Anxiety Flashcards
What tests on humans look at effectiveness of drugs to treat anxiety?
Lie detector test and galvanic skin reactions
What excitatory amino acids are involved with anxiety?
Glutamate and aspartate
What inhibitory amino acids are involved with anxiety?
GABA and glycine
What is the structure of GABAaR?
2a, 2B, Y
What are agonists and antagonists at the orthosteric site of GABAaR?
Agonist- muscimol
Antagonist- bicuculline (competitive), picrotoxin (non competitive)
what is the orthosteric site?
Primary binding site
Beta-carboline
Stabilises the close form of GABAaR, increase memory and learning in animals with unwanted side effects
Give examples of agonists and antagonist at allosteric site?
Agonist- Diazepam
Antagonist- flumazenil
What can GABAa be regulated by/
Allosteric agonists, barbiturates, neurosteroids, general anaesthetics
What do GABAb do?
Activates GIRK (potassium channels) to produce post synaptic inhibition
How does GABA open GABAa receptors?
2 GABA bind on a+B subunit interface
Where is the allosteric site on GABA?
Interface of a and Y subunit
What are GABAa receptors targets for?
Sedatives, anxiolytics, hypnotics, anti-convulsants, neurosteroids, some general anaesthetics
How are the subunits that respond to Benzos known?
Animal models- replace a2 gene with mutated/ KO, gives no anxiolytic effects of diazepam
What physiological effects does Benzo have?
Sedation, hypnotic, anterograde, anticonvulsant, reduce muscle tone
How does Benzo cause sedation?
Decrease responsiveness to constant level of stimulation, occurs with lowest doses
How does Benzo cause hypnosis?
Latency of sleep onset decreased, duration of stage 2 sleep increase, duration of rem sleep is decreased duration of slow wave decreased
How does Benzo cause anti-convulsant effects?
Prevents development and spread of epileptiform activity
How does Benzo cause reduced muscle tone?
By central action of spinal cord
What are Benzodiazapines split into and why?
Short, medium and long acting compounds- lipid solubility, drug half life, presence of active metabolites plasma protein binding
What does drug half life depend on?
Renal function and enzyme induction
What are the main drugs to treat anxiety?
SSRIs, bentos, Buspirone, anti epileptic, atypical antipsychotics, B adrenoceptor antagonist
Which Benzos are metabolised to produce active intermediates with long half life?
Diazapam
Zolpidem
Short half life, no active metabolites, actions limited to 4 hours, good for insomnia but not generalised anxiety
What is the half life of Diazapam?
20-40 hours
What are the adverse effects of Benzos?
Sleepiness, impaired psychomotor function, amnesia, additive effects with other CNS depressants, tolerance, misuse, physical dependance
What happens with physical dependanc to Benzos?
Withdrawel with increased anxiety, insomnia, CNS excitability, convulsion, more problematic with drugs with short half lives,
