Sedatives

Question 1

Sedative-Hypnotic drugs are CNS depressants that are used to

Answer 1

treat anxiety and enhance sleep

Question 2

sedative (anxiolytic) drugs should ….

hypnotic drugs produce ….

Answer 2

sedative (anxiolytic) drugs should reduce anxiety and exert a calming effect.

hypnotic drugs produce drowsiness and encourage the onset and maintenance of a state of sleep.

Question 3

The majority of sedative/hypnotic drugs do what?

Other sites of action include serotonin, melatonin, orexin and histamine systems.

Answer 3

enhance GABA actions on the GABAA receptor.

Question 4

Glutamic acid is metabolized to ____ by ____.

Answer 4

Glutamic acid is metabolized to GABA by glutamic acid decarboxylase (GAD).

Question 5

The primary mechanism for GABA elimination is…

Answer 5

reuptake into neurons and glia via a Na+/Cl- dependent transporter.

Question 6

After reuptake into the neurons or glia, GABA is metabolized to succinic semialdehyde by _____.

Succininc semialdehyde eventually generates glutamate.

Answer 6

GABA-transaminase (GABA-T).

Question 7

_____ are ligand-gated chloride channels and produce inhibitory post-synaptic potentials (IPSPs).

Answer 7

GABAA receptors

Question 8

GABAA receptors contain binding sites for ….

Answer 8

GABA
benzodiazepines
barbiturates
anesthetics 
channel blockers.

Question 9

Benzos MOA

Answer 9

allosteric effect: enhance GABA-induced activation of GABAA receptor and resulting increased Cl- current.

Question 10

BDZs do not have any direct effects on the GABAA receptor and require…

Answer 10

BDZs do not have any direct effects on the GABAA receptor and require the activation of the receptor by GABA

Question 11

Benzodiazepine antagonists will only block the effects of…

Answer 11

Benzodiazepine antagonists will only block the effects of benzodiazepines or drugs that bind to the benzodiazepine site.

Question 12

Pharm effects of benzos

Answer 12

Antianxiety (anxiolytic)
Sedation
Motor impairment/ataxia Anterograde amnesia Drowsiness/hypnosis
Muscle relaxation Anticonvulsant

Question 13

Effects can be dose dependent - The anxiolytic affects of benzos occur at low doses and as the doses increase…

Answer 13

Anxiolytic affects occur at low doses and as the doses increase, drowsiness occurs followed by motor impairment and hypnosis.

Question 14

Major side effects of benzos include motor impairment/ataxia, tolerance and dependence.

Answer 14

motor impairment/ataxia, tolerance and dependence.

Question 15

Benzodiazepines are listed as a Schedule___ due to their potential for _____

Answer 15

Benzodiazepines are listed as a Schedule IV controlled substance due to their potential for addiction and abuse.

Question 16

The benzodiazepines can have cross-tolerance with other CNS depressants, especially those whose site of action is the ____

Answer 16

The benzodiazepines can have cross-tolerance with other CNS depressants, especially those whose site of action is the GABAA receptor. (ETOH)

Question 17

While the BDZs are CNS depressants, they are relatively ___.

They produce very little respiratory depression even at high doses. When administered alone they rarely produce a fatal overdose. However, they may cause severe CNS depression, even death, when …..

Answer 17

Safe drugs.

when given in combination with other CNS depressants, especially alcohol. (or opiates)

Question 18

Benzodiazepines are very ____ and are rapidly absorbed in the ____

Answer 18

Benzodiazepines are very lipophilic and are rapidly absorbed in the GI tract

Question 19

Most of the BDZs are taken orally and are___.

The half-lives of the BDZs vary considerably and many have ….

Many of the BDZ metabolites are also pharmacologically active so ….

Answer 19

Rapidly acting (1-2 hours).

a long or very long half-life (16-48 hours).

The duration of action the BDZ may be longer than the half-life of the parent drug.

Question 20

Issues with benzos and the elderly

Answer 20

Duration of action of BDZs can be prolonged d/t diminished liver function in elderly.
The motor impairment/ataxia may be a problem - falls and fractures.
Elderly are more sensitive to cognitive effects like decreased alertness and memory and confusion.

Question 21

Diazepam (Valium)

Answer 21

widely used benzo

Used for anxiety disorders, epilepsy, alcohol withdrawal skeletal muscle relaxation, pre- anesthetic.

Long parent half-life 30-60 hrs. Long metabolite half-life 30-100 hr.

Question 22

Alprazolam (xanax)

Answer 22

Treats anxiety

half life 12-15 hrs

Question 23

Triazolam (Hacion)

Answer 23

hypnotic
banned in UK for abnormal behavior
half life 1.5-5.5 hrs

Question 24

Midazolam (Versed)

Answer 24

pre anesthetic and sedative for endoscopy

water soluble - IM, IV

short half life (2-4 hours)

Question 25

The ideal hypnotic drug would cause

Answer 25

The ideal hypnotic drug would cause a rapid onset of sleep, maintain sleep through the night and not have any lingering drowsiness or hangover effect in the morning.

