sedative-hypnotics/anxiolytics

Question 1

sedative

Answer 1

calming, anxiolytic

Question 2

hypnotic

Answer 2

induces sleep (can be achieved with most sedatives by increasing dose – more pronounced CNS depression)

Question 3

mechanism of sedative-hypnotic drugs

Answer 3

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

Question 4

benzos

Answer 4

• most bind both BDZ1 (omega1) and BDZ2 (omega2)
• sedation (anxiolytics) >> hypnosis, muscle relaxation, anticonvulsant activity

** end in “-am”

Question 5

benzodiazepines vs barbiturates/ethanol

Answer 5

• 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)

Question 6

alprazolam

Answer 6

• short-acting benzo (Xanax)
• t1/2- 12 hrs
• anti-anxiety

Question 7

lorazepam

Answer 7

• 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)

Question 8

triazolam

Answer 8

• very short acting benzo (t1/2 = 3 hrs)
• induce sleep

Question 9

zolpidem

Answer 9

• “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

Question 10

flumazenil

Answer 10

• synthetic benzo antagonist
• used to reverse benzo OD

Question 11

diazepam

Answer 11

• model benzo (valium)
• t1/2 = 43 hrs (active metabolite t1/2 = 100 hrs)
• anticonvulsant and muscle relaxation

Question 12

midazolam

Answer 12

• very short-acting benzo (t1/2=2 hrs)
• anesthesia (calming and produces anterograde amnesia)
• Versed

*think M for aMnesia

Question 13

chlordiazepoxide

Answer 13

• benzo
• active metabolite with long t1/2 (100 hrs)

** think diaz for benzoDIAZepam

Question 14

flurazepam

Answer 14

• benzo
• long half life (74 hrs) and active metabolite with long half life (100 hrs)

Question 15

thiopental

Answer 15

• 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

Question 16

phenobarbital

Answer 16

• barb
• less lipid soluble, slower onset, slow elimination (t1/2 = 4-5 days)
• antiepileptic/anticonvulsant
• significant p450 induction

Question 17

buspirone

Answer 17

• 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

Question 18

adverse effects of sedative-hypnotics

Answer 18

• drowsiness and “hangover”
• falls (esp in elderly)
• dose-related CNS depression
• tolerance
• psychologic and physiologic dependence (abrupt withdrawal can be life-threatening)

Question 19

adverse effects of benzos

Answer 19

• daytime sedation/drowsiness
• additive or synergistic depression of CNS with other drugs
• dose-related anterograde amnesia
• physiologic and psychological dependence with chronic use

Question 20

binding sites of benzos, barbs and ethanol on GABAa receptor complex

Answer 20

• benzos: between alpha1 and gamma2
• barbs: alpha or beta
• ethanol: alpha