Exam 4 Flashcards
1
Q
Behavior depends on
A
Perception, Genetics, Experience
2
Q
Biopsychosocial model
A
Biology, psychology, social, and environmental factors may ALL be important
3
Q
Interventions for mental illness
A
Non-pharm neuromodulation, pharmacological interventions, psychotherapy and illness education
4
Q
Neuroplasticity
A
Allows an individual to adapt to a rapidly changing environment through strengthening, weakening, pruning, or adding of synaptic connections and by promoting neurogenesis.
5
Q
Neuroplasticity in daily life
A
Long term potentiation (LTP)- strengthens neuronal connections.
Long term depression (LTD)- weakens neuronal connections.
Global processing- forms big picture understanding, context.
Local processing- perceives small details, faces
6
Q
Factors of change in neuroplasticity
A
Age
Illnesses
7
Q
Types of brain damage
A
Tumors/malignancies Strokes TBI Infections/toxins Congenital disease Epilepsy Neurodegenerative conditions- dementia, huntingtons, parkinsons Mental illness
8
Q
Common neurotransmitters in mental illness
A
BDNF, Glutatmate, GABA, acetylcholine, DA, serotonin, NE
9
Q
BDNF
A
Promotes neurogenesis
10
Q
Glutamate
A
Neuronal development, synapse organizations, DA regulation
11
Q
GABA
A
Neuronal circuitry in prefrontal cortex, inhibition
12
Q
Acetycholine
A
Cortical plasticity, processing senses
13
Q
DA
A
Reward, positive symptoms
14
Q
Serotonin
A
Multiple functions,modulates BDNF
15
Q
NE
A
Arousal, sensory integration, memory
16
Q
Illness education
A
Stigma- taking the vagueness out of mental illness, making it medical.
Expectations- time needed for neurons to grow or change. May not feel better with one dose/session.
Balancing interventions- behavior/environment, meds, both have neuronal impact
17
Q
Psychotherapy examples
A
Cognitive behavioral therapy
Dialectical behavioral therapy
Exposure therapy
Eye movement desensitization and reprocessing
18
Q
Who is most likely to benefit from psychotherapy?
A
Depression, anxiety, PTSD, OCD
May be effective in bipolar, ADHD
Minimal benefit in schizophrenia
19
Q
Bright light therapy
A
Bright light intended to mimic sun exposure
Controlled exposure of intense, but safe light
-6,000-10,000 lumens for 30 min/day
UV filtered
20
Q
Bright light therapy risk vs benefit
A
Risk- choosing a good product, photosensitive agents, AE
Benefits- may help sleep disorders, safe, patient accepted.
21
Q
Who is most likely to benefit from bright light?
A
Depression= first line in SAD
Bipolar disorder if absence of mania, must be on an anti-manic
22
Q
Repetitive transcranial magnetic stimulation
A
Brain stimulation therapy
Electromagnetic coil is placed against the head in a specific location and short pulses pass through the skull and stimulate nerve cells. Treatments lasts 4-6 wks and is 5 days/week
23
Q
Risks vs benefit of rTMS
A
Risks- very expensive, contraindications similar to MRIs, timely, AE
Benefits- less AE than ECT, well accepted if the patient has time and money, noninvasive
24
Q
Who is likely to benefit from rTMS?
A
Depression= 2nd or 3rd line
Bipolar- 3rd line
25
Electroconvulsive therapy (ECT)
A procedure given with neuromuscular blockers and generalized anesthesia (sedated then paralyzed then electrical current then seizure then recovery)
Can be done outpatient.
26
Process of ECT
Psychiatric and medical examination- informed consent- 3 treatments/week for 2-4 weeks, f/u
27
ECT risk vs benefit
Risk= AE
| Benefit- high efficacy rate, faster than antidepressants. Safe in pregnancy, elderly, very low mortality rates
28
Who is most likely to benefit from ECT?
