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Therapeutics 4 > Exam 5 part 2 > Flashcards

Exam 5 part 2 Flashcards

1
Q

Etiology and risk for bipolar disorder

A

High income > low income
Genetic predisposition
Males= females
Childbirth may trigger hypomania

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2
Q

Clinical course of bipolar disorder

A

Typical onset late adolescence to early adulthood

>90% who have a manic episode will have more

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3
Q

Diagnostic criteria for a manic episode

A

Abnormally and persistent

  • elevated, expansive, irritable mood
  • Increase in goal-directed activity or energy

Plus >3 of DIGFAST criteria, if mood is only irritable >4

Marked impairment in social and occupational function

Not caused by substance or medical condition

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4
Q

DIGFAST

A 
Distractibility 
Indiscretion 
Grandiosity
Flight of ideas
Acitivity decrease 
Sleep deficit
Talkativeness (pressured speech)
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5
Q

Diagnostic criteria for hypomanic episode

A

Change in functioning that is uncharacteristic and observable by others
Not severe enough to cause marked impairment in functioning, hospitalization
Patient cannot have symptoms of psychosis

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6
Q

Diagnostic criteria of a major depressive episode for bipolar

A

Same as MDD
>5 symptoms during a 2 week period
1 symptoms must be depressed mood or loss of interest/pleasure (D-SIGECAPS)
Significant impairment and substance/medical condition rule out applies

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7
Q

D-SIGECAPS (depression symptoms)

A 
Depressed mood most of the time
Sleep disturbances
Interest 
Guilt//worthlessness
Energy decrease
Concentration difficulties
Appetite decrease
Psychomotor agitation and retardation
Suicidal ideation
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8
Q

Rapid cycling diagnostic criteria

A

> 4 episodes in the previous 12 months

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9
Q

Bipolar 1 disorder

A

1 manic episode

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10
Q

Bipolar 2 disorder

A

1 hypomanic and 1 depressive

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11
Q

Pathophysiology of bipolar disorder

A

Excitatory/Inhibitory neurochemical dysregulation
Circadian rhythm abnormalities
Second messenger signaling dysregulation
Other neuronal and hormonal abnormalities

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12
Q

Neurochemical impact on bipolar disorder

A

Traditional theories of neurotransmission more recently come into question
Downstream effect- likely secondary to other dysregulatory mechs
DA, NE, 5-HT3- concentrated in limbic system, prefrontal cortex, implicated in mood and thought
GABA and glutamate

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13
Q

Second messengers and neuroplasticity

A

Treatment may act on second messenger systems
Effects on intracellular signaling, gene expression, apoptosis and neuronal pathways influence course and response in bipolar disorder

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14
Q

Neuroendocrine, cellular, and immune function in bipolar disorder

A

Stress response alteration

  • HPA axis
  • Increased cortisol

Greater rate of mitochondrial disorders

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15
Q

Circadian rhythm dysfunction in BD

A

Sleep wake disruptions common
Gene expressions in the hypothalamus responsible for sleep-wake have been linked to bipolar disorder
Sleep disturbances may kindle mood episodes in predisposed individuals.

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16
Q

Nonpharm therapy for BD

A

Maintaining appropriate diet and sleep
Supportive counseling and other therapies
ECT
Bright light therapy in depressive episodes
Transcranial magnetic stimulation

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17
Q

Monotherapy treatment for acute mania in BD

A

Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, cariprazine

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18
Q

First line monotherapy for precvention of mood episode in BD

A

Lithium, quetiapine, divalproex

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19
Q

Prevention of mania first line treatment

A

Lithium, quetiapine

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20
Q

Prevention of depression first line treatment BD

A

Lithium, quetiapine

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21
Q

Acute depression 1st line treatment

A

Quetiapine

Lurasidone + lithium/DVP

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22
Q

Prevention of mood episode after a depression episode in BD

A

Quetiapine

Lithium

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23
Q

Maintenance therapy for BD

A

Lithium, quetiapine, divalproex, lamotrigine, quetiapine + Li/DVP

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24
Q

What to do if immediate symptom relief is required in BD?

