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Pharm > Alzheimer Disease and Depression > Flashcards

Alzheimer Disease and Depression Flashcards

1
Q

What neuronal changes do we see with AD

A 
Reduced acetylcholine (ACh)
Reduced acetylcholinesterase (AChE)
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2
Q

Pharmacotherapy outlines for AD

A

Raise cortical acetylcholine

Decrease glutamate mediated neuronal cell death

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3
Q

Pharmacotherapy caveat of AD

A

No cure of slowing of the disease

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4
Q

Goals of pharmacotherapy for AD

A

Minimize behavioral disturbances

Improve sx

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5
Q

How many drugs are FDA approved for managing AD

A

4

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6
Q

FDA approved Acetylcholinesterase inhibitors for AD

A

Donepezil (Aricept)
Rivastigmine (Exelon)
Galantamine (Razadyne)

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7
Q

FDA approved NMDA antagonists for AD

A

Memantine (Namenda)

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8
Q

Acetylcholinesterase inhibitors summary

A

Most effective in treating AD
Typically result in small improvement in sx
Most studies involve mild-moderate sx
May reduce behavior disturbances (aggression)
May improve cognition and behavior
A switch can be made easily after stopping initial therapy

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9
Q

Adverse effects of AChE inhibitors

A

Increase ACh
GI tract issues
Severity of AE dose dependent

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10
Q

Increase ACh effects

A 
Depression
Headache
Anxiety
Dizziness
Insomnia
Stomach pain
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11
Q

GI tract AChE inhibitor AE

A 
Nausea
Vomiting 
Diarrhea
Dehydration
Decreased appetite
Weight loss
Stomach ulcers
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12
Q

Dose dependent AChE inhibitor AE

A

Ptx < 50 kg (110 lbs) and elderly have increased incidence
Minimized by starting low and dose titration
Some may require drug discontinuation (D/C)

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13
Q

Donezepil for AD

A

Approved for SEVERE AD
First agent approved
Give w/ or w/o food

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14
Q

Donezepil starting dosing for AD

A

5 mg (long half life)

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15
Q

Donezepil secondary dosage for AD

A

10 mg daily after 4-6 weeks

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16
Q

Donezepil final dosing for AD

A

23 mg daily after 3 months

For pts w/ mod-severe AD

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17
Q

Donezepil dosing forms

A 
Generic = 5 &amp; 10 mg IR tabs
Brand = 5 &amp; 10 mg orally disintegrating tabs
Brand = 23 mg extended release tabs
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18
Q

Galantamine

A

For mild-moderate AD

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19
Q

Galantamine IR tabs or solution dosing

A

Initially bid w/ breakfast or dinner

4,8, or 12 mg tablets (generic)

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20
Q

Galantamine ER capsule dosing

A

Daily w/ breakfast

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21
Q

MOA of Galatamine

A

Inhibits AChE and stimulates nicotinic receptors

Stimulates at non-ACh site (allosteric modulation)

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22
Q

Renal adjustments of Galatamine

A

Moderate renal impairment: 16 mg/day = MAX

DO NOT USE IN SEVERE RENAL IMPAIRMENT

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23
Q

Conversion to galantamine

A

Poor tolerability when switching from donepezil or rivastigmine
(wait until SE subside or allow 7 day washout period to galantamine)
No intolerance to donepezil or rivastigmine (begin galantamine the day after stopping)

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24
Q

Rivastigmine

A

TD patch is approved for severe AD

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25
Q

Oral dosing of Rivastigmine

A

Initial = 1.5 mg bid
Increase by 3 mg/day q2 weeks (pending tolerability)
Max dose = 6 mg bid

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26
Q

Advantages of Rivastigmine TD patch

A

Less NVD than oral forms
(But still bradycardia and syncope)
Immediately theraputic

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27
Q

Dosing forms of oral Rivastigmine

A

1.5, 3, 4.5, and 6 mg capsules (generic)

