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PHARM 557 > Midterm 2 > Flashcards

Midterm 2 Flashcards

1
Q

Neurochemical theories for anxiety

A

Noradrenergic model
GABA receptor model
Serotonin model

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2
Q

3 main categories for anxiety

A
  1. Anxiety disorder
  2. Obsessive compulsive disorders
  3. Trauma and stressor-related disorders
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3
Q

Types of anxiety disorders

A 
Social anxiety disorder 
Generalized anxiety disorder
Specific phobia
Separation anxiety disorder
Panic disorder
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4
Q

Types of obsessive compulsive disorders

A

Obsessive compulsive disorder
Hoarding disorder
Trichotillomania disorder - hair
Excoriation disorder - skin

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5
Q

Types of trauma and stressor-related disorders

A

Post-traumatic stress disorder (PTSD) - most common
Acute stress disorder
Reactive attachment disorder

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6
Q

Generalized anxiety disorder DSM-5 diagnosis

A
  • excessive anxiety/worry occurring more days than not for at least 6 months
  • 3 or more of the following 6 sx:
  • restlessness
  • fatigued
  • difficulty concentrating
  • irritability
  • muscle tension
  • sleep disturbance
  • only 1 item required for children
  • causes distress or impairment in important areas of functioning
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7
Q

Obsessive compulsive disorder DSM-5 diagnosis

A

-presence of time-consuming (over 1hr per day) obsessions and/or compulsions that cause significant distress and interfere with functioning

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8
Q

Criteria for panic attack

A
  • discrete (start and end) period of intense fear of discomfort
  • develops abruptly and reached peak within 10mins
  • includes 4 or more:
  • SOB, choking
  • sweating
  • palpitations, tachycardia
  • dizziness
  • numbness, tingling
  • abd discomfort/nausea
  • fear of dying/going crazy/losing control
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9
Q

Goals of therapy for all types of anxiety

A
  • eliminate signs and sx of anxiety
  • achieve and maintain remission/prevent recurrence
  • reduce fear of the physical sx associated with anxiety
  • improve and maintain QOL
  • prevent self-harm and harm to others
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10
Q

Medication options for anxiety

A 
BZs
Anticonvulsants - pregabalin 
Antidepressants
Buspirone 
Imipramine 
Hydroxyzine
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11
Q

Efficacy of BZs in anxiety

A
  • provides rapid relief, but no evidence for long term use past 4-6 weeks
  • primarily effective for the somatic sx (muscle tension, etc), rather than the key psychic features (worry)
  • the thoughts wont change from the BZ but the physical onset of the attack will be halted
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12
Q

BZs used in anxiety

A 
Alprazolam
Bromazepam
Lorazepam
Diazepam
-clonazepam has not been studied, though widely used (long half life)
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13
Q

BZs that dont have active metabolites

A

Lorazepam and Clonazepam

-so not worried about liver function and dosing too high

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14
Q

BZs place in therapy for anxiety

A

2nd line

  • ideally only for short-term use (4-6wks)
  • can be used ad adjunctive therapy while waiting for other meds to become effective (SSRIs)
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15
Q

Safer BZs to use in elderly

A

Lorazepam and Clonazepam

-no active metabolites so wont accumulate in the liver

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16
Q

General strategy on how to stop BZs

A

Reduce the dosage by 25% per week, until half of the dose is reached, then reduce the dose by one eighth every 4-7days

  • if therapy was over 8wks - taper off over 4-8weeks
  • if therapy was over 1 yr - taper off over 2-4months

Keep intervals the same as long as possible! Just make the dosage smaller and smaller and then bring down the interval

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17
Q

Recurrence/relapse vs withdrawal sx

A

Recurrence/relapse is the return of the original sx with similar intensity as before the treatment
Withdrawal sx are the emergence of NEW sx and worsening of pre-existing sx after stopping the BZ

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18
Q

Most studied anticonvulsant in use of anxiety

A

Pregabalin

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19
Q

Advantages of pregabalin use in anxiety

A

Rapidly relived anxiety in as early as 1 week
Does not cause sexual dysfunction
Carries less abuse potential than BZs

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20
Q

Antidepressant place in therapy for anxiety

A

First-line option

-particularly venlafaxine, duloxetine, escitalopram

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21
Q

How long does response take for antidepressants in anxiety

A

2-4 weeks

-could take 12 weeks for full response

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22
Q

How long should antidepressant be used for in anxiety

A

At least 1 yr, as risk of relapse is high

-can try to taper off/down and re-evaluate after 1 year

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23
Q

SSRI of choice for anxiety

A

Escitalopram

  • better than paroxetine and better than fluoxetine
  • may even be better than venlafaxine
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24
Q

SNRIs used for anxiety

A

Venlafaxine and duloxetine

-first line just like SSRIs are

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25
Q

Buspirone place in Therapy for anxiety

A

2nd line option

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26
Q

Downside of Busprione for use in anxiety

A

Short half-life of 2.5hrs, so has to be dosed BID-TID

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27
Q

When is full effect of busprione for anxiety seen

A

4-6 weeks

-better than SSRIs, but worse than BZs

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28
Q

Imipramine place in therapy for anxiety

A

2nd line option

  • TCA that is particularly effective for psychic sx
  • heart effects and risk of death with overdose is reason for 2nd line
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29
Q

