Sedatives and Hypnotics Flashcards
Which 3 have actions on GABA neurotransmission?
barbiturates, benzodiazepines, z-drugs
Sedative
reduces anxiety and produces a calming effect
Hypnotic
produces drowsiness; aids sleep onset or maintenance
sedative-hypnotics
drugs that can produce sedation at lower doses and can produce hypnosis at higher doses
CNS depressant
produces a net shift toward inhibitory neurotransmission (e.g. drugs that act at GABA(a) receptors are DNS depressants
To what receptor do barbiturates bind and what is the normal function of that receptor?
-GABA(a) receptor at multiple sites (alpha or beta subunits)
-they act as positive allosteric modulators of GABA(a), increasing the duration of chloride ion channel opening when GABA binds
-antagonist at glutamate AMPA receptors
-primary GABA(a) receptor agonist (only at high concentrations)
To what receptor do benzodiazepines bind and what is the normal function of that receptor?
-can only bind to GABA(a) receptor at a single site (those that have an alpha next to a gamma subunit)
-positive allosteric modulators of GABA(a) but they increase the frequency of channel openings (opens at lower GABA conc)
What receptor does flumazenil target?
GABA(a)
-acts as a competitive GABA(a) antagonist because it occupies the benzodiazepine and z-drug binding sites without producing an effect
-reverses CNS depression, respiratory depression and amnesia caused by benzos and z-drugs
Z drugs and their binding site
-hypnotic agents prescribed for insomnia
-binds selectively to alpha 1 GABA(a) receptor subunit; increase chloride ion conductance
-more selective than benzos therefore limited range of effects
2 clinical uses for barbiturates
antiepileptics and anesthetics
6 clinical uses for benzodiazepines
antiepileptics
anesthetics
muscle relaxants
alcohol withdrawal
anxiety (short-term)
insomnia (short-term)
ramelteon (drug type, indication, receptor binding site)
-unscheduled hypnotic for long-term use in insomnia
-melatonin 1/2 receptor agonist
buspirone (drug type, indication, receptor binding site)
-serotonin (5-HT 1A) receptor agonist which is a GPCR (no effect on GABAa receptors)
-sedative used for generalized anxiety disorder
Why are barbiturates most dangerous in overdose?
- Linear dose-response progresses to coma, death
- Tolerance develops to sedative and hypnotic effects, but not lethal effects (narrows TI)
- No antidote exists; treatment limited to supportive measure (e.g. mechanical ventilation)
Which 3 potentiate effects (interact with) of other CNS depressants?
Barbiturates, Benzos, and Z-drugs
Which tends to have many active metabolites?
Benzos
Which have highest and lowest risk of dependence?
Highest: barbiturates
Lowest: Z-drugs
Why have z-drugs replaced benzos as treatment for sleep disorders?
Carry less risk of dependence and withdrawal
What other 4 effects besides sedation are produced at the lowest dose?
anxiolysis, anti-convulsant, muscle-relaxant, disinhibition
Which has the highest risk of PK drug interaction due to its enzyme induction/inhibition properties?
barbiturates
2 clinical uses for barbiturates
antiepileptics
anesthetics
For the drugs with both sedative and hypnotic properties (barbiturates & benzodiazepines), name a major physicochemical property that affects time to onset of action, and a property that affects duration of action (see slides on benzodiazepines).
Barbiturates time to onset of action and duration of action is driven primarily by lipophilicity. Benzodiazepines time to action is determined mainly by lipophilicity and onset is determined by whether the benzodiazepines have active metabolites.
Which 3 have potential for abuse (i.e. are scheduled substances)?
Barbiturates, Benzodiazepines, and Z-drugs
