20 - Sedatives, hypnotics and anxiolytics Flashcards
What is sedation
Reduction in excitement, vigilance and physiological arousal so that the person is relaxed, calm and possibly sleepy
What is hypnosis
Ability to induce drowsiness and sleep
What do lesions of the anterior hypothalamus cause
Insomnia
What do lesions of the posterior hypothalamus cause
somnolence
What systems are part of the ARAS
NorA 5HT ACh DA HA Orexin
What systems are sleep promoting
GABA
Adenosine
Melatonin
What is insomnia
Unsatisfactory sleep onset, maintenance or early waking
What are some treatments for insomnia (5-6)
COGNITIVE BEHAVIOURAL THERAPY PHARMACOTHERAPY Barbiturates Benzodiazepines z-drugs Melatonin Antihistamines
Why did benzodiazepines replace barbiturates
Lower risk of abuse, overdose and induction of liver enzymes
How do benzodiazepines help with insomnia
Promote onset of sleep and ongoing sleep
What are most GABAA receptors made of
2 a, 2b and 1 y
What will the y subunit be replaced with in different brain regions
d, e and t
What subunits are benzodiazepines selective for
a1, a2, a3, a5
Benzo vs barbiturate action
Increase affinity and no. of openings vs
Increase length opening and increase channel
Are benzos active without GABA
No, but boosts GABA response
What are the clinical effects of benzodiazepines
Hypnotic Sedative Anxiolytic Amnesic Antiepileptic (Produce strange sleep behaviours)
What are some benzodiazepine sensitive GABAA receptor brain regions
Amygdala Prefrontal cortex Hypothalamus Striatum Bed nucleus of striatum Hippocampus
What does the a1 subunit mediate
Sedation
Hypnosis
Anticonvulsion
What do the a2 and a3 subunits mediate
Anxiolysis
What do the a3 and a5 subunits mediate
Myorelaxation
What are z-drugs
Chemically not benzodiazepines but act at BZ site
What are the effects of Z-drugs
Same benefits and problems of BZ
Possibly less memory/cognition side effects, shorter half life (no daytime sedation)
Which subunit do z-drugs show some preference for
a1
What are some issues with benzodiazepines
Ongoing use Tapered stopping Dependence liability Strange sleep behaviours Amnesiac Falls in elderly Combining with other sedatives
How do antihistamines help with insomnia
Histamines are arousing
What are first generation antihistamines
H1 inverse agonist
Why do antihistamines cross the BBB
Lipophillic
LMW, not PGP target
What are side effects of antihistamine
Dry mouth Constipation Blurred vision Urinary retention More daytime sedation Fog Memory issues even when drug no longer present
Where is endogenous melatonin synthesised
Pineal gland
What reduces melatonin production
Light, via thalamus, reduces melatonin production
What are the two receptors for melatonin
2 GPCR
MT1
MT2
What are the two functions of the two melatonin receptors
MT1 - sleep onset
MT2 - circadian timing
What is a synthetic analogue of melatonin
Ramelteon
Which neurotransmitters are activating
NorA, 5HT, ACh, DA, HA, Orexin
Which neurotransmitters are sleep promoting
GABA, adenosine and melatonin
What is fear
Threatening stimulus:
State of preparation for danger and results in arousal, vigilance, increased ability to respond and negative feelings
What is anxiety
State of preparation for danger and results in arousal, vigilance, increased ability to respond and negative feelings BUT NO immediate threatening stimulus
What is the criteria for anxiety
Patients have to experience symptoms causing significant personal distress with associated impairment in function
What appears to play a central role in anxiety
Amygdala activity up-regulated
Issues with synaptic plasticity
What are treatments for anxiety
Cognitive and behavioural therapy Benzodiazepines Selective serotonin reuptake inhibitors Serotonin/noradrenaline reuptake inhibitors Tricyclics Pregabalin Buspirone
What is the first line of treatment for anxiety
Benzodiazepines
What are pros and cons of benzodiazepines
+ act rapidly
- dependence potential, drowsiness
Which benzodiazepines are used for anxiety
Alprazolam
Clonazepam
Which drugs are not a good choice for anxiety
‘z drugs’
Where is serotonin released from
Raphe nuclei
What do serotonin axon projections influence
Sleep Arousal Attention Sensory processing in the cortex Emotion Mood
What are some SSRIs for anxiety
Fluoxetine and paroxetine
What is the first treatment for most anxiety disorders
SSRIs
What are pros and cons of SSRIs
Pros: Less side effects May allow dual treatment for depression Cons: Very slow to act Sometimes side effects difficult Have discontinuation syndrome
What are some other anxiolytics
Serotonin/noradrenaline reuptake inhibitors
Other antidepressants
Pregabalin (GABA analgoue)
Buspirone (Partial 5HT1A agonist for treatment of GAD)
Alcohol
