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Integrated Drug Structure, Action, and Therapeutics > Anxiolytics and Sedatives > Flashcards

Anxiolytics and Sedatives Flashcards

1
Q

What drugs reduce anxiety?

A

Anxiolytics

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2
Q

What drugs induce sedation and reduce anxiety?

A

Sedatives

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3
Q

What drugs induce drowsiness and sleep from which one can be aroused?

A

Hypnotics

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4
Q

When does anxiety become a disorder?

A

When it begins to interfere with normal life. When it is no longer useful as a warning system.

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5
Q

What part of the brain is used in the limbic system when anxiety and fear is involved?

A

The amygdala

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6
Q

What is the ascending arousal system?

A

It is the state of CNS activity and reactivity leading from sleep to wakefulness to excitement to panic . This is opposed to to the GABA system which promotes sleep.

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7
Q

What pathway needs to be shut off in order to sleep?

A

The ascending arousal pathway

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8
Q

What small molecules are used in the regulation of sleep?

A 
Glutamate
NE
ACh
5-HT
DA
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9
Q

What aa is used in the regulation of sleep?

A

GABA

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10
Q

What neuropeptide is used in the regulation of sleep?

A

Orexin/hypocretin

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11
Q

What else is present in the ascending arousal pathway?

A

Histamine. Specifically H1 (H1 antagonist has strong sedating and anti-emetic effects. H2 doesn’t cross BBB and has low CNS effects)

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12
Q

What biological components are important in the arousal system?

A

Biological clocks
Pineal gland (releases melatonin)
Suprachiasmic Nucleus - master clock in hypothalamus
Retina - light (synchronizes the endogenous clock)

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13
Q

What are some subjective features that are linked with anxiety?

A 
Apprehension
Worry
Anticipation
Fear
Jumpiness
Restlessness
Impaired concentration
Comorbid depression
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14
Q

What are some physiological features that are linked with anxiety?

A

tension, fatigue, tremor
dry mouth, difficulty swallowing
hyperventilation
palpitations

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15
Q

GAD

A

generalized anxiety disorder - excessive anxiety and worry most of the time about life

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16
Q

Panic disorder

A

discrete periods of intense fear

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17
Q

phobic anxiety disorder

A

irrational fear that interferes with normal behavior

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18
Q

SAD

A

social anxiety disorder

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19
Q

OCD

A

obsessive compulsive disorder (persistent thoughts/ideas and impulses for intentional behaviors)

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20
Q

PTSD

A

normal reaction to abnormal event

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21
Q

acute stress disorder

A

reaction to recent stress, lasts less than 6 months

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22
Q

What is the goal for a good anxiolytic?

A

A non-sedating drug that works against anxiety

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23
Q

Benzodiazepines

  • mechanism
  • advantages
  • disadvantages
A
  • GABAa receptors in the limbic system that control emotional behavior
  • rapid onset, high therapeutic index, effectiveness for acute and other form of anxiety (not GAD)
  • tolerance, CNS depressant/sedative, impaired cognition, additive alcohol danger, dependency
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24
Q

What do BZD’s do to the GABA receptor?

A

They increase the frequency of channel opening = enhanced inhibition.

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25
Q

Is potency or efficacy of GABA increased by BZDs?

A

Potency because the binding affinity of GABA for its receptor is increased when BZD binds to its spot.

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26
Q

What are the short-acting BZDs?

A

Chlorazepate

Oxazepam

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27
Q

What are the intermediate-acting BZDs?

A

Oxazepam
alprazolam
lorazepam

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28
Q

What are the long-acting BZDs?

A

Chlordiazepoxide
diazepam
clonazepam

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29
Q

What other things treat anxiety, but not acutely?

A

CBT
SSRI’s
SNRI’s
buspirone (5HT1A selective agonist)

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30
Q

What non-BZD can treat performance anxiety acutely?

A

A beta-blocker such as propranolol

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31
Q

What was the first non-BZD approved for GAD?

A

buspirone

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32
Q

What drug cannot be used in those with panic attacks?

A

buspirone - it may exacerbate (possibly due to metabolite that is has an alpha2 antagonist effect that heightens NE response)

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33
Q

Does buspirone have a risk of dependency?

A

No

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34
Q

What is the mechanism of action for buspirone?

