Benzos Flashcards
What alpha subunit(s) are required for sedative actions?
alpha-1
What alpha subunit(s) are required for anxiolytic actions?
Alpha-2 and 3
What alpha subunit(s) are required for anticonvulsant actions?
Alpha-2 and 3
What alpha subunit(s) are required for amnestic action?
Alpha-5
What subunit does BDZ bind to?
Alpha
What subunit does GABA bind to?
Beta
What subunits are required for BDZ action?
gamma-2, beta, and certain alpha subunits
What is flumazenil?
Flumazenil is a BDZ competitive antagonist; it binds the alpha subunit (BDZ binding site), shifting the response curve to the right (requires higher BDZ conc for effect)
NO EFFECT in healthy individuals - just people taking BDZ’s
What is picrotoxin?
A BDZ noncompetitive antagonist; it blocks the channel so GABA can’t go through. BDZ can still bind
What is bicuculline?
BDZ noncompetitive antagonist
Binds the GABA receptor
BDZ can still bind and increase affinity for GABA but GABA can’t bind so no effect!
NONCOMPETITIVE for BDZ
COMPETITIVE for GABA
What CNS effect(s) mediates the anxiolytic effect of BDZ’s?
Regulate firing of raphe nuclei neurons
Inhibits firing of the amygdala neurons
What CNS effect(s) mediates the amnestic effect of BDZ’s?
Inhibition of hippocampal LTP
What CNS effect(s) mediates the muscle relaxant effect of BDZ’s?
Enhanced presynaptic inhibition of the spinal cord
What CNS effect(s) mediates the anticonvulsant effect of BDZ’s?
Inhibit firing of epileptic foci
How do BDZ’s affect sleep?
Decrease sleep latency (time to fall asleep) and increase sleep time
They increase stage 2 sleep
DECREASE stage 1, 3, 4, and REM sleep (thought to mediate aggression - less REM sleep)
What effect do BDZ’s have on ion channels?
Increases frequency of chloride channel opening
Doesn’t increase duration of channel opening
What drugs inhibit metabolism of BDZ? What does this do to BDZ levels?
Cimetidine, Disulfiram, and oral contraceptives increase BDZ levels by inhibiting metabolism
What drugs increase metabolism of BDZ? What does this do to BDZ levels?
Chronic ethanol, isoniazid, and phenytoin decrease BDZ levels by increasing metabolism (inducing CYP3A4)
GRAPEFRUIT JUICE also induces CYP3A4
Describe flumazenil
Nonselective antagonist (binds alpha subunit, blocks BDZ from binding)
No effect alone (no effect in non-BDZ users)
Used for BDZ overdose (blocks BDZ from binding)
Extensive first-pass metabolism; IV only
t1/2 is 1hr
Is BDZ tolerance pharmacokinetic or pharmacodynamic? What does this mean?
Pharmacodynamic, meaning the body responds differently to the drug. There isn’t enzyme upregulation, there is subunit composition change to decrease responsiveness
CROSS-tolerance occurs to other sedatives
If someone is tolerant to BDZ, can they take other sedatives?
There is cross-tolerance to other sedatives because the tolerance to BDZ is due to pharmacodynamics
Tolerance to BDZ’s depends on the effect. Which effects show tolerance?
More to sedation
Less to anticonvulsant
Very little to anxiolysis
Tolerance to sedation requires what subunit
Alpha-5
How do you treat dependence of BDZ?
Switch to longer acting BDZ
Decrease dose over 10-21 days
or
Substitute with Zolpidem
Physical dependence is due to altered GABA-A receptor subunit composition. What happens?
Less alpha-1 and gamma-2 subunits
What effect do BDZ’s have on dopamine activity?
Very little effect on mesolimbic dopamine activity, so there’s very little abuse liability