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28
Q

Dosing forms of transdermal Rivastigmine

A

Apply once daily and rotate

  1. 6mg/24 hours (initial 4 weeks; then up to 9.5 mg/24 hours)
  2. 5 mg/24 hours (for 4 weeks then 13.3 mg/24 hours)
  3. 3 mg/24 hours (then back down to 9.5 mg/24 hours)
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29
Q

Caveat of oral Rivastigmine

A

Not immediately theraputic

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30
Q

MOA of Rivastigmine

A

Pseudo-irreversible

Inhibits G1 AChE > G4 AChE

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31
Q

Metabolism/Elimination of Rivastigmine

A

Results in fewer drug-drug interactions

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32
Q

Exelon Patch (EP)

A 
May cause allergic dermatitis
Be sure to rotate
Don't use same site for 14 days
Smart phone app to track 
Recommended sites: upper/lower back
Alternate sites: chest/upper arm
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33
Q

High dosing on EP

A

High dose oral rivastigmine (> 6 mg/d):

Switch directly to 9.5 mg/24h patch

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34
Q

Low dosing on EP

A

Lower dose oral rivastigmine (< 6 mg/d):

Start on 4.6 mg/24h patch

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35
Q

Switching from donepezil or galantamine to EP

A

Start on 4.6 mg/24h patch

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36
Q

AD Cholinesterase Inhibitors benefits are…

A

Similar for all 3

Chose based on pt factors

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37
Q

What line of treatment are AD Cholinesterase Inhibitors (AChEIs) for AD

A

First line agents

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38
Q

When should you start tx w/ AChEIs?

A

On diagnosis of AD

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39
Q

When are AChEIs therapeutic?

A

Immediately

PS responses are dose dependent

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40
Q

Side effects of AChEIs

A

NV (MC)

Bradycardia (under-reported) that could lead to syncope

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41
Q

How do we manage the side effects of AChEIs?

A

Slow dose titration

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42
Q

What is Memantine?

A

N-methyl D-aspartate (NMDA) antagonist

Recently approved for moderate-severe AD

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43
Q

Is Memantine a stand alone drug?

A

Not really. Usually add to AChI’s and see cognitive improvement

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44
Q

Initial dosing of Memantine IR tabs

A

5 mg daily

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45
Q

How often do you increase Memantine dosing

A

1 week intervals

46
Q

Second tier dosing of Memantine

A

5 mg bid

47
Q

Third tier dosing of Memantine

A

10 mg Q AM and 5 mg Q PM

48
Q

Final dosing of Memantine

A

10 mg BID (max of 20 mg daily)

49
Q

Switching form Memantine IR tabs to ER

A

May switch 10 mg BID pts to 28 mg ER tab daily
OR
Start with 7 mg ER tab daily, then increase to 28 mg daily

50
Q

Memantine side effects?

A

Infrequent

Mild

51
Q

Memantine dosage in renal impairment

A

Mild-moderate: no adjustment

Severe: 5 mg bid max

52
Q

Etiology and pathophysiology of depression

A 
Sx reflect changes in brain monoamine neurotransmitters
Ex: 
norephinephrine (NE)
Serotonin (5-hydroxytryptamine; 5-HT)
Dopamine
53
Q

Biogenic amine hypothesis of depression

A

Agents blocking reuptake/metabolism of these amines are effective antidepressants

54
Q

Medical conditions that can cause depression

A 
Hypothyroidism
Addison or Cushing disease
Pernicious anemia (B12 deficiency)
Severe anemia 
HIV/AIDS
55
Q

Drugs that cause depression

A

Antihypertensives (clonidine; diuretics)
Oral contraceptives
Steroids
ACTH

56
Q

Suicide risk evaluation

A

1) Evaluate major depression pts for suicidal thoughts
2) Evaluate factors increasing risk
3) Immediately refer if high risk

57
Q

Risk factors for suicide in increasing order

A 
Feelings of hopelessness
Inpatient status
Single or living alone
Male (females attempt more often; males succeed more often)
Suicidal plan/attempt
58
Q

General approach to depression treatment

A

3 phases:

