P: Anxiolytic and Hypnotic Drugs - Week 10 Flashcards
Name 6 forms of anxiety disorders
- Panic Disorder (PD)
- Obsessive Compulsive Disorder (OCD)
- Post-traumatic Disorder (PTSD)
- Phobias
- Generalised Anxiety Disorder
- Social Anxiety Disorder
Define Panic Disorder.
characterised by sudden episodes of overwhelming fear with somatic/physical symptoms (up HR, SOB, sweating)
Define OCD
compulsive and ritualistic behaviours as well as purposeless activities driven by irrational fears and thoughts (e.g. fear of contamination)
Define PTSD. Also Define Phobias
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
Define GAD. Also define Social Anxiety Disorder.
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
Name 4 neurotransmitter systems that anxiety is associated with the dysregulation of
- GABA
- Serotonin
- Noradrenaline
- Dopamine
What would be the most effective therapeutic agent to treat anxiety disorders?
One that potentiates GABA and serotonin neurotransmission
What are GABA and glutamate? Where are they found in high concentrations? What do they modify? Are they potent at this?
They are amino acid NTs found in high concentrations in the CNS. They are extremely potent modifiers of neuronal excitability
In regards to GABA:
- is it inhibitory or excitatory
- What processes is it involved in? list 4 things
GABA is inhibitory. It is involved in memory, motor control, cognition, and consciousness
Name the 2 classes of GABA receptors and explain how they differ
- GABA-A receptor: is an ionotropic receptor; selectively permeable to Cl-
- GABA-B receptor: is a G-protein coupled receptor; inhibit Ca2+ or activate K+ channels
Explain how the binding of the GABA-A receptor works
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)
Give another name for ionotropic
ligand-gated
Is glutamate excitatory or inhibitory? List 3 processes it is involved with?
Excitatory.
Involved with:
- learning + memory
- growth + development
- modulation of motor function
Name the 4 main receptor families for Glutamate. And state whether these receptors are ionotropic or g-protein coupled
- AMPA
- Kainiic acid
- NMDA
- Metabotropic
The first 3 are all ionotropic, whereas no.4 (metabotropic) is g-protein coupled
Describe the distribution of Serotonin in our body (3)
90% found in the gut
8% in platelets
1-2% in Brain + CNS
What is the function of Serotonin (5HT). What is it implicated in? (9)
It is implicated in the regulation of virtually all brain functions incl. mood, perception, anxiety, pain, sleep, temperature, appetite, neuroendocrine control, aggression
How many Serotonin receptors are there? Name them. Are there any subtypes?
- 5-HT1 – 5-HT7, with subtypes (A-F for 5-HT1 and A-C for 5-HT2)
What 2 classes of drugs can be used in the pharmacological treatment of anxiety disorders? Describe their effects (3, 2)
- Anxiolytics - relieve anxiety + tension, calm anxious/restless person without impairing consciousness (i.e. don’t induce sleep)
- Hypnotics - produce drowsiness, encourage onset and maintenance of a state of sleep
Define Insomnia. How does it differ to anxiety?
Is a common clinical manifestation of anxiety but NOT a disease entity
Name 5 Benzodiazepine anxiolytics. Describe their naming convention, what is similar about all their names?
- Alprazolam
- Diazepam
- Loraepam
- Nitrazepam
- Oxazepam
Note they all end in ‘pam’
What is the mechanism of action for Benzodiazepine Anxiolytics?
they potentiate the effects of GABA on GABA-A receptors by binding to benzodiazepine (BZ) site
How can we classify Benzodiazepine Anxiolytics? Rank the 5 drugs in terms of this classification
Classify based on half-life
Long = Diazepam
Medium = Alprazolam
Intermediate = Oxazepam
Short = Lorazepam
Ultra-short = Midazolam
List 5 common adverse effects of Benzodiazepine Anxiolytics
- confusion (esp. older people) (+ memory impair)
- drowsiness + impaired coordination
- long-lasting hangover effects
- tolerance + dependence
- suppression of REM sleep
How big is the therapeutic window for Benzodiazepine Anxiolytics?
