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)
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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
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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
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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)
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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
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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
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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
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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
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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