treatment of Anxiety and Sleep Disorders
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what are the neurotransmitters involved in the regulation of fears and anxieties
- gama amine butyric acid
Where is corticotropin releasing factor
cortex, amygdala, hippocampus and hypothalamus
what is the role of corticotropin releasing factor?
facilitate ACTH secretion from pituitary
what is the circuit of fear (short route)
emotional stimuls --> sensory thalamus--> amygdala--> emotional response
what is the circuit of fear (long route)
emotional stimuls --> sensory thalamus--> sensorycortex-->amygdala--> emotional response
what is nor epinephrin involved in?
- Involved in arousal, sleeping, and mood
- Role in the Induction of Panic attacks
what does dopamine do in the brain?
Conditioned Fear: activation of Dopamine pathways to the amygdala, role in phobias
what does serotonin do?
- Role in Sleep, aggression, and anxiety.
- 5-HT1A agonists 5-HT3 antagonists are anxiolytic
- Humans with low density 5-HT1A receptors are more anxious than control
what does acetylcholine do?
- Widely distributed neurotransmitter in the brain and body.
- Involved in memories, arousal and attention
what does GABA do?
- An inhibitory neurotransmitter
- Widely distributed in the brain.
- Produced from glutamate
- Inhibits release of neurotransmitters involved in anxious states
- Suppresses: corticolimbic noradrenergic and
- serotinergic projections
what is the biological basis of anxiety
- Increased activity of amygdala function along with concurrent lowered GABAergic inhibition of function produces anxiogenic responses
- Scans demonstrate increased blood flow to the amygdala concomitant with anxiety responses
what are the 3 sleeping disorders
the sleep cycle
stage 1 --> stage 2 --> stage 3--> stage 4--> stage 3 -->2-->REM
(electroencephalogram) a record of brain activity
(electromyogram) muscle activity
(electroculogram) eye movements
types of insomnia
- 1- prolonged sleep onset
- 2- Early waking
- 3- increase in waking time during the night.
how is sleep controlled?
by a group of brainstem nuclei that project widely throughout the brain and spinal cord
what inhibits production of melatonin?
what is the pathway for melatonin inhibition?
retina--? suprachiasmatic nucleus in the brain --> pinealocytes via adrenergic nerves and adrenergic receptors --> periphery
what does GABA do for sleep?
increases slow wave sleep and decreases cortical activity
What does 5-HT do for sleep?
increases sleep but decreases REM sleep
what is the effect of NE on sleep?
increased wakefulness and decreased REM sleep
what does ACh do for sleep?
increases REM sleep
what is the target for benzodizepines?
GABA _a receptor
what is the target for buspirone?
what is the target for antidepressants?
what is the target for Beta adrenergic receptor blockers?
B adrenergic Rs
what do barbiturates target?
what doe antihistamines target?
what do CNS stimulants target?
what does hypnotic mean?
- induce sleep
- go to sleep fast
- feel refreshed tomorrow
what does anxiolytic mean?
- reduce anxiety
- physical emotional cognitive
what type of receptor is a GABA_a receptor?
what type of receptor is a GABA_b receptor
what do benzodiazepines do?
they are allosteric modulators of GABA binding and increase the frequency of channel opening
What do barbiturates do?
that are allosteric modulators that increase the duration of channel opening (even without gaba)
two examples of benzodiazepine "like" drugs
zolpidem and zaleplon
what do benzodiazepine "like" drugs do?
bind to a subset of GABA recpetors w/ alpha1 subunits to produce pure sedation and does not really effect REM sleep
what are the 2 components of tolerance?
pharmaco kinetic and tissue tolerance
what is cross tolerance?
tolerance to one drug effects the tolerance of another drug (usually between 2 drugs that have similar effects)
strategies for anxiolytic discontinuation
- 1. Switch to longer-acting agent. (b/c you take less)
- 2. Cognitive-Behavioral therapy
- 3. Adjunctive
- – Antidepressant – Anticonvulsant
what is the metabolism and half life of BZD
– Hepatic oxidation: long-t1/2, active metabolites – Glucuronidation: short-t1/2, no active metabolites
is BZD lipid soluble or water soluble?
side effects of BZD
motor impairments, sedation, drowsiness, ataxia, lethargy, cognitive impairments, metal confusion, inhibion of learning behaviors, academic performance and psychomotor functioning, amnesia, dementia, disorientation slurred speech, decreased REM sleep
what happens with barbs toxicity?
respiratory and CV depression
what does alpha 1 on GABA_a do?
sedation, amnesia, antiseizure
what does alpha2 on GABA_a do?
anxiolytic muscle relaxing
what does alpha 5 on GABA do?
what subunits on GABA do BZDs bind to?
what subunits on GABA do barbiturates bind to?
alpha1, beta 1
what subunits on GABA do BZD like drugs bind to?
Buspirone and serotonin receptor
- nxiolytic but not sedating
- full agonist at 5-HT1A presynaptic receptors, partial agonist at 5-HT1A
- postsynaptic receptors
- No drug dependence, no abuse
- Slow onset of action (week or more)
- Indication: Chronic anxiety disorders (generalized anxiety disorder)
- what do beta blockers do?
- decrease autonomic arousal
when are beta blockers used?
adjunct for somatic symptoms of panic and generalized anxiety disorder but not as primary treatment
Which diagnosis is beta blockers used?
social phobia, performance anxiety subtype
- • Histamine involved in wakefulness and REM sleep
- • Postsynaptic sites: H1 and H2 receptors
- • Presynaptic receptor: H3 receptor
- • H1-agonists and H3-antagonists: Increase wakefulness
- • H1-antagonists and H3-agonists: Increase sleep
- • H2 receptor agonists or antagonists have no effect on wakefulness or sleep parameters
how does adenosine antagonists act?
- acts as a neurotransmitter in the CNS:
- •G-protein-coupled receptors, 7-transmembrane a-helical domains connected by intra- and extracellular loops
- •Stimulation of A2a receptor: hypnotic effect
- •Blocking A2a receptor: wakefulness –methylxanthines (caffeine and theophylline)
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