Wide therapeutic window (good safety margin)
How do Benzodiazepine Anxiolytics affect CV and respiratory system? (3)
In healthy consumers: little effect
In pathological states: can cause CVS + respiratory depression
If taken in excess with alcohol or other CNS depressants: lethal
Name 3 other CNS depressants. Should you take them in conjunction with Benzodiazepine Anxiolytics?
- opioids
- anticonvulsants
- TCA
No you absolutely should not
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)
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
Are drug interactions common or rare for Benzodiazepines?
common
What determines the level of absorption for benzodiazepines?
the lipophilicity of the drug
What are 4 warnings/precautions for the use of benzodiazepines?
- do not mix with alcohol
- more addictive than heroin
- increased risk of falls in older people
- can cross placenta + enter breast milk in pregnancy + lactation
Why shouldn’t you mix benzodiazepines with alcohol?
Leads to additive CNS depression and then death
How should you consider the increased risk of falls in older people when taking benzodiazepines? (3)
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
What are the typical withdrawal symptoms for benzodiazepines? (3)
- anxiety + restlessness; shakes
- rebound insomnia (worse than pre-treatment)
- weakness, orthostatic hypotension, generalized seizures
What are the consequences of a couple of weeks of continuous benzodiazepine use? (2)
Tolerance and dependence
What is the recommendation for how patients should stop taking benzodiazepines?
Gradual dose reduction over around 2 months
What is Buspirone? How does it differ from benzodiazepines? (2)
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
Describe the mechanism of action for Buspirone. How does this compare to other anxiolytics? (2)
- 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
Where in the body does Buspirone appear to have no affect on D2?
In the basal ganglia (i.e. in subcortical areas of the brain)
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
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
What are the adverse effects of Buspirone? Compared to other anxiolytics? (2)
- less psychomotor impairment and does not affect driving [that’s good!]
- dizziness, headache, GI upset [that’s bad!]
What type of metabolism does Buspirone undergo?
Extensive first-pass hepatic metabolism
What condition might slow the clearance of Buspirone?
Liver dysfunction
Name 2 short acting benzodiazepine hypnotics and 2 short-acting relating compounds
benzodiazepine hypnotics:
- Lorazepam
- Temazepam
Related compounds:
- Zopiclone
- Zolpidem
Describe the pharmacodynamics of Benzodiazepine Hypnotics
enhance GABA transmission by binding to a “BZ” site within GABA-A receptor; this is complex and not completely understood.
What are the roles of the 3 BZ sites?
BZ1 = mediates hypnotic effects (sleep)
BZ2 = mediates muscle relaxant effects (motor function)
BZ3 = mediates anxiolytic effects
What are the adverse effects of Benzodiazepine Hypnotics? (2)
Broken sleep (particularly with temazepam)
suppress REM sleep; rebound insomnia (after abrupt cessation)
Describe the mechanism of action for Zoplicone and Zolpidem (2)
Increase GABA transmission by selective binding to BZ1; lacks binding at BZ2 or BZ3
Does Sopiclone and Zolpidem suppress REM sleep?
No
How do the adverse effects of Zopiclone and Zolpidem differ from benzodiazepines? (4)
Zopiclone and Zolpidem can cause hallucinatory and/or psychotic features and sleep-related events such as sleep walking and sleep driving
List 5 other prominent adverse effects of Zoplicone and Zolpidem
binge eating + weight gain
QT interval changes
drowsiness
dizziness
confusion
What is a QT interval?
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
Describe the Pharmacokinetics of Zopiclone and Zolpidem (2)
Rapid sleep onset may be delayed by food; undergoes lipid metabolism
In what scenarios may the pharmacokinetics of Zopiclone and Zolpidem be altered? (3)
Older people and clients with renal or hapatic disease
Are SSRIs and SNRIs (antidepressants) approved for anxiety disorder treatment?
Yes. For all anxiety disorders
What is the advantage of antidepressants over benzodiazepines?
Antidepressants no not carry the risk of dependance and tolerance that occur with the benzodiazepines
What type of antidepressant is a first line treatment for PTSD?
SSRIs
What form of anxiety disorder is quetiapine useful for?
Generalised Anxiety Disorder (GAD)
