sedative and anxiolytic drugs

Question 1

Sleep stage 1

Answer 1

Deep drowsiness, 50% reduction of EEG activity, if woken May feel as if not been asleep.

Question 2

Sleep stage 2

Answer 2

Light sleep, periods of increased muscle tone, lower HR and temp

Question 3

Sleep stage 3

Answer 3

Deeper sleep

Question 4

Sleep stage 4

Answer 4

Deep slow wave sleep (SWS), a normally high frequency EEG is replaced by large slow waves, abscence of consciousness, cannot hear.

Question 5

Sleep stage 5

Answer 5

Rapid eye movement (REM)
General loss of tone ( protective, stops you acting in your dreams)
Increased EEG activity (dreaming)
Increased HR and breathing
Abnormalities lead to sleepwalking

Question 6

Reticular activating system (RAS)

Answer 6

Projects into cerebral cortex from the reticular formation, keeps cortex active, keeping you awake. Coma due to depression of this.

Question 7

In sleep regulating neurons

Answer 7

In brainstem reticular formation.
REM-on-cells; mainly cholinergic, switch on REM sleep.
REM-off-cells; release NA or 5HT, switch off REM sleep, inhihit REM-on-cells to end REM period.
Damage to REM-off-cells levaes REM-on-cells active, causing day/nightmares and insomnia.

Question 8

Complete sleep deprivation

Answer 8

Death within two weeks

Question 9

Sedatives/hypnotics

Answer 9

Reduce sleep latency
Improve depth and quality of sleep
Can cause hangover drowsiness and rebound insomnia
Give every 2-3 nights, withdraw slowly.

Question 10

Sedation anxiety continuum

Answer 10

Anxiety is a neurosis (patient is aware of it, unlike neurosis where patient is unaware)
2% pathological without cause
Symptoms include gut disturbances, headaches,sleep disturbance and sweaying.
Sedatives and anxiolytics are minor tranquilizers.

Question 11

Benzodiazepines (1,4 and 1,5)

Answer 11

Reduce aggressiom
Produce muscular relaxation
Produce motor incoordination
Prevent convulsions
Highly lipophilic, orally active, cross BBB
High TI
Few side effects
Psychological and physical dependance
High doss used to treat epilepsy
Allosterically bind GABA receptor

Question 12

GABA Receptor

Answer 12

Benzodiazepines bind between the alpha and gamma subunits. They increase the frequency of chloride channel opening, Potentiates GABA inhibition.
GABA subunits determine function. Sedative effects require alpha1 subunits but tolerance to sedation is via alpha5.
Anticonvulsant effects require alpha1, anxiolytic effects require alpha2 therefore it should be possible to have anxiolytic effect without sedation.

Question 13

Beta- carboline

Answer 13

Increases anxiety,possibly triggered by environmental factors, alcohol Potentiates its action.

Question 14

Barbiturates

Answer 14

Low TI due to respiratory depression
Tolerance to sedation faster than to respiratory depression
Increase duration of GABA opening
Addicyive
Potentiate ethanol
Urinary excretion, metabolised by hepatic enzymes.
Inducer of hepatic enzymes.

Question 15

Zopiclone

Answer 15

Not a benzo but acts like one, similar action but shorter acting.

Question 16

Zolpidem

Answer 16

Similar to benzo but rapid action, short lasting, no muscle relaxation, not an anyiconvulsant at sedative doses.

Question 17

Buspirone

Answer 17

5HT-1A receptor agonist.
More specific to anxiety
No direct action with GABA.
Similar properties to benzos.
No addiction, little interaction with ethanol, no muscle relaxayion or ataxia, no drowsiness or confusion.

Question 18

Propanolol

Answer 18

Beta-adrenoceptor antagonist, prevents peripheral aspects i.e. Tremor and tachycardia.

Question 19

Extremes of anxiety and phobia

Answer 19

Respond to antidepressants not anxiolytics. Probably a contimuum across depression and anxiety.

Question 20

Narcolepsy

Answer 20

Hypersomnia
Sudden unpredictable loss of consciousness
Affects some species of dog as well as humans
Intrusions of dream like hallucinations

Question 21

Narcolepsy treatment

Answer 21

Amphetamines - CNS stimulants
Ritalin
Modafinil “wakefulness promotor”, inhibits dopamine,NA, and 5HT reuptake. Activates Da and alpha1. Similar acyion to amphetamines but much more localised to limbic system, amygdala (fewer effects on mental state and movement). Facilitates glutamate neurons, knhibits GABA activity. Activates hypothalamixx neurones releasing orexins.

Question 22

Orexins (hypocretins)

Answer 22

Peptide hormones secreted by neurones in the hypothalamus. Promotes wakefulness. Low levels in humans blood/brain is associated with narcolepsy. Agonists may treat narcolepsy, antagonists are potential sedatives.

Question 23

Raphe nuclei and locus coeruleus

Answer 23

These areas control the onset of and balance of sleep, dreaming and wakefulness. Via 5HT and NA respectively.