09.03 - BzRA Hypnotics

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Sleep: Neurobiology, Medicine, and Society

61 calificaciones

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University of Michigan

Sleep: Neurobiology, Medicine, and Society

61 calificaciones

The objective of this course is to give students the most up-to-date information on the biological, personal, and societal relevance of sleep. Personal relevance is emphasized by the fact that the single best predictor of daytime performance is the quality of the previous night's sleep. The brain actively generates sleep, and the first section of the course is an overview of the neurobiological basis of sleep control. The course provides cellular-level understanding of how sleep deprivation, jet lag, and substances such as alcohol, ,caffeine, and nicotine alter sleep and wakefulness. The second section of the course covers sleep-dependent changes in physiology and sleep disorders medicine. Particular emphasis will be placed on disorders of excessive sleepiness, insomnia, and sleep-dependent changes in autonomic control. Chronic sleep deprivation impairs immune function and may promote obesity. Deaths due to all causes are most frequent between 4:00 and 6:00 a.m., and this second section of the class highlights the relevance of sleep for preventive medicine. The societal relevance of sleep will be considered in the final section of the class. In an increasingly complex and technologically oriented society, operator-error by one individual can have a disastrous negative impact on public health and safety. Fatigue-related performance decrements are known to have contributed as causal factors to nuclear power plant failures, transportation disasters, and medical errors.

De la lección

Unit 09 - Medicine: Treatments for Insomnia - (Standard Track)

Unit 9 further continues the Medicine section of the course with a lecture from J. Todd Arendt, Ph.D. on the range of available treatments for Insomnia.

09.01 - Behavioral and Pharmacological Treatments for Insomnia7:10

09.02 - Treatment Options for Insomnia4:36

09.03 - BzRA Hypnotics5:43

09.04 - Abuse Liability of Hypnotic Agents5:18

09.05 - Pharmacological Treatments for Insomnia3:57

09.06 - Nonpharmacological Treatments for Insomnia5:31

09.07 - How CBT-I Works6:27

09.08 - Pharmacological Treatments for Insomnia Part III6:26

09.09 - Summary 2:49

Conoce a los instructores

Ralph Lydic, Ph.D.
Professor Emeritus, Molecular and Integrative Physiology, Professor Emeritus, Anesthesiology
University of Michigan Medical School
Helen Baghdoyan, Ph.D.
Professor Emeritus, Anesthesiology, Professor Emeritus, Pharmacology, Professor of Psychiatry
University of Michigan Medical School

Let's start with the benzodiazepine receptor agonist hypnotics.

This table summarizes the newer benzodiazepine receptor agonist hypnotics

that are commonly used with people with insomnia.

Let's start with the benzodiazepine receptor agonist hypnotics.

The most commonly used newer benzodiazepine receptor hypnotics

are indicated in this table.

You can see they include Ambien or Zolpidem,

Ambien CR or Zolpidem MR,

Sonata or Zaleplon, Lunesta or Zopiclone,

and that newest agent, Intermezzo,

which is an under-the-tongue formulation of Zolpidem.

The next column indicates both the adult dosage and the geriatric dosage.

The next three columns indicate the pharmacokinetics or actions of the medications.

The T-Max indicates how long it takes for

maximum availability of the medication to occur in one's system.

You could see that they have a relatively fast onset of

action from about 35 minutes to up to two hours.

Their half lives range from about one hour to five to seven hours.

And as a result, their duration of action can range from short to intermediate,

and in some cases ultra short.

Sonata, for example, has

an ultra short duration of action so that it can be used not just

at the beginning of the night but also the end of the night or the middle of the night.

Finally, the last column indicates the indications for the medications.

Ambien, for example, is used for sleep onset only.

Sonata is used for both onset and maintenance.

And you can see Lunesta can be used also for onset and maintenance.

It's important to note that these medications all act

at the GABBA A benzodiazepine receptor complex,

which is thought to be their putative mechanism of action.

So, how do these benzodiazepine receptor agonists work?

There have been two large scale meta-analyses that have looked at the effects

of benzodiazepine receptor agonists largely the older benzodiazepines and Ambien.

This table shows the effects and the outcomes of these meta-analyses.

You could see the far most column

indicates variety of sleep parameters that we think are important,

sleep latency, wake after sleep onset,

number of awakenings, total sleep time, and sleep quality.

These would be subjective ratings of improvement on these various parameters.

The numbers in the table indicate effect sizes,

which are the difference in standard deviation units between

a treated individual and an individual from a controlled condition with,

by convention, a small effect size being between 0.2 and 0.5,

a medium effect size between 0.5 and 0.8,

and a large effect size greater than 0.8.

From looking at the table, you can see that

these benzodiazepine receptor agonist hypnotics

produce moderate to large effect size on these subjective sleep parameters.

One important factor to consider is that the average treatment length for

the studies in the first meta-analysis was

roughly 35 days and the average length from the second was 14 days.

So, it's important to note that these have largely been evaluated under acute conditions,

that is only for short periods of time.

Lunesta is one exception to that rule.

There have been two large-scale randomized controlled trials of Lunesta.

This slide shows the results from one of them.

In this particular study,

almost 800 individuals with primary insomnia were

randomized to receive either Lunesta 3 milligrams,

or placebo nightly for six consecutive months.

The graph shows the effects of the medication versus placebo on

wake after sleep onset which is middle of the night wakefulness.

You can see from the graph that Lunesta in yellow outperformed placebo

starting at month one and these benefits were

sustained across all six months of the study.

So, the results of both randomized controlled trials indicate that Lunesta,

when taken nightly under randomized controlled conditions,

has benefits on sleep maintenance insomnia for at least six months.

There's at least one open label study that additionally indicates that

the effects are beneficial up to one year in length.

What about if you take the medications not nightly but on a non-nightly basis?

Many patients are instructed to use the medications not every night but only when they

have insomnia difficulties or to sparingly use them under only certain conditions.

This study evaluated the effects of non-nightly use of

Zolpidem or Ambien in individuals with primary insomnia.

In this study, nearly 200 individuals with primary insomnia were

assigned to either intermittent Zolpidem or placebo.

Intermittent was they could use the medication or

placebo a minimum of three days and a maximum of five days.

The graph shows the effects on sleep latency,

that is time fall sleep,

when individuals took the pill on the left,

and when they didn't take the pill on the right.

You could see that relative to placebo,

when individuals took the active Ambien medication,

it benefited ability to fall asleep over the 12 weeks of the study.

However, when they didn't take the medication,

sleep latency returned to baseline and they were no different from placebo.

Results from this particular study indicate that individuals who use Zolpidem on

a non-nightly basis will benefit when taking the pill but there's

no carry over effect to nights when they don't take the medication.

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