Insomnia Pharm Flashcards
Phenelzine
MOA inhibitor
Antimuscarinic drugs and sleep
Act through ACh
Off when asleep
Helps put you to sleep
Pedunculopontine Tegmental
Antidepressants and sleep
Increase serotinin activity
Help with sleep
Dorsal Raphe
Amphetamines and sleep
Dopamine and NE increase wakefulness
Antihistamines and sleep
Help you sleep
Posterior hypothalamus
Benzodiazepines and sleep
Enhance GABA and promote sleep
Anterior hypothalamus
Orexin antagonists and sleep
promote sleep by blocking excitatory actions of orexin on NE-5HT neurons
Lateral Hypothalamus
Adenosine antagonists and sleep
ex Caffeine
increase alertness
Basal forebrain
Stages of sleep
Non-REM (70-75%):
Stage I- transition phase; EEG like wakefullness
Stage II- Light sleep EEG slower
Stage III and IV (delta)- EEG very slow, deepest level of sleep (described as “best”); stage where somnambulism and night terrors can occur
REM sleep (25-30%): Occurrence of rapid eye movements, decreased muscle tone, increased blood pressure, pulse, and respiration; stage of most recallable dreams
Benzodiazepines and Non-Benzodiazepine Receptor Agonists mechanism of action
facilitating the action of GABA at the GABAA receptor-chloride channel complex
GABA appears to interact with alpha or beta subunits triggering chloride channel opening with resultant membrane hyperpolarization
Bind to GABA-chloride channels with both α1 and α2/α5 subunits and result in both sleep and anxiolysis
GABA receptors with alpha 1 subunits
highly expressed in the cortex
Mediate sedative (sleep), amnestic, and anticonvulsant actions of benzodiazepines
GABA receptors with alpha-2/alpha-5 subunits
highly expressed in the limbic system /brain stem
Mediate myorelaxant, motor impairing, anxiolytic, and ethanol-potentiating effects of benzodiazepines
“z-drugs”
(zolpidem, zaleplon, eszopiclone)
Non-benzodiazepines - bind only to GABA-chloride channels with α1 subunits resulting in sleep without anxiolysis (reduced potential for dependence)
Name the 3 major Benzodiazepines used for sleep aid
Triazolam
Temazepam
Flurazepam
Triazolam
A benzodiazepine
Sleep aid
Eliminated within 1 dosing cycle (t1/2: 1.5-5 hrs),
less daytime sedation (hangover)
use cautiously in elderly with dose reduction
rapidly absorbed
Can see rebound insomnia next day due to rapid elimination
Temazepam
A benzodiazepine
Sleep aid
Intermediate t1/2 (9-13 hrs)
slowly absorbed
peak concentration at 2-3 hrs
minimal effect on latency to sleep onset
Flurazepam
A benzodiazepine
Sleep aid
Long t1/2 with active metabolite (75-90 hrs),
see effect at same dose for 28 consecutive days (i.e., little tolerance).
Can accumulate in elderly due to impaired hepatic clearance leading to daytime sedation (“hangover”) / overdosage (t1/2 extended to 120-160 hrs).
“Z-drugs” (name them!)
Zolpidem
Zaleplon
Eszopiclone
Zolpidem
A “z-drug” for sleep aid
Short durations of action (6-8 hours) and half-life (zolpidem: 2-2.5 hrs).
Rapid oral absorption.
Effective for reducing sleep latency and nocturnal awakenings with an increase in total sleep time and efficiency.
Zaleplon
A “z-drug” for sleep aid
Short durations of action (6-8 hours) and half-life (zaleplon: 1 hr).
Rapid oral absorption.
Best suited for use as a sleep aid for middle-of-the-night awakenings
Decreasing time to sleep onset
Eszopiclone
A “z-drug” for sleep aid
Structurally different from zolpidem or zaleplon with longer t1/2 (∼ 6 hrs)
safe for long term use with little or no suggestion for development of tolerance
Adverse effects of benxodiazepines
In general, very safe and fatal overdoses are rare unless they are taken in combination with other CNS depressants or alcohol.
Daytime sedation and performance impairment
Anterograde amnesia, rebound insomnia, Psychologic and Physical Dependence
What schedule are Benzodiazepines?
schedule IV
Adverse effects of “Z-drugs”
Zolpidem: Drowsiness, amnesia, dizziness, headache and GI complaints. Does not appear to have significant effects on next-day psychomotor performance. Rebound effects and withdrawal and tolerance with prolonged use appear minimal, but are possible.
Zaleplon: Most common side effects are dizziness, headache, and somnolence. Like zolpidem, no next-day psychomotor impairment or rebound insomnia
Eszopiclone: Similar to zolpidem but longer half-life associated with increased incidence of next day psychomotor impairment with higher doses - FDA required lower dose for initiation [2014]
What schedule are z-drugs?
schedule IV
Trazodone
Non-GABA-Benzodiazepine Receptor mechanism
Complex effects on 5HT neurons, including weak but specific inhibition of reuptake and both agonist and antagonist receptor actions
Antidepressant
Watch out in elderly (Oversedation and orthostasis)
Tricyclic Antidepressants (TCADs)
Non-GABA-Benzodiazepine Receptor mechanism
Block of reuptake of serotonin and/or norepinephrine
Adverse rxn: Antimuscarinic activity
Ramelteon
Non-GABA-Benzodiazepine Receptor mechanism
Agonist at melatonin MT1 (induce sleepiness) and MT2 receptors (regulation of circadian rhythms) in suprachiasmatic nucleus of hypothalamus. Decreases mean latency to sleep
Antihistamines
Non-GABA-Benzodiazepine Receptor mechanism
example: Diphenhydramine
Antagonist action at histamine H1 and muscarinic cholinergic receptors in the CNS resulting in sedating properties
Less effective than benzodiazepines
NOT recommended
May be useful short-term
Chloral Hydrate
Non-GABA-Benzodiazepine Receptor mechanism
Old drug (1800’s), may be effective hypnotic for a few nights for transient insomnia. Continued use often leads to physical dependence.
Which class of drugs for sleep aid decreases delta and REM sleep?
Benzodiazepines
What is the tolerance like for benzodiazepines and z-drugs
BZD: if used for more than one week, get tolerance
Z-drugs: little tolerance
Flumazenil
antagonist that binds to same site as BDZs and “Z”-drugs
Used in treatment of benzodiazepine overdose toxicity
NOT effective for BARB or ethanol toxicity
