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Flashcards in Sedatives Deck (61):
1

What NT mediate NREM sleep

GABA
Adenosine

2

What regulates REM sleep

Cholinergic cells turn REM on
Noradrenergic cells turn REM off

3

What facilitates arousal and wakefulness

Ascending reticular activating system and posterior hypothalamus
-NE, ACh, histamine, Substance P, corticotropin releasing factor

4

What is dopamine's effect on sleep

Dopamine is alerting!
Low dopamine promotes sleepiness

5

What are important sleep wake concepts

Young adults have difficulty falling asleep
Middle aged and elderly have trouble staying asleep
Those with insomnia often also have anxiety, depression, or substance abuse disorders- and use nonRx drugs or alcohol to treat (esp. chronic insomnia)

6

Transient insomnia may be 2/2

Separation
Death in family
Job change
College exams

7

Common etiologies of insomnia are

Situational
Medical: CV, respiratory, chronic pain, endocrine, GI, Neuro, pregnancy
Psych
Pharm induced: anticonvulsants, central adrenergic blockers, diuretics, SSRI, steroids, stimulants

8

Goals of treating insomnia are

Correct underlying sleep complaint
Consolidate sleep
Improve daytime fxn
Avoid ADE from select therapies

9

What stimulus control procedures can you attempt as non-pharm Tx of insomnia

Establish regular times to wake up and go to sleep
Sleep only as much as you need to feel rested
Go to bed only when sleepy, no reading or TV in bed
Avoid trying to force sleep
Avoid blue-spectrum light
Avoid daytime naps
Schedule worry time during the day

10

What are sleep hygiene recommendations

Exercise 3-4x week, not close to bedtime
Create comfortable sleep environment (avoid temp extremes, loud noises, and light)
D/c alcohol, nicotine, and caffeine
Avoid large quantity of beverage at night
Do something relaxing you enjoy before bed

11

What effect do sedatives have

Reduce anxiety and exert calming effect; Take lowest dose possible to minimize degree of CNS depression

12

What effect do hypnotics have

Produce drowsiness and encourage onset and maintenance of state of sleep
More pronounced CNS depression than sedatives

13

What are sedatives and hypnotics used for

*Relief of anxiety and insomnia
sedation and amnesia for surgical procedures
Tx epilepsy and seizures
*Control of ethanol or other withdrawal states
Muscle relaxation in some neuromuscular d/o
Diagnostic aids or Tx in psych

14

What is the good thing about benzos vs barbituates and alcohol

Benzos will typically level off at a level of anesthesia as the dose increases
Barbituates and alcohol can send you into a coma

15

What are the PK of sedatives and hypnotics

Absorption/Distribution: Lipid soluble, absorbed from GI tract, good distribution to brain
Metabolism/Excretion: metabolized before elimination by hepatic enzymes.

16

What are the MC used drugs for insomnia

*Eszopiclone, Zaleplon, Zolpidem* (new, non-benzo GABA agonists; sedatives only)
Estazolam, Flurazepam, Quazepam, Temazepam, Triazolam (benzos; sedative, anxiolytic, muscle relaxer, anti-convulsant)

17

What is the MOA of benzos

Benzo receptor is in the thalamus, limbic structures, and cerebral cortex
Binding their receptor facilitates GABA in creating inhibition

18

Benzos are used for

acute anxiety
panic attack
GAD
insomnia
skeletal muscle relaxer
seizure disorder

19

PK of benzos is

Hepatic metabolism
Active metabolites
CNS depression
2-4 hr half life

20

Benzo toxicity can lead to

Extension of CNS depressant actions
Tolerance
Dependence

21

Which benzos do NOT have active metabolites

Lorazepam
Oxazepam
Zolpidem

22

ADE of benzos are

high dose: daytime sedation, psychomotor incoordination, cognitive deficit, prolonged half life in elderly
Tolerance over time
Anterograde amnesia (no memory after taking dose)
Rebound insomnia after abrupt d/c
-take lowest dose possible to min rebound insomnia and amnesia

23

How long do most benzos maintain hypnotic efficacy

1 month

24

FDA requires this warning label on benzos AND barbiturates

Caution regarding anaphylaxis, facial angioedema, complex sleep behaviors

25

What substances interact with benzos MC

Alcohol
Antihistamines
Antipsychotics
Opioid analgesics
TCA

26

OD on benzos can cause

Potentially lethal respiratory and CV depression; more likely w/ alcohol, barbs, and carbamates; less common with new agents like zolpidem

27

What can reverse the CNS depressant effects of benzos

Flumazenil!
but no benefit on OD of other sedatives or hypnotics

28

How does Flumazenil work

Antagonist at benzo receptor site on GABA receptor (aka bring you up!)
IV but short half life

29

Toxicities of flumazenil ae

agitation
confusion
possible withdrawal syndrome

30

How do newer hypnotics work (zolpidem, zaleplon, eszopiclone)

they exert CNS effects via interaction w/ BZ1 or W1 benzo receptors.
They bind more selectively than benzos and bind only a1 GABA subunit near the benzo site (also facilitate Cl channel opening)
They are not benzos, but flumazenil still works on them
May cause dependence

31

What are the barbiturates

Amobarbital
Butabarbital
Pentobarbital
Phenobarbital
Secobarbital
Thiopental

32

How do barbiturates work

Facilitate and promote inhibitory effect of GABA and glycine- binds to different site than benzos
May also block excitatory glutamic acid and sodium channels
Flumazenil does NOT work on them

33

Barbiturates are used for

Anesthesia (thiopental)
Insomnia and sedation (secobarbital)
Seizure d/o (phenobarbital)

34

What is the PK of barbiturates

Oral activity
Hepatic metabolism
Induce metabolism of many drugs
4-6o hr half life

35

Toxicities of barbiturates are

CNS depressant actions
tolerance
high dependence

36

What effect do baribturates and carbamates have on the liver

induce liver enzymes= cause drug interactions
Precipitate acute intermittent porphyria
Chloral hydrate can increase anticoag effect

37

What is the role of antihistamines in sedation

They have sedating properties and are usually effective in treating mild insomnia
*Diphenhydramine and Doxylamine preferred*
But, tolerance can develop, and increasing does does not produce a linear effect.