Question 26

Benzodiazepine receptor agonists (“Z compounds”) are not chemically related to benzodiazepines, but ____ These drugs have ___ and do not produce ____.

Answer 26

bind to the benzodiazepine site on the GABAA receptor. half-lives (1-2 hrs.) hangover.

Question 27

Z Drugs can produce ___ and ____ especially at high doses.

Answer 27

can produce tolerance and dependence especially at high doses.

Question 28

Zolpidem (Ambien)

Answer 28

Z drug short half life - 2 hours Shortens onset and prolongs sleep duration Approved for only short term for insomnia.

Question 29

Zaleplon (Sonata)

Answer 29

Z drug short half life - 1 hour reduces onset time but does NOT increase sleep duration

Question 30

Eszopiclone (Lunesta)

Answer 30

Z Drug Half Life - 6 hours shortens onset and increases duration of sleep Used for long-term tx of insomnia and sleep maintenance

Question 31

Flumazenil (Romazicon)

Answer 31

Benzo Antagonist Blocks pharm actions of benzos but doesnt affect responses to GABA, barbiturates, etoh or general anesthetics short half life (1 hour) only given IV Only indication is to reverse benzo overdose

Question 32

The use of ____ as sedative-hypnotics has been replaced by benzodiazepines

Answer 32

The use of barbiturates as sedative-hypnotics has been replaced by benzodiazepines

Question 33

Barbiturates produce dose dependent depression of the ___. The low doses produce ____ and ____ and, as doses increase, progress to .....

Answer 33

CNS. The low doses produce anxiolysis and sedation and, as doses increase, progress to hypnosis, anesthesia, coma and death

Question 34

Barbiturates are also effective _____.

Answer 34

Barbiturates are also effective anticonvulsants.

Question 35

Barbiturates, especially those used as sedative-hypnotics produce pharmacokinetic and pharmacodynamics _____

Answer 35

tolerance. chronic administration shortens the half life

Question 36

Barbiturates also produce ___ and ____. These drugs were often abused and are listed as controlled substances schedule _____

Answer 36

physical dependence and addiction schedule II and III.

Question 37

Barbiturates depress _____. Barbiturates can be used as short term ____

Answer 37

respiration by depressing respiratory drive and the rhythmic character of respiration. anesthesia

Question 38

barbiturates also directly depress _____ muscle.

Answer 38

barbiturates also directly depress cardiac muscle.

Question 39

Barbiturates enhance ____-induced ____ conductance at the GABAA receptor.

Answer 39

Barbiturates enhance GABA-induced Cl- conductance at the GABAA receptor.

Question 40

Barbiturates bind to an allosteric site on the receptor and at low to intermediate doses, _____. At high doses barbiturates _____

Answer 40

Barbiturates bind to an allosteric site on the receptor and at low to intermediate doses, increase the duration of the GABA-induced Cl- channel opening. At high doses barbiturates directly activate the GABAA receptor.

Question 41

Buspirone

Answer 41

Barbiturate | Relieves anxiety without causing drowsiness or sedation

Question 42

Buspirone has a slow ____ and chronic therapy (approximately 1-2 week) is required before it is effective. Thus, it is more suited for ____, not ____

Answer 42

Buspirone has a slow onset of action and chronic therapy (approximately 1-2 week) is required before it is effective. Thus, it is more suited for generalized anxiety disorders, not acute anxiety states. Mechanism of Action:

Question 43

Buspirone is a partial agonist for the

Answer 43

5HT1A receptor

Question 44

Ramelteon (Rozerem)

Answer 44

Melatonin Agonist Hypnotic drug for pts having difficulty falling asleep. Shortens onset and increases duration of sleep.

Question 45

Ramelteon is a _____ receptor agonist.

Answer 45

Ramelteon is a melatonin MT1 and MT2 receptor agonist.

Question 46

Ramelteon is better at treating ___. It is not a ____ and has no ____

Answer 46

Sleep onset disorders controlled substance and has no abuse potential

Question 47

Tasimelteon (Hetlioz) agonist for ____ receptors. Used for ___ and ___ sleep disorders.

Answer 47

agonist for MT1 and MT2 receptors. Used for insomnia and circadian rhythm sleep disorders.

Question 48

Suvorexant (Belsomra) | A ___ receptor antagonist and was approved for the treatment of ____

Answer 48

A dual orexin receptor antagonist and was approved for the treatment of insomnia.

Question 49

diphenhydramine and doxylamine

Answer 49

2 Antihistamines over the counter sleeping aids. Half-lives of 9-10 hours and can produce daytime drowsiness