A

5HT1a receptor agonist. Over time may desensitize. Also dopamine receptor antagonist. Weakens serotonergic transmission, especially in the Raphe nuclei.

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35
Q

What type of medication works better in the first 4 weeks for anxiety?

A

BZD’s. Buspirone works moderately well until 4 weeks hit, and antidepressants work the least effectively until 4 weeks hit. Then they all work about the same.

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36
Q

What are sedative-hypnotic drugs used for?

A 
Anxiety
Insomnia
Sedation and amnesia
Component of balanced anesthesia
Epilepsy/seizures
muscle relaxant
Withdrawal from addictive substances
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37
Q

What are the types of sedatives/hypnotics?

A

BZD’s (triazolam, estazolam, temazepam, flurazepam and quazepam used for insomnia)
Z-drugs: zaleplon, zolpidem, eszopiclone
Barbiturates

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38
Q

What is the length of action of this barbiturate? Methohexital.

A

ultrashort (5-15 minutes) - for induction of anesthesia

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39
Q

What is the length of action of these barbiturates? Amobarbital, pentobarbital, secobarbital.

A

short-acting (3-8 hours) for insomnia or pre-operative sedation

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40
Q

What is the length of action of this barbiturate? phenobarbital.

A

Long-Acting (days) for seizures

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41
Q

Can GABA receptor activators be used for anesthesia?

A

Yes

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42
Q

What is the main difference between barbiturates/non-BZD hypnotics and BZD/Z-drugs?

A

Death can result from too much drug alone in the barbiturates/non-BZD hypnotics.

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43
Q

What anxiolytics/sedatives/hypnotics bind to GABAa receptors? What do they do?

A 
BZD
barbiturates
Z-drugs
chloral hydrate
meprobate
They increase the receptor activity as positive allosteric modulators.
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44
Q

How many subunits does GABA have?

A

5

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45
Q

What are the two main combinations?

A

2 alpha, 2 beta, 1 gamma

2 alpha, 2 gamma, 1 beta

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46
Q

What is the BZD antagonist that can reverse overdose but has no clinical effect alone?

A

Flumazenil

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47
Q

When tolerance develops, how does the curve shift?

A

To the right; it decreases potency.

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48
Q

What subunits do BZD’s bind to?

A

alpha 1,2,3 or 5 (not 4 or 6)

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49
Q

What subunits do Z-drugs bind to?

A

alpha 1

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50
Q

What are the main components you have to have in order to have insomnia?

A
  • daytime impairment

- difficulty initiating or maintaining sleep despite adequate opportunity

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51
Q

What classes of drugs aid in treating insomnia?

A 
Z-drugs
BZD
melatonin receptor agonists
orexin receptor antagonists
OTC antihistamine and melatonin
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52
Q

What percentage of your sleep is REM?

A

20-25% of your sleep

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53
Q

How long are your sleep cycles?

A

90-110 minutes

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54
Q

How do BZD affect sleep stages?

A

They increase stage 2, and decrease REM and time spent in deep sleep. Tolerance will occur

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55
Q

How do Z-drugs affect sleep stages?

A

less suppression of REM, but cause complex behavior such as sleep driving and cooking.

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56
Q

Are sleeping pills and alcohol good for sleep cycles?

A

They don’t recreate normal sleep, although it may feel more refreshing.

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57
Q

Do all GABAa receptors bind BZDs?

A

No

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58
Q

What gives diazepam the sedative, amnesic, and anticonvulsant effects?

A

The GABA receptors that contain the alpha1 subunit mediate these effects.

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59
Q

What drug is used for sedation and analgesia for intensive care patients over BZDs and propofol?

A

Dexmedetomidine. It acts as an agonist at a negative feedback loop to stop the release of NE.

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60
Q

What receptors do melatonin, ramelteon, and tasimelteon work at to regulate sleep?

A

The M1/M2 receptors to drive rhythmic signaling in the 24 hour clock.

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61
Q

What drugs do you use to treat restless legs?

A

ropinirole
pramipexole
rotigotine

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62
Q

How does chloral hydrate work?

A

At the GABAa receptor causing a barbiturate-like effect

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63
Q

How does flunitrazepam work?

