sedative-hypnotics/anxiolytics Flashcards
sedative
calming, anxiolytic
hypnotic
induces sleep (can be achieved with most sedatives by increasing dose – more pronounced CNS depression)
mechanism of sedative-hypnotic drugs
allosterically enhance GABA binding to GABA receptor –> opens Cl channel –> hyperpolarizes cell –> inhibits cell
GABA receptor is transmembrane chloride ion channel with multiple subunits –> great receptor heterogeneity
benzos
- most bind both BDZ1 (omega1) and BDZ2 (omega2)
- sedation (anxiolytics) >> hypnosis, muscle relaxation, anticonvulsant activity
** end in “-am”
benzodiazepines vs barbiturates/ethanol
- both allosterically enhance GABA binding to GABA receptor
- benzos have “ceiling effect”
- dont produce respiratory depression, death or coma
- barbs and alcohol can cause full CNS depression –> death (in high doses they directly open Cl- channel by acting as direct agonists)
alprazolam
- short-acting benzo (Xanax)
- t1/2- 12 hrs
- anti-anxiety
lorazepam
- short-acting benzo (Ativan)
- t1/2 = 14 hrs
- anti-anxiety, anti-convulsant, prevent withdrawal symptoms in alcoholics
- does not have an active metabolite (directly conjugated to inactive glucuronide)
triazolam
- very short acting benzo (t1/2 = 3 hrs)
- induce sleep
zolpidem
- “pseudobenzo” – BDZ1 agonist
- induce sleep (Ambien)
- sedation and hypnosis w/o muscle relaxation or anticonvulsant activity
- adverse side effects: sleep walking, eating, driving
**think ZzZzZolpidem = sleep
flumazenil
- synthetic benzo antagonist
- used to reverse benzo OD
diazepam
- model benzo (valium)
- t1/2 = 43 hrs (active metabolite t1/2 = 100 hrs)
- anticonvulsant and muscle relaxation
midazolam
- very short-acting benzo (t1/2=2 hrs)
- anesthesia (calming and produces anterograde amnesia)
- Versed
*think M for aMnesia
chlordiazepoxide
- benzo
- active metabolite with long t1/2 (100 hrs)
** think diaz for benzoDIAZepam
flurazepam
- benzo
- long half life (74 hrs) and active metabolite with long half life (100 hrs)
thiopental
- barbiturate
- highly lipid soluble, fast-on, fast-off
- very short acting (rapid offset is due to tissue redistribution)
- used to induce anesthesia
- significant p450 induction
phenobarbital
- barb
- less lipid soluble, slower onset, slow elimination (t1/2 = 4-5 days)
- antiepileptic/anticonvulsant
- significant p450 induction
buspirone
- no interaction with GABA receptor, may act as partional agonist at 5-HT receptors
- anti-anxiety w/o sedation
- euphoric, hypnotic, anticonvulsant or muscle relaxant effects
**I am going to miss my “bus” and miss my step 1 exam then am going to fail etc etc
adverse effects of sedative-hypnotics
- drowsiness and “hangover”
- falls (esp in elderly)
- dose-related CNS depression
- tolerance
- psychologic and physiologic dependence (abrupt withdrawal can be life-threatening)
adverse effects of benzos
- daytime sedation/drowsiness
- additive or synergistic depression of CNS with other drugs
- dose-related anterograde amnesia
- physiologic and psychological dependence with chronic use
binding sites of benzos, barbs and ethanol on GABAa receptor complex
- benzos: between alpha1 and gamma2
- barbs: alpha or beta
- ethanol: alpha
