Sedatives & Hypnotics

What clinical uses are listed for sedative-hypnotics?

Anxiety, insomnia, seizures, procedural sedation/amnesia, muscle relaxation, and control of alcohol or other sedative withdrawal.

How does sleep-onset insomnia differ from sleep-maintenance insomnia?

Sleep onset: difficulty falling asleep. Sleep maintenance: difficulty staying asleep.

How do pharmacokinetics influence hypnotic selection?

Rapid onset helps sleep initiation; longer duration helps sleep maintenance but can increase next-day hangover effects.

What is the benzodiazepine mechanism of action?

Potentiate GABA at GABA-A receptors and increase the frequency of chloride-channel opening.

How does increased chloride entry produce benzodiazepine effects?

It increases neuronal inhibition, reducing neuronal activity.

Which benzodiazepines are highlighted for insomnia versus conscious sedation?

Insomnia: flurazepam, temazepam, triazolam. Conscious sedation: midazolam.

Which benzodiazepines are commonly used for anxiety in the lecture?

Alprazolam, clonazepam, and lorazepam.

Which benzodiazepines are listed for alcohol withdrawal?

Chlordiazepoxide and diazepam.

What distinguishes midazolam's kinetics and uses?

Rapid onset and short duration; used for procedural sedation and seizures/status epilepticus. IV onset is faster than oral onset.

What distinguishes triazolam from temazepam?

Triazolam: rapid onset and short duration. Temazepam: slower oral absorption/onset; listed for both sleep onset and maintenance.

Why can flurazepam cause prolonged or next-day effects?

Long-lived active metabolites extend its duration.

What important pharmacokinetic concerns are listed for diazepam and chlordiazepoxide?

Active metabolites can prolong effects; IM absorption is erratic.

Which benzodiazepine has no active metabolites and is highlighted as safer in older adults if one is needed?

Lorazepam; benzodiazepines still require caution in older adults.

What are the major benzodiazepine adverse effects?

Sedation, dizziness, cognitive impairment, confusion, hangover effects, hypotension, and increased fall risk.

How do benzodiazepines affect sleep architecture?

Increase total sleep time but reduce time in REM sleep.

What is the recommended place of benzodiazepines in insomnia therapy?

As-needed short-term relief; long-term maintenance is not ideal because they are habit-forming and difficult to discontinue.

What abuse-related precautions apply to benzodiazepines?

Schedule IV controlled substances with abuse/misuse potential; use cautiously in patients with substance-use histories.

Why are benzodiazepines concerning in older adults?

Increased falls and cognitive impairment; slower clearance can prolong effects. They are on the Beers list.

What monitoring is emphasized for benzodiazepines?

Sedation/consciousness, sleep-pattern changes, and respiratory rate in hospitalized patients.

What symptoms suggest benzodiazepine withdrawal?

Anxiety/panic, rebound insomnia, tremor, sweating, palpitations, nausea/vomiting, headache, and altered perception; severe cases include hallucinations, psychosis, and seizures.

What patterns increase benzodiazepine withdrawal risk?

Higher doses, short-acting agents, and use longer than 4 weeks.

How does the barbiturate mechanism differ from benzodiazepines?

Barbiturates increase the duration of chloride-channel opening and can directly activate the channel; benzodiazepines increase opening frequency.

Do barbiturates and benzodiazepines bind at the same site?

No; they act at different binding sites.

Which barbiturates appear in the slides and chart?

Phenobarbital, pentobarbital, thiopental, and secobarbital.

Why are barbiturates no longer used routinely for insomnia?

Less predictable kinetics and extended half-lives can produce undesirable cumulative effects.

What are phenobarbital's major uses in the lecture?

Alcohol withdrawal, long-term epilepsy treatment, and acute status epilepticus management.

What are pentobarbital and thiopental used for in the lecture?

Sedation, refractory seizures/status epilepticus, and barbiturate-induced coma; lethal injection/euthanasia is also listed.

What are the major barbiturate adverse effects?

Sedation, dizziness, confusion, cognitive impairment, hangover effects, falls, hypotension, and bradycardia.

Which barbiturate cardiovascular effects are more common with IV administration?

Hypotension and bradycardia.

What monitoring is emphasized for barbiturates?

Sleep latency, daytime sedation, cognition, and inpatient respiratory rate; phenobarbital may require therapeutic drug monitoring.