Hydroxyzine place in Therapy for anxiety

A

2nd line option

-SE of drowsiness/sedation limiting for the chronic use for anxiety

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30
Q

Drugs that can exacerbate anxiety

A
  • anticonvulsants - carbamazepine, phenytoin
  • antidepressants - in initial phase
  • CSs - prednisone
  • bronchodilators - salbutamol, theophylline
  • antihypertensives - clonidine, felodipine
  • dopamine Agonists - levodopa, amantadine
  • illicit drugs - ecstasy, marijuana
  • NSAIDs - ibuprofen, indomethacin
  • stimulants - caffeine, cocaine, amphetamines, nicotine
  • sympathomimetics - PSE, PE
  • thyroid hormones - levothyroxine
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31
Q

General treatment approach to anxiety

A

Start with first line agent of SSRI or SNRI

  • if response is inadequate, evaluate adherence and optimization of doses, and time (8-12weeks)
  • another first line agent should be tried before considering a 2nd line agent (BZs, buspirone, imipramine, pregabalin)
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32
Q

First-line treatment for GAD

A

Paroxetine
Escitalopram
Sertraline
Venlafaxine

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33
Q

First-line treatment for OCD

A

Paroxetine
Sertraline
Fluoxetine
Fluvoxamine

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34
Q

First-line treatment for SAD

A 
Paroxetine
Escitalopram 
Sertraline 
Venlafaxine 
Fluvoxamine
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35
Q

First-line treatment for panic disorder

A 
Paroxetine 
Sertraline 
Escitalopram 
Venlafaxine
Fluoxetine
Fluvoxamine 
Citalopram
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36
Q

First-line treatment for PTSD

A

Paroxetine
Sertraline
Venlafaxine
Fluoxetine

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37
Q

Most effective psychotherapy for anxiety

A

CBT

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38
Q

CBT components

A 
Education
Cognitive interventions
Exposure
Problem solving
Relapse prevention
Emotion-regulation approaches
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39
Q

3 hallmark sx of ADHD

A

Inattention
Hyperactivity
Impulsivity

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40
Q

To have ADHD sx must be present…

A

In 2 or more settings
-home, school, work

Interfere with normal development, and have direct unfavourable impact on important areas of functioning

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41
Q

2 main dx for ADHD

A

Primarily inattentive
Primarily hyperactive/impulsive

Or majority of both

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42
Q

Sx for inattention ADHD

A

Need 6 or more for dx, that have perished for at least 6 months:

  • fails to give close attention to details/makes careless mistakes
  • difficulty sustaining attention in tasks
  • does not seem to listen when spoken to directly
  • does not follow through on instructions/fails to finish duties
  • difficulty organizing tasks
  • forgetful in daily activities
  • easily distracted
  • loses things necessary for tasks
  • avoids/dislikes/reluctant to engage int asks that require sustained mental effort
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43
Q

Sx for hyperactivity/impulsivity ADHD

A

For dx, 6 or more must have persisted for at least 6 months:

  • fidgets or taps/squirms in seat
  • leaves seat in situations where remaining seated is expected
  • restless/runs around/climbs
  • talks excessively
  • often “on the go”
  • blurts out answers before question is completed
  • interrupts or intrudes on others
  • difficulty waiting their turn
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44
Q

Investigations for diagnosis of ADHD

A 
Hearing - biggest one!!
Vision
Thyroid function
Neurological status
Anemia
Cardiac function
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45
Q

Goals of Therapy for ADHD

A

Eliminate or significantly decrease core ADHD sx
Improve behavioural, academic, and/or occupational functioning
Improve self-esteem and social functioning
Improve QOL
Minimize AEs of medications

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46
Q

17 considerations for the treatment of ADHD

A
  1. Age and individual variation
  2. Duration of effect
  3. Speed of action of the med
  4. ADHD clinical presentation
  5. Comorbid sx profile
  6. Comorbid psychiatric disorder
  7. Hx of family medication use
  8. Affordability
  9. Attitudes toward medication use
  10. Medical problems and other meds
  11. Associated features similar to medication SEs
  12. Combining stimulants with other meds
  13. Potential for misuse/diversion
  14. MD attitude towards ADHD med
  15. First-line treatments represents a balance of efficacy, tolerability, and clinical support and is approved by health Canada
  16. Second-line treatments are approved by health Canada but have lower efficacy rates
  17. Third-line treatments are reserved for situations where first-line and second-line treatments have no worked and are usually off-label medications
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47
Q

5 steps for treatment of ADHD when picking medication now

A
  1. Feedback and expectations
  2. Specific med selection
  3. Monitoring
  4. Titration
  5. Managing SEs
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48
Q

How to manage SEs of ADHD meds generally

A
  • taking the med each day will help develop a tolerance toward SEs
  • interrupting the med every weekend may increase SEs
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49
Q

Adderall XR generic

A

Amphetamine mixed salts

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50
Q

Biphentin generic

A

Methylphenidate HCl

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51
Q

Concerta generic

A

Methylphenidate HCl

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52
Q

Vyvanse generic

A

Lisdexamfetamine desmesylate

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53
Q

Strattera generic

A

Atomoxetine

Second-line for all ages of ADHD

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54
Q

Intuniv generic

A

Guanfacine

Second-line for children 6-12yr ADHD

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55
Q

Ritalin generic

A

Methylphenidate HCl

Second line for adolescent and adult ADHD

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56
Q

Dexedrine generic

A

Dextroamphetamine sulphate

Second line for adolescent and adult ADHD

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57
Q

First-line agents for children 6-12 for ADHD

A 
Adderall XR
Biphentin
Concerta
Vyvanse 
-all long acting
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58
Q

