[PHA 6118] Unit 4.1.2 Sedative-Hypnotic Drugs

Sedatives or Anxiolytics

Agents that reduce anxiety and exerts a calming effect

Hypnotics

Agents that produce drowsiness and encourage the onset and maintenance of a state of sleep

Degree of lipophilicity

What factor does the absorption of sedative-hypnotic drugs primarily depend on?

Degree of lipophilicity

Determines the rate a drug can enter the CNS and is responsible for its rapid onset of action

T

T or F

Sedative-hypnotic drugs can cross the placenta and breast milk, causing depression of vital signs in newborns and nursing infants

Benzodiazepines

What drug class does diazepam, midazolam, and lorazepam belong to?

Barbiturates

What drug class does phenobarbital, amobarbital, and thiopental belong to?

Newer hypnotics

What drug class does zolpidem, zaleplon, and eszopiclone belong to?

Melatonin-receptor agonists

What drug class does ramelteon and tasimelteon belong to?

Orexin antagonists

What drug class does suvorexant and lemoborexant belong to?

5-HT receptor agonist

What drug class does buspirone belong to?

Benzodiazepines

Widely used class with effects attributed to the presence of halogen or nitro group at C7

F

with the —OH group: easily metabolized

without the —OH group: long-acting, not readily metabolized

T or F

The metabolism of benzodiazepines are highly dependent on the absence of the 3-hydroxyl group

Benzodiazepines

Which drug class is primarily metabolized by CYP3A4, followed by glucuronidation and urinary excretion, producing many active phase 1 metabolites, some of which have long half-lives?

T

T or F

Short-half life BZDs are rapidly conjugated and are more useful as hypnotics than as sedatives

Alprazolam, Chlordiazepoxide, Clonazepam, Clorazepate, Diazepam, Estazolam, Flurazepam, Lorazepam, Midazolam, Oxazepam, Quazepam, Temazepam, Triazolam

What are the drugs included under the benzodiazpine class?

Barbiturates

A drug class with effects attributed to its 5,5-substitution of the barbituric acid structure

F

used less due to numerous ADRs, drug interactions, and high degree of tolerance

T or F

Barbiturates are used more as anxiolytics due to lesser ADRs, less drug interactions, and low degree of tolerance

Barbiturates

What drug class is primarily metabolized via hepatic metabolism through oxidative reactions leading to alcohol, acids, and ketone metabolites; glucuronidation in phase 2 then slow urinary excretion?

Thiobarbital

What barbiturate does not undergo phase 2 glucuronidation?

T

T or F

20%-30% phenobarbital is excreted unchanged and elimination can be increased via urinary alkalinization (barbiturates are weak acid)

Amobarbital, Butabarbital, Mephobarbital, Pentobarbital, Phenobarbital, and Secobarbital

What are the drugs included under the barbiturate class?

Newer hypnotics

Agents with novel chemical structure that are not related to BZDs but exhibit similar mechanism of action

Zolpidem

Which newer hypnotic drug has an imidazopyridine structure?

Zaleplon

Which newer hypnotic drug has an pyrazolopyrimidine structure?

Eszopiclone

Which newer hypnotic drug has an cyclopyrrolone structure?

CYP 3A4

What enzyme is primarily involved in the metabolism of newer hypnotics via oxidation and hydroxylation reactions; glucuronidation in phase 2 then urinary excretion?

Melatonin-receptor agonists

Acts on melatonin receptors found in the suprachiasmatic nuclei (SCN) in the anterior part of the hypothalamus

Suprachiasmatic nuclei

It is responsible for regulating the circadian rhythm of the body

Melatonin

Which molecule activates receptors to reduce arousal and induce sleep?

Orexin Antagonists

Blocks orexin and other neuropeptides that are responsible for promoting wakefulness

Orexin Antagonists

Drugs included in this class:

• Suvorexant

• Lemoborexant

CYP3A4

Orexin Antagonists are primarily metabolized by what enzyme?

Suvorexant

What drug is mainly excreted in the feces and less in the urine

5-HT Receptor Agonists

Action is uncertain but hypothesized as partial agonist of 5-HT receptors with possible affinity of D3 receptors (centrally inhibitory)

5-HT Receptor Agonists

Azaspirodecanedione is what category?