What is the mechanism of Z-drugs?

Potentiate GABA and increase chloride-channel opening frequency at the benzodiazepine binding site, despite being structurally unrelated to benzodiazepines.

Which medications are Z-drugs?

Zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta).

Which Z-drug is useful for sleep onset but not sleep maintenance, and why?

Zaleplon; its short duration makes it ineffective for maintaining sleep.

Which Z-drug is useful for both sleep onset and maintenance?

Eszopiclone; its longer duration also makes next-day hangover effects more likely than with shorter-acting options.

What formulation and pharmacokinetic features distinguish zolpidem?

No active metabolites; sublingual formulation for patients unable to swallow tablets and controlled-release formulation for longer duration.

What are the major Z-drug adverse effects?

Sedation, dizziness, amnesia, confusion, cognitive impairment, falls, and hangover effects, especially with extended-release formulations.

What distinctive safety problem is associated with Z-drugs?

Complex sleep behaviors, including sleepwalking, sleep-driving, and sleep-eating.

What is the recommended place of Z-drugs in insomnia treatment?

As-needed short-term relief; the lecture advises against nightly or long-term maintenance use because they are habit-forming.

What abuse and older-adult concerns apply to Z-drugs?

Schedule IV with abuse/misuse potential; Beers-list concerns include falls and cognitive impairment, with prolonged effects from slower clearance.

What is the mechanism of dual orexin receptor antagonists?

Block orexin A/B signaling, preventing its wake-promoting effects.

Which medications are DORAs, and what insomnia patterns can they treat?

Daridorexant, suvorexant, and lemborexant; used for sleep onset and sleep maintenance.

What adverse effects and dose-related pattern are listed for DORAs?

Dizziness, fatigue, headache, next-day somnolence, and possible abnormal dreams; adverse effects increase at higher doses.

How do CYP3A4 inhibitors affect DORAs, and which examples are listed?

Increase drug concentrations and adverse effects. Examples: amiodarone, grapefruit juice, fluconazole, diltiazem, and verapamil.

How do CYP3A4 inducers affect DORAs, and which examples are listed?

Decrease drug concentrations and effectiveness. Examples: carbamazepine, rifampin, phenytoin, and St. John's wort.

What is the mechanism of melatonin receptor agonists?

Stimulate MT1 and MT2 receptors; MT1 induces sleepiness and MT2 influences circadian rhythm.

How do ramelteon and tasimelteon differ in indication?

Ramelteon: sleep-onset insomnia. Tasimelteon: non-24-hour sleep-wake disorder.

Why may melatonin receptor agonists be useful when avoiding habit-forming medications?

They are noncontrolled and useful for patients with substance-use disorders; the lecture describes them as an option when long-term medication is needed.

What adverse effects and sleep-architecture advantages are listed for melatonin receptor agonists?

Dizziness, fatigue, headache, and possible abnormal dreams; they do not appear to alter sleep architecture or interfere with REM sleep.

How do CYP1A2 inhibitors and inducers affect melatonin receptor agonists?

Inhibitors increase concentrations/adverse effects: fluvoxamine, ciprofloxacin, verapamil. Inducers reduce effectiveness: cigarette smoke, carbamazepine, rifampin, omeprazole.

Which sedating antidepressants are covered, and what receptor effect contributes to sedation?

Amitriptyline, doxepin, mirtazapine, and trazodone; histamine H1 antagonism contributes to drowsiness.

What distinguishes doxepin from the other sedating antidepressants in this lecture?

Doxepin is FDA-approved for sleep-maintenance insomnia; the other listed antidepressant uses for insomnia are generally off-label.

When may sedating antidepressants be useful, and what risks are emphasized?

Insomnia with concomitant depression; noncontrolled, but can cause next-day sedation, dizziness, and increased falls in older adults.

Which medications should be used for sleep latency/onset for insomnia?

Eszopiclone, ramelteon, temazepam, triazolam, zaleplon, and zolpidem.

Which medications should be used for sleep maintenance for insomnia?

Doxepin, eszopiclone, temazepam, suvorexant, and zolpidem.

Which medications are not recommended for insomnia?

Diphenhydramine, melatonin, tiagabine, trazodone, L-tryptophan, and valerian; trazodone is discussed as an off-label option but is not recommended in this table.