Therapeutics Neuro/psych Exam 1- Anxiety/insomnia

Front 1

spectrum of anxiety disorders

Back 1

Panic Disorder w/o agoraphobia

Panic Disorder w/ agoraphobia
GAD

(other stuff?)

Front 2

Societal Impact of Anxiety Disorders (2)

Back 2

Economic impact - SIGNIFICANT! (45 billion dollars)
High consumption of medical resources (difficult to recognize due to vague sx)

Front 3

costs of anxiety- direct and indirect

Back 3

indirect costs- morbidity, mortality, lost productivity

direct- healthcare expenditures

Front 4

Lifetime prevalence of any anxiety
disorder

Back 4

28%

Front 5

GAD lifetime prevalence

Back 5

5%

Front 6

panic disorder prevalence:
in community
clinical setting
what % has agoraphobia

Back 6

low in community (1-3.5%)

but higher rate in clinical samples (10-30%)

with agoraphobia 30-50%

Front 7

social phobia incidence

Back 7

3-13%

Front 8

PTSD in men vs. women incidence

Back 8

60% of men and 51% of women in general
population have 1+ traumatic event in life

Front 9

Estimated lifetime prevalence for PTSD- and gender

Back 9

7.8%

women more so than men even though men expeirence more trauma

Front 10

lifetime prevalence of OCD

Back 10

2-3%

Front 11

7 common obsessions for OCD

Back 11

Contamination (50%), pathologic doubt (42%),
somatic (33%), need for symmetry (32%),
aggressive (31%), sexual (24%), and multiple
(72%)

Front 12

7 most common compulsions in OCD

Back 12

Checking (61%), washing (50%), counting
(36%), ask/confess (34%), symmetry/precision
(28%), hoarding (18%), and multiple (58%)

Front 13

Charcteristic Features of Anxiety
Disorders (2)

Back 13

anxiety
avoidance behavior- avoiding situation that causes anxiety

Front 14

DSM-IV criteria for panic attacks

Back 14

A discrete period of intense fear or discomfort, in
which four (or more) of the following symptoms
developed abruptly and reached a peak within
10 minutes:

Front 15

need to know target sx!
UGH just...know the weird ones (4 weird ones)
Panic attacks sx (need 4 or more)
physical sx (split up between phyiscal and psych sx)

Back 15

• Sweating
• Trembling or shaking
• Feeling of choking*
• Chest pain or discomfort
• Nausea or abdominal distress
• Fear of dying
• Paresthesias
• Palpitations, pounding heart, or
accelerated HR
• Sensations of shortness of breath or
smothering
• Feeling dizzy, unsteady, lightheaded,
or faint
• Derealization or depersonalization*
• Fear of losing control or going crazy*
• Chills or hot flushes*

Front 16

DSM-IV for panic DISORDER (different from attacks)

Back 16

1. Recurrent unexpected panic attack(s); and
2. At least 1 attack followed by 1 month of more than 1 of the following:
• Persistent concern about having additional attacks
• Worry about the implications of the attack or its
consequences (e.g., losing control, “going crazy”,
having a heart attack)
• A significant change in behavior related to the attacks
3. Not due to the direct physiological effects of a
substance or general medical condition
4. Not accounted for by another mental disorder
* There may also be the presence of agoraphobia

Front 17

DSM-IV for GAD (4)
6 target sx

Back 17

1. Excessive anxiety and worry occurring more
days than not for more than 6 months
2. Person cannot control worry
3. 3+ of the following are present:
• restlessness
• easily fatigued
• difficulty concentrating or mind going blank
• irritability
• muscle tension
• insomnia
4. Worry not confined to another diagnosis
• e.g., panic, OCD, anorexia nervosa, somatization
disorder, PTSD

Front 18

DSM-IV Criteria for Social Phobia

(7)

