stages of sleep are there? What are they?
Awake - normal wakefulness (beta waves, 13-30 Hz) OR awake and relaxed (alpha waves, 8-12 Hz)
Stage 1 – theta waves (3.5-7.5 Hz)
Stage 2 - theta waves with sleep spindles and K complex
Stage 3 – delta waves, less than 3.5 Hz
Stage 4 – delta waves, less than 3.5 Hz
REM
Zif-268 expression level changes after experience in a sleep stage manner. When is it usually high? What happens in an enriched environment?
Sleep can consolidate memories through gene expression changes.
It is usually high during wakefulness and low in REM sleep, but with an enriched environment, it is high during REM sleep.
What are the three types of insomnia?
Transient (e.g. jet lag)
Short-term (e.g. associated with illness, bereavement, stress)
Chronic (lasts longer than 3 weeks)
What may sleep disorders may be a prodromal sign of?
Neurodegeneration
What causes 50% of insomnia cases?
Psychiatric disorders
At present, which drugs are used to treat insomnia?
Benzodiazepines (short-acting) and Z-drugs
Which anxiolytics/hypnotics are given for short-term use? (2)
Lorazepam, temazepam
Which anxiolytics/hypnotics are given for long-term use?
Eszopiclone and extended release zolpidem (chronic insomnia)
Which have a longer half-life - benzodiazepines or Z-drugs?
Benzodiazepines
What are the Z-drugs? (3)
Zaleplon, zolpidem, zopiclone
What are the unwanted effects of benzodiazepines as hypnotics? (5)
Change in sleep patterns (suppress deep sleep and REM sleep)
Daytime sedation
Rebound insomnia
Tolerance
Dependence (withdrawal syndrome characterised by anxiety, nausea, muscle cramps, seizures)
What does pregabalin bind to?
What is its benefit for the treatment of insomnia?
What can it also be used to treat?
Alpha-2 delta sub-unit of voltage gated calcium channels
No disruption of sleep architecture and no tolerance
Used as an anxiolytic
Why should prolonged prescription of hypnotics be avoided?
This can create a spiral of dependence
How can chronic insomnia be treated non-pharmacologically?
CBT
What is orexin/hypocretin? What are the two forms?
A peptide produced in the hypothalamus
Orexin A and orexin B (or hypocretin 1 and 2)
What do orexin OX1 and OX2 receptors mediate?
The effects of the wide distribution of projections. They regulate arousal, appetite, and wakefulness.
What does a deficiency in orexins cause?
Narcolepsy (condition characterised by excessive
sleepiness; increased frequency of falling asleep in daytime)
What is suvorexant?
A dual orexin receptor antagonist (treatment of insomnia)
What are the benefits of orexin antagonists over some other insomnia medication?
Orexin antagonists don’t have: Anticholinergic effects Orthostasis Respiratory depression Rebound insomnia Dependence Amnesia
(Although they can cause morning sedation, hallucinations and sleep paralysis.)
What are the types of anxiety disorder? (7)
Panic disorder Agoraphobia Social phobia Simple phobia OCD PTSD Generalised anxiety disorder
How many % of mental disorders in the EU are anxiety disorders?
10%
Is panic disorder more common in men or women?
Women (2:1)
Is OCD more common in men or women?
Women (3:2)
Is agoraphobia more common in men or women?
Women (8:3)
Which structures and transmitters are involved in anxiety disorders? (4)
Amygdala, insula, anterior cingulate, prefrontal cortex, thalamus
Abnormalities of the HPA axis
Monoaminergic systems
GABAergic systems
Hyperactivity of what structures is a common feature of anxiety disorders?
Hyperactivity of limbic structures (e.g. lateral and central amygdala) and the inability of higher cortical structures to control this hyperactivity
What are the symptoms of panic? (7)
Heart rate, blood pressure (lateral hypothalamus)
Bradycardia, ulcers (dorsal vagal nucleus)
Panting, respiratory distress (parabrachial nucleus)
Arousal, vigilance, attention (basal forebrain)
Increased startle response (pontis caudalis)
Freezing, social interaction (central grey area)
Corticosteroid release (paraventricular nucleus)
There are indications that what transmitter is involved in the genetic risk for anxiety disorders?
5-HT transmission
What genes are associated with specific anxiety disorders? (6)
COMT Cholecystokinin CCK B receptor Adenosine A2 receptor MAOA 5-HT2 receptor
What does KF-1 ubiquitin ligase act as?
What is co-localised with this protein?
An anxiety suppressor (knock out animals have increased fear/anxiety behaviour) Presenilin proteins (involved in Alzheimer’s disease)
KF-1 expression is increased after ___ or ___.
Chronic administration of SSRIs
After ECT
What are the types of anxiolytics?
Benzodiazepines 5-HT1A agonists β-adrenoceptor antagonists SSRIs Barbiturates
Give two examples of benzodiazepines.
Clonazepam and alprazolam
Give two examples of 5-HT1A agonists.
Buspirone and ipsapirone
Give three examples of SSRIs.
Fluoxetine, escitalopram and paroxetine
Give an example of a beta-adrenoceptor antagonist.
Propranolol
What problems are associated with the use of barbiturates? (6)
Drug dependence
Tolerance
Induction of liver microsomal enzymes
Fatal toxicity in overdose (respiratory depression)
Accumulation causes drowsiness, disorientation, ataxia, slurred speech
Withdrawal syndrome: agitation, insomnia, depression, feeling of tension, seizures
Why is the GABAergic synapse important clinically?
Key target of several hypnotic and anxiolytic drugs, e.g. benzodiazepines target GABA A
Benzodiazepines are positive allosteric modulators at what receptor complex?
GABA A receptor complex
What does diazepam potentiates?
GABA-induced hyper-polarization
Benzodiazepines and barbiturates increase what in relation to the GABA A channel?
Frequency of the open state and the opening duration of the GABA A channel
How do you manage a benzodiazepine overdose?
Flumazenil (antagonist at the benzodiazepine binding sites)
Generalised anxiety disorder is one of the most common psychiatric disorders. How is it treated?
Buspirone (5-HT1A agonist)
venlafaxine, duloxetine (SNRI)
fluoxetine, escitalopram (SSRI)
risperidone, quetiapine, olanzapine (APD)
What are the non-pharmacological treatments for anxiety?
Individual psychotherapy, family therapy, CBT, rational emotive therapy, hypnosis, meditation, acupuncture, yoga
What are the complications of benzodiazepine use in the elderly? (8)
Psychomotor impairment Risk of falls Daytime drowsiness Intoxication Amnesia Depression Respiratory problems Abuse and dependence
What is the target of Z-drugs?
Which subunit is linked to anxiolytic effects?
Which subunit is linked to hypnotic role?
α subunits of GABA A receptor
α3 subunits
α1 subunit (e.g. zaleplon and zolpidem)