Depression- 1st line in severe/psychosis
Bipolar- 2nd line in bipolar depression
Some evidence in schizophrenia
29
Sedative
A drug that produces a calming state and reduction of anxiety
30
Hypnotic
A drug that produces drowsiness, facilitates sleep
31
Anxiolytic
A drug that reduces anxiety
32
Barbiturates
Classified based on duration of action
Tolerance- greater to sedation than to anticonvulsant or lethal effects; thus narrow therapeutic index
Thiopenal, methohexital, pentobarbital, secobarbital, amobarbital, phenobarbital
33
Which barbiturates are ultrashort acting (5-15 minutes)
Thiopental, methohexital, pentobarbital
34
Which barbiturates are short acting (3-8 hours)?
Pentobarbital, secobarbital, amobarbital
35
Which barbiturate is long acting (days)
Phenobarbital
36
Benzodiazepines
Term refers to portion of chemical structure composed of benzene ring; halogens (F, Cl) increase lipid solubility.
Broad spectrum of activity- anxiolytics, sedatives, hypnotics, muscle relaxants, anti-convulsants
37
Advantages of benzodiazepines
High margin of safety, little respiratory or CV depression
38
Which therapeutic uses of benzodiazepines require a long 1/2 life?
Anticonvulsant, anxiolytic
38
Which therapeutic uses of benzodiazepines require a long 1/2 life?
Anticonvulsant, anxiolytic
39
Which therapeutic uses of benzodiazepines requires rapid entry into the brain?
Status epilepticus
40
Which therapeutic use of benzodiazepines requires short elimination 1/2 life
Hypnotic
41
Short acting benzodiazepines
Midazolam, triazolam
42
Intermediate acting benzodiazepines
alprazolam, clonazepam, oxazepam, temazepam
43
Long acting benzodiazepines
Chlordiazepoxide, diazepam, flurazepam
44
GABA/Benzodiazepine receptor complex
All clinically important actions are mediated by the GABA-benzodiazepine receptor complex.
Ion channel that facilitates chloride entry into neuron leading to hyperpolarization and reduced neuronal firing.
45
GABA-Benzo receptor ligands
GABA, Benzo,
| Benzo antagonist- flumazenil
46
What drug is used for Benzo OD
Flumazenil
47
Benzo AE
CNS depression: sedation, psychomotor impairment, ataxia, abuse
Anterograde amnesia
Physical dependence/withdrawal
Interactions with alcohol and other sedatives.
48
Buspirone
Non-benzo anxiolytic.
Agonist at 5-HT1A receptors. Does not exhibit cross tolerance with benzos
Anxioselective- has no other properties
49
Buspirone advantages and disadvantages
Advantage- fewer and less severe CNS effects compared to benzos (no physical dependence)
Disadvantage- slower OOA, 1-2 weeks
50
Benzo vs. buspirone
| Relief of generalized anxiety
Both
51
Benzo vs buspirone
| Which has addiction liability
Benzo
52
Benzo vs buspirone, which has rebound anxiety?
Benzo
53
Benzo vs buspirone, which has physical dependence?
Benzo
54
Benzo vs buspirone, which has delay in anxiolytic effect?
Buspirone
55
Benzo vs buspirone, which potentiates alcohol sedation
Benzo
56
Hypnotics: Novel benzodiazepine agonists
Zolpidem, Zaleplon, Eszoplicone
| Non-benzo that act as agonists or positive allosteric modulators at the GABA/Benzo receptor complex
57
Novel benzo agonists BBW
Risk of serious injuries in sleepwalking
58
Novel benzo agonists (z drugs) properties
```
Strong sedative effects mask anxiolytic action
Only weak anticonvulsant effect
Little evidence of physical dependence
Short 1/2 life
No rebound insomnia
```
59
Novel benzo agonists (z drugs) MOA
Binds to alpha-1 subunit containing sites
60
Hypnotics: melatonin receptor agonists
Ramelteon and Tasimelteon
Activates melatonin receptors
Rapid onset with minimal rebound insomnia
61
Suvorexant
Orexin antagonist
Lacks abuse potential
Hypnotic but not sedating
62
Drugs for bipolar disorder
Lithium
| Carbamazepine, valproate, lamotrigine, quetiapine, cariprazine
63
Etiology of depression
Biogenic amine hypothesis
-Disorders of mood result from dysfunction of brain monoamine neurotransmitters (serotonin and NE primarily)
Newer focus on neuroplasticity
64
What type of diet promotes depression?