Back 18

no specific time frame for sx

jesus christ long list

1. Marked and persistent fear of one or more social or
performance situations
• Person exposed to unfamiliar people or to possible scrutiny by
others
• Fears that he/she will act in a way (or show anxiety) that will be
humiliating or embarrassing
2. Exposure to feared situation invariably provokes anxiety, which
may take the form of a situationally bound or predisposed panic
attack
3. Recognition that fear is excessive or unreasonable
4. Feared social or performance situations are avoided or else
endured with intense anxiety or distress
5. Avoidance, anxious anticipation, or distress in the feared
situation interferes significantly with the person’s normal
routine, occupational functioning, or social activities and
relationships
6. If child/adolescent, duration > 6 months (have to distinguish between normal changes and disorder)
7. Fear/avoidance not due to substance, general medical
condition, or another mental disorder

Front 19

DSM-IV Criteria for PTSD- first criteria

Back 19

A. The person has been exposed tto a
ttraumattiic eventt with both of the
following present:
1) Person witnessed, experienced or was
confronted with events that involved
death, injury, or threat to integrity of self
or others
2) Response involved fear, helplessness or
horror

Front 20

DSM-IV Criteria for PTSD- second criteria

Back 20

B. Event is re-experiienced in one of the
following ways:
1) Recurrent, intrusive recollections
2) Recurrent dreams
3) “Flashbacks”
4) Intense distress at “cues”
5) Physiologic activity in response to “cues”

Front 21

DSM-IV third criteria for PTSD

7 target sx

Back 21

C. Persistant avoiidance of stimuli associated
with the trauma and numbing of general
responsiveness, indicated by 3 or more of
the following:
1) Avoidance of thoughts, feelings, or conversations assoc. with the
trauma
2) Avoidance of person, places, or activities assoc with the trauma
3) Inability to recall specifics of trauma
4) Decreased interest in activities
5) Detached feelings
6) Restricted range of affect
7) Sense of foreshortened future

Front 22

DSM-IV fourth criteria for PTSD (arousal cluster)

5 target sx

Back 22

C. Symptoms of iincreased arousall by 2
or more of the following:
1) Problems falling/staying asleep
2) Anger outbursts/irritable
3) Problems concentrating
4) Hypervigilence (e.g. sitting in corner so they can observe the whole room)
5) Exaggerated startled response

Front 23

DSM-IV fifth criteria for PTSD (2)

duration and one other thing

Back 23

E. Duration longer than 1 month
F. Distress in social, occupational or
other functioning

Front 24

PTSD- acute vs. chronic vs. delayed onset timing

Back 24

– Acute: less than 3 months
– Chronic : greater than 3 months
– Delayed onset: symptoms at least 6 months after event

Front 25

DSM-IV criteria for OCD (4)

Back 25

Either obsessions or compulsions


The person realizes that the obsessions or
compulsions are excessive or unreasonable


The obsessions cause marked distress, are
time consuming (> 1 hour/day), or
significantly interfere with normal function


If another Axis I diagnosis is present, the
content of the obsessions/compulsions is not
restricted to it

Front 26

4 other conditions to r/o before diagnosing anxiety

Back 26

• Metabolic
• Neurological (dementia, seizures)
• Cardiovascular
• Respiratory

Front 27

substance induced conditions that are similar to anxiety (3)

Back 27

• Illicit substances
• Prescribed medications (e.g inhalers)
• Other substances/OTCs (energy drinks, etc)

Front 28

Age of onset for anxiety

Back 28

Typically late adolescence to early
adulthood

Front 29

clinical course "types" of anxiety disorderS (4)

Back 29

• Chronic, and depends on which disorder
– Waxing and waning/episodic, with or without
triggers (zoned out)
– Continuous (e.g. social phobia)
– Fluctuating, with worsening during periods of
stress

Front 30

5 co-morbid conditions with high rate of occurrence with anxiety

Back 30

– Mood Disorders
• MDD
• Dysthymia
• Bipolar Disorder
– Anxiety Disorders
– Substance-Related Disorders
• Abuse and Dependence
• Alcohol, sedatives/anxiolytics, nicotine
– Eating DO
– Avoidant PD (personality disorder)

Front 31

Patients with a lifetime history of an anxiety
disorder report higher rates of medical
illness, including (not sure of causation/correlation)