1) Acute phase -> 3 months
2) Continuation phase -> 4-9 months
3) Maintenance phase: 12-36 months
* Duration of therapy depends on risk of recurrence*

59
Q

Acute phase treatment

A

Evaluate weekly or biweekly
Continue until substantial improvement occurs
Start med doses low, increase gradually
Keep an eye on side effects
If <50% improvements at 4 weeks, change meds
Do NOT prescribe a lot of meds to seriously depressed out-pt patients

60
Q

Continuation phase treatment

A

4-9 months
All pts should get 3 months of acute phase treatment and 4 minimum of continuation phase
Residual sx may indicate recurrence, early relapse, or chronic course
Continuation until sx resolve

61
Q

Maintenance phase tx

A 
Maintenance for 12-36 months decreases recurrence by 2/3
Indicated for pts w/:
1) yearly episodes
2) impairment from mild residual sx
3) chronic major depression
4) severe episodes
5) high risk of suicide
62
Q

Discontinuation of depressive tx

A

If no recurrence or relapse during continuation phase
Most pts qualify 7 months (minimum length of therapy)
Early discontinuation increases risk of relapse
Taper meds down over several weeks

63
Q

Non-pharmacotherapy for depression

A

Psychotherapy for those willing (might be first line for mild-mod depression)

64
Q

Are all antidepressants equal?

A

Pretty much

Similar efficacy when given at comparable doses

65
Q

How do we chose what antidepressant to use?

A 
Previous response history
Pharmacogenetics (hx of familial response)
Presenting sx (fatigue vs. agitation)
Side effect profile
Pt preference
Cost
66
Q

Selective Serotonin Reuptake Inhibitors (SSRIs)

A

Superior to other antidepressants for major depression

67
Q

Why are SSRIs first line?

A

Overdose safety

Tolerability

68
Q

SSRI side effects

A

Mild and short

Decreased libido

69
Q

What happens if you abruptly stop taking your SSRI?

A

Withdrawal sx or discontinuation

70
Q

Which SSRI has less of a chance of withdrawal sx happening if stopped abruptly

A

Fluoxetine

71
Q

When are SSRIs contraindicated

A

Pts that were recently (5-6 weeks) taken off of MAOIs -> causes serotonin syndrome

72
Q

Fluoxetine

A

First SSRI FDA approved for kids

Only SSRI w/ consistent efficacy in children and adolescents

73
Q

Fluoxetine black box warning

A

Increased suicidal ideation in kids and adolescents

74
Q

Does fluoxetine have a longer or shorter half-life than its counterparts?

A

Longer

Allows for once daily dosing

75
Q

Precautions with fluoxetine and bipolar disorder

A

One metabolite may persist for weeks

May aggravate the manic state

76
Q

Fluoxetine dosing

A

Increase by 20 mg/day each week over several weeks to 80 mg/day max

77
Q

Paroxatine

A

SSRI
Blocks serotonin reuptake at lower doses
Blocks dopamine reuptake at higher doses

78
Q

Paroxetine dosing

A

Max of 50 mg/day

79
Q

Sertraline

A

Blocks serotonin reuptake at lower doses
Blocks dopamine reuptake at higher doses
Might contribute to anti-depressive action

80
Q

Sertaline dosing

A

Max of 200 mg/day

81
Q

Fluvoxamine

A

Oldest SSRIs
May cause or worsen sexual dysfunction
300 mg/day MAX

82
Q

Citalopram

A

FDA approved to treat sx of major depression

FDA warning in 2011 -> 40 mg/day might prolong QT interval

83
Q

When to avoid citalopram

A

Congenital long QT syndrome
Other drugs causing QT prolognation are already taken
Risk for Torsade des Pointes

84
Q

Citalopram dosing

A

Increase by 20 mg after at least one week to max 40 mg/day

originally at 60 mg/day

85
Q

Escitalopram

A

S isomer of citalopram
May reduce frequency of hot flashes in perimenopausal women
20 mg/day max

