Sedative Hypnotic Agents Flashcards
Reduces anxiety and exerts a calming effect
Sedative (anxiolytics)
Promotes drowsiness and encourages the onset and maintenance of sleep
Hypnotic drug
Indicated for patients experiencing symptoms severe enough to produce functional disability
Anxiolytic medication
The most effective and commonly prescribed drugs for rapid relief of acute anxiety symptoms in GAD and panic disorder
Benzodiazepines (BZs)
A major determinant of the rate at which a given BZ enters the CNS
Lipophilicity
Cross the placental barrier and may contribute to depression of neonatal function
BZs
BZs for which the parent drug or its active metabolites have long t1/2’s are more likely to cause cumulative effects with
Multiple doses
The BZs bind to the molecular components of the
GABA-A receptor
Functions as a Cl- ion channel
GABA-A receptor
A heteropentameric glycoprotein assembled from 5 subunits
GABA-A receptor
All neuropharmacological agents are usually very
Lipophilic
Interacts at 2 sites between the alpha and beta subunits, triggering Cl- ion channel opening with resulting membrane hyperpolarization
GABA
The binding of BZs to GABA-A occurs at a single site between the
-BZ antagonists also target here
Alpha and gamma subunits
Potentiate the Cl- ion channel effects of GABA as well as GABAnergic inhibition at all levels of the neuraxis
BZs
Which BZ has the fastest time to peak blood level?
Midazolam
Have a fast time to peak blood level and a long half life
BZs
There is little justification for long-term therapy of
BZs
In the elderly, we want to decrease the dose of BZs by
1/2
Do not combine with any other anti-anxiety agents, antihistamines, anticholinergics, and ethanol
BZs
The BZ that acts the fastest but has the shortest half-life
-Labeled for sedation prior to medical or surgical procedures
Midazolam
Can cause significant dose-related anterograde amnesia and can significantly impair the ability to learn new information
BZs
Can present as lethargy or a sate of exhaustion. Or, alternatively, as gross symptoms of ethanol intoxication
BZ toxicity
Tolerance, psychological dependence, and physiologic dependence can result from
Prolonged BZ use
The drugs most frequently involved in deliberate overdoses
Sedative-hypnotics
Increase the frequency at which the Cl- channel opens
BZs
Are addictive, can cause depression of CNS functions, and cause amnesia effects
BZs
Synthetic BZ derivative that binds to the BZ site on the GABA-A receptor
Flumazenil (Romazicon)
Antagonizes the actions of the BZs and the newer hypnotics zolpidem, zaleplon, and eszopiclone, but NOT the barbiturates
Flumazenil (Romazicon)
Approved for use in reversing the CNS depressant effects of BZ overdose and hastens recovery after BZ use in medical procedures
Flumazenil
Newer-generation antidepressants for the chronic management of GAD include:
SSRIs and SNRIs
A lack of dependency and a tolerable adverse effect profile make these drugs the preferred choice for long term treatment of GAD
SSRI’s and SNRI’s
The anti-anxiety response of antidepressants requires
2-4 weeks or longer
Has selective anxiolytics effects without causing marked sedative, hypnotic, or euphoric effects
Buspirone
Thought to exert its anxiolytics effects by acting as a partial agonist at brain 5-HT1A receptors
Buspirone
Also has affinity for brain dopamine D2 receptors
Buspirone
It’s anxiolytics affect take 2 weeks or longer to become established, making the drug unsuitable for acute anxiety states
Buspirone
Buspirone interacts with
Inducers and inhibitors of CYP and MAO inhibitors
Thought to increase the presynaptic release of GABA by binding to voltage-gated Ca2+ channels and altering Ca2+ influx
Pregabalin
Pregabalin also increases GABA biosynthesis by modulating the actions of which two enzymes?
Glutamate decarboxylase and Branched-chain aminotransferase
Is also GABAergic, though it does not bind the GABA receptor like BZs
Pregabalin
Produces anxiolytics effects similar to the BZs and antidepressants
Pregabalin
A prototypical tricyclic antidepressant that acts like an SNRI
Imipramine
Although effective in the treatment of GAD, it is considered a second-line agent due to higher toxicity and adverse effect rates than the newer antidepressants
Imipramine
Has antiadrenergic, anticholinergic, and antihistamine properties
Imipramine
A potent H1 antihistamine that also acts as a strong antagonist t 5-HT receptors
Hydroxyzine
The anxiolytic properties of Hydroxyzine are from its
Antiserotonergic effects
Adverse effects are related to antihistamine, anticholinergic, and anti dopaminergic properties, and include dry mouth, GI disturbances, and blurred/double vision
Hydroxyzine
An atypical antipsychotic with antagonist activity at 5-HT receptors
Quetiapine XR
Classified as an alternative agent due to numerous adverse effects that are related to blockade of muscarinic, a-adrenergic, and dopamine receptors
Quetiapine XR
Drugs used to treat insomnia
Hypnotics
GABAergic drugs can also be used as
Hypnotic Agents
At hypnotic doses, increase total sleep time and decrease sleep latency and the number of awakenings
BZs
Bind to the same sight on the GABA-A receptor as the BZs and exhibit similar GABAergic effects
Non-BZ hypnotics
More selective in their binding than the BZs
-All decreases time to persistent sleep
Non-BZ Hypnotics
Non-BZ hypnotics that increase total sleep time
Zolpidem and eszopiclone
Non-BZ Hypnotic that does NOT increase total sleep time
Zaleplon
Occurs with both zolpidem and zaleplon if used at higher doses
Rebound insomnia
Unlike certain BZs, ALL lack anticonvulsant and muscle relaxing activities
Non-BZ Hypnotics
Both act as agonists at melatonin receptors in the brain and have NO GABAergic effects in the CNS
Ramelteon and Tasimelteon
Decreases sleep latency and increases sleep periods with no rebound insomnia or risk of dependence
Non-GABAergic Hypnotics (Ramelteon and Tasimelteon)
Approved for non-24 hour sleep-wake disorder
Tasimelteon
Can cause decreased testosterone and increased prolactin
Ramelteon
A neurotransmitter in the wake pathway that acts as a central promoter of wakefulness
Orexin (OX)
Acts as an antagonist at OX1 and OX2 receptors in the brain with no GABAergic CNS effects
Suvorexant
Decreases sleep latency and increases sleep periods, but is associated with a risk of abuse or dependence
Suvorexant
Sedation and somnolence are what type of effects?
Antihistamine
Dry mouth, constipation, blurred/double vision, and tachycardia are what type of effects?
Anticholinergic effects
Orthostatic hypotension is which type of effect?
Antiadrenergic