Back 31

– Hypertension and other cardiovascular disease
– Autoimmune Disease
– Chronic Pain, arthritis
– Infectious Disease
– Diabetes
– Dyslipidemia
– COPD, asthma
– IBS
– Peptic ulcer disease and other GI problems
– Genitourinary disorders
– Migraine

Front 32

pathophys of anxiety (4)

3 NTs involved with anxiety

Back 32

1) stimulus presented to self
2) passes through thalamus, hippocampus or pfc
3) activation of amygdala
4) actigation of motor escape, HPA-axis, hypervent, HR

serotonin NE and GABA- 3 NTs involved with anxiety

Front 33

motor response- fight or flight- pathway

which NT

Back 33

fear stimulus goes through amygdala and to periaqueductal grey area

moderated by NE

Front 34

HPA axis/endocrine role in stress

Back 34

amygdala-->CRF released from HT-->release of ACTH from pituitary-->glucocorticoids from adrenal cortex-->negative feedback

Front 35

cardiorespiratory pathway in anxiety (3)

Back 35

amygdala-->cardiorespiratory systems in brain stem/loecus ceruleus-->increase BP and HR and hyperventilation

Front 36

PTSD represents a...

does not represent what?

Back 36

represents a specific type of adaptation
to trauma
– Does not reflect typical stress responsiveness

Front 37

biological modifications in pTDS (3)

Back 37

involves HPA axis which becomes highly sensitized in PTSD patients

decrease basal cortisol levels
increased negative feedback regulation (upregulation of corticosteroid receptors? idk)

Front 38

pathophys chart PTSD

Back 38

33:10

Front 39

pathophys of OCD

NTs involved (2)

Back 39

Unlikely to explain OCD with one
neurotransmitter system
– Serotonin
– Dopamine
– Combination of serotonin & dopamine

Front 40

non pharm tx of anxiety disorders (5)

Back 40

Psychotherapy

Support Groups

Meditation

Exercise

Avoid substances precipitating anxiety (e.g. caffeine, drugs of abuse, stimulants)

Front 41

3 CBT techniques commonly employed

Back 41

• Exposure therapy
• Cognitive restructuring
• Stress inoculation

Front 42

tx of choice for panic disorder (2)

why? (3)

Back 42

SSRIs or venlafaxine

– Lack of dependency
– Tolerable adverse effect profile
– Response = 50%–70%

Front 43

BZD use in panic disorder (2)

Back 43

SSRIs and BZDs both used clinically


Data support the combined use of SSRIs and benzodiazepines in the first weeks of
treatment
– Offset the delay in the SSRI effect (and jittery syndrome in initial 10 days- over anxiety)

ONLY if no hx of abuse

Front 44

efficacy of tx for panic disorder (in order form highest to lowest) (5)

Back 44

SSRIs = VFX wayyy better than TCAs = BZD > MAOIs > placebo

Front 45

Choosing a Pharmacologic Agent:
Generalized Anxiety Disorder tx of choice and evidence

Back 45

Current literature is not conclusive on
the optimal sequence of
pharmacologic therapies

Antidepressants - treatment of choice (less dependency, tolerable AEs)

Front 46

options in GAD (5) and efficacy

Back 46

SSRIs = SNRIs = BZDs = TCAs = buspirone > placebo

Front 47

tx of choice for social phobia (2)

Back 47

SSRIs, VFX treatment of choice

Front 48

when/how long to add benzos for social phobia (3)

Back 48

Combined use of SSRIs and
benzodiazepines in the first weeks of
treatment
– Offset the delay in the SSRI effect
– If urgency in relief necessary

Front 49

options for social phobia (5) and efficacy)

Back 49

SSRIs = VFX = CMP??? didn't talk about = BZD = MAOIs

Front 50

algorithm for PD, GAD, social phobia (4 first line agents)
define clinical failure (and when you'd move to next step)

Back 50

buspirone- can be used as first line for GAD

if they fail (12 weeks at moderate dose)- can try a different agent as second line

third line- keep trying ones you haven't tried already

basically just alternate monotherapy trials


SSRI, VFX, BSP, DLX- first line

try other first line agents

then try the class you haven't tried yet

TCA/BZD next

any alternate agents not yte tried

if at any point you get a response- continue for 12 mo

Front 51

1st and 2nd line with PTSD tx

Back 51

SSRI’s should be used first line (Most data available)

