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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
Guidelines for maintenance therapy in BD
After about 6 months stable | Maintaining adherence and optimal dosage very important
26
Lithium
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
27
Lithium dosing
300 mg BID-TID increase based on serum levels and response Typical dosing range: 900-1800mg/day BID most common
28
Lithium pharmacokinetics
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
29
Lithium monitoring
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
30
Lithium serum levels
Acute mania- 0.8-1.2 mEq/L | Maintenance and elderly- 0.6-1mEq/L
31
Lithium BBW
Narrow therapeutic index/high risk drug
32
Lithium AE
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
33
What to do about lithium induced tremor
Administer propranolol
34
What to do about nephrogenic DI like syndrome
Diuretics if severe (amiloride)
35
Lithium toxicity
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
36
When to dialyze lithium toxicity
>2.5 mEq/L- if patient is symptomatic >4 mEq/L- regardless of symptoms Do not give activated charcoal
37
Lithium DDI
``` Thiazides ACE inhibitors Loop diuretics ARBs NSAIDs Sodium ```
38
Valproic acid/divalproex "VPA"
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
39
VPA PK and monitoring
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
40
VPA bbw
Hepatotoxicity- contraindicated in liver disease Pancreatitis- may be life threatening Teratogenic
41
VPA AE
``` Thrombocytopenia- dose related AND idiosyncratic Sedation N/V/diarrhea Weight gain and PCOS Alopecia Tremor Hyperammonemia ```
42
VPA toxicity
Typically at 150mcg/mL Greatest concern- hepatotoxicity, hyperammonemic encephalopathy L-carnitine supplementation may ameliorate acute effects Can give activated charcoal or lactulose
43
Carbamazepine
BD, acute manic or mixed episodes | MOA is unclear in BD
44
PK and monitoring of carbamazepine
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
Carbamazepine AE
Sedation, photosensitivity, alopecia, nystagmus, N/V, constipation, Vitamin D/calcium deficiency Hepatotoxicity, systemic hypersensitivity rxns, fetal abnormalities in pregnancy
46
BBW of carbamazepine
HLA-B *1502 positive risk of rash and systemic reactions | Anemia/agranulocytosis
47
Lamotrigine
Bipolar I disorder- maintenance NOT for acute mania MOA unclear for BD Safer in pregnancy than other mood stabilizers
48
Lamotrigine PK and monitoring
Metabolized by UGT, variable T1/2 | Monitoring- skin, CBC, LFTs, SCr baseline and annually
49
Lamotrigine BBW
Skin rash and SJS/TEN | More common in young age, fast titration, concomitant valproate
50
Lamotrigine AE
``` DRESS dizziness and ataxia GI effects Diplopia, blurry vision Hematological effects rare Hepatitis Aseptic meningitis HLH ```
51
Dose of lamotrigine without inducers/inhibitors
25mg daily x 2 weeks, 50 mg daily x 2 weeks, 100mg daily x 1 week, max 200 mg QD
52
Lamotrigine doses with inducers (phenytoin, CBZ)
50 mg daily x 2 weeks, 100mg daily x 2 weeks, 200 mg daily x 1 week, max 400mg QD
53
Lamotrigine dosing with inhibitors (VPA)
25mg every other day x 2 weeks, 25mg QD x 2 weeks, 50mg daily x 1 weeks, max 100 mg daily
54
Antipsychotics approved for BD
Cariprazine Lurasidone Olanzapine/fluoxetine Quetiapine
55
Antipsychotics approved for acute manic/mixed episodes
``` Aripiprazole Asenapine Cariprazine Olanzapine Quetiapine Risperidone Ziprasidone ```
56
Children and BD
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
Pregnancy and BD
Avoid VPA and CBZ ECT is considered same in depression Acute mania- avoid benzos, avoid lithium in 1st trimester
58
BD in lactation
High concetrations Lithium excreted in high levels of breastmilk VPA, CBZ, LAM- enter breast milk Floppy baby syndrome
59
BP in elderly
New-onset illness unlikely | Start low, go slow
60
Etiology of insomnia
Situational Medical Psychiatric Medication induced
61
Which meds can cause insomnia?