First-line agent for adolescents in ADHD

A 
Adderall XR
Biphentin 
Concerta
Vyvanse
-all long acting
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59
Q

First-line agents for adults in ADHD

A

Adderall XR
Biphentin
Concerta
Vyvanse

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60
Q

Adderall XR for ADHD

A 
Blocks reuptake of dopamine 
Stimulant
Made up primarily of dextroamphetamine 
Sx control lasts for 10-12hrs
Capsules can be opened and sprinkled on food
50/50 delivery system
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61
Q

Vyvanse in ADHD

A

Blocks reuptake of dopamine
Pro-drug! - inactive, until enzymatic transformation to dextroamphetamine
Sx control lasts 13-14hr
Only one that you can open capsule and put into water!

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62
Q

Biphentin in ADHD

A

Long-acting
Sx control for 10-12hrs
40% immediate, 60% gradual
Capsules can be opened and sprinkled on food

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63
Q

Concerta in ADHD

A

Long-acting
Sx control 10-12hrs
22% immediate, 78% gradual
Non-deformable shell reduced abuse potential

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64
Q

Ritalin IR vs Ritalin SR

A

Short-acting vs intermediate-acting

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65
Q

Ritalin in ADHD

A

Considered second-line due to duration being shorter than long-acting agents (Ritalin has peak/valley effects)
Ritalin IR good top-off agent - more flexibility with scheduling
Can be useful for adults who need medication for situational use
Ritalin SR lasts 5-6hrs longer than IR

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66
Q

Dexedrine in ADHD

A

Second-line since duration of action is shorter than long-acting (peak/valley effects)
Sx control for 3-5hrs (Spansules 6-8hrs)
Good for top-off dosing, or adults requiring use for situational purposes
Spansules can be opened and sprinkled on food

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67
Q

Stimulant AEs

A 
Appetite suppression 
Decrease in weight 
Initial insomnia
HA
Dry mouth
Anxiety
BP and HR increase
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68
Q

Growth issue with stimulants in ADHD?

A

Inconsistent results

  • some suggest ADHD itself can affect growth
  • stimulants could be associated with growth effect in first 1-3years of therapy
  • average growth of 2cm, and 2.7kg less than non-medicated pts

Should have weight/height and BMI monitored 1-2x per year of treatment

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69
Q

The 2 non-stimulants used in ADHD

A

Strattera and Intuniv

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70
Q

Strattera in ADHD

A

Noradrenaline reuptake inhibitor
Onset of action is slower than stimulants
Capsule must be swallowed whole
Continuous coverage including late evenings and early mornings
May be useful for comorbid enuresis

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71
Q

Intuniv in ADHD

A

Not going to see unless somebody has money and wants to try it
Onset of action is slower than stimulants
Tablet must be swallowed whole
Controls sx over long period of times - late evenings and early mornings
May be useful in pts with other comorbidites like tic, anxiety, and aggression

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72
Q

Depression is most common in …..

A

Females

Rates are equal in children

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73
Q

Assessment tools to evaluation severity of depression

A

Clinician-rated - Hamilton Depression Scale (HAM-D)

Patient-rated - Patient Health Questionnaire (PHQ-9)

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74
Q

Dysregulation of what 2 neurotransmitters are associated with depression

A

Serotonin and norepinephrine

Also involved in pain perception in the spinal cord

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75
Q

Response and remission defined by HAM-D scores

A

Over 15 = MDD
50% or greater reduction in baseline score = response
Score of 7 or less = remission

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76
Q

Always check which labs when investigating depression

A

B12 and thyroid

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77
Q

Diagnostic criteria for depression

A

SADIFACES

  • sleep
  • appetite (loss or gain)
  • depressed mood
  • interest (lack of)
  • fatigue
  • agitation/anxiety
  • concentration
  • esteem
  • suicidality
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78
Q

SSRIs

A 
Citalopram 
Escitalopram 
Fluoxetine 
Paroxetine
Sertraline 
Fluvoxamine 
Vortioxetine
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79
Q

Citalopram usual dose

A

20mg

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80
Q

Escitalopram usual dose

A

10mg

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81
Q

Fluoxetine usual dose

A

20mg

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82
Q

Paroxetine usual dose

A

20mg

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83
Q

Sertraline usual dose

A

50-75mg

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84
Q

Fluvoxamine usual dose

A

100mg

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85
Q

Vortioxetine usual dose

A

20mg

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86
Q

Most studied SSRIs for use in elderly

A

Citalopram
Escitalopram
Sertraline

Fewest DIs are well

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87
Q

AEs of SSRIs

A 
HANDS
-HA
-anxiety - imbalance in neurotransmitters
-nausea
-diarrhea
-sexual dysfunction 
And increased risk of GI bleeding
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88
Q

Sexual dysfunction comparison between SSRIs

A
  • worse with fluoxetine and paroxetine

- less frequent with citalopram and escitalopram

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89
Q

Clinical features of serotonin syndrome

A 
Anxiety
Agitation
Delirium
Sweating
HTN
Tachycardia 
Tremor 
Hyperthermia

Presents usually within 24hrs, mostly 6-8hrs of a change or initiation of another serotonergic drug