Second line therapies (Limited data)
– NSRI’s

(don't have to know third/fourth line)

also good evidence in prazosin in nightmares- first line

Front 52

OCD tx- 1st and 2nd line

Back 52

SSRI’s
– 1st line treatment

2nd line- clomipramine (most serotonergic TCA- but more AEs)

Front 53

dosing of SSRIs in OCD (2)

Back 53

• Doses needed/targeted are typically higher than those
used in depression
– Generally max dosing should be targeted for 12 week trial
• May also take longer to achieve response than seen in
depression

Front 54

3rd line in OCD

Back 54

venlafaxine- 225-350 mg/day

usually will try all the SSRis/clomipramine before 3rd line- don't have to know 4th line

Front 55

Anxiety Disorders:
Other alternative pharmacotherapies (3)

Back 55

β-blockers (propranolol)- for performance anxiety

Hydroxyzine

Trazodone

these 2 are used a lot in ppl with substance abuse to avoid using BDZ

Front 56

Pharmacodynaimc interactions with SSRIs (4)

Back 56

– Drugs that promote serotonergic activity
– Drugs that increase potential for bleeding
– Drugs with CNS sedative effects
– MAOIs

Front 57

CYP chart with SSRIs

Back 57

---


inhibitors of CYPs!!!!!

Front 58

duloxetine only approved for which anxiety disorder

Back 58

DLX only approved for the treatment of GAD

Front 59

CYP interactions with SNRIs (3)

Back 59

– VFX and DLX: Substrates for CYP2D6
– DLX: Substrate for CYP1A2
– DLX: Inhibitor of CYP2D6

Front 60

PD considerations in SNRIs (4)

Back 60

– Drugs that promote serotonergic and/or
noradrenergic activity
– Drugs with CNS sedative effects
– MAOIs
– DLX: drugs that slow gastric emptying/motility

Front 61

reconcile drug info on these slides with fowler's

Back 61

--

Front 62

TCA drug interactions= PD (5)

Back 62

Drugs that prolong QTc
Drugs that promote 5HT/NE activity
bleeding drugs
CNS sedative effects
MAOIs

Front 63

6 advantages with SSRIs in treating anxiety disorders

Back 63

Effective for comorbid depression

Well-documented efficacy across the
full spectrum of anxiety disorders

Documented long-term safety

Prevention of relapse

No abuse potential

Once daily dosing

Front 64

5 disadvantages with SSRIs

Back 64

Onset of action delayed usually for days
to weeks

May activate and transiently worsen
anxiety at onset of treatment

Sexual dysfunction is common

May induce withdrawal reactions when
discontinued (25-60%)

Weight gain

Front 65

BDZ- MoA

Back 65

Bind to recognition site on GABA-A
receptors and in the presence of GABA, will potentiate response to GABA

Front 66

BDZ dosing

Back 66

multiple daily dosing...duh..

Front 67

BDZ DDI
PD
PK (2 enzymes and one with no enzymes)

Back 67

PD: CNS depressants or respiratory depressants

PK: 3A4 and diazepam also 2C19- LORAZEPAM no cyps (glucuronidation)

Front 68

5 advantages and uses for BDZ

Back 68

Rapid onset

Can be useful as needed for
breakthrough symptoms

Augmentation of SSRI therapy may
enhance adherence to treatment and
alleviate activating symptoms of SSRIs

No activation or mild sexual dysfunction

Safe with good tolerability

Front 69

BDZ for anxiety: disadvantages (5)

Back 69

No antidepressant activity

Need for multiple doses with some agents

Potential early sedation and incoordination

Risk for withdrawal reactions with abrupt
discontinuation (usually a re-emergence of
anxiety symptoms)

Low but definite abuse potential, especially
in polysubstance abusers

Front 70

Buspirone MoA (2)

