Kruse DSA: Sedative Hypnotics Flashcards
What are the benzos that DONT end is pam or lam?
- Chlordiazepoxide
- Clorazepate
Benzo antagonist
-Flumazenil
Barbiturates
- end in “bital”
- except for Thiopental
What are the newer sedative-hypnotic drugs?
- Buspirone
- Exzopiclone
- Meprobamate
- Ramelteon
- Zaleplon
- Zolpidem
What is a sedative?
- a drug that decrases CNS activity, moderates excitement, and calms the recipient
- Anxiolytic because it reduces anxiety
What is a hypnotic?
- a drug that produces drowiness and facilitates the onset and maintenance ofa state of sleep
- recipient can be aroused easily from it
MOA of benzodiazepenes?
-promote the binding of major inhibitory NT GABA to the GABAa receptor and enhance the GABA induced ion currents
Do benzos have a low capacity to produce fatal CNS depression?
- yes
- so they are preferred over barbiturates
Barbiturates MOA:
-Bind to GABAa receptors and potentiate GABA induced chloride currents
=Can activate the cahnnel directly by acting as a GABA mimetic at high concentrations
=narrow therapeutic index and it is often not possible to achieve a desired effect without evidence of general depression of the CNS
What is absorption rate dependent on?
-the lipid solubility
What enzyme does the phase 1 rxn for benzos?
- CYP3A4
- then glucuronidation (phase 2)
Which benzos would be good to use in someone who has hepatic insufficiency?
-oxazepam and lorazepam
What is the result of GABAa receptor activation?
- increased Cl- influx
- reduced number of AP’s
What do benzodiazepines do to the GABA concentration-response curve?
- shift it to the left
- less GABA required to activate the receptor
- benzos just enhace the effect of GABA allosterically
Barbiturates MOA
- increase the duration of GABA-gated chloride channel openings
- less selective
Which drugs are agonists only when the alpha 1 subunit of the GABA receptor is included?
-Eszopiclone, zaleplon, and zopidem
the GABA antagonist
-flumazenil
inverse agonists
- negative allosteric modulators of GABA receptor
- ex: B-carboline class of compounds
Which drug will increase total sleep time?
-eszopiclone
what is the usual cause of death due to overdose of sedative hypnotics?
-depression of the medullary respiratory center
what is tolerance?
-decrease in responsiveness to a drug following repeated exposure and a common feature of sedative hypnotic use
what is dependence?
-the compulsive use of a substance despite significant problems resulting from such use
What doe Flumazenil do?
-binds to benzo binding sit eon GABAa receptors and acts as a competitive antagonist
what drugs does flumazenil block the action of?
-benzos, zolpidem, zaleplon, and eszopiclone
=does not block CNS effects of other sedative hypnotics, ethanol, opioids, or general anesthetics