A

Benzodiazepines short term

Need for sleep, significant agitation

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25
Q

Guidelines for maintenance therapy in BD

A

After about 6 months stable

Maintaining adherence and optimal dosage very important

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26
Q

Lithium

A

For BD in acute manic episodes and maintenance
Data supports efficacy in preventing relapse and hospital admission
Suicide protective properties
Inorganic cation that performs multiple functions within the CNS, true MOA unclear

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27
Q

Lithium dosing

A

300 mg BID-TID increase based on serum levels and response
Typical dosing range: 900-1800mg/day
BID most common

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28
Q

Lithium pharmacokinetics

A

Slow accumulation in CSF; two compartment model
Slow body distribution and delayed onset of action, all cellular membranes crossed slowly.
Renally eliminated by filtration, follows sodium, no metabolism
Slow elimination from cells- patients may present toxic
SS 5 days

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29
Q

Lithium monitoring

A

CBC, TSH weight, metabolic profile with calcium
Thyroid changes, thyroid mistakes lithium with other ions
Check all twice in 6 months then periodically

Pregnancy test- cardiac abnormalities in 1st trimester
EKG- baseline and annual if >40 years old

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30
Q

Lithium serum levels

A

Acute mania- 0.8-1.2 mEq/L

Maintenance and elderly- 0.6-1mEq/L

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31
Q

Lithium BBW

A

Narrow therapeutic index/high risk drug

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32
Q

Lithium AE

A

Nausea/diarrhea
Hypothyroidism
Tremor
Weight gain
Nephrogenic diabetes insipidus-like syndrome
Memory impairment
Renal insufficiency (minor GFR decrease)
Hypercalcemia
Cardiac arrhythmias (T waves or ST segment abnormalities)
Acne, psoriasis

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33
Q

What to do about lithium induced tremor

A

Administer propranolol

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34
Q

What to do about nephrogenic DI like syndrome

A

Diuretics if severe (amiloride)

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35
Q

Lithium toxicity

A

May be acute or chronic
Mild- N, vomiting, diarrhea, lethargy, hand tremor
Moderate- coarse hand tremor, slurred speech, unsteady gait, confusion, muscle fasciculation
Severe- seizures, stupor, coma, arrhythmias, death

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36
Q

When to dialyze lithium toxicity

A

> 2.5 mEq/L- if patient is symptomatic
4 mEq/L- regardless of symptoms
Do not give activated charcoal

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37
Q

Lithium DDI

A 
Thiazides
ACE inhibitors
Loop diuretics
ARBs
NSAIDs
Sodium
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38
Q

Valproic acid/divalproex “VPA”

A

FDA approved for bipolar disorder, acute manic or mixed episodes
Mechanism in bipolar disorder unclear- enhances GABA activity, inhibits reuptake, normalizes sodium and calcium channels
10-20 mg/kg/day adjusted by level
MAX 60mg/kg/day

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39
Q

VPA PK and monitoring

A

PK-
Nonlinear, highly protein bound, pharmacodynamic interaction with topiramate

Monitoring- trough serum levels after 3-5 days, acute mania 50-125mcg/ml
Monitor CBC, LFTs, SCr baseline, 3 months and annually
Ammonia level when indicated

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40
Q

VPA bbw

A

Hepatotoxicity- contraindicated in liver disease
Pancreatitis- may be life threatening
Teratogenic

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41
Q

VPA AE

A 
Thrombocytopenia- dose related AND idiosyncratic 
Sedation
N/V/diarrhea
Weight gain and PCOS
Alopecia
Tremor
Hyperammonemia
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42
Q

VPA toxicity

A

Typically at 150mcg/mL
Greatest concern- hepatotoxicity, hyperammonemic encephalopathy
L-carnitine supplementation may ameliorate acute effects
Can give activated charcoal or lactulose

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43
Q

Carbamazepine

A

BD, acute manic or mixed episodes

MOA is unclear in BD

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44
Q

PK and monitoring of carbamazepine

A

Global inducer and autoinducer
Induces own metabolism
Hepatic metabolism through 3A4

Monitoring- CBZ serum levels at 10-14 days
CBC baseline, 3 months, annually
LFTs/electrolyes/ SCr/ BUN baseline, 3 mo, annually
EKG

45
Q

Carbamazepine AE

A

Sedation, photosensitivity, alopecia, nystagmus, N/V, constipation, Vitamin D/calcium deficiency
Hepatotoxicity, systemic hypersensitivity rxns, fetal abnormalities in pregnancy

46
Q

BBW of carbamazepine

A

HLA-B *1502 positive risk of rash and systemic reactions

Anemia/agranulocytosis

47
Q

Lamotrigine

A

Bipolar I disorder- maintenance
NOT for acute mania
MOA unclear for BD
Safer in pregnancy than other mood stabilizers

48
Q

Lamotrigine PK and monitoring

A

Metabolized by UGT, variable T1/2

Monitoring- skin, CBC, LFTs, SCr baseline and annually

49
Q

Lamotrigine BBW

A

Skin rash and SJS/TEN

More common in young age, fast titration, concomitant valproate

50
Q

Lamotrigine AE

A 
DRESS
dizziness and ataxia
GI effects
Diplopia, blurry vision
Hematological effects rare
Hepatitis
Aseptic meningitis
HLH
51
Q