86
Q

Mixed 5-HT/NE reuptake inhibitors

A

Newer
2nd generation
Block monoamines more selectively than TCAs
No cardiac conduction effects like TCAs

87
Q

Other names for mixed 5HT/NE reuptake inhibitor

A

Serotonin NE reuptake inhibitors (SNRIs)
OR
Dual action antidepressants

88
Q

Mixed 5HT/NE reuptake inhibitor agents

A

Venlafaxine
Duloxetine
Desvenlafaxine

89
Q

Venlafaxine

A

Superior for severe depression than SSRIs or TCAs
Effective for chronic pain
May DOUBLE risk for miscarriage

90
Q

Desvenlafazine

A

Metabolite of venlafaxine
10xs more effective at blocking serotonin than NE uptake
Higher rates of discontinuation syndrome
Not really needed for treating major depressive disorder

91
Q

What is Duloxetine FDA approved for

A

Major depressive disorder
Neuropathic pain
Fibromyalgia pain

92
Q

Duloxetine

A

No need to choose w/ so many other options
Not recommended w/
1) CrCL < 30 minutes
2) w/ hepatic impairment

93
Q

Wellbutrin

A

Inhibits NE and dopamine reuptake
No action on serotonin
Similar efficacy to TCAs and SSRIs
Less nausea, diarrhea, somnolence, and sexual dysfunction than SSRIs
Effective alternative of adjunctive therapy for SSRI non-responders

94
Q

Tricyclic antidepressants (TCAs)

A

Mixed serotonin/NE reuptake inhibitors

Effective for all depressive subtypes

95
Q

TCA SE

A 
*Limits use*
Anticholinergic effects
Sedation
Orthostatic hypotension 
Seizures
Cardiac conduction abnormalities
96
Q

TCAs have:

A

Tertiary amines
Secondary amines
and higher risk of death with overdose

97
Q

Monoamine oxidase inhibitors (MOIs)

A

Older, first generation agents
Irreversibly, non-selective binding MAO A&B
Similar effects to TCA

98
Q

Why are MAOIs no longer first line tx

A

Serotonin syndrome and drug-drug interactions

99
Q

MAOI agents

A

Phenelzine

Selegiline

100
Q

Serotonin syndrome (SS)

A

Potentially life threatening adverse drug reaction

101
Q

When can SS happen

A

W/ therapeutic drug use with SSRIs
Intentional self-poisoning w/ SSRIs
Drug interactions (SSRI and another drug)
Tyramine containing foods while on MAOIs

102
Q

Why is pt counseling critical for SS

A

Gives dietary and med restrictions for MAOIs

Early sx recognition for pts AND clinicians

103
Q

SS triad

A

Mental status change
Autonomic hyperactivity
Neuromuscular abnormalities

104
Q

How frequent is SS in SSRI overdoses

A

14-16%

105
Q

Presentation of SS

A

Autonomic findings:

1) shivering, diaphoresis, mydriasis
2) labile BP/HTN
3) Hyperthermia (>41 C is critical)

106
Q

Tx of SS

A

STOP PRECIPITATING AGENT

5-HT2A antagonist; cyproheptadine

107
Q

Tx of SS if fever > 41 C

A

Immediate sedation with benzodiazepines (diazepam)
Neuromuscular paralysis (vercuronum -> non-depolarizing)
Orotracheal intubation
Monitor and treat hypotension

108
Q

Triazolopyridines

A

New, mixed action agents
Less sexual, sleep, and anticholinergic SE
Similar to TCas
Black box warning of possible liver failure

109
Q

Mirtazapine

A

Similar efficacy to TCAs and SSRIs

110
Q

Trazadone

A

Alpha 1
Not associated w/ increased appetite or weight gain
Limited by dizziness, orthostatic hypotension, and sedation
Less anticholinergic effects (dry mouth, constipation, tachycardia)
Less sexual effects than TCAs

111
Q

Aripiprazole

A

FDA approved for adjunctive depression in 2007

Originally approved as an atypical anti-psychotic agent

Pharm (32 decks)

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