A

It is a fast-acting BZD causing amnesia… date-rape

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64
Q

How does propofol work?

A

A tepid-acting sedative for induction and maintenance anesthesia acting at the GABAa receptor. (not used as much as dexmedotomide).

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65
Q

What antidepressants are sedating?

A

trazodone
doxepin
mirtazipine

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66
Q

What is the target of the OTC benadryl?

A

H1 receptor

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67
Q

What did the narcoleptic dogs in the Stanford study lack?

A

Orexin receptors, which are in the ascending arousal pathway.

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68
Q

What do the orexin projection neurons cause?

A

Awakening, wakefulness

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69
Q

What does a deficit of orexin neurons cause?

A

narcolepsy

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70
Q

What is DORA?

A

dual orexin receptor antagonists (OX1R, OX2R). Orexin is a neuropeptide secreted by the hypothalamus. They block alertness in insomnia.

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71
Q

What is special about DORA?

A

It avoids GABA receptors

72
Q

When should belsomra be taken?

A

within 30 minutes of sleep, with at least 7 hours remaining before planned awakening

73
Q

What is the common dose of belsomra? Common warnings?

A

20mg once daily. Like other insomnia medications, the warning is drowsiness and possible daytime impairment.

74
Q

Onset of BZDs: what are the fastest?

A

Chlorazepate and diazepam.

75
Q

Onset of BZDs: intermediate onset?

A

clonazepam
lorazepam
alprazolam
chlordiazepoxide

76
Q

Onset of BZDs: slow?

A

oxazepam

77
Q

What kinds of disorders can have secondary anxiety?

A 
Cardio-pulmonary disorders
Endocrine disorders
Autoimmune
Neurological
Medication (use or withdrawal): BZD, nicotine, alcohol, opioids, albuterol, caffeine
78
Q

What drug classes can you use to treat anxiety disorders?

A

BZDs
Antidepressants (SSRIs, SNRIs, TCA, MAO-Is)
Z-drugs
Misc. GABA agonist, 5HT1a agonist

79
Q

Which BZDs have the shortest half-life?

A

lorazepam and oxazepam

80
Q

Which BZDs have the longest half-life?

A

Clonazepam, chlorazepate, and diazepam

81
Q

What anxiety disorders are clomipramine indicated for?

A

Panic disorder, OCD (TCA)

82
Q

What anxiety disorders are imipramine indicated for?

A

Panic disorder, MDD, enuresis (TCA)

83
Q

What anxiety disorders are desimipramine indicated for?

A

MDD, panic disorder, IBD (TCA)

84
Q

What anxiety disorders are nortriptyline indicated for?

A

MDD, panic disorder, IBD (TCA)

85
Q

What anxiety disorders are phenelzine indicated for?

A

SAD, MDD, PTSD, panic disorder (MAOI)

86
Q

What anxiety disorders are nefazodone indicated for?

A

GAD, SAD, MDD (TCA)

87
Q

What anxiety disorders are hydroxyzine indicated for?

A

GAD, SAD, panic (antihistamine)

88
Q

What anxiety disorders are meprobamate indicated for?

A

Just GAD, short-term (GABAa)

89
Q

What anxiety disorders are buspirone indicated for?

A

GAD, SAD (5HT1a receptor agonist)

90
Q

What criteria do you need to meet to have general anxiety disorder (GAD)?

A
  • excessive worry and anxiety for at least 6 months
  • at least 3 other qualifications
    edginess
    fatigue
    impaired concentration
    irritability
    muscle tension
    difficulty sleeping
91
Q

What is the difference between psychic and somatic anxiety?

A

Psychic symptoms are more emotional, such as edginess, irritability, impaired concentration. Somatic anxiety is more physical, such as muscle soreness, difficulty sleeping, fatigue, GI issues, palpitations, etc.

92
Q

What do most other people with GAD have?

A

Another psychiatric disorder, such as depression or dysthymia.

93
Q

What kind of overlapping symptoms do GAD and MDD have?

A

worry, fatigue, irritability, sleep disturbances, psychomotor agitation, impaired concentration

94
Q

Hamilton Anxiety Rating Scale (HAM-A)

A

Most used

scores greater than 18-20 indicate need for treatment

95
Q

Generalized Anxiety Disorder Severity Scale (GADSS)

A

severity of scale indicates whether they need to be treated

96
Q

Penn State Worry Questionnaire

A

Discriminates among anxiety disorders

97
Q

What are the most educated mental health counselors?