Tryptophan deficient diet
65
Classification of antidepressants
Tricyclic antidepressants (TCAs)
Selective serotonin (5-HT) reuptake inhibitors (SSRIs)
Selective serotonin-NE reuptake inhibitors (SNRIs)
Monoamine oxidase inhibitors (MAOIs)
Heterocyclics
Ketamine
66
TCA drugs
Amitriptyline, desipramine, imipramine
67
TCA MOA
Inhibit the reuptake mechanisms (transporters) responsible for the termination of the synaptic actions of both NE and 5-HT in the brain. Results in potentiation of their neurotransmitter actions at postsynaptic receptors
68
TCA effects
Acute- block the reuptake of NE and 5-HT.
| Delayed- Weeks, therapeutic onset with all antidepressants (except ketamine)
69
Tricyclic antidepressants AE
Muscarinic ACh blockade- dry mouth, urinary retention, constipation
a-adrenergic (NE) blockade- orthostatic hypotension
Histamine blockade- sedation, weight gain
Sodium channel blockade- cardiac toxicity
70
Selective serotonin reuptake inhibitor agents
Fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram
71
SSRIs acute effects
Selectively block reuptake of 5-HT. Minimal inhibitory effect on NE transporter or blockade of ACh or NE receptors
72
What is better tolerated, SSRIs or TCAs?
SSRIs
73
Serotonin-norepinephrine reuptake inhibitors (SNRIs) MOA
SNRIs bind and inhibit transporters for both NE and 5-HT
| Enhance the actions of both neurotransmitters
74
SNRIs drugs
Desvenlafaxine, duloxetine, venlafaxine, levomilnacipramine
75
How do SNRIs differ from TCAs?
In lacking significant blocking effects on peripheral receptors including H1, muscarinic, or a-adrenergic receptors
76
Serotonin receptor antagonists/ SRI agents
Trazodone, nefazodone (not us)
77
Serotonin receptor antagonists actions
5-HT2A/C receptor antagonist and 5-HT uptake inhibitor
78
Vilazodone
Antidepressant
| 5-HT reuptake inhibitor/ 5-HT1a partial agonist`
79
Vortioxetine
Antidepressant
| 5-HT stimulator/modulator
80
Monoamine oxidase inhibitors drugs
Phenelzine and tranylcypromine
Non selective inhibitors of MAO A and B, inhibit NE and 5-HT
Selegiline- selective inhibitor of MAO-B at low doses
81
MOA of MAOIs
Inhibit monoamine oxidases that metabolize NE and 50HT and dopamine
Increase vesicular stores of 5-HT and NE
82
DDI and MAOIs
Foods containing tyramine with MAOIs can lead to htn crissi
83
Which antidepressants have the worst sexual AE
SSRIs
Venlafaxine
Some- tricyclics, MAOIs
84
Which antidepressants have the worse conduction AE
Tricyclics
85
Which antidepressants have the worst seizure AE
Bupropion is worst
Tricyclics
Some- venlafaxine, SSRIs, trazadone
86
Which antidepressants have the worst sedation?
Tricyclics, trazodone
87
Which antidepressants have the worst anti-adrenergic (orthostatic hypotension) AE
Tricyclics
| Trazodone
88
Which antidepressants have the worst anticholinergic AE
Tricyclics
89
Acute antidepressant drug action
Increased concentrations of transmitter in synapse, Predictive of antidepressant action.
