BZDs

Question 1

Why are benzos much safer than barbiturates/alcohol?

Answer 1

Barbs/alcohol - if you keep ingesting effect/toxicity is linear until coma/death
Benzos - Caps at the anesthesia effect - ceiling effect (at normal doses)

Question 2

BZD Structure-Activity Relationships

Answer 2

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

Question 3

BZD MOA

Answer 3

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

Question 4

Why do BZDs have different effects?

Answer 4

Hit different receptors due to different GABA receptors!!!
Antiseizure, muscle relaxer, etc
Binds His AA in alpha subunit

Question 5

BZ1

Answer 5

Sedation, amnesia, (anti-seizure)

Ambien, Lunesta, and Sonata - selective!

Question 6

BZ2/3

Answer 6

Anxiolytic, muscle relaxer

Question 7

BZD Antagonists

Answer 7

Flumazenil

Question 8

Barb Binding to GABA Receptor

Answer 8

Different site, but increase duration of hyper polarization - shift dose-response curve further left than BZDs

Question 9

Diazepam AD

Answer 9

Quick/complete absorption

High Vd

Question 10

Lorazepam AD

Answer 10

Lower Vd, slower onset - longer duration

Question 11

BZD ME

Answer 11

P450 and glucuronidation to urinary excretion

Question 12

Uses of BZDs

Answer 12

Antianxiety/sedative
Amnesia - procedures
Hypnosis - insomnia
Anesthesia
Antiseizure
Muscle relaxer
Alcohol withdrawal

Question 13

AEs of BZDs

Answer 13

Respiratory/cardiac depression
Teratogen (1st trimester)
Abuse
D/C syndrome