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90
Q

Most safe SSRI in pregnancy

A

Fluoxetine and other SSRIs are 1st line for pregnancy
-Paroxetine should be avoided

Citalopram, nortriptyline, sertraline, and paroxetine are 1st line foe breastfeeding

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91
Q

SSRI that has longest half-life

A

Fluoxetine 4-6days

All others 24hrs

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92
Q

SNRIs

A

Venlafaxine
Desvenlafaxine
Duloxetine

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93
Q

MOA of SNRIs

A

Inhibits serotonin reuptake at low doses

Dose-dependent norepinephrine reuptake inhibition at higher doses

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94
Q

Superior SNRI

A

Venlafaxine

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95
Q

Less well-tolerated SNRI

A

Duloxetine

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96
Q

Upside with duloxetine

A

Chronic neuropathic pain efficacy

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97
Q

AEs of SNRIs

A

HANDS + anticholinergic effects

Possible BP increases with high doses

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98
Q

Worse SNRI for discontinuation syndrome

A

Venlafaxine

Some people describe electrical shock-like feelings

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99
Q

bupropion MOA

A

Not fully understood

  • does NOT effect serotonin or MAO!!
  • inhibits NE and dopamine reuptake
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100
Q

Bupropion CI

A

Should not be used in those with concurrent anxiety
-may worsen

Has activating AEs

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101
Q

Place in therapy for bupropion in MDD

A

Lower degree of sexual dysfunction and weight gain than SSRIs

May be used in conjunction with SSRI so you can reduce dose and have less sexual dysfunction

Black box warning for suicidal

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102
Q

Mirtazapine MOA

A

MANY!

-makes it different from others

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103
Q

AEs of Mirtazapine

A

Sedation!!
Weight gain, increased TGs

Significantly less sexual dysfunction!!

Black box warning with suicidality

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104
Q

Dosing of Mirtazapine

A

Typically 15mg HS but would bump up to 30mg much sooner if sedation is bothersome

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105
Q

Mirtazapine place in therapy for MDD

A

First line
Can be used as monotherapy or add-on therapy for pts with antidepressant-associated sexual dysfunction
Good for pts with insomnia

106
Q

Moclobemide MOA

A

Reversible MAOI

so tyramine is NOT a concern at normal doses
-loses specificity at higher doses though

107
Q

Moclobemide AEs

A

Reason why we dont see it often

  • tachycardia
  • hypotension
  • NVD
  • sexual dysfunction
  • anticholinergic effects
  • anxiety
  • tremor
108
Q

TCAs

A 
Tertiary amines:
-amitriptyline 
-doxepin
-imipramine
Secondary amines:
-noritriptyline - twice as potent and half the anticholinergic SEs of amitriptyline 
-desipramine
109
Q

TCA concerns

A

Not safe in overdose, and cardiotoxicity!

110
Q

AEs of TCAs

A

Anticholinergic effects and sedation are most common

CV effects are most concerning (conduction abnormalities and arrhythmias)

111
Q

Trazadone place in Therapy for MDD

A

2nd line due to sedation

Most commonly used as a hypnotic

112
Q

Quetiapine for depression

A

Use with extreme caution in elderly for MDD
Should only be used if they are at a risk to themselves or others or having distressing hallucinations

Quetiapine is an atypical antipsychotic

113
Q

Quetiapine place in therapy for MDD

A

Adjunct to antidepressant therapy for treatment resistant depression

2nd line as monotherapy for MDD

114
Q

Medication options for depression

A 
SSRIs
SNRIs
TCAs
Bupropion 
Trazadone 
Moclobemide 
Mirtazapine 
Quetiapine
115
Q

GI bleeding risk with antidepressants

A

Peripheral serotonin stored in platelets and released during a thrombotic event
-SSRIs do not cause the bleeding, but can influence the duration of bleed and/or volume of blood loss

116
Q

Serious AE with SSRIs

A

Dose-dependent QT prolongation

So do not dose citalopram over 40mg, or escitalopram over 20mg per day

117
Q

Suicidality with antidepressants

A

Less than 18yrs - possible association
18-24yrs - ambiguous
-MOST WORRIED ABOUT THE UNDER 24YRS OF AGE POPULATION
25-64yrs - protective

118
Q

Meds for depression associated with lowest rate of sexual dysfunction

A

Mirtzapine, and bupropion!

-also moclobemide

119
Q

Equivalent dose of venlafaxine

A

75mg

120
Q

When is discontinuation syndrome a concern

A

More likely in those who have been treated for over 6-8weeks

121
Q

Discontinuation syndrome sx

A 
FINISH
-flu-like sx
-insomnia 
-nausea 
-imbalance 
-sensory disturbances
-hyperarousal (anxiety, agitation)
Most common is dizziness and vertigo
122
Q

Non-pharm therapy for depression

A 
Electroconvulsive therapy
Counselling (655-7777)
Music therapy 
Mind-body interventions
Dietary and herbal supplements
123
Q