Dose of lamotrigine without inducers/inhibitors

A

25mg daily x 2 weeks, 50 mg daily x 2 weeks, 100mg daily x 1 week, max 200 mg QD

52
Q

Lamotrigine doses with inducers (phenytoin, CBZ)

A

50 mg daily x 2 weeks, 100mg daily x 2 weeks, 200 mg daily x 1 week, max 400mg QD

53
Q

Lamotrigine dosing with inhibitors (VPA)

A

25mg every other day x 2 weeks, 25mg QD x 2 weeks, 50mg daily x 1 weeks, max 100 mg daily

54
Q

Antipsychotics approved for BD

A

Cariprazine
Lurasidone
Olanzapine/fluoxetine
Quetiapine

55
Q

Antipsychotics approved for acute manic/mixed episodes

A 
Aripiprazole
Asenapine
Cariprazine
Olanzapine
Quetiapine
Risperidone
Ziprasidone
56
Q

Children and BD

A

Difficult to diagnose
Aim for short term treatment and frequent re-evaluation
SGAs: risperidone, olanzapine, quetiapine, aripiprazole, asenapine
Mood stabilizers- lithium (best), valproic acid, carbamazepine

57
Q

Pregnancy and BD

A

Avoid VPA and CBZ
ECT is considered same in depression
Acute mania- avoid benzos, avoid lithium in 1st trimester

58
Q

BD in lactation

A

High concetrations
Lithium excreted in high levels of breastmilk
VPA, CBZ, LAM- enter breast milk
Floppy baby syndrome

59
Q

BP in elderly

A

New-onset illness unlikely

Start low, go slow

60
Q

Etiology of insomnia

A

Situational
Medical
Psychiatric
Medication induced

61
Q

Which meds can cause insomnia?

A 
Anticonvulsants
Central adrenergic blockers (clonidine, guanfacine, methyldopa)
Diuretics
SSRIs
Steroids
Stimulants
62
Q

Sleep cycle

A

Non-rapid eye movement (NREM)

Rapid eye movement (REM)- brain is electrically and metabolically activated

63
Q

Wake promoters

A 
Acetylcholine
Dopamine
Histamine
NE
Orexin
Serotonin
64
Q

Sleep promotors

A

Adenosine
GABA
Melatonin
Galanin

65
Q

Classification of insomnia

A 
Duration: 
Transient <1 week
Short term: 1 week to 3 months
Chronic >3 months
Primarily secondary insomnia
66
Q

Sleep onset latency

A

Definition- time to fall asleep

Goal: Reduce to <30 minutes

67
Q

Total sleep time (TST)

A

Def- time in bed minus time spent awake

Goal >6 hours

68
Q

Wake time after sleep onset

A

Definition- time awake after initial sleep onset until final awakening
Goal- reduce to <30 minutes

69
Q

Sleep efficiency

A

Ratio of TST/time spent in bed

Goal: >80-85%

70
Q

Guideline recommendations for insomnia

A

Nonpharm is standard of care
Sleep hygiene as monotherapy is insufficient
Initial treatment should include behavioral intervention
If pharmacologic treatment is indicated, want to use lowest possible dose for shortest time period

71
Q

1st line non pharm recommendations for insomnia

A

CBT-i

72
Q

Pharmacologic treatment options for insomnia

A 
Benzos
Non-benzo GABA-A agonists
Dual orexin receptor antagonists (DORA)
Melatonin receptor agonists
Antidepressants
Antihistamines
OTC supplements and herbals
73
Q

Benzodiazepines for insomnia

A

Decreases sleep latency, increases stage 2 slee, increases TST, decreases delta and REM sleep
Do not stop abruptly- withdrawal

74
Q

Benzos for insomnia contraindications and BBW

A

Contraindications- pregnancy, sleep apnea, pulmonary insufficiency, history of substance abuse.
BBW- combining with opioid medicaitons

75
Q

Benzos for insomnia

A 
Estazolam
Temazepam
Triazolam
Flurazepam
Quazepam
76
Q

Non-Benzo GABA A agonists

A 
Associated with less withdrawal, tolerance, and rebound insomnia than benzo hhypnotics
BBW- complex sleep related behaviors
Take on an empty stomach
Avoid alcohol and other CNS depressants
Zolpidem, Zaleplon, Eszopiclone
77
Q

Melatonin receptor agonists

A

Ramelteon

Can use in sleep apnea, COPD, and substance abuse

78
Q

When do you use antidepressants for insomnia?

