Anxiolytics & Hypnotics Flashcards
What is the definiton for anxiolytic?
Reduces anxiety
What is the definiton of hypnotic?
Assists sleep (also called soporifics)
What is the definition of relaxants?
Usually mean muscle relaxants
Minor tranquillisers are AKA
Sedatives
Major tranquillisers are AKA
Antipsychotics
What is anxiety?
Normal human emotional state: we have things we rationally need to worry about.
The difference between normal and pathological anxiety is not clear, true or false?
True
What are the two concepts of anxiety?
Fear
Generalised anxiety
What are the different types of anxiety disorders?
- Panic disorder
- Social anxiety disorder (SAD)
- Phobias
- Obsessive-compulsive disorder (OCD)
- Generalised anxiety disorder (GAD)
- Post-traumatic stress disorder
What part of the brain is responsible for anxiety & emotional processes ?
Amygdala & prefrontal cortex (PFC)
In anxiety disorders, what happens in the brain?
Dysfunctional PFC-amygdala communication
Amygdala hyperactivity
Amygdala hyperactivity is associated with?
Anxiety
5-HT associated with
Mood stability
What are the pharmacological strategies for Anxiolytics?
Increased monoaminergic / serotinergic activity:
Antidepressants, especially SSRIs
5-HT1A agonists (buspirone)
Atypical antipsychotics
Increase GABAergic (inhibitory) activity:
GABAA receptor stimulation
What are the other options for anxiolytics?
Beta-blockers (propranolol) for physical symptoms
Pregabalin
Ketamine? Cannabidiol?
Main anxiolytics drugs used are?
Antidepressants drugs (5-HT) - Work through monoaminergic (esp. serotonergic) pathways
5-HT antidepressant drugs in anxiolytics are poor at dealing with?
Acute anxiety attacks
What are the preferred antidepressants as anxiolytics?
SSRIs preferred (e.g. sertraline, citalopram, fluoxetine)
Antidepressants as anxiolytics are effective against?
generalised anxiety, phobias, social anxiety disorder and post-traumatic stress
may also treat depression associated with anxiety
Buspirone, function and effect?
5-HT1A partial agonist
- Used for general anxiety states; weak for panic attacks and severe anxiety. No antidepressant action.
- Clinical effects not observed for up to 2 weeks.
- Also binds to dopamine receptors; possible function in anxiety unclear
Most common GABAA receptors subunit combination is?
a1b2g2
In GABAA receptors, a1 subunits more associated with?
Hypnotic effects
In GABAA receptors, a2/3 subunits more associated with?
Anxiolytics effects (amygdala)
What are Benzodiazepines?
BDZs are GABAAR positive allosteric modulators; increase likelihood of channel opening
What happens when benxodiazepines ( i.e. diazepam) binds to GABA
With GABA bound, receptor flits between open and closed states > more CL- enter
GABAA receptors are ionotropic, which means?
Cl- channels
Administration and use of Benzodiazepines
Orally active
Useful for acute anxiety; fast acting (~30 mins)
All BDZs largely identical in side effects
True or false
True
Therapeutic use of benzodiazepines are determined by duration of effect: long lasting? Medium acting? Short acting?
Long lasting – anticonvulsants, anxiolytics
Medium acting – anxiolytics
Short acting – anxiolytics, hypnotics
Side effects of benzodiazepines in abuse, dependency, tolerance, overdose & toxicity
Abuse: calming, dream state, also + alcohol
Dependency: withdrawal rebound anxiety: hallucinations, tremor, seizures
Tolerance: downregulation of a2-containing GABAARs?
OD & toxicity: relatively safe except with alcohol. Treat with flumazenil, BDZ site antagonist
Side effects of benzodiazepines
Side effects: Well tolerated; drowsiness, confusion, amnesia, loss of co-ordination, enhancement of other depressants
Diazepam
Anxiolytic, muscle relaxant, anticonvulsant. ~70% of BDZ prescriptions
Clobazam
Anticonvulsant only
Clonazepam
Anticonvulsant – very uncommon as anxiolytic
Midazolam
Ultra-short-acting, i.v. surgical sedation, i.v. anaesthesia induction (rare), i.v. anticonvulsant oral hypnotic (rare in UK)
Some old literature may refer to “benzodiazepine receptors”. These are AKA?
GABAA receptors
What is used for benzodiazepines overdose?
Flumazenil
What was the preferred medication for anxiolysis before BDZs?
Barbiturates
Barbiturates are very similar in MoA and effects to but more powerful?
Benzodiazepines
Side effects of Barbiturates
Higher abuse risk
Higher addiction risk
Dangerous in OD
What benzodiazepines drugs can be used as hypnotics?
“Z-drugs”: e.g. zolpidem, zopiclone & zaleplon
moa of “Z-drugs”?
Structurally dissimilar, but bind to same site as BDZs
Only active at a1 subunit-containing GABAARs.
Hypnotic»_space;> anxiolytic
Ultrashort duration (<4h)
Side effects of “z drugs”
tolerance & dependency, abuse risk
Which Z drug is thought to improve function after brain damage?
Zolpidem
Diazepam subunit selectivity
a1, a2, a3, a4, a5, a6
Flunitrazepam subunit selectivity
a1, a2, a5
Midazolam subunit selectivity
a1, a2, a3, a4, a5, a6
Flumazenil subunit selectivity
(antagonist) a1, a2, a3, a4, a5, a6
Zolpidem subunit selectivity
a1
