P: Anxiolytic and Hypnotic Drugs - Week 10

Question 1

Name 6 forms of anxiety disorders

Answer 1

1. Panic Disorder (PD)
2. Obsessive Compulsive Disorder (OCD)
3. Post-traumatic Disorder (PTSD)
4. Phobias
5. Generalised Anxiety Disorder
6. Social Anxiety Disorder

Question 2

Define Panic Disorder.

Answer 2

characterised by sudden episodes of overwhelming fear with somatic/physical symptoms (up HR, SOB, sweating)

Question 3

Define OCD

Answer 3

compulsive and ritualistic behaviours as well as purposeless activities driven by irrational fears and thoughts (e.g. fear of contamination)

Question 4

Define PTSD. Also Define Phobias

Answer 4

PTSD = anxiety triggered by recall of past traumatic and stressful experiences

Phobias = intense fears of objects or situations, such as fear of flying, insects or open spaces

Question 5

Define GAD. Also define Social Anxiety Disorder.

Answer 5

Generalised Anxiety Disorder. A feeling of nervousness, tension or worry not associated with a specific event, situation or object

SAD = fear of being with and interacting with people i.e. meeting new people, public performances

Question 6

Name 4 neurotransmitter systems that anxiety is associated with the dysregulation of

Answer 6

• GABA
• Serotonin
• Noradrenaline
• Dopamine

Question 7

What would be the most effective therapeutic agent to treat anxiety disorders?

Answer 7

One that potentiates GABA and serotonin neurotransmission

Question 8

What are GABA and glutamate? Where are they found in high concentrations? What do they modify? Are they potent at this?

Answer 8

They are amino acid NTs found in high concentrations in the CNS. They are extremely potent modifiers of neuronal excitability

Question 9

In regards to GABA:
- is it inhibitory or excitatory
- What processes is it involved in? list 4 things

Answer 9

GABA is inhibitory. It is involved in memory, motor control, cognition, and consciousness

Question 10

Name the 2 classes of GABA receptors and explain how they differ

Answer 10

1. GABA-A receptor: is an ionotropic receptor; selectively permeable to Cl-
2. GABA-B receptor: is a G-protein coupled receptor; inhibit Ca2+ or activate K+ channels

Question 11

Explain how the binding of the GABA-A receptor works

Answer 11

Binding this receptor with GABA triggers the opening of a chloride ion selective pore. Increased chloride conductance (i.e. more -ve ions enter neuron) drives the membrane potential of the neuron to become more -ve and therefore less active (neuronal firing is suppressed)

Question 12

Give another name for ionotropic

Answer 12

ligand-gated

Question 13

Is glutamate excitatory or inhibitory? List 3 processes it is involved with?

Answer 13

Excitatory.
Involved with:
- learning + memory
- growth + development
- modulation of motor function

Question 14

Name the 4 main receptor families for Glutamate. And state whether these receptors are ionotropic or g-protein coupled

Answer 14

1. AMPA
2. Kainiic acid
3. NMDA
4. Metabotropic

The first 3 are all ionotropic, whereas no.4 (metabotropic) is g-protein coupled

Question 15

Describe the distribution of Serotonin in our body (3)

Answer 15

90% found in the gut
8% in platelets
1-2% in Brain + CNS

Question 16

What is the function of Serotonin (5HT). What is it implicated in? (9)

Answer 16

It is implicated in the regulation of virtually all brain functions incl. mood, perception, anxiety, pain, sleep, temperature, appetite, neuroendocrine control, aggression

Question 17

How many Serotonin receptors are there? Name them. Are there any subtypes?

Answer 17

7. 5-HT1 – 5-HT7, with subtypes (A-F for 5-HT1 and A-C for 5-HT2)

Question 18

What 2 classes of drugs can be used in the pharmacological treatment of anxiety disorders? Describe their effects (3, 2)

Answer 18

1. Anxiolytics - relieve anxiety + tension, calm anxious/restless person without impairing consciousness (i.e. don’t induce sleep)
2. Hypnotics - produce drowsiness, encourage onset and maintenance of a state of sleep

Question 19

Define Insomnia. How does it differ to anxiety?