A

For patients with concomitant depression, pain, or risk of substance abuse
TCAs- doxepin, amitriptyline
Mirtazapine
Trazodone

79
Q

Dual orexin receptor antagonists (DORAs)

A

Suvorexant
Lemborexant
Turns off wake signaling
Contraindicated for patients with sleep paralysis. Plan for at least 7 hours of sleep before wakening.

80
Q

OTC supplements and herbals for sleep disorders.

A

Melatonin

Valerian

81
Q

Antihistamines for insomnia

A

diphenhydramine
Doxylamine
Hydroxyzine

82
Q

Sedating meds used to treat pain

A

Gabapentin, amitriptyline, doxepin

83
Q

Sedating meds used for depression

A

Mirtazapine, amitriptyline, doxepin, trazodone

84
Q

Sedating meds used to treat anxiety

A

Hydroxyzine, mirtazapine, amitripyline, doxepin, trazodone

85
Q

Sedating meds that you can use in patients with substance abuse

A

Hydroxyzine, mirtazapine, amitriptyline, doxepin, trazodone, gabapentin

86
Q

Treatment algorithm for insomnia

A

Short term- sleep hygiene and Z drug or ramelteon. With inadequate response add trazodone, change Z drugs, or suvorexant
Chronic- CBT-i +/- sleep hygiene, treat underlying condition, add Z drug if necessary

87
Q

Narcolepsy

A

Type 1- narcolepsy with cataplexy

Type 2- narcolepsy without cataplexy

88
Q

Narcolepsy tetrad

A

Excessive daytime sleepiness
Cataplexy (sudden bilateral loss of muscle tone)
Hallucinations
Sleep paralysis

89
Q

Pathophysiology of narcolepsy

A

Loss of function of the hypocretin-orexin neurotransmitter system
Genetic
Environmental influences

90
Q

DSM-5 Criteria for narcolepsy

A

Recurrent episodes of an irresistible need to sleep, fall asleep, or nap.
Occurs at least 3 times per week for the past 3 months.
Must experience one of the following:
-cataplexy
hypocretin deficiency
REM sleep latency of 15 minutes or less

91
Q

Nonpharm for narcolepsy

A

Good sleep hygiene

2 or more scheduled daytime naps lasting 15 minutes each

92
Q

Pharmacologic therapy for narcolepsy

A

Goal: reduce symptoms that adversely affect the patients QOL and allow for the possible return of normal function
Treatment focused on EDS and REM sleep abnormalities

93
Q

EDS treatment

A

Modafinil, Armodafinil

Lack efficacy for treatment of cataplexy

94
Q

Stimulants for narcolepsy

A

Amphetamines, Vyvanse, Methylphenidate

95
Q

Solriamfetol and pitolisant

A

Pitolisant- contraindicated in severe hepatic impairment, recommend additional contraceptive up to 21 days after discontinuing, may take 8 weeks to see effect
Qt prolongation
Tx for narcolepsy

96
Q

Cataplexy treatment

A

TCAs (imipramine, nortripyline, clomipramine)
SNRIs/SSRIs (venlafaxine, fluoxetine)
Selegiline
Sodium oxybate

97
Q

Sodium oxybate

A

REMS program

BBW- CNS depression, abuse or misuse, restricted distribution via REMS

98
Q

Sleep apnea

A

Characterized by repetitive episodes of cessation of breathing during sleep

99
Q

Treatment of OSA

A

Positive airway pressure, weight reduction, surgery, position therapies
No drug therapy
Medications that worsen sleep should be avoided

100
Q

Tx od CSA

A

Treat underlying cause

Acetazolamide and theophylline

101
Q

Jet lag tx

A

Short acting R drugs
Ramelteon
Melatonin

102
Q

Shift work sleep disorder tx

A

Short acting Z drugs
Ramelteon
melatonin
Modafinil and armodafinil for EDS

103
Q

Non-24-hour sleep-wake disorder

A

Melatonin and tasimelteon

104
Q

Tasimelteon

A

MT1 and MT2 receptor agonist
Take sweeks to months to work
Admin with food 1 hour before bedtime

105
Q

Restless legs syndrome

A

Characterized by paresthesias usually felt deep in the calf muscles that lead to the urge to keep limbs in motion.

106
Q

Treatment for RLS

A

Dopamine agonist or gabapentinoid

107
Q

Dopamine agonists for RLS

A

Pramipexole, ropinirole, rotigotine

108
Q

Additional therapies for RLS

A

Iron supplementation
Opioids
Sedative/hypnotics

109
Q

Parasomnias tx

A

NREM disorders- benzos, SSRIs, or TCAs

REM behavior disorder- clonazepam DOC, can also use melatonin and pramipexole

Therapeutics 4 (8 decks)

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