Anxiolytics and Hypnotics Flashcards
Give a summary of GABA neurotransmission
Glu converted to GABA via glutamate decarboxylase (GAD)
GABA release into the synapse
Binds to postsynaptic Cl- ionophore receptor (GABAa)
What are the ways in which GABA is taken back up from the synapse
Uptake into glial cell or pre-synaptic terminal
Conversion to SSA via GABA-T
Explain how GABA is metabolised
GABA converted to succinic semialdehyde by GABA transaminase (GABA-T)
SSA converted to succinic acid by succinic semialdehyde dehydrogenase (SSDH)
What is the effect of GABA metabolism inhibitors and give examples
Inhibitors of GABA metabolism - large increase in brain GABA
Sodium valproate
Vigabatrn
Describe the action of Benzodiazepines and Barbiturates at the GABA-a receptor complex
No activity alone (allosteric actin)
Different binding sites and different mechnaisms
What are the mechanisms of Benzodiazepines and Barbiturates at the GABA-a receptor complex
BZs - increase frequency of Ca2+ channel openings
BARB - increase duration of Ca2+ channel openings
Compare Benzodiazepines and Barbiturates
BARBs are less selective than BZs
This causes a decrease in excitatory transmission and other membrane effects
What effects of barbiturates are explained by its differences form benzos
decrease in excitatory transmission and other membrane effects
Induction of surgical anaesthesia
Low margin of safety
What are the clinical uses of Benzodiazepines and Barbiturates
Anaesthetics (BARB: thiopentone) Anticonvulsant (diazepam, clonazepam, phenobarbital) Anti-spastics (diazepam) Anxiolytics Sedative/hypnotic
Define anxiolytics
Removes anxiety without impairing mental or physical activity (minor tranquillisers)
Define sedatives
Reduce mental and physical activity without producing loss of conscioussness
Define hypnotic
Induces sleep
What are the ideal features of anxiolytics, sedative and hypnotics
Have a wide margin of safety Not depress respiration Produce natural sleep Not interact with other drugs Not produce hangovers Not produce dependence
Give an example of a barbiturate used as a sedative/hypnotic, stating what its used for and its half life
Amobarbital
Severe intractable insomnia
20-25h half life
What are the unwanted effects of barbiturates
Low safety margins -> depress respiration, overdose is lethal
Alters natural sleep
Leads to hangovers and irritability
Enzyme inducers
Potentiates effects of other CNS depressants e.g. alcohol
Tolerance
Withdrawal syndrome
What re the symptoms of withdrawal syndrome
Insomnia Anxiety Tremor Convulsions Death
Describe benzodiazepines
Around 20 available, all act at GABA-A receptors
All have similar potencies and profiles
Pharmacokinetics largely determine its use
Describe the administrative and absorptive pharmacokinetics of benzodiazepines
Well absorbed PO
Peak in plasma = 1 hour
IV vs status epilepticus
Describe the distributive pharmacokinetics pf benzodiazepines
Binds plasma proteins strongly
Highly lipid soluble - wide distribution
Describe the metabolic and excretory pharmacokinetics of benzodiazepines
Usually extensive metabolisms by the liver
Excreted in the urine (glucuronide conjugates)
What is the duration of action for benzodiazepines
Varies greatly
Short action or long acting
Long due to slow metabolism and/or active metabolites
Describe the metabolism of diazepam, lorazepam and nitrazepam (diagram)
Refer to notes
Both lorazepam and nitrazepam are metabolised directly into glucuronide
Give an example of anxiolytics (long acting)
Diazepam (valium)
Chlordiazepoxide (librium)
Nitrazepam
What is the half life of oxazepam and give a side effect
8 hours
Hepatic impairment
Give examples of sedative/hypnotics (short acting)
Temazepam
Oxazepam
What is the half life of temazepam
28 hours
What are the advantages of benzodiazepines
Wide margin of safety Overdose - prolonged sleep (rousable) Flumazenil Mild effect on REM sleep Does not induce liver enzymes
What are the unwanted effects of benzodiazepines
Sedation Confusion and amnesia Ataxia (impaired manual skills) Potentiates other CNS depressants (alcohol, BARBs) Tolerance (less than BARBs) Dependence Free [plasma] by aspirin, heparin
Describe the dependence from benzodiazepines
Withdrawal syndrome similar to BARBs
Withdraw slowly
Describe zopiclone
Short actin sedative (5h half life)
Acts as Bz receptors
Similar efficacy to BZs
Minimal hangover effect but dependency is still a problem
What are the advantages and disadvantages of SSRIs as an antidepressant drug compared to others
Less sedation and dependence
Long term treatment
Delayed response
Give examples of antiepileptic drugs
Valproate
Tiagabine
Give examples of antipsychotic drugs
Olanzapine
Quetiapine
What is busiprone
5HT-1A agonist
Fewer side-effects (
Where are the enzymes involved in GABA synthesis and metabolism found
GAD - cytoplasmic
GABA-T and SSDH - mitochondrial