Back 70

5-HT1A partial agonist post-synaptically and full
agonist presynaptically

Therapeutic effect by virtue of adaptive neuronal and receptor
events rather than receptor occupancy

Front 71

buspirone dosing freq

Back 71

Multiple daily dosing

Front 72

Side effects (5) for buspirone

Back 72

– Nausea – Lightheadedness
– Dizziness – Insomnia
– Headache

Front 73

buspirone CYP interactions

Back 73

CYP Interactions
– Substrate for CYP3A4

Front 74

buspirone PD interactions (2)

Back 74

– Serotonergic or noradrenergic drugs
– MAOIs

Front 75

buspirone advantages (3)

Back 75

– Appears to have no abuse potential
– No impairment in psychomotor activity
– No additive effects with alcohol

Front 76

buspirone disadvantages (4)

Back 76

– May not work well in case of severe anxiety
– Only been shown to be effective in GAD
– Continued efficacy in long term trials is questionable
– Delayed onset of action

Front 77

buspirone onset of action (3)

Back 77

• Anxiolytic effect = 1 week
• Maximum effect = 4 to 6 weeks
• Probably better patient acceptance in BZD “naïve” patients

Front 78

Phases of Treatment and Clinical Outcomes (3)

Back 78

symptomatic
response
remission- continuation/maintenance

Front 79

Knowing that these scales exist for anxiey/depression

Back 79

GAD- HAM-A
PD- PDSS
social phobia- LSAS'

Front 80

not accountable for response vs. remission slide

Back 80

--

Front 81

do know when continuation/maintenance, etc are indicated (slide) for PD, GAD, SP, PTSD (and the OCD one)

initial improvement should be seen how soon? what is an adequate trial time?

Back 81

Initial improvement should be seen in 2-6 weeks but
adequate trial = 12 weeks

Front 82

Long-term continuation treatment of anxiety disorder
is recommended following the amelioration of acute
symptoms (4) for how long? ( i think that's what this slide is saying) PD, GAD, SP, PTSD

Back 82

– GAD: 1 year
– PD: 1+ year
– SP: 1 year or longer
– PTSD:
• Acute PTSD: 6-12 months
• Chronic PTSD: 12-24 months

Front 83

relapse and tapering and maintenance in tx of PD, GAD, SP, PTSD

Back 83

Relapse is common after discontinuation of
medication for most anxiety disorders
– Tapering should be very gradual

Lifelong maintenance therapy may be indicated for
individuals who frequently relapse

Front 84

OCD slide about continuation/maintenance (adequate trial, when to give long term maintenance, how to avoid relapsing when d/cing drug)

Back 84

adequate trial = 12 weeks at max doses (minimum)

due to relapses with abrupt d/c, always use gradual taper; if sx return, increase dose to last effective dose

long term maintenance for- 2-4 severe relapses OR 3-4 mild/moderate relapses

Front 85

adult sleep cycles (3)

Back 85

Adult sleep consists of repetitive
cycles
– Last 90-120 minutes
– Advancing through non-REM stages to REM

Front 86

Stage 1-4 and REM sleep definitions

Back 86

Stage 1: drowsiness
Stage 2: light sleep
Stages 3 & 4: deep, “slow wave” sleep
REM: dream sleep

Front 87

neurobiology of sleep (general)

Back 87

Complex, and likely involves many areas of
the brain and multiple neurotransmitter
systems

Front 88

NTs involved in NREM sleep, REM (2) sleep and wakefulness (6)

Back 88

– NREM Sleep: Serotonergic
– REM Sleep: Cholinergic and Noradrenergic
– Wakefulness: Dopaminergic, Noradrenergic,
Histaminic, and Cholinergic; Substance P, CRF
(neuropeptides)

Front 89

sleep requirements as we age (4)

Back 89

1) infants/cihldhood/adolesnce- 18 hours a day as baby, then 9 to 10 hours as adolescent

adults: declines in 20-30s- 7-8 hours (less REM sleeP)

middle age- sleep lighter, more awakenings, and harder to fall asleep but still need 7-8 hours

elderly- even more fragmented sleeP (details on slide)- but no change in total sleep time due to napping

Front 90

incidence of insomnia

chronic insomnia incidence

Back 90

9-50%

chronic:10%

Front 91

insomnia is often the underlying symptom of...