90
Chronic antidepressant drug action
Enhanced 5-HT and NE transmission
| Down regulation of receptors
91
Rapid acting antidepressant
Ketamine
| -lack of sustained response
92
Post-partum depression
Brexanolone
93
Bipolar agents (mood stabilizers)
Prophylactic treatment
| Lithium
94
AE of lithium
Low therapeutic index
Polydipsia and polyuria
Renal toxicity
CNS AE is tremor
95
Biopsychosocial model
Biology, psychology, social, and environmental factors may all be important in psych disorders
96
Prevalence of MDD in US adults
Very common
Female
Native Americans
Low socioeconomic status
Stressors- medical, mental, socioeconomic
First-degree relative with depression (40-50% heritability)
97
DSM-5 Diagnosis of MDD
Depressed mood and/or anhedonia (lack of pleasure) occurring almost every day for >2 weeks
AND
5+ additional symptoms that cause significant distress and/or impairment in social or occupational functioning
98
Signs of depression (D-SIGECAPS)
```
Depressed mood
Sleep- insomnia or hypersomnia
Interest- diminished
Guilt- feelings of worthlessness
Energy- loss
Concentration- diminished
Appetite- significant weight loss or gain
Psychomotor agitation or retardation
Suicide
```
99
Standardized rating scales for MDD
```
HAM-D
MADRS
PHQ-9
PHQ-2
QIDS
```
100
MDD differential diagnosis
Rule out non-organic causes
- substance use (alcohol, benzodiazepines)
- Medications can cause "depression-like" symptoms
- Other medical conditions- hypothyroidism, anemia, heart disease
101
Drug induced depression
Antihypertensives- Beta blockers, calcium channel blockers
CNS depressants- alcohol, benzodiazepines, opioids
Anti-infectives- fluoroquinolones, acyclovir
Misc. - Isotretinoin, oral contraceptives, corticosteroids
102
Response and remission of depression
Untreated episodes usually last around 6 months
Periods of remission shorten with subsequent episodes
1/2 will fully respond
15% may never experience remission/recovery
103
Depression recurrence
About 1/2 of patients will experience a single episode
Patients who have experienced 3 or more episodes exhibit a 90% recurrence.
Other risk factors-chronic medical conditions, other psychiatric comorbidities, childhood maltreatment
104
Depression and suicidality
If untreated, lifetime risk of suicide is about 20%
Highest in older (>75 yo) white males, LGBTQ+, teenager/ adolescents
Other risk factors: IS PATH WARM
105
IS PATH WARM suicide risks
```
ideation
substance abuse
Purposelessness
anxiety
Trapped
Hopelessness
Withdrawal
Anger
Recklessness
Mood change
```
106
Pathophysiology of depression
Monoamine deficiency
Receptor dysregulation
Chronic stress
Unknown
107
Monoamine hypothesis of depression
Based on the MOA of the earliest antidepressants.
MAOIs and TCAs work to increase the levels of NE, Serotonin, and Dopamine
Hypothesis: Depressed patients are deficient in monoamine neurotransmitters
....but antidepressants increase neurotransmitters in the synapse on day 1 and antidepressants dont work for weeks.
108
Neurotransmitter receptor hypothesis (AKA sensitivity hypothesis) of depression
Extension of monoamine hypothesis
Attempts to account for delayed antidepressant activity
Hypothesis: Depletion of monoamine neurotransmitters leads to neural hypersensitivity and receptor up-regulation.
...but there is no reproducible evidence of consistent monoamine deficiency in depressed patients
109
Monoamine hypothesis of gene expression (stress model) of depression
Evidence that despite normal monoamine levels and their receptors, these systems do not respond normally in depressed patients.
Cortisol is released causing a reduction in brain-derived neurotrophic factor (BDNF)
Hypothesis: Serotonin enhances BDNF and neurogenesis in the hippocampus, reversing negative effects of cortisol. Glutamate modulation quickly releases BDNF in the brain.
110
Summary of theories of depression
There appears to be a dysfunction in the frontal cortex and limbic structures
Manipulation of serotonin and NE systems can alter depressive symptoms
111
MDD: Treatment algorithm
1st line- SSRI (except fluvoxamine), SNRI, NaSSA, NDRI, vortioxetine
Titrate for 1-4 weeks
No response- change agent, test for weeks 4-8
Partial response- augment, increase dose, change agent, psychotherapy
Full response- continue for 4-9 months or indefinite
3rd line- TCAs, MAOIs, misc, augmenting agents
112
St. Johns Wort
```
Modest efficacy
TID
Induces multiple CYP enzymes
ADRs- N/V/D, photosensitivity, sexual dysfunction
Just put them on an SSRI instead
```
113
A-adenosyl methionine (SAMe)
Low/modest efficacy in depression
| ADRs include dizziness, dry mouth, constipation, insmonia
114
L-methylfolate in depression
Prescribed medical food
Well tolerated, mixed efficacy
Adjunt in MTHFR polymorphism
115
Omega 3 fatty acids in depression
Safe
| Low efficacy
116
Vitamin D in depression
Deficiency more common in depressed patients
| Efficacy is mixed, does not prevent depression
117
Classes of antidepressants
```
SSRIs
SNRIs
NDRIs
NaSSa
ASRIs/SPARI
TCAs
MAOIs
Misc.
