Sleep Wake

Question 1

Which location of the brain and which neurotransmitter are associated w/ sleep-wake disorders?

Answer 1

Cannot be localized to area of brain or neurotransmitter

Question 2

Numerous neurotransmitters mediate NREM sleep including ____ and _____.

Answer 2

• y-aminobutyric acid (GABA)
• adenosine

Question 3

REM sleep is turned on by ________.

Answer 3

Cholinergic cells

Question 4

REM sleep turned off by _________.

Answer 4

Noradrengeric cells

Question 5

What 2 things facilitate arousal and wakefullness?

Answer 5

• Ascending reticular activating system
• Posterior hypothalamus

Question 6

An increase in ____ has an alerting effect

A decrease in ____ promotes sleepiness

Answer 6

Dopamine

Question 7

• Neurochemicals involved in wakefullness include _______ and _______ in the cortex

and

• ______ and ______ such as substance P and corticotropin releasing factor in the hypothalamus.

Answer 7

• norepinephrine & acetylcholine
• histamine & neuropeptides

Question 8

• Which age group has difficulty falling asleep?
• Which 2 age groups have middle of the night awakening or early morning awakening?
• 40% of individuals w/ insomnia also have concurrent ____ _____. along w/ anxiety, depression, or substance abuse.

Answer 8

• Young adults
• Middle aged and elderly adults
• Psychiatric disorder

Question 9

Significant percentrage of those w/ insomnia use _____ or ____ to self treat.

Answer 9

• Nonprescription drugs
• Alcohol

Question 10

Complaint of transient / short term insomnia is usually due to what?

Answer 10

Recent stressors

• separation
• death in family
• job change
• college exams

Question 11

Chronic insomnia is frequently comorbid w/ ____ or ______.

Answer 11

• psychiatric or medication conditions

Question 12

3 common etiologies of insomnia

Answer 12

• Situational (work/financial stress)
• Medical (cardiovascular, respiratory, endocrine)
• Pscyhiatric (mood disorders, anxiety disorders, substance abuse)

Question 13

What drugs interfere w/ REM sleep?

Answer 13

• Anticonvulsants
• Central adrengergic blockers
• Diuretics
• Selective serotonin reuptake inhibitors
• Steroids
• Stimulants

Question 14

What is the goal of drug therapy for insomnia?

Answer 14

Lowest possible dose for shortest possible time period

Question 15

2 types of medications for insomnia

Answer 15

Sedation & Hypnotic

Question 16

• Effective sedative (anxiolytic) agent should reduce anxiety and exert a calming effect

Answer 16

Sedation meds for insomnia

Question 17

Hypnotic drug should produce drowsiness and encourage the onset & maintenance of a state of sleep

Answer 17

Hypnotic meds for insomnia

Question 18

3 clinical uses of Sedative-Hypnotics

Answer 18

• Relief of anxiety
• Insomnia
• For control of ethanol or other sedative hypnotic withdrawal states

Question 19

Which sedative-hypnotics lead to coma/death?

Answer 19

Barbiturates / alcohol

Question 20

Which sedative-hypnoticc drugs have a ceiling effect and does not work for surgical anesthesia

(no coma/death)

Answer 20

Benzodiazepines

Question 21

Absorption/Distribution of which drug?

• lipid soluble (crosses BBB)
• absorbed well from GI tract
• good distribution to brain

Answer 21

Sedative-Hypnotic drugs for Insomnia

Question 22

Metabolism/Excretion of which drug?

• Metabolized before elimination from body
• mainly by hepatic enzymes
• active and inactive metabolites

Answer 22

Sedative-Hypnotic Drugs for Insomnia

Question 23

What is the most commonly used tx for insomnia?

Answer 23

Benzodiazepines

Question 24

What are the 3 “newer” non-benzodiazepines GABA agonists which possess only sedative properties?

Answer 24

• Eszopiclone
• Zaleplon
• Zolpidem

Question 25

**What type of drugs are these?** * Estazolam * Flurazepam * Quazepam * Temazepam * Triazolam

Answer 25

**Benzodiazepines** | (most common used tx for insomnia)

Question 26

Traditional benzodiazepines have which 4 properties?

