Pharmaclogy - Sedatives and Hypnotics Flashcards
What is a sedative?
Sedative = calming = anxiolytic effect (ideally with little effect on motor or mental functions)
What is a hypnotic?
Hypnotic = induce sleep
more pronounced CNS depression than sedation; can be achieved with most sedative drugs simply by increasing dose
MOA: Sedatives and Hypnotics
bind to some site on
GABA-A Receptor complex and potentiate GABA-mediated inhibition
GABA-A receptos is what kind of channel?
Chloride
Where do benzodiazepines bind to the GABA-A receptor?
binding site between α1 – γ2 sub-units
Where do barbituates bind to the GABA-A receptor?
bind to α or β sub-unit
Where does ethanol bind to the GABA-A receptor?
binds to α
T/F: Most benzodiazepines bind to both GABA-A receptor subtypes.
True
omega-1 and omega-2
What is the “ceiling effect” of benzos?
Increasing doses do not produce respiratory arrest/coma, whereas barbs and alcohol can induce full CNS depression
T/F: In high doses, barbituates and alcohol can directly open chloride channels, resulting in full CNS depression (total GABA rush)
True
Give the class: Diazepam Chlordiazepoxide Lorazepam Flurazepam Alprazolam Midazolam i.v. or i.m. Triazolam
Benzodiazepines
Most benzos are metabolized how?
most benzos undergo microsomal oxidation (Phase I, via P450 system; particularly CYP3A4 and CYP2C19, with only modest P450 induction), and subsequent conjugation
What is the half life of flurazepam?
74 hours
Which benzo has the shortest half life?
Midazolam, 1.9 hrs
How is Zolpidem different from the more traditional benzodiazepines?
Zolpidem is specific for BDZ1 agonist (omega-1) whereas traditional benzos act on both omega 1 and 2.
This results in sedation w/o muscle relaxation/anticonvulsant activity
Use: Flumazenil
Benzo-antagonist
Use to reverse overdoses of benzos
What is the half life of phenobarbital?
4-5 days
less lipid soluble therefore slower onset
What is a barbituate commonly used to induce anesthesia due to its lipid solubulity and subsequent “fast on fast off” character?
Thiopental
known for its rapid redistribution
Does buspirone interact with the GABA-A complex?
No
Relieves anxiety w/o marked sedation
Use: alprazolam
Anti-anxiety;
shorter-acting benzo
Use: Lorazepam
Anti-anxietyl
Anti-convulsant
shorter-acting benzo
Use: Triazolam
Induce sleep;
very short-acting benzo
Use: Zolpidem
Induce sleep, a “pseudo-benzo”
What benzo is used in anesthesia to produce anterograde amnesia?
Midazolam
very short-acting benzo
Use: Diazepam
Anticonvulsant;
muscle relaxer
Use: Phenobarbital
Anticonvulsant
Name 3 adverse effects of the sedatives-hypnotics classes.
- drowsiness & “hangover”
- falls! – especially in the elderly - use caution – it is easy to produce confusion, sedation, unsteadiness with these drugs in the elderly
- dose-related CNS depression
(additive CNS depression with more than one agent) - tolerance = common feature of sedative-hypnotic drug use -cross tolerance
- metabolic tolerance - induce enzymes (notably with barbiturates and alcohol)
- dynamic tolerance - decreased CNS responsiveness (receptor down-regulation) - psychologic & physiologic dependence is significant problem;
Note: abrupt withdrawal can be life-threatening, notably with non-benzo seditive-hypnotics (e.g. alcohol and barbiturates)