Answer 19

Is a common clinical manifestation of anxiety but NOT a disease entity

Question 20

Name 5 Benzodiazepine anxiolytics. Describe their naming convention, what is similar about all their names?

Answer 20

• Alprazolam
• Diazepam
• Loraepam
• Nitrazepam
• Oxazepam

Note they all end in ‘pam’

Question 21

What is the mechanism of action for Benzodiazepine Anxiolytics?

Answer 21

they potentiate the effects of GABA on GABA-A receptors by binding to benzodiazepine (BZ) site

Question 22

How can we classify Benzodiazepine Anxiolytics? Rank the 5 drugs in terms of this classification

Answer 22

Classify based on half-life
Long = Diazepam
Medium = Alprazolam
Intermediate = Oxazepam
Short = Lorazepam
Ultra-short = Midazolam

Question 23

List 5 common adverse effects of Benzodiazepine Anxiolytics

Answer 23

1. confusion (esp. older people) (+ memory impair)
2. drowsiness + impaired coordination
3. long-lasting hangover effects
4. tolerance + dependence
5. suppression of REM sleep

Question 24

How big is the therapeutic window for Benzodiazepine Anxiolytics?

Answer 24

Wide therapeutic window (good safety margin)

Question 25

How do Benzodiazepine Anxiolytics affect CV and respiratory system? (3)

Answer 25

In healthy consumers: little effect In pathological states: can cause CVS + respiratory depression If taken in excess with alcohol or other CNS depressants: lethal

Question 26

Name 3 other CNS depressants. Should you take them in conjunction with Benzodiazepine Anxiolytics?

Answer 26

- opioids - anticonvulsants - TCA No you absolutely should not

Question 27

Describe the pharmacokinetics of Benzodiazepine Anxiolytics, in terms of: A: Absorption level and form of administration B: What is necessary for clearance? C: What drugs they interact with and is this good or bad (2)

Answer 27

A: Good absorption after oral administration B: Metabolic transformation (or "biotransformation") to hydrophilic metabolites is necessary for clearance of this drug C: Mood stabilisers and SSRIs = reduce the elimination of benzodiazepines. Therefore is BAD and should not be given together

Question 28

Are drug interactions common or rare for Benzodiazepines?

Answer 28

common

Question 29

What determines the level of absorption for benzodiazepines?

Answer 29

the lipophilicity of the drug

Question 30

What are 4 warnings/precautions for the use of benzodiazepines?

Answer 30

1. do not mix with alcohol 2. more addictive than heroin 3. increased risk of falls in older people 4. can cross placenta + enter breast milk in pregnancy + lactation

Question 31

Why shouldn't you mix benzodiazepines with alcohol?

Answer 31

Leads to additive CNS depression and then death

Question 32

How should you consider the increased risk of falls in older people when taking benzodiazepines? (3)

Answer 32

Should "Start low and Go Slow" i.e. start at a low dose of benzodiazepines and then slowly increase. Decrease dose if drowsiness and confusion occur

Question 33

What are the typical withdrawal symptoms for benzodiazepines? (3)

Answer 33

- anxiety + restlessness; shakes - rebound insomnia (worse than pre-treatment) - weakness, orthostatic hypotension, generalized seizures

Question 34

What are the consequences of a couple of weeks of continuous benzodiazepine use? (2)

Answer 34

Tolerance and dependence

Question 35

What is the recommendation for how patients should stop taking benzodiazepines?