A

Psychiatrists

98
Q

What are some nonpharm ways to treat GAD?

A

Biofeedback
Relaxation techniques
CBT
cognitive therapy

99
Q

How does CBT help a patient?

A

A lot of work has to be put in by the patient to change their way of thinking. It addresses distorted beliefs or misconceptions about self and others.

100
Q

What medications are most effective for somatic symptoms of GAD?

A

BZDs

101
Q

What medications are most effective for psychic symptoms of GAD?

A

Antidepressants, for longterm use

102
Q

What are the 1st, 2nd, 3rd line treatments for GAD? How long do you use them?

A

1st: CBT w/ or w/o SSRI (citalopram, escitalopram, sertraline, paroxetine)
2nd: SNRI (duloxetine or venlafaxine)
3rd: SSRI/SNRI + second gen antipsychotic (risperidone, quetiapine, olanzapine)
Continue meds for at least 1 year

103
Q

Bad things: SSRIs

A

If stopped abruptly, can cause dizziness, seizures, insomnia, flu-like symptoms

104
Q

Bad things: SNRIs

A

If stopped abruptly, can cause “electrical zing”, flu-like symptoms, headache. Associated with increased blood pressure, need monitoring.

105
Q

Bad things: TCAs

A

Anti-cholinergic, avoid in those with high risk of suicide, possibility of toxicity with overdose

106
Q

Bad things: MAOIs

A

lots of dietary restrictions. SSRI and clomipramine interactions

107
Q

Bad things: tetracyclics

A

Weight gain, drowsiness

108
Q

Bad things: BZD

A

If stopped abruptly may cause seizures, withdrawal, psychosis, delirium, confusion

109
Q

Bad things: pregabalin

A

abused, discontinuation symptoms

110
Q

Bad things: second gen antipsychotics

A

weight gain, less tolerable. Quetiapine is used to augment SSRIs for OCD, can be abused in prison system.

111
Q

What is SAD?

A

social anxiety disorder. Anxiety related to social or performance situations

112
Q

What % of American adults have SAD?

A

6% or so

113
Q

What is used to treat SAD?

A

CBT produces longer-lasting results
Meds work faster
1st line meds: SSRI (paroxetine, sertraline, citalopram, excitalopram)
2nd line meds: different SSRI or SNRI (venlafaxine, mirtazipine). Use BZD as needed (lorazepam).
3rd line meds: 2nd gen antipsychotic, MAOI, anticonvulsant

114
Q

What can beta blocker be used for in SAD?

A

Only performance anxiety

115
Q

How long should CBT and meds be used to treat SAD?

A

At least 6-12 months

116
Q

What three characteristics would a person with PTSD be experiencing/exhibiting?

A 
Exposure
Intrusion
Avoidance
Cognition/mood
Arousal and reactivity
>1 month
Exclusion
117
Q

What two parts to disassociation are there in PTSD?

A

Depersonalization

De-realization

118
Q

What types of comorbidities exist with PTSD?

A 
Depression
Suicide
Head trauma
Pain
Substance abuse
119
Q

What is the primary treatment for PTSD?

A

Psychotherapy, with or without medications

120
Q

What are the first line meds for PTSD? What about second line?

A

1st line: SSRIs (sertraline, fluoxetine, paroxetine) or SNRIs (duloxetine, fluoxetine) or TCAs (amitriptyline, nortriptyline, desipramine)
2nd line, it depends on what else they have issues with. (sleep, nightmares, mood, psychosis)

121
Q

Are BZDs usually used for PTSD?

A

No, because of abuse potential

122
Q

Treatment resistant PTSD?

A

Atypical antipsychotics, divalproex, gabapentin augmentation

123
Q

What anticonvulsants can you use for PTSD?

A 
Gabapentin
lamotrigine
topiramate
valproate
divalproex
tiagabine
carbamazepine
pregabalin
124
Q

What are the typical antipsychotics used for PTSD?

A

risperidone
olanzapine
quetiapine

125
Q

What are atypical antipsychotics good for in PTSD?

