Pharmacotherapy of sleep - French

Question 1

Ramelton.

What is the mode of action?
Where are the receptors located.

Answer 1

Agonist at melatonin MT1 (induce sleepiness) and MT2 receptors (regulation of circadian rhythms) in suprachiasmatic nucleus of hypothalamus.

Question 2

Triazolam

Answer 2

Short half life (1.5-5 hrs), so can decrease sleep latency, but may see rebound insomnia. No daytime drowsiness.

Dose reduction required in elderly.

Question 3

Flurazepam

Pharmacokinetics (t1/2)

Answer 3

Long t1/2 with active metabolite (75-90 hrs), see effect at same dose for 28 consecutive days (i.e., little tolerance). Can accumulate in elderly due to impaired hepatic clearance leading to daytime sedation (“hangover”) / overdosage (t1/2 extended to 120-160 hrs).

Question 4

Temazepam

Pharmacokinetics (t1/2)

Answer 4

Intermediate t1/2 (9-13 hrs), slowly absorbed, peak concentration at 2-3 hrs, thus minimal effect on latency to sleep onset.

Question 5

True or False: BDZ open the GABA channel in the absence of GABA.

Answer 5

False. BDZs enhance channel opening in presence of GABA only [Summary slide 108]

[Handout: Binding of benzodiazepines (or non-BDZs like zolpidem) to the gamma subunit or an to an area of the alpha subunit influenced by the gamma unit facilitates the process of GABA channel opening, but does NOT directly initiate chloride current as does higher levels of barbiturates.]

Question 6

GABA receptor complexes with alpha1 subunits are located primarily in the ____, where agonist activity causes _____ at low doses and ____ at high doses.

Answer 6

cortex;

sleep

amnesia, additive CNS depression

Question 7

These two Z drugs have rapid oral absorption and short durations of action (6-8 hours).

Answer 7

Zapleon (t1/2 ~1 hr)

Zolpidem (t1/2 ~2hrs)

Question 8

This Z drug has a different structure, and a much longer duration of action.

Answer 8

Eszopiclone (t1/2 6 hrs)

Question 9

This Z drug is useful for reducing sleep latency but not decreasing nighttime awakenings.

Answer 9

Zapleon

Question 10

This Z drug is useful for reducing sleep latency and nocturnal awakenings. It is the most widely prescribed sleep aid (#16 overall).

Answer 10

Zolpidem (Ambien)

Question 11

This Z drug is the least likely to cause tolerance, and has the longest half life of the non-BDZ agents.

Answer 11

Eszopiclone (Lunesta)

Question 12

What non-GABA sleep aid might you prescribe to a patient suffering from depression who is a recovering alcoholic and has a history of substance abuse?

Answer 12

Trazodone.

Question 13

Before elimination, Diazepam undergoes P450 interactions forming an active metabolite called _____.

Answer 13

Oxazepam.

Question 14

These three BDZs are NOT metabolized by P450 ezymes.

Answer 14

Oxazepam
Temazepam
Lorazepam

Question 15

Your patient is worried about a lack of REM sleep. Which class of agent would you NOT prescribe?

Can you prescribe a Z drug

Answer 15

BDZ. decrease REM sleep.

Z drug is indicated.

Question 16

Your patient is worried about a lack of “slow-wave” sleep. Which class of agent would you not prescribe?

Can you prescribe a Z drug?

Answer 16

BDZ. decrease slow wave sleep.

Z drug is indicated.

Question 17

Fatal overdoses are extremely rare in BDZ/Z drugs unless taken in combination with ____.

Answer 17

other CNS depressants (e.g., alcohol)

Question 18

If you had to prescribe a BDZ to an elderly patient as a sleep aid, would you likely use Temazepam, Flurazepam, or Triazolam?

Answer 18

Triazolam - quick onset, oral absorption, accumulation in elderly

TEMAZEPAM - Intermediate half-life –> less nocturnal awakenings

Flurazepam - longest half-life - accumulation in elderly  daytime sedation-overdosage possible