Sedatives and hypnotics

Question 1

What are the GABA-a agonists?

Answer 1

Benzos
Barbituates
Newer agents (zolpidem, zaleplon, eszopiclone)

Question 2

Where does Buspirone act?

Answer 2

5-HT1a partial agonist; used for anti-anxiety

Question 3

What does Ramelteon act on?

Answer 3

Melatonin receptor; agonist

Question 4

List some of the Benzos:

Answer 4

1. Diazepam
2. Chlordiazepoxide
3. Flurazepam
4. Oxazepam
5. Lorazepam

Question 5

List some of the Barbituates:

Answer 5

1. Phenobarbital
2. Pentobarbital
3. Gluthemide
4. Meprobemate

Question 6

What are the inhibitory NTs/receptors?

Answer 6

GABA, glycine, M2, M4, D2, D4

Question 7

What are the excitatory NTs/receptors?

Answer 7

Glutamate, M1, M3, M5, D1, D5, Nicotine, NE

Question 8

Where do benzodiazepines act, and do they plateau?

Answer 8

1. The GABA-alpha and gamma subunits

2. Yes, they plateau in CNS depression

Question 9

What increases the frequency of the chloride channels?

Answer 9

Benzos

Question 10

What increases the duration of the chloride channels?

Answer 10

Barbituates; can activate without GABA!

Question 11

Most rapid acting benzo?

Answer 11

Triazolam; followed by Diazepam. Benzos with long half-life also cause a more cumulative effect!

Question 12

Which benzos are used in the elderly or patients with liver dysfunction?

Answer 12

Lorazepam, Oxazepam, Temazapam

Question 13

What are the long elimination benzos, and what are they used for?

Answer 13

Chlorazepate, Diazepam, Flurazepam. Used for anti-anxiety; but cause more daytime drowsiness, falling, etc.

Question 14

What is the shortest elimination benzo, and a side effect?

Answer 14

Triazolam; more withdrawal effects

Question 15

Does phenobarbital cause p450 inhibition or induces it?

Answer 15

Induces p450! Can cause less jaundice in mothers, but don’t use in liver disease.

Question 16

What are withdrawal symptoms of benzos and how do you treat it?

Answer 16

Anxiety, CNS depression, insomnia; treat w long acting benzos or phenobarbital

Question 17

What is the antidote for benzos?

Answer 17

Flumazenil, has high affinity for GABA-a site, act as competitive antagonists.

Question 18

What is the most toxic benzo?

Answer 18

Alprazolam in overdose; cause respiratory depression. Treat w/ Flumazenil, but can cause withdrawal symptoms in long time use pts.

Question 19

What are the two benzos for alcohol withdrawl?

Answer 19

Chlordiazepoxide and Diazepam

Question 20

What benzo is used for seisures?

Answer 20

Lorazepam due to prediction of activity

Question 21

In what patients are barbituates contraindicated in?

Answer 21

Patients with a history of poryphria

Question 22

What is used to treat an acute panic attack?

Answer 22

Alprazolam

Question 23

What are benefits of using buspirone in anxiety?

Answer 23

Relieves anxiety without sedative, hypnotic, or euphoric effects, no anti-convulsant or muscle relaxant properties, and no dependence

Question 24

What are the preferred agents for insomnia?

Answer 24

Benzos and ZZesZ’s; can also use Ramelteon

Question 25

How do benzos and barbituates change sleep properties?

Answer 25

1. Decrease latency of falling asleep
2. Increase stage 2
3. Decrease stage 4
4. Decrease REM

Question 26

What’s a side effect of benzos in insomnia?

Answer 26

Anterograde amnesia; and daytime sedation with long half life benzos.

Question 27

How do the ZZesZ’s affect sleep?

Answer 27

1. Zaleplon decreases sleep latency; T1/2 = short
2. Eszopiclone increases total sleep time; T1/2 = 6hr
3. Zolpidem most prescribed

Affect sleep architecture less; and not as strong binding to GABA thus less effect on cognitive function

Question 28

What is Ramelteon used for?

Answer 28

MT1 & MT2 agonist used for sleep problems, decreases latency with no affect on sleep architecture; safe to use in COPD patients

Question 29

What are contraindications of Ramelteon and ADRs?

Answer 29

1. Can’t use w/ CYP1A2 (ciprofloxacin, fluvoxamine); use with caution in liver damage pts
2. Decrease testosterone, increase prolactin