``` Anticonvulsants Central adrenergic blockers (clonidine, guanfacine, methyldopa) Diuretics SSRIs Steroids Stimulants ```
62
Sleep cycle
Non-rapid eye movement (NREM) | Rapid eye movement (REM)- brain is electrically and metabolically activated
63
Wake promoters
``` Acetylcholine Dopamine Histamine NE Orexin Serotonin ```
64
Sleep promotors
Adenosine GABA Melatonin Galanin
65
Classification of insomnia
``` Duration: Transient <1 week Short term: 1 week to 3 months Chronic >3 months Primarily secondary insomnia ```
66
Sleep onset latency
Definition- time to fall asleep | Goal: Reduce to <30 minutes
67
Total sleep time (TST)
Def- time in bed minus time spent awake | Goal >6 hours
68
Wake time after sleep onset
Definition- time awake after initial sleep onset until final awakening Goal- reduce to <30 minutes
69
Sleep efficiency
Ratio of TST/time spent in bed | Goal: >80-85%
70
Guideline recommendations for insomnia
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
1st line non pharm recommendations for insomnia
CBT-i
72
Pharmacologic treatment options for insomnia
``` Benzos Non-benzo GABA-A agonists Dual orexin receptor antagonists (DORA) Melatonin receptor agonists Antidepressants Antihistamines OTC supplements and herbals ```
73
Benzodiazepines for insomnia
Decreases sleep latency, increases stage 2 slee, increases TST, decreases delta and REM sleep Do not stop abruptly- withdrawal
74
Benzos for insomnia contraindications and BBW
Contraindications- pregnancy, sleep apnea, pulmonary insufficiency, history of substance abuse. BBW- combining with opioid medicaitons
75
Benzos for insomnia
``` Estazolam Temazepam Triazolam Flurazepam Quazepam ```
76
Non-Benzo GABA A agonists
``` 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
Melatonin receptor agonists
Ramelteon | Can use in sleep apnea, COPD, and substance abuse
78
When do you use antidepressants for insomnia?
For patients with concomitant depression, pain, or risk of substance abuse TCAs- doxepin, amitriptyline Mirtazapine Trazodone
79
Dual orexin receptor antagonists (DORAs)
Suvorexant Lemborexant Turns off wake signaling Contraindicated for patients with sleep paralysis. Plan for at least 7 hours of sleep before wakening.
80
OTC supplements and herbals for sleep disorders.
Melatonin | Valerian
81
Antihistamines for insomnia
diphenhydramine Doxylamine Hydroxyzine
82
Sedating meds used to treat pain
Gabapentin, amitriptyline, doxepin
83
Sedating meds used for depression
Mirtazapine, amitriptyline, doxepin, trazodone
84
Sedating meds used to treat anxiety
Hydroxyzine, mirtazapine, amitripyline, doxepin, trazodone
85
Sedating meds that you can use in patients with substance abuse
Hydroxyzine, mirtazapine, amitriptyline, doxepin, trazodone, gabapentin
86
Treatment algorithm for insomnia
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
Narcolepsy
Type 1- narcolepsy with cataplexy | Type 2- narcolepsy without cataplexy
88
Narcolepsy tetrad
Excessive daytime sleepiness Cataplexy (sudden bilateral loss of muscle tone) Hallucinations Sleep paralysis
89
Pathophysiology of narcolepsy
Loss of function of the hypocretin-orexin neurotransmitter system Genetic Environmental influences
90
DSM-5 Criteria for narcolepsy
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
Nonpharm for narcolepsy
Good sleep hygiene | 2 or more scheduled daytime naps lasting 15 minutes each
92
Pharmacologic therapy for narcolepsy
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
EDS treatment
Modafinil, Armodafinil | Lack efficacy for treatment of cataplexy
94
Stimulants for narcolepsy
Amphetamines, Vyvanse, Methylphenidate
95
Solriamfetol and pitolisant
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
Cataplexy treatment
TCAs (imipramine, nortripyline, clomipramine) SNRIs/SSRIs (venlafaxine, fluoxetine) Selegiline Sodium oxybate
97
Sodium oxybate
REMS program | BBW- CNS depression, abuse or misuse, restricted distribution via REMS
98
Sleep apnea
Characterized by repetitive episodes of cessation of breathing during sleep
99
Treatment of OSA
Positive airway pressure, weight reduction, surgery, position therapies No drug therapy Medications that worsen sleep should be avoided
100
Tx od CSA
Treat underlying cause | Acetazolamide and theophylline
101
Jet lag tx
Short acting R drugs Ramelteon Melatonin
102
Shift work sleep disorder tx
Short acting Z drugs Ramelteon melatonin Modafinil and armodafinil for EDS
103
Non-24-hour sleep-wake disorder
Melatonin and tasimelteon
104
Tasimelteon
MT1 and MT2 receptor agonist Take sweeks to months to work Admin with food 1 hour before bedtime
105
Restless legs syndrome
Characterized by paresthesias usually felt deep in the calf muscles that lead to the urge to keep limbs in motion.
106
Treatment for RLS
Dopamine agonist or gabapentinoid
107
Dopamine agonists for RLS
Pramipexole, ropinirole, rotigotine
108
Additional therapies for RLS
Iron supplementation Opioids Sedative/hypnotics
109
Parasomnias tx
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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