sedatives/hypnotics/anxiolytics

Question 1

sedative def.

Answer 1

calms anxiety, decreases excitement and activity, does not produce drowsiness or impair performance

Question 2

hypnotic

Answer 2

induces sleep, implies restful, refreshing sleep, not “hypnotized”, natural sleep

Question 3

anxiolytic

Answer 3

antianxiety, relieves anxiety without sleep or sedation (not all are sedative)

Question 4

narcotic

Answer 4

actually means “sleep producing”, refers to opiods or illegal drugs

Question 5

the reticular formation

Answer 5

contains dopamine, adrenergic, serotonergic and cholinergic neurons; regulates the sleep-wake cycle

Question 6

factors that regulate sleep

Answer 6

age, sleep history, drug ingestion, circadian rhythms

Question 7

benzodiazepine chemistry

Answer 7

annealating the 1-2 bond with an electron rich ring (triazole or imidazole) yields high affinity and decreased t1/2
no ring = antagonist

Question 8

long acting benzos

Answer 8

accumulation, active metabolites

Question 9

short acting benzos

Answer 9

midazolam, anasthetic

Question 10

bezodiazepine antagonist

Answer 10

flumazenil
no phenyl ring
used to treat benzo overdose
SE: induce convulsions and panic attacks in those that are benzo dependent

Question 11

Z-hypnotics

Answer 11

zolpidem, zaleplon, eszopiclone (long term use)
3A4 to some extent
oversode treatment (flumazenil)
SE: daytime drowsniness, dizziness, ataxia, NV, doing activities in sleep

Question 12

illicit use of sedative-hypnotics

Answer 12

benzos:
flunitrazepam (“roofies”), clonazepam
nonbenzos: zolpidem

Question 13

barbituates compared to benzos

Answer 13

“worse at everything”

Question 14

benzo and barbituate binding

Answer 14

benzos are only allosteric

barbituates are allosteric and orthosteric

Question 15

GHB

Answer 15

not common, used to next day wakefulness

Question 16

melatonin agonists

Answer 16

ramelteon, tasimelteon

preferred over melatonin because FDA approved

Question 17

buspirone

Answer 17

anxiety tx
longer onset of action ~ weeks (dont use for an acute situation)
used for: GAD, social anxiety, comorbid depression, adjunct in OCD, PTSD; not good for panic disorders

Question 18

propranolol

Answer 18

uses: social anxiety, PTSD

Question 19

tolerance and withdrawl from benzos

Answer 19

normal: Cl- moves through
add benzo acutely: more Cl- moves through: hyperpolarized
chronic: downregulation of receptors, return to baseline
withdrawl: not enough Cl- is coming in, neurons being firing

Question 20

DSM 5 for generalized anxiety

Answer 20

Excessive worry around a number of life events that is difficult to control, present for at least 6 months

Question 21

generalized anxiety disorder treatment

Answer 21

SSRI (first line) x 2-4 weeks for initial onset of symptom relief, take 6-8 weeks to see full impact (paroxetine and escitalopram are FDA approved; any can be used - lower doses and slower titrations that depression)
SNRIs can be helpful: duloxetine and venlafaxine are FDA approved (useful for concomitant pain syndrome)
Benzodiazepines are used for bridge therapy until other meds kick in; if used longer than 30-60 days, must be tapered to avoid withdrawal (seizures)
Buspirone: dosed high enough (15 TID) and patient is aware of how long it takes to work

Question 22

social anxiety disorder epidemiology

Answer 22

Persistent fear about social and/or performance situations in which the patient fears embarrassment or humiliation that is unreasonable; duration at least 6 months

Question 23

Social Anxiety Disorder Treatment

Answer 23

SSRI are first line: paroxetine and sertraline are FDA-approved (any can be used)
SNRI: may be useful for failure of SSRI: Venlafaxine is FDA-approved (any can be used)
Beta-blockers: may be useful for non-generalized, performance-related SAD

Question 24

Panic Disorder etiology

Answer 24

Recurrent, unexpected panic attacks
Panic Attack: abrupt surge of intense fear or discomfort that reaches a peak in minutes and is accompanied by at least 4 physical and psychological symptoms
May lead to agoraphobia: isolating themselves in a safe place

Question 25

panic disorder treatments

Answer 25

SSRIs are first-line maintenance therapy: most are FDA approved SNRIs: Venlafaxine approved, Duloxetine has good clinical data TCAs, mirtazapine, MAO-inhibitors: show efficacy similar to SSRIs but have worse side effects Benzodiazepines should NOT be considered for maintenance therapy unless after several treatment failures (clonazepam and alprazolam FDA approved)

Question 26

OCD

Answer 26

Obsessions: recurrent thoughts or images that are intrusive and cause anxiety Compulsions: repetitive behavior or mental acts performed in response to obsession Must cause marked distress and take more than 1 hours per day or interfere significantly with functioning

Question 27

OCD treatment

Answer 27

SSRIs are first-line treatment for OCD; most are FDA approved Failure of a few trials of SSRIs, can try clomipramine (TCA) Venlafaxine XR has been studied with effectiveness Antipsychotics can be considered for augmentation therapy with antidepressants

Question 28

PTSD

Answer 28

Exposure to real or threatened death, serious injury, or sexual violence leading to distressing memories, avoidance of associated stimuli, negative alterations in mood, or marked alterations in reactivity or arousal