2 main types of eating disorders

A

Anorexia Nervosa

Bulimia Nervosa

124
Q

More severe eating disorder

A

Anorexia

125
Q

Anorexia MOA

A

Relentless pursuit of thinness

-excessive exercise, barely eating, may include purging

126
Q

Bulimia MOA

A

Binge on huge amount of food, followed by purging

127
Q

Bulimia dx

A

Binge eating/behaviour occurs 2x weekly over 2 months

Specifier is frequency of episodes (moderate is 4-7per week)

128
Q

Anorexia specifier

A

BMI (moderate 16-16.9)

129
Q

Anorexia complications

A

Consequences of starving
Total organ impairment leading to electrolyte abnormalities
-endocrine: amenorrhea, OP
-CV: arrhythmias
-GI: impaired absorption due to decreased motility

130
Q

Bulimia complications

A 
Consequences of chronic purging
-dental caries
-esophageal rupture
-parotid gland enlargement 
-callus on dorsu of hand from acids
Electrolyte abnormalities
131
Q

Anorexia specific goals

A

Restore pt to ideal body weight - cant do anything until their body weight has been somewhat normalized
Treat medical complications of the eating disorder

132
Q

Goal for anorexia in terms of weight gain

A

2lbs/week

Dont want to shock the body so have to go gradually

133
Q

Commonly prescribed vitamins and trace elements with eating disorders

A

Calcium 1000-1500mg
Vit D 400 IU
Zinc 2-4mg

134
Q

Anorexia medication treatment

A

GI Motility agents - domperidone 10-20mg TID before meals
BZs for in hospital use
Antidepressants, lithium, olanzapine (if willing)

135
Q

Bulimia medication treatment

A

All antidepressants demonstrated efficacy in impulsive behaviours
1st-line is SSRIs - fluoxetine 40-60mg daily

136
Q

Role of pharmacists in eating disorders

A

ID those abusing laxatives or diuretics
ID resources and support groups in our community
Advise and recommend treatment for those affects
Keep up with literature

137
Q

Sleep cycle norm

A

NonREM 1-4 and then REM (25%)

Typically 4-6 cycles each night, each cycle lasting 70-120mins

138
Q

Variables evaluating in polysomnography (sleep labs)

A 
Sleep onset
Arousals
Sleep stages
Eye, leg, jaw movements
Arrhythmias
O2 sats
Resp effort
139
Q

NonREM sleep seems to be associated with ….

A

GABA - so we see BZs used often

140
Q

3 factors of insomnia

A

Difficulty initiating sleep
Difficulty maintaining sleep
Early morning waking

141
Q

How long for dx of insomnia

A

Occurs at least 3x per wk and present for 3 months

142
Q

2 main non-pharmacological changes for insomnia

A

Stimulus control

Sleep hygiene

143
Q

Sleep hygiene recommendations

A

Increase exercise
Create comfortable sleep envt
D/c or reduce caffeine, alcohol, nicotine
Avoid drinking large quantities before bed
Wind down before bed
Milk - tryptophan is a precursor to serotonin

144
Q

Stimulus control recommendations

A

Things you do to promote sleep

  • establish regulator times to go to sleep and wake
  • sleep only as much as you need to feel rested
  • go to bed only when sleepy
  • avoid daytime naps
  • schedule worry time during the day
145
Q

Non-prescription meds for insomnia only help with

A

Decreasing sleep latency (time to falling asleep)

-not going to keep asleep most of the time

146
Q

Non-prescription meds used for insomnia

A

Diphenhydramine (Benadryl)
Tryptophan
Melatonin
Valerian

147
Q

Prescription non-hypnotic meds for insomnia

A

Antidepressants

Antipsychotics

148
Q

Antidepressants used for sleeping disorders

A

Mostly tertiary TCAs - amitriptyline and imipramine
Doxepin
Trazadone - tolerance doesnt occur
Mirtazapine

149
Q

Prescription hypnotic meds used for insomnia

A

BZs
Zopiclone
Zolpidem

150
Q

Why we want to limit BZ use in insomnia to 1 month

A

Tolerance
Suppression of REM sleep
Leads to REM rebound when d/c med

Use prn instead of continuous when possible - save for bad nights

151
Q

Most popular BZ used for sleep disorders

A

Temazepam 15-30mg (6-10hr duration)

Triazolam (short half-life) and flurazepam (too long of half-life)

152
Q

Why are z-drugs easier to come off of than BZs for sleep disorders

A

Less disruption on sleep stages such as REM and less long term problems such as rebound

153
Q

Problem with Z-drugs for sleep disorders

A

Non-formulary

154
Q

Narcolepsy triad sx

A

Excessive daytime sedation
Cataplexy - muscles are paralyzed (no tone) - no LOC!
Sleep paralysis when falling asleep or waking up
Hallucinations occurs when falling asleep (hypnagogic) or waking up (hypopompic)

155
Q

Pathophysiology of narcolepsy

A

Deficiency in function of hypocretin-orexin neurotransmitter which helps regulate sleep

Sleep stage begins in REM

156
Q

Non-pharm management for narcolepsy

A

Careful scheduling daytime naps for 15-20mins 2-3x per day

157
Q

Pharmacological treatment for narcolepsy is aimed towards

A

Managing the excessive daytime sleepiness and correcting REM sleep abnormality

158
Q

Daytime sedation treatment for narcolepsy

A

CNS stimulants - methylphenidate and dextroamphetamine

Modafinil - only Indication is for narcolepsy

159
Q

Cataplexy/sleep paralysis/hallucination treatment management for narcolepsy

A

No great therapy for this part of narcolepsy
Antidepressants - TCAs can suppress REM sleep
Sodium oxybate - liquid given before bed at then 2.5hrs later