Answer 35

Gradual dose reduction over around 2 months

Question 36

What is Buspirone? How does it differ from benzodiazepines? (2)

Answer 36

Buspirone is a non-bensodiazepine anxiolytic drug with selective anxiolytic effects but a different pharmacological profile compared to benzodiazepines. Buspirone: - relieves anxiety without causing marked sensitive/hypnotic effects and euphoria - lacks muscle relaxant and anticonvulsive properties

Question 37

Describe the mechanism of action for Buspirone. How does this compare to other anxiolytics? (2)

Answer 37

- is a partial agonist at 5-HT1A, and also has affinity for D2 receptors - is completely different from other anxiolytics: b/c it has no direct effects on GABA-A

Question 38

Where in the body does Buspirone appear to have no affect on D2?

Answer 38

In the basal ganglia (i.e. in subcortical areas of the brain)

Question 39

In regards to Buspirone: A: Describe how liable this drug is to abuse B: how long may its anxiolytic effects take to become established? What does this infer? C: Describe the speed of absorption after oral administration

Answer 39

A: Minimal abuse liability: no rebound anxiety or withdrawal syndrome B: anxyiolytic effects may take 3-4 weeks to become established (therefore this drug is not useful for acute anxiety states) C: Rapid absorption

Question 40

What are the adverse effects of Buspirone? Compared to other anxiolytics? (2)

Answer 40

- less psychomotor impairment and does not affect driving [that's good!] - dizziness, headache, GI upset [that's bad!]

Question 41

What type of metabolism does Buspirone undergo?

Answer 41

Extensive first-pass hepatic metabolism

Question 42

What condition might slow the clearance of Buspirone?

Answer 42

Liver dysfunction

Question 43

Name 2 short acting benzodiazepine hypnotics and 2 short-acting relating compounds

Answer 43

benzodiazepine hypnotics: - Lorazepam - Temazepam Related compounds: - Zopiclone - Zolpidem

Question 44

Describe the pharmacodynamics of Benzodiazepine Hypnotics

Answer 44

enhance GABA transmission by binding to a "BZ" site within GABA-A receptor; this is complex and not completely understood.

Question 45

What are the roles of the 3 BZ sites?

Answer 45

BZ1 = mediates hypnotic effects (sleep) BZ2 = mediates muscle relaxant effects (motor function) BZ3 = mediates anxiolytic effects

Question 46

What are the adverse effects of Benzodiazepine Hypnotics? (2)

Answer 46

Broken sleep (particularly with temazepam) suppress REM sleep; rebound insomnia (after abrupt cessation)

Question 47

Describe the mechanism of action for Zoplicone and Zolpidem (2)

Answer 47

Increase GABA transmission by selective binding to BZ1; lacks binding at BZ2 or BZ3

Question 48

Does Sopiclone and Zolpidem suppress REM sleep?

Answer 48

No

Question 49

How do the adverse effects of Zopiclone and Zolpidem differ from benzodiazepines? (4)

Answer 49

Zopiclone and Zolpidem can cause hallucinatory and/or psychotic features and sleep-related events such as sleep walking and sleep driving

Question 50

List 5 other prominent adverse effects of Zoplicone and Zolpidem

Answer 50

binge eating + weight gain QT interval changes drowsiness dizziness confusion

Question 51

What is a QT interval?

Answer 51

The time in ECG between from the beginning of the QRS complex, representing ventricular depolarisation, to the end of the T wave, resulting from ventricular repolarisation

Question 52

Describe the Pharmacokinetics of Zopiclone and Zolpidem (2)

Answer 52

Rapid sleep onset may be delayed by food; undergoes lipid metabolism

Question 53

In what scenarios may the pharmacokinetics of Zopiclone and Zolpidem be altered? (3)

Answer 53

Older people and clients with renal or hapatic disease

Question 54

Are SSRIs and SNRIs (antidepressants) approved for anxiety disorder treatment?

Answer 54

Yes. For all anxiety disorders

Question 55

What is the advantage of antidepressants over benzodiazepines?

Answer 55

Antidepressants no not carry the risk of dependance and tolerance that occur with the benzodiazepines

Question 56

What type of antidepressant is a first line treatment for PTSD?

Answer 56

SSRIs

Question 57

What form of anxiety disorder is quetiapine useful for?

Answer 57

Generalised Anxiety Disorder (GAD)