Anxiolytics & Sedatives Flashcards
pharmalogic targets of anxiolytics and sedatives
adrenergic modification
serotonin
GABA
orexin
beta-1 receptors
cardiac m.
- inc HR/contractility
- lipolysis and renin secretion
beta-2 receptors
smooth m.
- smooth m. relaxation
- skeletal m. stim, glycogenolysis, gluconeogenesis)
Propanolol
non-selective beta blocker
atenolol
beta-1 selective blocker
metoprolol
beta-1 selective blocker
Buspirone
MOA
side effects
advantages/disadvantages
increases 5HT
side effects: dizziness, nausea, HA
advantages: low cost, easy admin, low abuse
disadvantages: short acting, but takes 1-4 weeks to produce anxiolytic effects
Selective Serotonin Re-uptake Inhibitors (SSRIs)
fluoxetine paroxetine sertraline citalopram escitalopram
serotonin and NE re-uptake inhibitors (SNRIs)
venlafaxine
duloxetine
GABA-A receptor stimulation
Cl- enters channel
Hyperpolarizes cell
CNS depression
GABA-A-α1: Agonism causes
sedation
GABA-A-α2,3: Agonism causes
anxiolysis
GABA-A-α5: Agonism causes
ataxia
Benzodiazepines
MOA
GABA facilitators (they themselves cannot open channel)
Bind to specific site to inc frequency of Cl- channel opening –> HYPERPOLARIZATION –> generalized CNS depression
(sedation, anti-convulsant, anxiolytic, muscle relaxation)
Benzodiazepines
effect on cognition
Produces ataxia and short-term memory/cognitive deficits (anterograde amnesia).
- can be used advantageously during surgery
- disadvantage for elderly
Why are benzodiazepines controlled substances?
Can develop tolerance and dependence, –> w/d sx [tonic-clonic seizure, anxiety] if halted abruptly (risk for abuse; schedule IV).
w/d med slowly!!
If combined with other CNS depressants (+opioid, alcohol, etc.) –> higher risk of death
Benzodiazepines are often rx’d for ______ w/d
Benzodiazepines are often rx’d for ALCOHOL w/d, because alcohol binds to GABA-A receptors and produces similar CNS depressant effects
How do benzos affect sleep architecture?
sedating.
- reduce awakenings
- inc sleep time
- improve sleep quality
Examples of benzos
end w/ -epam
diazepam
lorazepam
conditions where benzodiazepines are indicated
insomnia, anxiety, seizures
What drug can reverse the benzodiazepine overdose?
What are the concerns with use of this reversing agent?
flumazenil (Romazicon)
- essentially a benzodiazepine receptor antagonist
- competitive neutral ligand for GABA receptor causing no effect; reduces binding of benzos
CONCERNS OF USE: fear of inducing withdrawal (quickly displaces benzo from receptor)
Benzodiazepine-like drugs
- bind preferentially to GABA-A-α1 (sedation)
- relatively quick onset, short duration
- hepatic clearance (less efficient in elderly, adult females (any age))
exp.
zolpidem (ambien)
zalepon (sonata)
eszopiclone (lunesta)
Zolpidem (ambien)
benzo-like drug
preferentially binds to GABA-A-α1
Barbiturates
MOA
side effects
Enhance GABA activity and more widespread CNS depression
- POTENT, binds mult GABA sites –> inc duration of channel opening
HIGH TOXICITY at high doses (coma, death)
CYP450 inducer –> lots of drug-drug interactions
exp. phenobarbital (for seizures, severe alc w/d)
orexin
orexin neurons bind to receptors that PROMOTE AROUSAL
orexin-receptor antagonists
INDUCE SLEEP
- dose w/i 30 min of sleep, 7hr before wake time
- concerns: daytime drowsiness, cataplexy, suicidal thoughts
- schedule IV
exp. suvorexant (belsomra)
melatonin
serotonin analogue
useful for sleep disturbances due to circadian rhythm differences
ramelteon (rozerem)
melatonin-like
way more expensive bc rx version so controlled, know what you’re getting
suvorexant
orexin-receptor antagonist
induces sleep
melatonin and ramelteon
to induce sleep
short-acting
especially useful for circadian rhythm disorder
Why are barbiturates more toxic than benzos?
Rather than increasing the frequency of Cl- channel openings, barbiturates prolong the duration of Cl- channel openings.
Also barbiturates tend to induce CYP450.