160
Q

Sleep apnea definition

A

Sudden cessation of breathing 10-30secs
Followed by blood O2 desaturation, and brief arousals from sleep to restart breathing

Loud snoring is an indicator
Up to 30 episodes per night which leads to fragmented sleeping

161
Q

Biggest risk factor for sleep apnea

A

Obesity (BMI over 30)

162
Q

2 classification of sleep apnea

A

Central (10%) - impaired resp drive

Obstructive (90%) - upper airway collapse and obstruction (neck obesity, narrow airways, lesions, tonsils)

163
Q

Management of sleep apnea

A

Non-pharm is starting point - weight reduction, continuous positive airway pressure (CPAP), prevent sleeping on back, avoid CNS depressants

Modafinil can be used to combat daytime sedation
Surgery for obstructive
Resp stimulants - efficacy is questionable

164
Q

2 circadian rhythm disorders

A

Jet lag and shift work

165
Q

Jet lag

A

Sleep problem lasts 2-10days - worse travelling east than west
Can consider melatonin or short acting BZ (like triazolam)
Keep awake for the time zone you are in!
Dont take naps

166
Q

Shift work

A

Management is proper sleep hygiene, daytime sleep when working at night (different than jet lag)
Consider melatonin or short-acting BZ like triazolam

167
Q

Restless leg syndrome is associated with…

A

Kidney disease
Pregnancy
Iron deficiency anemia
Worsened by alcohol, caffeine, stress

168
Q

Dx of restless leg syndrome

A

Urge to move limb because of unpleasant/uncomfortable sensation
Occurs at rest and always at night
Sx temporarily relieved by movement

169
Q

Meds for restless leg syndrome

A

Dopamine agonists -ropinorole, pramipexole
Clonazepam for frequent awakening
Gabapentin

170
Q

Parasomnias characterized into

A

Sleep walking
Sleep terrors
REM behaviour

171
Q

Bipolar initial presentation

A

Most general in women, but most common in general is depression

Men have more initial manic episodes than women

172
Q

Big challenge with bipolar disorder dx

A

Delay to dx - average 10yrs to dx after first presentation (depression)

173
Q

Biologic abnormalities (“biogenic amine hypothesis”) for bipolar disorder

A

Dysregulation between excitatory and inhibitors neurotransmitter systems

  • excitatory: NE, dopamine, glutamate, aspartate
  • inhibitory: serotonin, GABA
174
Q

Requirement to be bipolar I

A

A manic episode

175
Q

Manic episode duration requirement

A

At least 1 week

-any duration if hospitalization

176
Q

Hypomanic episode duration requirement

A

At least 4 days

177
Q

Manic/hypomanic episode sx

A

3 or more present for dx

  • inflated self-esteem or grandiosity
  • decreased need for sleep
  • distractibility
  • flight of ideas/thoughts are racing
  • more talkative than usual
  • increase in goal-directed activity
  • excessive involvement in activities that have a high potential for painful consequences

For hypomanic - the episode is NOT severe enough to cause marked impairment in social or occupational functioning. If there are psychotic features, it automatically a manic episode

178
Q

Diagnostic criteria for bipolar I

A

One manic episode and major depressive disorder

179
Q

Diagnostic criteria for bipolar II

A

Never been a manic episode

At least one hypomanic episode, and at least one major depressive episode

180
Q

Course of bipolar specifiers

A

Severity, features, pattern

-seasonal pattern, +/- psychotic features, rapid cycling (4 or more episodes a year)

181
Q

Goals of therapy for bipolar disorder

A

Eliminate mood episode with complete remission of sx
Prevent recurrences or relapses of mood episodes
Improved QOL and optimize psychosocial functioning
Reduced the number and severity of mood episodes
Prevent suicide
Improve inter-episode functioning

182
Q

Steps to treatment of acute main/acute depression in BD

A

Review general principles and assess medication state
Initiate or optimize therapy, and check adherence
Add-on or switch therapy with 1st-line agents
Add-on or switch therapy with 2nd/3rd-line agents
Add-on novel or experimental agents

183
Q

First-line agents for acute mania in BD

A 
Lithium 
Divalproex 
Atypical Antipsychotics:
-quetiapine 
-olanzapine
-ziprasidone 
-risperidone 
-aripiprazole
184
Q

Lithium predicts of response for acute mania in BD

A

Classic mania
Few episodes of illness
Elated mood without depressive sx, or psychiatric features

185
Q

Divalproex predictors of response in acute mania in BD

A

Rapid cycling
Mixed state
Multiple prior episodes of illness
Comorbid substance use disorder

186
Q

Atypical antipsychotics predictors of response in acute mania in BD

A

Early age of onset
Rapid cycling
No prior substance use disorder
No prior antipsychotic use

187
Q

First line treatment options for acute depression in BD

A 
Lithium
Quetiapine 
Lamotrogine 
Lithium + SSRI/divalproex/bupropion 
Divalproex + SSRI/bupropion
188
Q

Qualification for maintenance phase in BD

A

Once a pt has recovered from an acute episode and remains well for at least 2 months

189
Q

First choice for maintenance phase in BD

A

Lithium

-high efficacy in maintaining remission and preventing suicidal behaviour

190
Q

Prevents manic episodes moreso than depressive episodes in BD

A 
Lithium
Olanzapine
Aripiprazole 
Risperidone 
Ziprasidone 
Carbamazepine
191
Q

Prevents depressive episodes moreso than manic episodes

A

Lamotrogine

192
Q

Similar efficacy in preventing both manic and depressive episodes in BD

A

Valproic acid

Quetiapine

193
Q

Onset of effect for lithium

A

6-10 days

Full effect in 10-21 days

194
Q

How long to discontinue lithium when stopping

A

At least over 2 weeks!!

