Flashcards in BZDs Deck (13):
Why are benzos much safer than barbiturates/alcohol?
Barbs/alcohol - if you keep ingesting effect/toxicity is linear until coma/death
Benzos - Caps at the anesthesia effect - ceiling effect (at normal doses)
BZD Structure-Activity Relationships
Ring A - aromatic (part of binding site) - C7 EWG (good) - any other position (bad)
Ring B - N1 + methyl = good but not necessary; C2 - proton acceptors (good); C3 OH - faster elimination
Ring C - not necessary, but EWG is ortho - good, para - BAD
Bind to BZD receptor (between alpha and gamma) on GABAa receptor (Cl- channel) - allosteric
GABA must bind between alpha and beta subunits to open Cl- channel (hyper polarization)
Shifts GABA dose-response curve to the left (less GABA needed to achieve anesthetic effect
Why do BZDs have different effects?
Hit different receptors due to different GABA receptors!!!
Antiseizure, muscle relaxer, etc
Binds His AA in alpha subunit
Sedation, amnesia, (anti-seizure)
Ambien, Lunesta, and Sonata - selective!
Anxiolytic, muscle relaxer
Barb Binding to GABA Receptor
Different site, but increase duration of hyper polarization - shift dose-response curve further left than BZDs
Lower Vd, slower onset - longer duration
P450 and glucuronidation to urinary excretion
Uses of BZDs
Amnesia - procedures
Hypnosis - insomnia