38

ADE of antihistamines are

anticholinergic ADE!
blind, dry, red, hot

39

How do antidepressants work in sedation

Amitriptyline, Doxepin, and Nortriptyline are sedating antidepressants that induce sleep continuity
*Low dose doxepin is FDA approved for insomnia
Mirtazapine promotes sleep
Trazodone improves sleep continuity at bedtime

40

ADE of antidepressants are

daytime sedation
anticholinergic ADE
Mirtazapine: also weight gain
Trazodone: carryover sedation, a-adrenergic block (orthostais, worse in elderly), priapism

41

Who is Trazodone good for

Those prone to substance abuse- does not cause dependence
Those with SSRI and buproprion induced insomnia

42

What is Suvorexant

recently approved dual Orexin A and B receptor antagonist
Instead of inducing sleepiness, it turns off the wake signaling! Taken at bedtime

43

What is orexin (hypocretin)

Excitatory action on 5-HT, histamine, ACh, and DA
Facilitatory role on GABA and glutamate induced neurotransmission
Has a primary role in sleep and arousal; energy regulation

44

MC ADE of Suvorexant are

Somnolence
Sleep paralysis, cataplexy, other narcolepsy-like Sx

45

What is Ramelteon

Melatonin receptor agonist approved for sleep-onset insomnia
Selective MT1 and 2 receptor to help melatonin regulate circadian rhythm and sleep onset
-Forms active metabolite via CYP1A2

46

What are ADE of ramelteon

HA, dizziness, and somnolence

47

Who is Ramelteon good for

Those with hx of substance abuse- not a controlled substance!
Those w/ COPD and sleep apnea

48

What is Valerian

Herb with sedative-hypnotic properties for those w/ insomnia (can drink as tea at bedtime)
MOA may involve increasing GABA, but not fully known
-bad? it smells like gym socks

49

What drugs do you do in different states

Anxiety: Alprazolam, Clonazepam
Sleep d/o: Estazolam, Flurazepam, Triazolam, Zolpidem, Zaleplon, Eszopiclone
Induce anesthesia: Thiopental
Component of anesthesia: diazepam, midazolam
Seizure d/o: Clonazepam, phenobarbital
Bipolar: Clonazepam
Muscle spasticity: diazepam
Managing withdrawal (longer acting): Chlordiazepoxide*, diazepam

50

What do you need in order to diagnose anxiety disorder

overt anxiety or overt manifestation of a copine mechanism
Not just an adjustment disorder
Somatic Sx (dyspnea, palpitations, paresthesias)
Not 2/2 physical disorder or psych condition or drug abuse

51

What medical illnesses are associated with anxiety

Cardiovascular: angina, arrhythmia, CHF, HTN
Endocrine: cushings, DM, hyper/hypothyroid, hypoglycemia
GI: IBS, IBD, PUD
Neuro: migraine, Sz, stroke
Resp: asthma, COPD, PE, PNA
anemia, cancer, SLE

52

What are some drug classes associated with anxiety Sx

anticonvulsants
antidepressants
antiHTN
antibiotics
bronchodilators
corticosteroids
dopamine agonists
herbals
ecstasy, marijuana
NSAIDs
caffeine, cocaine, amphetamines, nicotine
Sympathomimetics
thyroid hormones

53

What is first line for GAD

Duloxetine
Escitalopram
Paroxetine
Sertraline
Venlafaxine

54

What is first line for panic disorder

SSRI
Venlafaxine

55

What is first line for social anxiety disorder

Escitalopram
Fluvoxamine
Paroxetine
Sertraline
Venlafaxine

56

What is Buspirone

a selective anxiolytic;
Partial 5HT agonist +/- D2 agonist
Partial 5HT1a agonist
Minimal CNS depressant effects; can still drive while on it
No anticonvulsant or muscle relaxant properties
Safe in pregnancy!
Minimal dependence with long term use
Little rebound anxiety

57

PK of Buspirone are

Slow onset (1 week)
Forms active metabolite
Interacts with CYP3A4 inducer and inhibitor

58

Who is Buspirone good for

Generalized anxety disorder
Less effective for panis disorder

59

ADE of Buspirone are

GI distress
tachycardia
paresthesia

60

What drugs treat panic disorder (specifically)

SSRI: Citalopram, Escitalopram, Fluoxetine, Fluvoxatine, Paroxetine, Sertraline
SNRI: Venlafaxine
Benzo: Alprazolam, Clonazepam, Diazepam, Lorazepam
TCA: Imipramine
MOI: Phenelzine

61

What type of alprazolam is best for panic disorder

Xanax XR! it has a longer half life so you dont get panic Sx when you stop taking it like you do with regular xanax