Back 91

psych illnesses

Front 92

initial insomnia

Back 92

Difficulty initiating sleep
– More than 30 minutes to fall asleep

Front 93

middle insomnia (3)

Back 93

Difficulty staying asleep
– Waking several times during the night, with difficulty
in falling back to sleep
– Drifting in and out of light, restless sleep

Front 94

late or terminal insomnia (3)

Back 94

Waking too early
– Falling asleep with relative ease and sleep through
the first part of the night
– Waking early in the morning, usually after < 6 hours
of sleep

Front 95

transient insomnia and cause

Back 95

– Acute, periods up to a month
– Underlying triggers, situations or new environments

Front 96

intermittent insomnia (2)

Back 96

– On and off, occurs longer than one month
– Periods of insomnia may come closer together and
last slightly longer each time

Front 97

chronic insomnia (2)

Back 97

– Affected on most nights
– Period greater than one month

Front 98

sleep disorders DSM-IV: primary insomnia (5 target sx)

Back 98

2+ of following sx for at least 1 month:

difficulty initiating sleep (30+ min)
difficulty maintaining sleep (30+ min awake at night)
poor sleep efficiency (ratio of time asleep:time in bed less than 85%)
sleep disturbance 3+ times weekly
significant impairment of functioning

Front 99

3 things to take in assessing insomnia

Back 99

hx
sleep log diary
sleep questionnaire

Front 100

hx of assessment of insomnia- items to focus on

Back 100

– Identification of specific characteristics
– Severity
– Chronicity
– Predisposing factors
– Precipitating events
– Functional impact

Front 101

substance that may cause insomnia

Back 101

---WTF like 20 things

large qt of alcohol can be counterproductive to sleep

Front 102

Medical Conditions that May Cause
Insomnia or Sleep Disruption (8)

Back 102

Arthritis or any other painful condition

Chronic respiratory disease

Cardiovascular disease

Gastrointestinal disease

Neurological disorders

Endocrine disorders

Menopause

Psychiatric Illness

Front 103

impact of sleep on quality of life (6)

Back 103

cognitive impairment
decrease performance
impaired interpersonal relationships
occupational injury
other injury
poor coping skills

Front 104

Untreated sleep disorders and sleep
deprivation have been associated with medical
illnesses including (7)

Back 104

– High blood pressure
– Heart attack
– Heart failure
– Stroke
– Obesity
– Psychiatric problems, including depression and other mood
disorders
– Fetal and childhood growth retardation

Front 105

behavioral/cognitive tx for insomnia (6)

Back 105

– Stimulus Control Therapy
– Sleep Restriction Therapy
– CBT
– Relaxation and Stress Management Techniques
– Light Therapy
– Sleep Hygiene Education

Front 106

good sleep hygiene advice (5)

Back 106

• Fix a bedtime and fix an awakening time
• Avoid napping during the day
• Don’t stay in bed or go to bed if you aren’t
sleepy
• Reserve the bedroom for sleep and sex –
NOT work
• Avoid stimulating substances/medications
close to bedtime

Front 107

more good hygiene advice (5)

Back 107

Avoid alcohol at bedtime
• Avoid foods in the evening that may lead to
GI upset
• Regular exercise - not before bedtime (4-5
hours before)
• Bedroom cool, dark, quiet with comfortable
bedding
• Bedtime ritual

Front 108

rx options for insomnia (6)

Back 108

Non-benzodiazepine hypnotics

Benzodiazepines

Antihistamines

Antidepressants

Melatonin receptor agonist

Natural Products/Supplements

Front 109

what happens when you bind to GABAa and activate it? (3)

Back 109

ligand-gated ion channel
– Binding to BZ recognition sites on GABA-A receptors
(in the presence of GABA) potentiates response to
GABA
• Leads to influx of chloride ions through channel, resulting in
membrane hyperpolarization, neuronal inhibition