```
118
STAR*D trial
The largest, longest duration controlled trials ever conducted to study depression.
Studied patients in multiple settings and in multiple phases of treatment.
Level one- start with citalopram and then add additional agents or switch if necessary
119
BBW for all drugs approved for MDD
Increased risk of suicidality
120
Serotonin syndrome
Applies to any agents with serotonergic properties
Potentially life threatening
Management- remove offending agent, 5-HT2A antagonists (cyproheptadine)
121
Serotonin syndrome triad
Mental status changes, autonomic instability, neuromuscular abnormalities
122
Serotonin syndrome s/s
Mental status changes- agitation, pressured speech
Autonomic instability- tachycardia, diarrhea, shivering, diaphoresis, mydriasis
Neuromuscular abnormalities- Clonus, hyperreflexia tremor, seizure
123
Anti-depressant withdrawal
```
Agents should be tapered over weeks if able (except fluoxetine, it self tapers)
Abrupt d/c can precipitate withdrawal syndrome
Flu-like symptoms
Insomnia
Nausea
Irritability
Sensory disturbance
HA
(FINISH)
```
124
Serotonin selective reuptake inhibitors (SSRI) MOA
Inhibition of reuptake of serotonin in the presynaptic neuron of the CNS.
125
When to use SSRIs
1st line agent for MDD
| Low risk of toxicity in overdose
126
SSRIs agents
```
Fluvoxamine
Fluoxetine
Paroxetine
Escitalopram
Citalopram
Sertraline
```
127
Citalopram dosing
10-40mg QD
| *max 20mg if >60 years old, significant hepatic impairment, and 2C19 PM
128
Which SSRI has the longest T1/2?
Fluoxetine
4-6 days T1/2
Metabolite in 4-16 days
129
SSRIs: sexual dysfunction
Very common, about 1/3 of patients
Decreased libido, delayed ejaculation, anorgasmia
Treatment strategies- wait before changing therapy as tolerance may develop, use sildenafil for erectile problems, add bupropion, mirtazapine, buspirone
130
Which SSRI causes sexual dysfunction most commonly?
Paroxetine
131
SSRIs AE
```
N/V/D
Insomnia
Fatigue/sedation
Weight gain
Diaphoresis
Seizures
SIADH (rare)
Anxiety/agitation in early treatment
Risk of bleeding- increased with other antiplatelet therapy added
```
132
Which SSRI causes insomnia the most?
Fluoxetine
133
Which SSRI causes N/V/D the most?
Sertraline
134
Which SSRI causes fatigue the most
Paroxetine
135
Which SSRI causes weight gain the most?
Paroxetine
136
Paroxetine-specific SSRI AE
Anticholinergic effects (avoid in elderly)
137
Citalopram-specific SSRI effect
QTc prolongation
| Do not give more than >40mg/day or 20mg if >60 years old
138
SSRIs DDI
All SSRIs:
MAOIs- hypertensive crisis, serotonin syndrome. Linezolid also has MAOI effects.
Triptans, sibutramine- serotonin syndrome
NSAIDs, antiplatelets, anticoagulants- bleeding risk
Fluoxetine, paroxetine- Potent CYP2D6 inhibition, may increase conc of tricyclic antidepressants, may interfere with tamoxifen treatment
Fluvoxamine- CYP1A2 potent inhibition
139
Serotonin/NE Reuptake Inhibitors (SNRIa) MOA
Inhibit both serotonin and NE presynaptic reuptake
More specific to NE-5HT than TCAs (better safety and tolerability)
1st line
140
SNRI agents
Levomilnacipran
Duloxetine
Venlafaxine
Desvenlafaxine
141
SNRIs AE
All:
N, dizziness, insomnia, sedation, constipation, sexual dysfunction, urinary retention, risk of SIADH
Dose related increase in diastolic BP
142
Which SNRIs do you have to caution with uncontrolled narrow angle glaucoma?
