Sedatives and Hypnotics

Question 1

What do sedatives do?

Answer 1

Relieve anxiety, cause relaxation, mild CNS depressants

Question 2

What do hypnotics do?

Answer 2

Cause drowsiness and sleep

Question 3

What drug class do barbiturates fall under?

Answer 3

Schedule IV (USA)

Question 4

What are some characteristics of sedatives and hypnotics?

Answer 4

Orexin antagonists, melatonin agonists, anti-histamines

Question 5

What drugs treat anxiety?

Answer 5

Benzos = ‘aze’-pams

Question 6

What type of drugs treats seizure disorder?

Answer 6

Anti-convulsants
Longer-acting
Phenobarbital

Question 7

What type of drugs causes anesthesia?

Answer 7

Short-acting drugs
Thiopental, midazolam, trazolam

Question 8

What is the difference between sedatives and hypnotics?

Answer 8

Sedatives are for calming
Hypnotics are for sleeping

Question 9

How are sedatives classified?

Answer 9

Lipophilic class = faster onset due to rapid distribution
Longer-acting = anticonvulsants, muscle relaxants, anxiolytics
Shorter-acting = pre-anesthetic sedatives or to treat insomnia

Question 10

What does the presence of a triazole ring do?

Answer 10

Higher potency
Decreased duration of action
Binds GABA better

Question 11

What are the routes of administration of sedatives?

Answer 11

Oral, rectal, injection

Question 12

How are benzos and barbiturates distributed?

Answer 12

Benzos are less lipid soluble than barbituates, absorbed more slowly, slower onset of action
Both are highly bound to plasma proteins
Cross the placenta

Question 13

What metabolized sedatives?

Answer 13

Liver CYP450

Question 14

What do some sedatives do during metabolism?

Answer 14

Some produce active metabolites that prolong the duration of action

Question 15

What is the half-life of midazolam?

Answer 15

2 hours

Question 16

What is the half-life of diazepam?

Answer 16

100 hours

Question 17

How many half-lives are required for elimination?

Answer 17

4-5

Question 18

What types of people have decreased sedative metabolism?

Answer 18

Infants, pregnant women, those with liver disease, the elderly

Question 19

What is floppy infant syndrome?

Answer 19

Reduced muscle tone in infants that causes an inability to nurse that can last for months

Question 20

What is the mechanism of GABAa receptor binding of sedatives?

Answer 20

GABA binds between alpha and beta subunits
Benzos bind between alpha and gamma subunits in those receptors that contain these subunits

Question 21

What is the mechanism of benzo binding?

Answer 21

Bind to a site on the GABAa receptor which increases the frequency of chloride channel openings

Question 22

Where are GABA receptors with benzo binding sites located?

Answer 22

Limbic system, reticular activating system, cortex

Question 23

Do GABA receptors that control respiration have benzo sites?

Answer 23

Not many

Question 24

What is the mechanism of barbiturate binding?

Answer 24

More general effect on GABA receptors
When they bind, the enhance the affinity of the receptor for GABA, which increases the duration of time that they chloride channel is open which leads to neuronal inhibition
Can do this even when GABA isn’t present

Question 25

Benzos are allosteric _?

Answer 25

Modulators

Question 26

Barbiturates are allosteric _?

Answer 26

Activators

Question 27

What are the acute effects of sedatives?

Answer 27

Reduce muscle tone, impair coordination, and increase sedation and sleep -total sleep time increased, but deep sleep reduced Reduce anxiety, learning, memory, and can cause bizarre and uninhibited behaviours

Question 28

What are the common side effects of sedatives?

Answer 28

Drowsiness, lethargy, dizziness, confusion, reduced libido, diminished concentration, incoordination, and impairment of driving skills Prevent consolidation of short-term memories, especially alpha subunit-containing receptors Combined with alcohol to facilitate assault

Question 29

What are the effects of sedatives on a fetus?

Answer 29

Rapid entry, increased half-life due to under-developed liver Potential increased risk of cleft palate, floppy infant syndrome, withdrawal No risk of major malformations

Question 30

What are the drugs interactions of sedatives?

Answer 30

Synergistic with other depressants such as alcohol and opioids Interact with other drugs metabolized by CYP450 system

Question 31

How is sedative overdose treated?

Answer 31

With flumazenil Relatively rare for benzos by themselves Barbiturates have a low therapeutic index

Question 32

What rate does tolerance to sedatives happen at?

Answer 32

Different rates Tolerance for sedative effects = days to weeks Tolerance for anxiolytic effects = 3-4 months Does not develop for respiratory depression Users can require 40x the original dose

Question 33

What mechanisms for tolerance develop to barbees?

Answer 33

Cellular and metabolic mechanisms

Question 34

What are benzos well-known for?

Answer 34

Producing tolerance

Question 35

What are the chronic effects of sedative tolerance?

Answer 35

Associated with daytime fatigue, accidents, depression, violence, and increased overall mortality

Question 36

Is withdrawal worse for short-acting or long-acting sedatives?

Answer 36

Short-acting Should be medically supervised due to hyperexcitability

Question 37

What are the symptoms of sedative withdrawal?

Answer 37

Insomnia, anxiety, tremor, headache, confusion, difficulty concentrating

Question 38

What is sedative dependence like?

Answer 38

Physical and psychological dependence

Question 39

Are benzos or barbiturates more addictive?

Answer 39

Barbiturates are more addictive

Question 40

What is the abuse potential in sedatives like?

Answer 40

Lower than drugs like cocaine and opioids

Question 41

What does disinhibition of VTA DA-ergic neurons increase?

Answer 41

Increases DA release in the NAc

Question 42

What is GHB?

Answer 42

Date rape GABAb receptor agonist = Gi/o linked, inhibits Ca channels, activates GIRK Precursor of GABA, Glu, and Gly Dose dependent effects

Question 43

What do low doses of GHB do?

Answer 43

Stimulatory effect

Question 44

What do high doses of GHB do?

Answer 44

Binds to GABA receptors and can cause sedation