Front 110

BZ receptors (3) where they are located in brain and what they do

Back 110

BZ1/omega 1- cerebellum; anxiolytic/sedative

BZ2/omega 2- spinal/striatum; muscle relaxation

BZ3- peripheral kidney; NO ONE KNOWS FUNCTION

Front 111

Z ypnotics MoA

Back 111

act by relatively selective binding to the BZ-1 binding site on GABA A receptor

Front 112

z hypnotics (3)

Back 112

zolpidem
zaleplon
eszopiclone (lunesta)

Front 113

4 properties of z hypnotics

Back 113

– Lack of anticonvulsant, myorelaxant, and anxiolytic
effects at therapeutic doses
– General preservation of sleep architecture
– Less rebound insomnia and lower risk of
tolerance/physical dependence
-trials support use in transient AND chronic insomnia

Front 114

PK comparisons of Z hypnotics (onset, metabolism, duration)

Back 114

all have really fast onsets

all metabolized through 3A4, lunesta also 2E1)
duration about 6-8 hours

Front 115

dosing recs for elderly for z hyptnotics- KNOW THESE (4)

Back 115

--age 65+

basically cut in half (zolpidem 5 mg, CR 6.25 mg, zaleplon/sonata 5 mg, lunesta/eszoplicone- 1-2 mg

Front 116

dosing chart for z hypnotics- for adults
hepatic?

Back 116

zolpidem- 10 mg
CR- 12.5 mg
zaleplon- 10 mg
eszopiclone- 2-3 mg

hepatic dosing (half) for all- severe hepatic avoid sonata

Front 117

AE of z hypnotics (non bdz) (4)

Back 117

Memory & psychomotor function mostly with zolpidem but maybe a class effect
Tolerance- little evidence of this
Dependence- lower than with BDZ
Withdrawal/rebound- none with sonata, mild with zolpidem and lunesta

Front 118

more shit on AE of z hypnotics

Back 118

--

Front 119

zolpidem specific AE (5)

Back 119

Drowsiness (2%), dizziness (1%), diarrhea (1%),
dizziness (5%), drugged feeling (3%)

Front 120

Zaleplon (3) specific AE

Back 120

Abdominal pain (6%), headache (30%),
paresthesia (3%)

Front 121

eszoplicone AE (4)

Back 121

Altered taste (17%*), headache (21%), dry mouth
(5%), dizziness (5%)

Front 122

BDZ hypnotics info- MoA

additional effects (4)

effect on sleep (2)

Back 122

Binds to BZ1/2 binding sites on GABAA...so...

has anticonvulsant, myorelaxant, anxiolytic and sedative properties

redues sleep latency and increases total sleep time
DOES have effect on sleep architecture by incresaing stage 2 sleep, while decreasing deeper sleep

Front 123

BDZ hypnotics PK0 which ones have no renal/hepatic dose adjustments

metabolic enzymes

Back 123

tempazepam- does not have CYP metabolism, so no hepatic dose adjustments (or renal)

triazolam- also no renal adjust

others are CYP3A4


more details- mentioned stuff about renal/hepatic

Front 124

BDZ dosing in elderly

Back 124

avoid or dose reduce-- see slide considered BEERS criteria meds)

Front 125

dosing for BDZ in insomnia (adults vs. elderly) (5)

Back 125

traizolam- 0.125-5 mg (0.25 max for elderly)
estazolam- 1-2 mg (0.5 max for elderly)
quazepam- 7.5-15 mg (elderly avoid; or cap at 7.5)
flurazepam- 15-30 mg (avoid in elerly or cap at 15)
temazepam- 15-30 mg (half dose in elderly)

Front 126

BDZ hypnotics- choice of therapy depends on what? (4)

Back 126

• Difficulty initiating sleep = short-acting BZDs
• Difficulty maintaining sleep or early morning awakening =
intermediate acting BZDs
• Short term use: limited to 7-14 days
• Chronic insomnia: BZD use should be intermittent, shortterm,
and aimed at using during particularly stressful
periods

Front 127

8 AE of BDZs

Back 127

– Daytime sedation
– Anterograde amnesia
– Rebound insomnia
– Withdrawal
– Dependency
– Increased risk for falls
– Increased risk of MVA – Tolerance

Front 128

caution for use in BDZ (4)

Back 128

– In those whose jobs require mental alertness
– History of alcohol, drug, substance abuse
– Pregnant or lactating women
– Use with other/multiple CNS depressants

Front 129

histmaine receptors and ligands that cause increased sleepiness (2)

Back 129

H1-antagonists and H3-agonists known to increase sleep

Front 130

H1 antagonists do what to your sleep

dose dependency?

tolerance?

