5 CNS effects of BDZ
Muscle relaxant, anticonvulsant, sedation/hypnosis
Anxiolytic effect of BDZ
Regulate firing of raphe nuclei neurons
Amnestic effects of BDZ
Inhibition of hypocampal LTP
Muscle relaxing effects of BDZ
Enhanced presynaptic inhibition in spinal cord
Anticonvulsant effect of BDZ
inhibit firing in epileptic foci
Sedation effect of BDZ
Decrease sleep latency, increase sleep time
Increase stage 2, decrease 1,3,4, REM
Anesthetic: combined with other full anesthetics
4 other effects of BDZ
Improve anxiety related GI disorders
Decrease BP and increase HR
Slight respiratory depression
Worsens sleep related breathing disorders
All MOA of BDZ are due to
enhanced GABAa receptor activation
BDZ increases (2)?
Increase affinity of GABA binding site for agonists, opening frequency of Cl channels
Require a gamma-2, a beta, and certain alpha subunits
Alpha 2 and 3
BDZ competitive antagonist
What are picrotoxin, bicucullin?
BDZ noncompetitive antagonists
7 SE of BDZ
Sedation, memory dysfunction
Nightmares, uninhibited behavior, rage, suicide
SE's are due to
withdrawal from short acting agents
Pharmacokinetics and metabolism of BDZ (5)
Orally absorbed, 70-99% protein bound
Metabolized in liver by 3A4, 2D19, conjugation
Pharmacokinetics for specific agents is determined by
half life of parent drugs and active metabolites
how BDZ interact with CNs depressants
BDZ's metabolism is inhibited by (3)
Cimetidine, disulfiram, OC
Metabolism of BDZ is increased by
Chronic ethanol, Phenytoin, isoniazid
chlordiazepoxide, lorazepam, oxazepam, clonazepam, clorazepate, diazepam, alprazolam, prazepam
halfe life of anxiolytics?
Except Lorazepam, alprazolam, Oxazepam: Medium
half life of alcohol?
6 sleeping agents and their half lifes
Triazolam, Zolpidem: S
Estazolam, Temazepam: M
Flurazepam, Quazepam: L
4 preanesthetics and their half life
Diazepam could be used for? Except?
Chlordiazepoxide could be used for? Except?
D: All except sleep
C: all except Sleep and anticonvulsant
MOA of flumazenil
Used for BDZ overdose
IV: extensive first pass
Full agonist at A5, antagonist at A1
Anticonvulsant, anxiolytic, Little sedation
Less tolerance, alteration of subunit composition
MOA of zolpidem, eszopiclone, indiplon?
Only binds to A1 subunits
Very potent sedative effects
less effect on REM, rebound insomnia, tolerance and dependence
MOA of L838417
Agonist at A2,3, antagonist at A1
Anxiolytic with no sedation
Partial agonsists or subtype slective
MOA of loreclezole?
Selective for receptors containing B2 subunit
Selective anticonvulsant with no sedation
Can stimulate GABAa receptor in absence of GABA
More tolerance to? Less to?
More tolerance to sedation, less to anticonvulsant, very little anxiolysis
Due to altered GABAa receptor subunit composition
Tolerance to sedation requires
Anxiety, insomnia, increase REM
Most severe if?
panic, muscle twitches, convulsant
If flumazenil is given
Physical dependence is due to?
Altered GABAa receptor subunit composition
Less A1 and Gama 2 subunits
3 treatment of dependence
Switch to longer Acting BDZ
Decrease dose over 10-21 days
Substitute with Zolpidem.