Duloxetine, Levomilnacipran
143
Which SNRI has the most pronounce increase in diastolic BP?
Venlafaxine and desvenlafaxine
144
Which SNRI has risk of tachycardia?
Levomilnacipran
145
Which SNRI has risk of rare interstitial lung disease?
Venlafaxine, desvenlafaxine
146
Duloxetine-specific SNRI AE
More anticholinergic AE, urinary retention
| Increases risk of hepatotoxicity, esp with ETOH
147
SNRIs DDI
All-
| serotonin syndrome, bleeding risk
148
Duloxetine DDI
Substrate of CYP 1A2, 2D6
| Inhibitor of 2D6
149
Venlafaxine DDI
Substrate of 3A4, 2D6
150
Levomilnacipran DDI
Substrate of 3A4`
151
Norepinephrine dopamine reuptake inhibitor (NDRI) agent
Bupropion
152
Bupropion MOA and use
1st line, augmenting agent
MOA: Inhibits reuptake transporters of synaptic dopamine, NE
Has NO serotonin effects
153
Bupropion AE
N, V, weight loss, tremor, insomnia, xerostomia, HTN
| Low risk of sexual dysfunction
154
Bupropion DDI
MAOIs- HTN crisis
Seizure threshold lowering agents, beta lactam abx, alcohol, antipsychotics
CYP2B6 substrate, 2D6 inhibitor
155
Bupropion contraindications
Seizure disorder
High alcohol/benzo intake
Bulimia, anorexia
156
Noradrenergic and specific serotonergic antidepressant (NASSA) agent
Mirtazapine
157
Mirtazapine MOA and use
1st line with compelling reason
| MOA: antagonizes presynaptic a-2 adrenergic receptors (increase NE, serotonin) , H1 receptor antagonist
158
Mirtazapine ADR
sedation, increased triglycerides, dry mouth, sexual dysfunction, appetite stimulation
159
Vortioxetine MOA
1st line agent
| SSRI with 5-HT1A agonism, mixed antagonist/partial agonist
160
Vortioxetine AE
Nausea, constipation, vomiting, sexual dysfunction
161
Vortioxetine DDI
CYP2D6 primary substrate- dose adjustment
| Wait 21 days before starting MAOI (long t1/2)
162
Serotonin antagonist/reuptake inhibitor (SARI) agents
trazodone, vilazodone
163
Trazodone use and MOA
3rd line/ augmenting (d/t sedation)
| MOA: Antagonist at post-synaptic 5HT2, inhibits reuptake of serotonin
164
Trazodone AE
Sedation, dizziness, orthostatic hypotension
| Priapism
165
Trazodone DDI
Similar to SSRIs
| Trazodone is 3A4 substrate
166
Vilazodone use and MOA
MOA- SSRI and 5-HT receptor PARIAL agonist (SPARI)
Newer, less data
3rd line
167
Vilazodone ADR
GI: Diarrhea, N, V, xerostomia
Neurologic: dizziness, insomnia
CYP3A4 substrate
168
Tricyclic antidepressants use and MOA
3rd line for MDD
MOA: Inhibits reuptake of NE and 5-HT
Antagonizes histamine, alpha-adrenergic and muscarinic receptors, cardiac sodium channels (AE)
169
Why has use fallen out of favor with TCAs?
