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Lecture 5B - Benzodiazepines.docx

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Carleton University
PSYC 3403
Tarry Ahuja

Lecture 5B - Benzodiazepines Chapter 7 Lecture 5B – February 5, 2014 Benzodiazepines Overview • benzodiazapines • Flumazenil: a GABAA antagonist • second-generation anxiolytics Benzodiazepine • thought of as a next generation barbiturate • anxiolytic, sedative, anticonvulsant • most widely used psychotherapeutic drug • Valium, Librium, Xanax • next generation anxiolytics are more common Benzodiazepine (structure)(pg. 238) Lecture 5B - Benzodiazepines Benzodiazepine (mechanism of action) • potent GABA agonists - It binds to GABA receptors • facilitate binding of GABA • causes influx of Cl-  hyperpolarization Lecture 5B - Benzodiazepines Lecture 5B - Benzodiazepines 1) Causes calcium to come through 2) Filled with GABA, when the calcium comes in it releases GABAinto the synaptic clef 3) 4) Binds to the GABAreceptor, normally you require two GABAto open the channel, but since we have benzodiazapines in our system they make it easier for GABAto bind - Does not require two GABA, only requires one to open the channel when benzodiazapines are present***must know and understand this process*** Benzodiazepine (mechanism of action) • potent GABA agonists • facilitate binding of GABA • causes influx of Cl- a hyperpolarization • site of action: limbic system • side effects: cerebral cortex and brainstem Structure (Limbic System) Lecture 5B - Benzodiazepines (don’t worry about this diagram –just wanted to show us so we knew where it was) Benzodiazepine (mechanism of action) • anxiety, panic, behavioral response to fear: • amygdala • orbitofrontal cortex • insula • experimental stimulation of these structures • experimental lesions of these structures Benzodiazepine (mechanism of action) • blockade of GABAergic function in amygdala • chronic blockade of GABA R A • increased amygdala function • anxiogenic responses to stimuli - Basically we are blocking the function so we see a difference in fear responses • BZ may increase threshold for responsiveness in amygdala - A benzodiazepine would increase your threshold for fear therefore they would feel less fear as their threshold for fear would be increased (increases threshold in the amygdala) Benzodiazepine (pharmacokinetics) • over 20 different BZ available (all do something similar and all are equally effective and all pretty much the same) • differences include: • rates of metabolism • active metabolites • plasma half-lives • well absorbed with peak BAC in 1 hr Benzodiazepine (pharmacokinetics) • many BZ produce active metabolites • Valium, Librium, Centrax • Nordiazepam is a metabolite of Valium • half-life of 60 hrs Lecture 5B - Benzodiazepines Benzodiazepine (pharmacokinetics) Benzodiazepine (pharmacokinetics) • many BZ produce active metabolites • Valium, Librium, Centrax • Nordiazepam is a metabolite of Valium • half-life of 60 hrs • active metabolite can accumulate and persist even after administration stops Lecture 5B - Benzodiazepines Benzodiazepine (pharmacokinetics) • elderly have trouble metabolizing longacting BZ and their metabolites • lower dosage required (~ 50%) at shorter-acting BZ • blood plasma concentration of the drug can persist • long-term use can cause significant cognitive dysfunction Benzodiazepine (pharmacokinetics) Lecture 5B - Benzodiazepines Benzodiazepine (pharmacological effect) • complete agonists(this drug binds very well): Diazepam • facilitate GABA binding • moderate anxiolytic activity at  amygdala  orbitofrontal cortex  insula • action at other GABA receptors produces side effects (confusion and amnesia) Benzodiazepine (pharmacological effect) • mental confusion & amnesia • cerebral cortex and the hippocampus • muscle relaxant effect • spinal cord, cerebellum and brain stem • antiepileptic actions • cerebellum & hippocampus • behavioral rewarding effects (makes you feel good, so you can become addicted – because it activates structures found in the reward part of the brain) • ventral tegmentum & nucle
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