W7 31 sedative and anxiolytic drugs

Question 1

What are some types of anxiety disorders?

Answer 1

Anxiety or fear-related disorders
Obsessive compulsive or related disorders
Disorders specifically associated with stress

Question 2

What are some anxiety or fear-related disorders?

Answer 2

Generalised anxiety disorder - high background level of anxiety all the time
Panic disorder - background level of anxiety is quite low, but intermittent episodes of anxiety
Phobic disorder (irrational anxiety)

Question 3

What are some obsessive compulsive or related disorders?

Answer 3

OCD
Hypochondriasis - always thinking something is wrong with you

Question 4

What are some disorders specifically associated with stress?

Answer 4

PTSD - prominent after war but can be domestic
Prolonged grief (bereavement)

Question 5

What are some common anxiety symptoms?

Answer 5

Dry mouth, difficulty in swallowing
Palpitations, discomfort in chest, awareness of missed beats
Sensitivity to noise
Restlessness, tremor, aching in muscles
GI discomfort, excessive wing, frequent or loose motions, frequent or urgent micturition, failure or erection, menstrual discomfort amenorrhoea
Fearful anticipation, irritability, poor concentration, worrying thoughts, headache, dizziness, insomnia, avoiding the situation/object
Constriction in the chest, difficulty inhaling, feeling of breathlessness

Question 6

What are the 2 domaines causing symptoms?

Answer 6

Cognitive domain: sense of dread or fear, feeling as if about to die etc
Physical domain: palpitation, sweating, nausea, urge to void, dyspnoea

Question 7

What are symptoms of anxiety similar to?

Answer 7

Symptoms are similar to evoking the defence response - fight or flight
As getting a level of arousal and you increased your performance and develop defence response, you get an optimal response. But with these disorders you go past the optimal with an overstimulation, ending up with an impaired performance

Question 8

How is the hypothalamus involved in the neurobiology of anxiety? (PG327)

Answer 8

Hypothalamus is a major integration area
Communicates with pituitary, releasing hormones for a hormonal response, eg affecting metabolism.
Implications for autonomic function eg changing HR, BP
Reticular formation, linked to wakefulness and sleep, so if keep stimulating this then alertness
Limbic system is a conditioning area through the nucleus accumbens, looking at emotions and mood

Question 9

What are some parts of the limbic system?

Answer 9

Amygdala, hippocampus, cingulate gyrus

Question 10

What does the limbic system do?

Answer 10

Provides a bridge between autonomic and voluntary control
Voluntary control can come through the cortex at the front
Cortex will be feeding in social situations, pressures etc

Question 11

What is the PAG?

Answer 11

Periaqueductal grey (PAG) in the brainstem

Question 12

What does the PAG do in the neurobiology of anxiety?

Answer 12

PAG for descending pain control, linked to fight or flight response
Linked into bladder control
Feeds upto higher parts of brain to link to systems

Question 13

What parts of the brain are stimulated by anxiety and disorders?

Answer 13

Integrates motor, social, emotion, mood

Question 14

What are some psychological ways to ease anxiety?

Answer 14

Relaxation techniques
Distraction
Cognitive behavioural therapy (CBT)

Question 15

How can sedation help anxiety?

Answer 15

It would inhibit ascending arousal pathways
Quietening down the overstimulation of brain areas

Question 16

What is the spectrum of quietening down brain areas?

Answer 16

Anxiolytics to quieten down anxiety quiet brain down a little; sedation a bit more; anaesthesia; overdose

Question 17

What 2 ways can we dampen overactive brain areas by reducing the release of excitatory neurotransmitters?

Answer 17

Stimulate pre-synaptic receptors
Facilitating release of inhibitory transmitter eg GABA

Question 18

What drugs can stimulate pre-synaptic receptors and what do they do?

Answer 18

Clonidine - a2 agonist - reduces NA release and thus reduces excitation
Buspirone - 5HT1A agonist - inhibiting this release reduces excitation
Promethazine - 1st generation anti-histamine receptors
(alpha receptors only, beta receptors don’t have sedative properties)

Question 19

What drugs are there from the pre-benzodiazepine era?

Answer 19

Bromides
Barbiturates
Antihistamines

Question 20

How do benzodiazepines work? Mechanism of action.

Answer 20

Not GABA-mimetic (not an agonist), facilitating the effect
Allosteric effects - separate benzodiazepine binding site. As BZD site is occupied, there is a change in the shape of the protein, to increase the frequency of opening.
Facilitates opening (increased frequency) of GABAa
Subunit heterogeneity may explain diverse effects

Question 21

What is the safety margin and issues with benzodiazepines?

Answer 21

Wide safety margin but issues with tolerance, dependence and withdrawal

Question 22

What is the most commonly prescribe BZD?

Answer 22

Alprazomol

Question 23

Other uses of benzodiazepines

Answer 23

Jet lag - triazolam
Insomnia - quazepam

Question 24

Examples of short/intermediate acting BZD and their half life elimination

Answer 24

Temazepam - 10-20hrs
Triazolam - 1.5-5hrs

Question 25

Examples of long acting benzodiazepines and their half life elimination time

Answer 25

Diazepam - 30-60hrs
Quazepam - 40hrs

Question 26

What is the difference between short acting and long acting BZDs?

Answer 26

Short acting affects phase II metabolism only - so become inactivated after this
Long acting affects phase I and II metabolism - after phase I metabolism, the metabolite is still acting, giving a longer half-life.

Question 27

Which BZDs should be used in elderly and why?

Answer 27

Use shorter acting in elderly because phase II metabolism is less affected by age.

Question 28

What post-benzodiazepine era drugs are used for anxiety/sedation?

Answer 28

Antidepressants
Buspirone
Non-BZD anxiolytics
Non-BZD hypnotics

Question 29

What effects do anti-depressants have?

Answer 29

SSRIs, SNRIs, TCAs
Have an anxiolytic effect (although BZDs don’t have antidepressant effects)

Question 30

Describe buspirone

Answer 30

5HT1A partial agonist
No sedation but take 2 weeks to work
Symptoms may worsen initially - desensitisation over time?
Used mainly in generalised panic disorders but not really effective in panic or phobia disorders

Question 31

What do non-BDZ anxiolytics do?

Answer 31

Pregabalin - blocking VDCC
Blocking voltage dependent calcium channels. Neurotransmitter release is calcium dependent, so blocking these will reduce transmitter release

Question 32

What non-BDZ hypnotics are there and what are they used for?

Answer 32

Z-drugs - zolpidem, zalepon, zopiclone - not anxiolytics
Often used for insomnia

Question 33

Why were barbiturates replaced with benzodiazepines?

Answer 33

Barbiturates have a lower safety margin, faster development of tolerance and dependence and more drug interactions through off-target effects

Question 34

What are the implications of BZD use for dentistry?

Answer 34

Sedation: wide safety margin; highly effective; well tolerated; interactions with other OTC drugs; combined with propofol for GA procedures (as have both sedative and anxiolytic and muscle relaxant effects)
Anxiety - premedication
Remember - dependence and tolerance can occur with long term usage and they can enhance other CNS depression effects (eg alcohol)

Question 35

What OTC drugs do BZDs interact with?

Answer 35

1st gen antihistamines, which will enhance depressant effects. So be cautious driving after dental surgery.

Question 36

What other properties do benzodiazepines have which means they can be used in a certain medical emergency?

Answer 36

Anticonvulsant properties - epileptic seizures are a medical emergency

Question 37

What BZD is used for epileptic seizures?

Answer 37

Midazolam