OD can occur with a 1 week supply
| Poor tolerability
170
TCA agents
```
Amitripyline
Imipramine
Doxepin
Clomipramine
Maprotiline
Protriptyline
Desipramine
Nortriptyline
```
171
TCA AE
```
Sedation
Decreased seizure threshold
CV events- orthostatic hypotension/syncope, arrhythmias
Sexual dysfunction
Tremor
Photosensitivity
Heat intolerance
Risk of seizure
```
172
Anticholinergic effects of TCAs
Cholinergic rebound
| Drying effects: SLUD
173
Anti-histaminic effects of TCAs
Weight gain
| Sedation
174
Alpha-1 adrenergic effects of TCAs
Orthostasis
Hypotension
Dizziness
175
TCA DDI
```
CNS depressants
QT prolonging agents
alpha-adrenergic blockers (increases hypotension)
Serotonin syndrome
CYP interactions:
2D6 substrates (except comipramine)
2C19 substrates (nortriptyline, doxepin)
1A2 substrate: clomipramine
```
176
Monoamine oxidase inhibitors (MAOIs) moa and use
3rd+ line for MDD
MOA: Inhibition of MAOa and MAOb causing increased concentrations of NE, 5-HT, and dopamine in neuronal synapse
Infrequently used
177
MAOI agents
Tranylcypromine
Isocarboxazid
Phenelzine
Selegiline
178
MAOI AE
```
Hypotension, dizziness common
Anticholinergic AE
Sedation or insomnia
HA
Sexual dysfunction
Cautions in cardiac disease, hepatic impairment
Contraindicated with pheochromocytoma
```
179
MAOIs food interactions
Hypertensive crisis:
Food interaction from MAO-a inhibition in GI- excess of tyramine
Symptoms: stiff neck, HA, n, v, diaphoresis, increased BP
Dietary tyramine- cheese, wine, beer, fermented foods, MSG, coffee, chocolate
ALL MAOIs except selegiline patch
180
MAOIs DDI
Serotonin syndrome- 2 week washout when changing to/from MAOI (5 weeks for fluoxetine, 3 weeks for vortioxetine)
Increased BP= stimulants, sympathomimetics *epinephrine, albuterol, decongestants
181
MAO regeneration
14 days
182
Esketamine
Intranasal jetamine
Used for augmentation in severe depression that has failed 2 trials of antidepressants
REMS program- must be administered by registered clinician and monitored for 2 hours after
183
Antipsychotics in depression
FDA approved agents for augmentation- aripiprazole, brexpiprazole, olanzapine, quetiapine XR
184
Additional depression augmenting agents
Stimulants
| Buspirone
185
Pharmacogenomics in depression
Polymorphisms in 2D6, 2C9, and 2C19 may affect medication levels
Short S or long L in 5-HT transporters, alterations in expression of BDNF and tryptophan hydroxylase may alter antidepressant response
186
Depression in pregnancy
SSRIs most common (AVOID paroxetine)
SNRI
TCAs less frequently used, but has more data
Augmenting agents- mirtazapine, bupropion, antipsychotics
187
AE of brexanolone
Presyncope, drowsiness, sedation, dizziness, xerostemia
BBW: Impairment/loss of consciousness
REMS required
188
Depression drugs effects on lactation
Risk of AE from breastfeeding low
Some cases of somnolence with citalopram
Bupropion may decrease milk supply
"pump and dump" not recommended
189
Pediatrics and adolescents depression agents
Start LOW and SLOW
recommend f/u in 1 week
Within 6 weeks change therapy if not effective
190
Depression in elderly
```
More physical symptoms- insomnia, pain
Less likely to respond to therapy
Low and slow
ECT is safe
SSRIs first line (avoid paroxetine, citalopram dose restriction)
Stimulants (methylphenidate) may help
```
191
Which drugs are 1st line in depression?
SSRIs
192
Is delirium reversible?
Yes
193
Delirium
Disturbance of consciousness, attention, cognition, and perception.
Develops over a short period of time (hours to days)
Tends to fluctuate during the course of the day.
194
DSM5 criteria for delirium
Alteration in attention and awareness
The alteration is abrupt and fluctuates throughout the day
There is also an alteration in cognition
Alterations are not better accounted for by any other disorder.
There is physical evidence that the alteration is caused by a medical condition, substance, or variety of causes
195
Where is delirium found?
```
Hospital
Long term care
ER
Palliative care
Hospice
```
196
How common is delirium in patients > 65 years old
50% of patients
197
Where is delirium most common?
ICU
198
Consequences of delirium
More than doubles mortality rate
Increases LOS by 2-5 days
1 in 3 patients have some residual cognitive impairment
Common cause of new institutionalization (delirium and incontinence most common causes)
199
Confusion assessment method (CAM)
Must have acute fluctuation course and inattention
| And disorganized thinking or LOC
200
Delirium S/S
```
Disturbed attention
Fragmented sleep
Memory impairment
Disoriented to time and place
Abrupt altered change in consciousness can be hyper or hypoactive
```
201
Types of delirium
Hyperactive
Hypoactive
Mixed
202
Symptoms of hyperactive delirium
Restlessness, agitation, hallucinations, delusions
203
Which type of delirium is most common in the elderly?
