Anxiolytics Flashcards
What is an anxiolytic?
Reducing anxiety or tranquilizing
What is a sedative?
Calming, relaxing, or sleep
inducing
What is a hypnotic?
Sleep inducing or sopoforic
What is anxiety?
Anxiety is the anticipation of potential danger
Describe the physiological anxiety response
Physiological responses including sympathetic activation
What is normal anxiety?
Normal anxiety is a survival response leading to activation of the sympathetic nervous system for fight-or-flight response to danger
Describe sympathetic effects of chronic anxiety
Sympathetic effects e.g. increased muscle tension, digestive problems, sleep disturbance
What leads to an escalated anxiety spiral?
Escalating anxiety cycle due to performance decrease and fear of failure (driving further
anxiety)
What anxiety disorder has the highest comorbidity for alcohol abuse?
Social anxiety disorders
Describe panic disorder
- Accompanied by strong sympathetic NS activation
- Panic attack in response to a cue can lead to phobia
- Susceptibility for un-cued panic attacks leads to panic disorder
Name 2 early anxiolytics and sedative hypnotics
Alcohol was the first ‘drug’ in widespread
use to reduce anxiety and cause sedation –
still a common self-medication
- Bromides– 19th and 20th century (esp. KBr,
NaBr)
Describe contemporary sedative hypnotics
- Barbiturates
- Benzodiazepines
Why is bromide toxicity a big concern?
- Bromide has a half-life of ~8-12 days making dosing
difficult and intoxication problematic
Describe barbital
- Barbital was the first psychoactive barbiturate synthesized in 1903 and marketed as
Veronal (after the Italian town of Verona) - Barbital found to have relaxing and sopoforic effects
- Long half-life meant drowsiness extended for days
Describe phenobarbital
Phenobarbital was developed in 1912 and was noted to be faster acting, of shorter
duration, and having excellent anticonvulsant properties
Describe barbiturate classification
Barbiturates can be classed
according to the relative
lipophilicity of the compound.
Increasing the lipophilicity of
barbiturates results in faster
uptake into the brain and more
rapid sedation.
Give an example of an ultrashort barbiturate
- Thiopental
- Unconsciousness lasts 20-30 minutes and
ends due to redistribution of lipophilic
barbiturates into fatty tissues
Give an example of an intermediate barbiturate
- Amobarbital (Amytal)
- Prescribed for insomnia, high abuse
potential
Give an example of a longer-acting barbiturate
Phenobarbital
Describe adverse effects
- Intoxication (high doses) leads to
staggering, jumbled speech, impaired
thinking - Coma and death due to respiratory
depression
Describe illicit use
- High abuse potential due to rapid tolerance
and dependence - Often used in conjunction with
amphetamines - Amphetamines during the day (uppers or
pep-pills) - Barbiturates at night (downers or goofballs)
- High potential for interactions with ethanol
- Decreasing safety margin with tolerance
leads to high potential for overdose
Describe synaptic effects of barbiturates
- Positive allosteric
modulation at the
barbiturate binding site - Increases GABA affinity
- Prolongs open time
- High doses – GABA
mimetic (opens GABAA in
absence of GABA)
Describe barbiturate drug effects
- Barbiturates are CNS depressants and cause
broad increases in inhibitory neurotransmission - Important effects in the reticular formation
- Pontine – normally activates cortical centres
- Medullary – normally supresses cortical centres
- Balance of barbiturate effect in the reticular
formation - Medullary first – euphoria resulting from cortical
activation (disinhibitory) - Pontine first – relaxation, drowsiness, sleep from
cortical depression (inhibitory)
Describe barbiturates & dopamine
Paradoxically, barbiturates decrease
mesolimbic DA release in the NAc
through effects on VTA GABA
interneurons.
Describe barbiturate tolerance
- Metabolic tolerance:
- Barbiturates induce microsomal enzymes leading to greater liver metabolism
- Increased drug dose required to achieve same blood levels
- Leads to cross-tolerance among different barbiturates
- Pharmacodynamic tolerance:
- Cellular changes in GABAA receptor function and expression
- Greater barbiturate dose required to elicit inhibitory effect
Tolerance leads to decreased safety margin
Describe barbiturate dependence study
- Drugs were abruptly withdrawn at end of trial and monitored
Describe barbiturate withdrawal
- 24-36 hours: increasing anxiety and weakness developed
- At peak subjects could not stand unassisted
- Drop in blood pressure – fainting on standing
- Tremors, anorexia, vomiting, abdominal distress, insomnia, weight loss,
increased startle response, hyperreflexia - Significant appearance of convulsions and psychosis
Describe rebound hyperactivity
- Since barbiturates enhance GABAA
function, rebound results in
hyperexcitability and convulsions
Psychosis developed 3-5 days after
withdrawal lasting as long as 9 days
* Delirium, agitation, insomnia,
confusion, disorientation, auditory
and visual hallucinations
* High BP, temperature, pulse