A

They work at the 5HT1a and 5HT2 receptors, and have high limbic activity. High SE profile. Have some effectiveness for intrusive thoughts, flashbacks, emotional regulation. Usually used in adjunct to SSRis or SNRIs.

126
Q

What are clonidine and prazosin used for in PTSD?

A

Aha adrenergic activity associated with the fear and startle response.
Clonidine is an alpha 2 agonist - reduces severity and duration of nightmares
Prazosin is an alpha 1 antagonist

127
Q

What is a personality characteristic that focuses on order, but still functions in society with minimal conflict?

A

Obsessive compulsive personality

128
Q

What is OCPD?

A 
Obsessive compulsive personality disorder
A person needs to have 4 of the following patterns to be considered:
- Control
- Perfectionism
- Dislike of teams
- Prioritizing work over relationships
- Miserly
- Inflexible
- Hoarder
- Stubborn in morality
129
Q

What is OCP and OCPD treatment?

A

CBT, no medication unless physical or mental illness accompanies

130
Q

OCD is a what kind of disorder?

A

Anxiety disorder rather than a personality disorder

131
Q

What are the qualifications for having OCD?

A
  • obsessions
  • compulsive activity takes up at least 1 hour/day
  • rituals performed to reduce severe anxiety caused by obsessive thoughts
132
Q

What are abnormal about obsessions?

A

They feel to the person like they are out of control, and are more distressing than everyday worries

133
Q

What is the difference between the compulsions of a person with OCP and OCD?

A

A person with compulsive personality will think they are normal while being compulsive, while a person with OCD will realize that something is wrong.

134
Q

What are some non-pharm options for OCD?

A

Relaxation techniques

Psychotherapy (CBT and Exposure and Response Prevention)

135
Q

What are the four steps of medication use for OCD?

A

1st line - fluvoxamine and clomipramine, or SSRIs/SNRIs
2nd line - different SSRI or TCA
3rd line - SSRI/TCA + atypical antipsychotic/mirtazipine
4th line - different combos of SSRI/ TCA and clomipramine/buspirone/pindolol

136
Q

If a person is resistant to treatment, what theory opens up a door to another type of medication?

A

Glutamate transporter imbalance theory: extra glutamate in OCD patients. N-acetylcycteine hits an NMDA receptor for glutamate, and could be used for this.

137
Q

How is panic disorder defined?

A
  • 4 or more attacks in a 4-week period
  • 1 or more followed by a month of fear of another panic attack
  • symptoms are of brief periods of intense fear and hit at least 4 out of 15 symptoms
138
Q

What are some common panic triggers?

A

Cannabis, SSRI withdrawal in someone with a panic disorder, stimulants, illness, interpersonal stress, injury

139
Q

During a panic attack, what is there an urge to do? And after?

A

Flee, and after, avoid situations where it might occur again. Intense worry.

140
Q

What are some co-morbidities associated with panic disorder?

A

OCD, depression, agoraphobia, IBS, migraine headache

141
Q

What neurotransmitters are targeted in panic disorder?

A

5HT2 - antagonist blocks reuptake, leaving more serotonin in synapse to reduce anxiety
alpha adrenergic antagonism - increases synaptic NE and serotonin

142
Q

What is the treatment of choice for panic disorder?

A

CBT. It is more effective than medication, and it can be combined with medication.

143
Q

What medications can be used to treat panic disorder?

A 
SSRIs - 1st line
SNRIs
TCAs
MAOIs
BZDs - for use in acute situations. Not longterm
144
Q

What drugs used in panic disorder have concerns for cardiac disorders?

A

Citalopram (QT prolongation and cimetidine interaction 2C19)

TCAs - risk of arrhythmias

145
Q

What is the most common comorbid condition seen with insomnia?

A

depression (40-50% psychiatric illness)

146
Q

What percent of the population will complain about insomnia in their lifetime?

A

50%. Over 70 years old, 80% will.

147
Q

Chronic insomnia affects what percentage of the population and requires treatment?

A

5-16%. involves daytime impairment and often anxiety and depression later in life

148
Q

What are the 3 insomnia diagnostic criteria?