2-4weeks best

195
Q

Target serum level for lithium

A

1-1.5mmol/L in acute phase

0.8-1.1mmol/L in maintenance phase

Doses for lithium are higher in acute phase, than maintenance

196
Q

Atypical antipsychotics (2nd gen) used for BD

A 
Olanzapine
Risperidone
Quetiapine 
Paliperidone
Asenaphine
Ziprasidone - adherence issues
Aripiprazole (3rd gen)
197
Q

Atypical antipsychotics that are most weight neutral

A

Ziprasidone and Aripiprazole

198
Q

Primary MOA for all antipsychotics

A

Dopamine blockade

199
Q

Doses are lower for antipsychotics in ….. than schizophrenia

A

Bipolar disorder

200
Q

Antipsychotic recommended for acute depressive episode

A

Quetiapine

Olanzapine + SSRI is less ideal

201
Q

Maintenance therapy for BD with antipsychotics?

A

Combination therapy is often warranted

Quetiapine has monotherapy indication for pts with depressive sx

202
Q

Anticonvulsants used for acute mania

A

Divalproex

203
Q

Anticonvulsants used for acute bipolar depression

A

Lamotrogine

204
Q

Anticonvulsants used for maintenance therapy in BD

A

Divalproex

Lamotrogine - has limited evidence in preventing mania

205
Q

Antidepressant role in maintenance therapy of BD?

A

Never used alone!!! Not recommended for monotherapy in BD

  • have in role in combo therapy for acute and maintenance
  • antidepressants can WORSEN manic episodes - so d/c during manic episodes no matter what
  • can also contribute to rapid cycling
206
Q

SSRI Indication for acute depressive episode

A

First line

  • lithium or divalproex + SSRI
  • olanzapine + SSRI
207
Q

Bupropion indication for acute depressive episode in BD

A

1st line

-lithium or divalproex + bupropion

208
Q

TCAs, SNRIs, or MAOIs Indication in BD?

A

Not as first line therapy

209
Q

For pts with hx of rapid cycling or severe mania, strategies that DO NOT include a ______ should be tried first

A

Antidepressant

210
Q

Preferred antidepressants if using in BD

A

SSRI or bupropion

Prudent to use short course of 3-4 months and then get off!

211
Q

Definition of rapid cyclers in BD

A

4 or more episodes per year
-switching between poles without a period of euthymia

Cycles continue despite aggressive treatment - need complex combo therapy

212
Q

1st line maintenance therapy for rapid cyclers

A

Lithium or divalproex

213
Q

Most evidence for preventing suicide in BD

A

Lithium

-could also be from the non-specific benefit from long-term monitoring provided during therapy with lithium

214
Q

TCA Toxicity general notes

A

Can appear fairly well, then quickly slip into arrhythmias

  • early ID is key
  • fast progression
  • highly variable due to genetic polymorphism
215
Q

Signs and sx of TCA toxicity

A

Most toxicities are from acute ingestions

  • main concern = CV: cardiac dysthymias and hypotension so early ECG is important!
  • coma and seizures
  • resp depression and aspiration
216
Q

Diagnostic lab tests for TCA toxicity

A

Serum TCA levels NOT useful
ECG is single most important diagnostic tool
-esp interested in widening of QRS

217
Q

Management of TCA Toxicity

A

Symptomatic/supportive care is main part

  • for dysrhythmias: give sodium bicarbonate - give 12-24hr after ECG resolution
  • for hypotension: give vasopressor (NE), while still administering sodium bicarbonate. Also five fluid boluses prn
  • for seizure: give BZs
218
Q

Antidote for TCA toxicity

A

IV lipid emulsions - efficacy is questionable

219
Q

Decontamination method for TCA toxicity

A

SDAC

220
Q

Significant lithium intoxication is more common in acute or chronic?

A

Chronic use

-takes longer to distribute in tissues with lithium

221
Q

Signs and sx of lithium toxicity

A

Neurological! - slurred speech, dizziness, delirium, coma, seizures

NVD

222
Q

Diagnostic lab test for lithium toxicity

A 
Serum lithium levels q2hr
Electrolytes - especially Na!
Glucose 
ECG
Creatinine
223
Q

Elimination for lithium toxicity

A 
Fluid resuscitation with NS!
Polystyrene sulfonate (Kayexalate)
Hemodialysis only in severe cases
224
Q

Most important consideration in BZ toxicity

A

Coingestants!!
ROA
Tolerance
Short-acting vs long-acting BZ

225
Q

Management of BZ toxicity

A

Oxygen assisted ventilation and fluids
SDAC
Flumazenil - antidote - risk for seizures, dysrhythmias, sedation
-people will argue can use supportive care until BZ is out of the system to get around using this antidote

