Anxiolytics and hypnotics Flashcards
Name the benzodiazepines
Alprazolam, clonazepam, diazepam, lorazepam, midazolam, ozaxepam.
The “zepam” drugs.
What is the MOA of benzodiazepines?
GABA-A enhancement
Benzodiazepines: Indications?
Anxiety disorder; panic disorder; insomnia (shortterm); preanesthetic; status epilepticus (anticonvulsant); Alcohol Withdrawal
Benzodiazepines: Side effects?
Common: drowsiness, memory impairment, reduced motor coordination, somnolence
Severe: potential for addiction/abuse, respiratory depression, teratogen (cleft lip), neonatal toxicity/withdrawal
Benzodiazepines: Metabolism?
Rapidly absorbed from gut and metabolized by liver.
Which benzodiazepines require glucuronide conjugation (not hepatic oxidation)?
Lorazepam, oxazepam, and temazepam (LOT)
Which benzodiazepines are preferred agents for elderly or those with liver impairments? Why?
Lorazepam, oxazepam, and temazepam (LOT)
Why?
No active metabolites, and are generally shorter-acting.
Which benzodiazepines have shorter half-life and high potency?
Alprazolam, lorazepam,
midazolam, oxazepam, temazepam
LOT + MA
Which benzodiazepines have longer half-life and lower potency?
Clonazepam, diazepam.
CD!
What are contraindications of benzodiazepines?
acute narrow-angle glaucoma,
respiratory insufficiency, sleep apnea
What are precautions that should be taken for people on benzodiazepines?
abrupt discontinuation → withdrawal, active or
history of alcohol abuse → addiction, co-administration with
other CNS depressants → respiratory depression
Flumazenil: MOA
Potent benzodiazepine R antagonist;
competitively inhibits benzodiazepine
recog site on GABA/benzodiazepine R complex, reversing benzodiazepine effects on CNS. Used for benzodiazepine overdose or toxicity.
Flumazenil: Side effects
Carries risk of precipitating an abrupt benzodiazepine withdrawal (can lead to seizures).
Buspirone: MOA
Serotonin (5-HT1A) R partial
agonist.
Buspirone: Indications
Indicated for generalized
anxiety disorder; chronic anxiety
(especially in patients with active or history of substance abuse).
Can buspirone be used for acute anxiety?
INEFFECTIVE in treating acute
anxiety (i.e., not prescribed p.r.n.).
Buspirone: Side effects
Dizziness,
drowsiness,
headaches
Buspirone: Metabolism
Hepatic metabolism; oral absorption
Half-life = 2-11 hours (admin BID)
Non-benzodiazepine hypnotics: Are they safer than benzodiazepines?
Non-benzodiazepine hypnotics offer advantages over benzodiazepines in terms of safety (less
tolerance/dependence) and have largely replaced benzodiazepines as hypnotic medicines.
However, they lack the anxiolytic,
anticonvulsant, and muscle-relaxant
properties that benzodiazepines offer.
Difference between hypnotics and sedatives?
A sedative lowers excitement and calms the awake patient, whereas a hypnotic
produces drowsiness and promotes sleep
What are the non-benzodiazepine hypnotics?
Zolpidem, zaleplon, eszopiclone.
Non-benzodiazepines: MOA
Benzodiazepine R agonists,
bind to GABA receptors subtypes
that specifically modulate sleep →
less unwanted SE’s
Non-benzodiazepines: Indications
Short term (<4 weeks) treatment of insomnia a. Sleep onset insomnia: zolpidem and zaleplon b. Sleep onset and sleep maintenance insomnia: zolpidem ER and eszopiclone
Non-benzodiazepines: Side effects
Shorter duration of action than most benzodiazepines and therefore less likely to cause next day sedation. However, drowsiness, dizziness, unsteady gait, rebound insomnia, and memory impairment have been reported. Potential for abuse/addition, but more of a concern in patients who already suffer from addiction.
Non-benzodiazepines: Metabolism
a. Metabolized by the p450 system and are therefore affected
by inducers/inhibitors of this system.
b. Drugs do not significantly induce/inhibit enzymes themselves.
Melatonin receptor agonist?
Ramelteon
Ramelteon: MOA
M1 and M2 melatonin R agonists in
the suprachiasmatic nucleus of the
hypothalamus.
Ramelteon: Indications
sleep onset insomnia
Ramelteon: Side Effects
Headache, dizziness, drowsiness, fatigue, nausea. Ramelteon is the only FDA-approved
drug for insomnia that is not a controlled substance because it has not been
associated with abuse or withdrawal.
What are other drugs used in clinical practice to treat insomnia?
Sedating antidepressants (tricyclics, trazodone, and
mirtazapine); antihistamines (diphenhydramine); and benzodiazepines (temazepam). The choice of which hypnotic to use is largely based on side
effects, comorbidities, and patient preference.