A
  1. Difficulty in initiating sleep (30 minutes or more) 3 x/week
  2. Difficulty maintaining sleep. Waking 3 times a night or waking too early in the morning
  3. Feeling unrefreshed after 7 hours of sleep3x a week
    Persist for at least 3 months
    Not due to underlying medical causes
149
Q

What neurotransmitters promote sleep?

A

GABA, melatonin, adenosine (may inhibit wake-promoting neurons)

150
Q

When is melatonin expressed?

A

At night. It is suppressed in the daytime.

151
Q

What neurotransmitters promote wakefulness?

A 
NE
5HT
ACH
histamine
Dopamine
Orexin
152
Q

What are the treatment guidelines for insomnia?

A

1st line - behavioral intervention, CBT
2nd line - antihistamine (3 days), short-acting BZD, z-drugs, sedating antidepressant (trazodone, doxepin)
3rd line - ramelteon, sedating antipsychotics

153
Q

What is ramelteon indicated for?

A

Sleep onset, not maintenance

154
Q

What is tasimelteon indicated for?

A

Non-24 hour sleep-wake disorder (blond people)

155
Q

What are the sedating antidepressants used for insomnia?

A

Trazodone, doxepin, mirtazipine

156
Q

At what dose is mirtazipine useful as a sleep aid?

A

At lower doses.

157
Q

What are the barbiturates used for? Why are they not useful in insomnia?

A

They are mostly used in anesthesia because of their long half-lives. Phenobarbital is useful in treating seizures.

158
Q

When do barbiturates lose their effectiveness as sleep aids?

A

Within 2 weeks. Also addictive, additive with alcohol, cause ‘hangovers” and can cause seizures if stopped abruptly.

159
Q

What is chloral hydrate used as?

A

It is a GABAa receptor agonist used as a sedative and a hypnotic in sever treatment resistant insomnia, pre-operative sedation or post-op pain.

160
Q

What should elderly insomniacs avoid in terms of BZDs?

A

Triazolam and flurazepam, because of their long half-lives and anterograde amnesia

161
Q

Which BZD is used mosts often for sleep?

A

Temazepam, because of the intermediate half-life

162
Q

Which BDZ is used in dental procedures?

A

Triazolam

163
Q

Which GABA subunits are responsible for anxiolytic, amnesia, and muscle relaxant properties?

A

alpha 2, 3, and 5 subunits

164
Q

Which BZD is like the Z drugs in terms of what subunit it binds to?

A

quazepam. But it has a long half-life.

165
Q

What other BZDs should you avoid in the elderly?

A

Triazolam and alprazolam. They are short-acting and could increase the risk of falls.

166
Q

What are the intermediate-acting BZDs?

A

Lorazepam, temazepam, oxazepam. They are more likely to be used longterm.

167
Q

What are the long-acting BZDs?

A

Clonazepam, diazepam, flurazepam

168
Q

What type of sleep are zolpidem and eszopiclone used for?

A

Sleep onset and maintenance. Need 7-8 hours of sleep.

169
Q

What type of sleep is zaleplon used for?

A

Onset only. Administer immediately before bed. Only need 4 hours of sleep.

170
Q

What sedating antipsychotic is used for insomnia?

A

Quetiapine. It has abuse potential and SEs though, so not used very much. Use at doses under 150mg for sleep to hit H1 receptors.

171
Q

Which sedating antidepressant has anticholinergic SE’s?

A

Doxepin. Avoid in the elderly. Use for sleep maintenance, take on empty stomach.

172
Q

Which sedating antidepressant acts as an antihistamine under 15mg?

A

Mirtazipine. Low Ach. SEs though of weight gain, limb movements in sleep.

173
Q

Which sedating antidepressant is safe for the elderly?

A

Trazodone. Risk of priapism.

174
Q

What is the Orexin receptor antagonist?

A

Suvorexant. It blocks Orexin neuropeptides A and B to receptor types 1 and 2. It assists in sleep onset and fewer awakenings. Can impair daytime wakefulness.

175
Q

Which is the Z drug with the bitter taste?

A

Eszopiclone

176
Q

Which has the longer half-life, eszopiclone or zolpidem?

A

Eszopiclone

177
Q

Which antidepressant is FDA approved for sleep?

A

Doxepin (H1 blocker)

Integrated Drug Structure, Action, and Therapeutics (20 decks)

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