226
Q

What other substances do you always ask schizo pts

A

Cigarette smoking and marijuana

227
Q

Factors associated with improved prognosis in schizo

A 
Older age of onset
Female
Being married
Family support
Tx soon after dx (EPIP)
Absence of affective sx
228
Q

Positive sx are said to be caused by …

A

Excessive dopamine activity in the brain

So dopamine antagonists will improve positive sx

229
Q

Serotonin contributes to negative or positive sx in schizo

A

Negative

230
Q

Serotonin decreases ______

A

Dopamine

So block serotonin to increase dopamine

231
Q

Marijuana theory in schizo

A

Cannot say that is doesnt cause schizo

Age to legalize should be 25yrs
-brain development reasons, and will know if schizophrenic by then

232
Q

DSM-5 dx of schizo

A

At least 2 of the following:

  • delusions
  • hallucinations
  • disorganized speech
  • disorganized or catatonic behaviour
  • negative sx

At least 6 months

233
Q

Negative sx of schizo

A

4 A’s

  • affective flattening
  • avolition/asociality
  • anhedonia
  • alogia
234
Q

Positive sx of schizo

A

Suspiciousness
Delusions
Hallucinations
Conceptual disorganization

235
Q

Delusion types in schizo

A

Persecutary
Grandiose
Ideas of reference
Somatic

236
Q

Top 4 types of voiced heard in schizo

A

Commanding, critical, abusive, frightening

237
Q

Similar MOA for all antipsychotics

A

Blocking dopamine receptors

Differ only in potency (mg dose) and SEs

238
Q

All 1st and 2nd gen antipsychotics are first line for schizo EXCEPT

A

Clozapine

239
Q

1st generation is good for treating what sx of schizo

A

Positive

240
Q

2nd gen antipsychotic are good for treating what sx of schizo

A

Both positive and negative

241
Q

SEs associated with affinity for D2

A

EPS

Hyperprolactinemia

242
Q

SEs associated with affinity for H1

A

Sedation

Weight gain

243
Q

SEs associated with affinity for M1

A

Anticholinergic effects

244
Q

SEs associated with affinity for alpha1 adrenergic

A

Orthostatic hypotension

245
Q

1st gen antipsychotic SEs

A 
Dystonia - locking up
EPS
Increased prolactin
NMS
Weight gain
Lowers seizure threshold
246
Q

1st gen antipsychotic dosing

A

Dosing is lower for IV than oral

247
Q

Aripiprazole uniqueness

A

“Goldilocks principle”

  • referred to as a dopamine system stabilizer
  • if have high levels of dopamine (pos sx), will act as antagonist
  • if have low levels of dopamine (neg sx), will act as agonist
248
Q

Olanzapine downsides

A

Big weight gain - wont use if at CVD risk already

Smoking causes induction! - have to cut dose in half if hospitalized or stopping smoking

249
Q

Paliperidone (Invega) uniqueness

A

Shell of oral dose will pass in stool

-causes rhinitis

250
Q

Ziprasidone uniqueness

A

Have to administer with a full on meal!!!

  • rapidly have to titrate up to avoid activation syndrome
  • weight neutral
251
Q

When to use clozapine in schizo

A

For use in treatment-resistant schizo
-no sig improvement of psychopathology and/or target sx despite treatment with 2 different antipsychotics from at least 2 different chemicals classes (one should be 2nd gen) at their recommended antipsychotics dose for a period of at least 2-8 weeks per drug

252
Q

Why is clozapine not considered first line for schizo

A

Risk of agranulocytosis (lowered WBC count, mostly neutrophils) and seizure risk

253
Q

Green light for clozapine monitoring

A

WBC over 3.5 x 10^9
ANC over 2.0 x 10^9

Weekly monitoring of clozapine for the first 6 months (highest risk)

254
Q

Yellow light for clozapine monitoring

A

WBC 3-3.5 x 10^9
ANC 1.5-2 x 10^9

Would continue, sample blood 2x per week until stabilized counts

255
Q

Red light for clozapine monitoring

A

WBC below 3 x 10^9
ANC below 1.5 x 10^9

Immediately stop clozapine, monitor for infection. Do not ever restart clozapine

256
Q

Monitoring frequency for clozapine does not need to be modified if missed a dose for

A

3 days or less

257
Q

Antipsychotics that have LOW risk of metabolic syndrome

A

Ziprasidone and Aripiprazole

258
Q

Antipsychotics with HIGH risk for metabolic syndrome

A

Olanzapine and clozapine

Weight gain, dyslipidemia, glucose metabolism dysregulation

259
Q

BB used to treat EPS in schizo

A

Propranolol

-most lipophilic BB so gets through BBB

260
Q

NMS sx in schizophrenia

A

Fever is most common sx
-hyperthermia, crying, sweating, peeing, ALOC, muscle rigidity
Treatment with dantrolene

Big increase in CK

261
Q

Rationale for monitoring of lithium

A

High rates of noncompliance

SEs and toxicities

262
Q

Therapeutic range for lithium

A

General range = 0.6-1.5mmol/L
-most dosage regimens aimed for 0.8mmol/L and then adjusted accordingly

Level needs to be drawn 12hrs after dose!
1 week to steady state (able to begin drawing levels)

PHARM 557 (3 decks)

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