Back 130

– Suppress REM sleep, may produce REM rebound
upon withdrawal
– Increasing dose does not increase sedation, only
AEs
– Tolerance to sedative effects can occur with
continued administration

Front 131

Dosing for H1-antagonists (3)

Back 131

-diphenhydramine (Benadryl®) 25-50 mg
– doxylamine (UniSom®) 25-50 mg
– hydroxyzine (Atarax®) 25-50 mg

Front 132

AE of H1-antagonists (3) and caution in what pop

Back 132

next-day sedation, anticholinergic
effects, mental fogginess

caution in elderly

Front 133

antidepressants sedation mechanism

Back 133

Sedation and somnolence likely due to
effects of either/both 5-HT2 and H1-
antagonism

Front 134

sedative antidepressants (3)

Back 134

– Mirtazepine, trazodone, TCAs

Front 135

antidepressant sedative effect properties (3)

Back 135

– Reduce sleep latency, increase total sleep time
– May reduce REM sleep, reports of both
improvement and disruption of slow-wave sleep
– “Dirty” receptor profiles may cause AE’s,
particularly with increased doses

Front 136

4 ADs used for sleep and dosing

Back 136

– mirtazapine (Remeron®) 15 mg
– trazodone (Deseryl®) 50-150 mg
– amitriptyline (Elavil®) 10-50 mg
– doxepin (Sinequan®) 10-50 mg

Front 137

AEs of antidepressants used for sleep (3)

Back 137

Antimuscarinic: xerostomia, blurred vision,
constipation, urinary retention, anterograde
amnesia, sinus tachycardia
– Histamine-1 antagonism: weight gain
– α-1 receptor antagonism: orthostatic hypotension (TCAs thought to have these)

Front 138

melatonin- endogenous secretion from where
what causes it's release

Back 138

Endogenous secretion from pineal gland controlled
by the hypothalamus
• Darkness → endogenous melatonin production and
release

Secretion of melatonin believed to ↓ with age

Front 139

melatonin- exogenous admin does what to sleep cycles?

Back 139

Exogenous administration leads to circadian phaseshifting
effect – advance delayed rhythms

Front 140

Exogenous melatonin downside (3)

Back 140

poor pharmacokinetic profile
• Low bioavailability, subject to first-pass metabolism
• Non-selective binding to melatonin receptors

Front 141

melatonin receptor agonist

Back 141

ramelteon

Front 142

ramelteon slides (all)

Back 142

– Agonist with high selectivity for MT1 and MT2
receptors

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Front 143

dosing of ramelteon
avoid what

Back 143

• 8mg taken 30 min before bedtime; avoid high fat meals as they delay absorption (no dose response effect)

Front 144

ramelteon AE (4)

Back 144

• Headache (7%), fatigue (4%), dizziness (5%)
• Increase in serum prolactin levels, particularly among
females

Front 145

melatonin- as a drug (2)

Back 145

– Exogenous administration thought to be of
benefit particularly in those with low
endogenous melatonin
– Tolerance not reported with continued use

Front 146

melatonin AE (4) (missing some other shit on those slides)

Back 146

AE: HA, tachy, depression, itching

Front 147

melatonin efficacy in trials (3)

Back 147

• Reduced sleep onset latency by 4 min
• Increased sleep efficiency by 2.2%
• Increased total sleep duration by 13 min

Front 148

melatonin in elderly

Back 148

pretty benign


idk can add it? check slide

Front 149

natural products- recommend?
2 options

Back 149

recommend against

kava kava

valerian extract