Answer 26

* Sedative * Anxiolytic * Muscle relaxant * Anticonvulsant properties

Question 27

Which benzodiazepine is a "true hypnotic?"

Answer 27

Flurazepam

Question 28

Which benzodiazepine can lead to homicidal ideation?

Answer 28

Triazolam

Question 29

The receptors for benzodiazepines are located in which 3 areas of the brain?

Answer 29

* Thalamus * Limbic structures * Cerebral cortex

Question 30

* Binding of benzodiazepines facilitates the inhibitory actions of \_\_\_\_\_. * What does BZDRA stand for?

Answer 30

* GABA * Benzodiazepine receptor agonists

Question 31

**What should you prescribe for:** * Acute anxiety states * Panic attacks * Generalized anxiety disorder * Insomnia * Skeletal muscle relaxation * Seizure disorders

Answer 31

Benzodiazepines

Question 32

**PK of which drug?** * Hepatic metabolism * Active metabolites * Additive CNS depression w/ many drugs * **Half lives:** 2-4 hrs

Answer 32

Benzodiazepines

Question 33

3 toxicities of Benzodiazepines

Answer 33

* Extension of CNS depressant actions * Tolerance * Dependence liability

Question 34

Which benzo was the 1st benzo on the market and was drug of choice for alcohol withdrawal?

Answer 34

Chlordiazepoxide

Question 35

Which benzo is the "active metabolite?"

Answer 35

Oxazepam

Question 36

Which benzo has active metabolites and erratic bioavailability from IM injection

Answer 36

Diazepam

Question 37

Which benzo has active metabolites w/ long half lives?

Answer 37

Flurazepam

Question 38

Which 3 benzos have no active metabolites?

Answer 38

* Lorazepam * Oxazepam * Zolpidem

Question 39

**BZDRA adverse drug events** _High doses w/ long/intermediate elimination half lives have a greater potential to:_ * produce daytime sedation * psychomotor incoordination * cognitive deficits * _half lives are shortened or prolonged in older patients?_

Answer 39

Prolonged

Question 40

* Most traditional benzodiazepines maintain hypnotic efficacy for ___ month. * Tolerance can develop w/ time. How many days?

Answer 40

* 1 * 10-14 days

Question 41

2 effects from BZDRA ADEs

Answer 41

* Anterograde amnesia * Rebound insomnia

Question 42

* What has been reported the most w/ use of BZDRAs? * And is more likely to occur w/ short acting agents

Answer 42

**Anterograde amnesia** (impairment of memory and recall of events occurring after the dose is taken has been reported with most )

Question 43

Increased wakefulness beyond baseline amounts that last for a few nights after abrupt discontinuation

Answer 43

Rebound insomnia

Question 44

How can you prevent / minimize rebound insomnia and avoid adverse effects on memory w/ use of BZDRAs?

Answer 44

Use lowest effective dose

Question 45

The FDA requires BZDRA labeling to include a caution regarding what 3 things?

Answer 45

* **anaphylaxis** * **facial angioedema** * **complex sleep behaviors** (sleep driving, phone calls, sleep eating)

Question 46

What is the most common type of drug interaction w/ sedative-hypnotics?

Answer 46

CNS depression

Question 47

What are the 5 "interacting substances" w/ sedative-hypnotics?

Answer 47

* Alcohol * Antihistamines * Antipsychotics * Opioid analgesics * Tricyclic antidepressants

Question 48

Overdose on BZDRAs / sedative-hypnotics can result in what 2 things?

Answer 48

* severe respiratory depression * cardiovascular depression

Question 49

Potentially lethal effects of BZDRAs are more likely to occur w/ what 3 substances as compared to benzodiazepines or newer hypnotics such as zolpidem?

Answer 49

* alcohol * barbiturates * carbamates

Question 50

\_\_\_\_\_ may reverse CNS depressant effects of benzodiazepines, eszopiclone, zolpidem, & zaleplon

Answer 50

Flumazenil

Question 51

\_\_\_\_\_ is a reversing agent for BZDRAs

Answer 51

Flumazenil

Question 52

What are the 3 effects/toxicities of Flumazenil?

Answer 52

* Agitation * Confusion * Possible withdrawal syndrome