Anxiolytics & Sedatives [4] Flashcards
Anxiolytics treat _
Anxiety
Sedatives treat _
Insomnia
2 animal models of anxiety
Conflict test (smaller box but with food)
Elevated cross (rats subside in path with walls and become immobilised in new environment)
Evaluation of anxiety in man (3)
Diagnostic & statistic manual of mental disorders
Galvanic skin resistance
Use of placebo
Current anxiolytics/sedatives (5)
Benzodiazepines
Z-drugs
5-HT1A agonists
Barbiturates
Beta-adrenergic antagonists
What are Z-drugs
Non-benzodiazepine drugs for insomnia
What is the most important anxiolytic/sedative
Benzodiazepine
Benzodiazepine structure
Benzene ring (6c & 3 double bonds)
Attached to diazepam ring
Addition of phenyl & halogen for pharmacology
How many groups of benzodiazepine is there
4
R1 R2 R3 R4
What are benzodiazepines similar in structure to
Chlorodiazepoxide which was synthesised by accident
What is used for a benzodiazepine overdose
Antagonist: Flumazenil
- blocks binding to GABA
4 things that benzodiazepines do
Reduce anxiety and depression
Increase sleep duration (decrease REM sleep)
Reduces muscle tone and coordination
Anticonvulsant effects (for epilepsy)
Where are GABA receptors
Chloride channels with binding sites for endogenous GABA and exogenous BDZ
What does GABA binding do
Opens Cl- channel
Influx of Cl-
Hyperpolarisation of cell
Where does BDZ bind and what does it do
An independent site on the same Cl- channel-receptor complex
Increases GABAs affinity to receptor
Enhances inhibitory effect
Why does BDZ accumulate in body fat
High lipid solubility
What are BDZs excreted as
Glucoronides in urine
What makes short activity BDZs
Inactive when metabolised
Short half life
(Sleeping tablets)
What makes long acting BDZs
Metabolised to long-lasting active metabolite
(Eg diazepam -> N-dismethyldiazepam)
Long half life
Adverse effects of BDZs
Long lasting hangover (drowsiness/confusion)
Dependence (withdrawal)
Are BDZs safe in overdose
Reasonably safe
Advantageous as they are often used for suicide
What do barbiturates do
Non-selective CNS depressant activity
Useful as anticonvulsants
(Rarely used)
Pharmacokinetics of barbiturates
Inducers of CYP450s and some phase II enzymes
Example of 5-HT agonist and what do they do
Buspirone
Act of inhibitory pre-synaptic receptors
How do beta-adrenergic antagonists exhibit thru anxiolytic effect
Antagonists of peripheral sympathetic response
What to beta-adrenergic antagonists do
Relieve physical symptoms of anxiety
Sweating, tremor, tachycardia