Hypoactive or mixed.
| Often unrecognized
204
S/S of hypoactive delirium
Lethargy, sedation, slow response and movement
205
Dementia vs delirium
Dementia- insidious onset, gradual deterioration
Awareness is often clear until advanced stages in dementia
Dementia pts do not have hallucinations or delusions until late stage
Dementia patients have reversed sleep cycles.
206
Depression vs delirium
Depression- onset takes a while to develop.
Patients have low mood, does not fluctuate.
Depression is chronic
ADL- compromised in patients with depression
207
Sundowning
Dysfunction of circadian rhythm
Behaviors that occur in the evening- confusion, agitation, pacing/wandering, increased verbal activity
Management- proper sleep hygiene. trazodone, melatonin
208
Risk factors for delirium
```
H/O ETOH use
Age >70
Kidney or liver disease
Poly pharmacy (>6 meds)
Sensory impairment
Dementia, depression, underlying brain disease, previous delirium
```
209
Pharmacology of drug induced delirium
Dopamine activation
| Cholinergic inhibition
210
What causes delirium?
```
Dementia and drugs
Electrolytes/Eyes, ears other senses
Lungs, liver, kidney, brain, heart
Infection
Retention
Injury
Unfamiliar environment
Metabolic
Sleep
```
211
What electrolytes cause delirium
Hyponatremia
| Hypercalcemia
212
Anticholinergic drugs and delirium
TCAs (amitriptyline)
Antihistamines
Incontinence agents- tolterodine, oxybutynin
Antipsychotics- olanzapine
```
Promethazine
Digoxin
Skeletal muscle relaxants
Paroxetine
benztropine
Cefepime, quinolones, imipenem, linezolid
```
213
Psychotropics
Lunesta, belsomra, sonata, ambien
Benzos
Antidepressants
214
Other medication causes of delirium
```
Metoclopramide
Steroids
H2RAs
all antihypertensives and diuretics
Drug withdrwaawl
Antiarrhythmics
NSAIDs
```
215
Opioids and delirium
Highest risk-codeine, tramadol
| All others have risk
216
Prevention of delirium
Ensure sensory aids
Encourage hydration, mobility, senses intact
Maintain sleep pattern
Avoid sedation, catheters, loud noices
217
Management of delirium principles
Treat underlying cause
D/C any new medication added if no clear cause.
Non pharm management is critical.
Antipsychotics are DOC, but no drug is FDA approved for delirium
218
Evaluation of delirium
```
BMP, ammonia and calcium
CBC
Urinalysis
B12
TSH
Tox screen
Vital signs
O2 saturation
```
219
Non pharm delirium tx
Family involvement, sitter, normalize sleep-wake cycle, sensory evaluation, music, remove catheters, mobilize pt, avoid restraints, hydration and nutrition
220
Medication tx of delirium hyperactive
Haloperidol, olanzapine, quetiapine
BBW- 7 days or less
Use only when delirium puts patients at risk to themselves or others
221
Haloperidol for delirium
First line, especially if severe
Low doses Q 4 H
QTc prolongation
More effective in pts halllucinatinf
222
Olanzapine for delirium
More sedating than haloperidol, but less likely to cause EPS
223
Quetiapine in delirium
More appropriate for mild delirium
More sedating than haloperidol
Safest in parkinsons disease
224
Acetylcholinesterase inhibitors in delirium
Consider with patients who have dementia
225
Benzos in delirium
Only use for alcohol withdrawal or parkinsons related delirium
226
Valproic acid in delirium
Appropriate for patients with underlying behavioral manifestations of dementia.
Not for acute delirium
227
SAR of benzodiazepines
Aromatic ring
Electronegative electron withdrawing group (Cl, F, nitro)
Phenyl group- increases activity
Carbonyl or H-bond acceptor (could also be NH)
Hydroxyl group= shorter duration of action
