Sedatives & hypnotics Flashcards
An effective sedative agent should reduce _____ & exert a _______
anxiety
a calming effect
Hypnotic drugs should produce _______ & encourage the onset & maintenance of a ______
drowsiness
state of sleep
Describe the absorption & distribution of sedative-hypnotic drugs
lipid soluble
Good distribution to the brain
Describe the metabolism & excretion of sedative-hypnotic drugs
Metabolized by hepatic enzymes
Active & inactive metabolites
What is the MOA of benzos?
Facilitates the inhibitory actions of GABA
Receptors for benzodiazepines are located in what 3 brain regions?
Thalamus
Limbic structures
Cerebral cortex
What are benzos used for?
Anxiety Panic attacks Insomnia Skeletal muscle relaxation Seizures
Toxicity of sedative-hypnotics (benzos, newer hypnotic drugs, barbiturates) can lead to what?
Extension of CNS depressant actions
Dependence (barbiturates > benzos)
What should you remember about diazepam?
Active metabolites
Erratic bioavailability from IM injection
Which drug has active metabolites w/ long half-lives?
Flurazepam
Which drugs have no active metabolites? (3)
Lorazepam
Oxazepam
Zolpidem
High doses of benzos w/ long or intermediate half-lives have a greater potential to produce…
daytime sedation
psychomotor incoordination
cognitive deficits
What are ADEs of benzos?
anterograde amenesia
rebound insomnia
*Start at lowest effective dose to avoid these
The FDA requires labeling for benzos & barbiturates to include a caution regarding… (3)
anaphylaxis
facial angioedema
complex sleep behaviors (sleep driving or eating, phone calls)
What is the MC type of drug interaction w/ sedative-hypnotics?
Additive CNS depression effects
What are examples of substances that interact w/ sedative-hypnotics?
Alcohol Antihistamines Antipsychiotic Opioids TCAs
Overdosage of sedative-hypnotics can result in…
respiratory & CV depression
What drug may reverse CNS depressant effects?
Flumazenil
What is the MOA of flumazenil?
Antagonist at benzo sites on GABA receptor
Antagonist to benzos & the newer hyponotic drugs only
What are ADEs of flumazenil?
Agitation, confusion
Withdrawal syndrome
What are 3 newer hypnotic drugs (not among the benzo class)?
Zolpidem
Zaleplon
Eszopiclone
What is the MOA of the newer hypnotics?
Bind to GABA receptor sites
Facilitate Cl channel opening
What is the MOA of barbiturates (“tal”) ?
Prolongs the inhibitory effects of GABA & glycine
What are barbiturates (“tal”) used for?
anesthesia
insomnia & sedation
seizures
Which 2 drug classes induce liver enzymes?
What does this cause?
Barbiturates & carbamates
Drug interactions
Which 2 antihistamines are more sedating than pyrilamine?
Diphenhydramine & doxylamine
Which antidepressant has FDA approval for the tx of sleep maintenance insomnia?
Doxepin
Which antidepressant may promote sleep?
Mirtazapine
Which antidepressant can be given at bedtime to improve sleep continuity?
Trazodone
What are ADEs of trazadone?
Carryover sedation
Alpha-adrenergic blockade - orthostasis
Priapism
What are 2 ADEs of mirtazapine?
Daytime sedation
Wt gain
Which melatonin-receptor agonist is approved for the tx of sleep-onset insomnia?
Ramelteon
Ramelteon forms active metabolite via…
CYP1A2
What are the MC ADEs of ramelteon?
HA, dizziness, somnolence
Ramelton is helpful for sleep- onset difficulties in what 2 conditions?
COPD & sleep apnea
What is the main complaint regarding valerian (an herbal sleep remedy)?
Smells like old gym socks
What is the MOA of buspirone?
Selective anxiolytic
Partial agonist at 5-HT receptors & D2 receptors
Interacts w/ 5-HT1A subclass of serotonin receptors
What effects does buspirone express?
Minimal CNS depressant effects
Describe the onset of action of buspirone
Slow (> 1 week)
Does buspirone form active metabolite?
What does buspirone interact w/?
Yes
CYP3A4 inducers & inhibitors
What are the ADEs of buspirone?
GI distress, tachy
Paresthesia
Tolerance is minimal w/ chronic use
Little rebound anxiety or withdrawal sx upon discontinuance
Is buspirone safe in pregnancy?
yes appears to be
Which classes of drugs are used for tx of panic d/o?
SSRIs, SNRI
Benzos
TCA
MOI
Which SSRI can cause QT prolongation?
Citalopram
What classes of drugs are used for tx of social anxiety d/o?
SSRIs, SNRI
Benzos
What are examples of stimulus control procedures used for sleep hygiene?
Avoid blue spectrum light from TV, phones, tablets
Schedule worry time during the day; do not take troubles to bed
What is another sleep hygiene recommendation?
Avoid illuminated clocks the bedroom
What are some of the clinical uses of sedative-hypnotics?
Relief of anxiety
Insomnia
Control of withdrawal states
What 2 drugs have the potential to lead to coma?
Barbiturates & alcohol
