Sedative and Hypnotic Drugs Flashcards
(33 cards)
What is the mechanism of action of benzodiazepines (ex: diazepam, alprazolam, clonazepam, lorazepam, temazepam, midazolam)?
–binds to GABA-A receptor and increases frequency of opening of the GABA-mediated chloride ion channel
–hyperpolarizes the cell membrane and makes it less excitable
In what clinical application does diazepam prove to work better than other benzodiazepines?
-diazepam is a better skeletal muscle relaxant than other benzodiazepines
What enzyme metabolizes diazepam, and is it a short- or long-acting benzodiazepine?
-CYP3A4, long-acting
What is the main benzodiazepine used in treatment of anxiety?
-alprazolam
also used are: clonazepam, and lorazepam
Is alprazolam short- or long-acting?
short-acting
What is the clinical application of temazepam?
insomnia
Is temazepam short- or long-acting?
short-acting
What are the main clinical applications of midazolam?
- preoperative sedation, anxiolytic, amnesia for scopes, caths, etc.
- induction of GA
What unique pharmacokinetics does midazolam have?
–its acid is water-soluble
–but in vivo, it’s highly lipid-soluble
What is a major side effect of IV midazolam?
-respiratory depression, even respiratory arrest
What is the mechanism of action of non-benzodiazepine BZ agonists (ex: zolpidem, eszopiclone, zaleplon)?
-binds selectively to the BZ1 receptor (a subgroup of GABA-A receptors) and hyperpolarizes the cell membrane
What is the clinical application of BZ1 agonists such as zolpidem, eszopiclone, and zaleplon?
-insomnia
What modes of administration are available for zolpidem?
- IR sublingual tablets and oral sprays
- -for difficulty of sleep onset or getting back to sleep
- ER tablet
- -difficulty of sleep onset and/or maintenance
What is a major side effect of zolpidem?
- complex sleep behaviors
- -sleep walking or sleep driving
- -preparing and eating food
- -making phone calls
- -having sex
What makes eszopiclone stand out amongst the other non-benzodiazepine BZ agonists?
–it was the first agent approved for long-term use since there’s no tolerance or dependence
What is the mechanism of action of flumazenil?
-it’s an antagonist at the benzodiazepine binding site on the GABA-A receptor (blocks benzos and zolpidem)
What are the clinical applications of flumazenil?
–management of benzodiazepine OD
–reversal of benzo-induced sedation during surgical procedures (works in 1-2min)
What is a major adverse side effect of flumazenail?
-seizures
so watchful waiting is generally preferred
What barbiturate is actually on the top 300 drug list and what is its clinical indication?
-butalbital in combo w/ acetaminophen for HA pain
What is the mechanism of action of barbiturates?
–binds to GABA-A receptor and increases the duration of GABA-gated chloride ion channel openings
–GABA-independent, so high doses work in the absence of GABA (unlike benzos)
–barbiturates also inhibit a subset of excitatory glutamate receptors
What part of the CNS is most affected by barbiturates?
-reticular activating system
Which barbiturates have the highest and lowest lipid solubility?
- thiopental = highest (ultra-short time of onset)
- phenobarbital = lowest (1hr to onset)
What effect do barbiturates have on CYP3A4?
-inducers of CYP3A4
What are the characteristics of buspirone (a non-benzo anxiolytic)?
–Mechanism of Action: partial agonist at 5-HT receptors
- -slow onset (1-2wks)
- -has no additive CNS depression