Question 29

PTSD treatment

Answer 29

SSRIs/SNRIs are first-line treatment - With multiple failed trials, can consider mirtazapine Prazosin may be helpful for sleep or nightmares (10mg/day) Benzodiazepines are NOT recommended for PTSD Substance abuse disorders should be treated simultaneously

Question 30

PTSD prevention

Answer 30

Beta-blockers and opioids have been studied in civilian and combat trauma surviviors (give everyone in an IED attack morphine) Varying degrees of success

Question 31

Selected Drug Therapy Issues in Anxiety Disorders

Answer 31

Jitteriness: results from the use SSRIs and SNRIs - Lower doses than depression doses and slower dose titration Onset of action for SSRIs/SNRIs is 2-4 weeks with maximal response at 6-8 weeks and withdrawl symptoms (flu like symptoms) Abrupt discontinuation of benzodiazepines can be life-threatening

Question 32

nonpharm anxiety counseling

Answer 32

Psychotherapy and cognitive behavioral therapy are mainstays of treatment Drug therapy often helps the effectiveness of these modalities

Question 33

insomnia

Answer 33

Difficulty with sleep initiation, sleep maintenance, and/or early-morning awakening Takes place at least 3 weeks per night and present for at least 3 months

Question 34

insomnia treatment

Answer 34

First line is non-pharmacological! - Behavior therapy: stimulus control, sleep restriction, relaxation, Sleep hygiene principles are necessary The Z-hypnotics: Zolpidem has several dosage forms, including a sublingual form (Intermezzo), Eszopiclone: FDA-approved for long-term use (6 months) Benzodiazepines: temazepam is most common, Longer-acting agents (diazepam, chlordiazepoxide) cause significant daytime hangover, Any benzodiazepine can be used for insomnia, Must consider taper to discontinue to avoid life-threatening withdrawal Melatonin agonists are useful for sleep latency (staying asleep) Doxepin: lower, branded dose of doxepin = same side effects, suicidality warning, and sleep behavior warning All medications FDA-approved for sleep have sleep behavior warning

Question 35

Suvorexant (Belsomra)

Answer 35

Selective dual orexin receptor antagonist = blocking the wake promoting neuropeptides orexin to suppress “wake drive” Daytime somnolence risk: 10mg dose carries risk for impaired driving; patients taking 20mg should be warned against daytime driving Should NOT be used in patients with narcolepsy (absolutely CI, patients already don't have enough orexin) 3A4 inhibitor

Question 36

sleep apnea

Answer 36

Breathing related sleep disorders are divided into obstructive sleep apnea, central sleep apnea, and sleep-related hypoventilation Patients must have evidence of at least 5 obstructive apneas per hour of sleep confirmed by polysomnography

Question 37

sleep apnea treatment

Answer 37

Weight loss Initially CPAP: continuous positive airway pressure Excessive daytime sleepiness: modafinil or armodafinil Surgery is an option Ensure that obstructive apnea is addressed before recommending sedative/hypnotic drug therapy

Question 38

narcolepsy

Answer 38

Cataplexy: emotional response (tearfulness, laughter), losing muscle tone - Sodium oxybate (Xyrem) = Gamma-hydroxy butyrate: Dosed twice nightly, must set alarm to take 2nd dose, Black Box Warning: respiratory depression and misuse risk Excessive daytime sleepiness: Methylphenidate, dextroamphetamine, mixed amphetamine salts, Modafinil/ amodafinil, Sodium oxybate, Selegiline

Question 39

Shift Work Sleep Disorder

Answer 39

Problem for those working night shifts or those with changing shifts throughout the week Sleep hygiene may be helpful: black-out curtains, noise markers Drug Therapy: focuses on improving wakefulness during wake time Modafinil and armodafinil are drugs of choice

Question 40

Restless Leg Syndrome

Answer 40

Urge to move the legs in response to an uncomfortable or unpleasant sensation that begins/worsens during periods of rest, partially or completely relieved by movement, worse in the evening/night Dopamine agonists are first line: pramipexole and ropinirole Levodopa/carbidopa can be considered Gabapentin encarbil: unclear benefit/risk Others: opioids not recommended, iron supplementation has little evidence, and clonazepam may be considered

Question 41

GAD treatment overview

Answer 41

SSRI SNRI buspirone/benzos

Question 42

SAD treatment overview

Answer 42

SSRI SNRI BB phenelzine

Question 43

panic disorder treatment overview

Answer 43

SSRI SNRI TCAs, MAOIs, Mirtazapine

Question 44

OCD treatment overview

Answer 44

SSRI clomipramine venlafaxine XR augment: antipsychotics

Question 45

PTSD treatment overview

Answer 45

SSRI/SNRI mirtazapine nightmares: prazosin

Question 46

sleep apnea treatment overview

Answer 46

weight loss/CPAP | modafinil/armodafinil (daytime sleepiness

Question 47

insomnia treatment overview

Answer 47

``` nonpharm Z-hypnotics benzos melatonin agonists doxepin ```

Question 48

narcolepsy treatment ovreview

Answer 48

cataplexy: Xyrem | daytime sleepiness: stimulants, modafinil/armodafinil, Xyrem