8005 final Flashcards

(296 cards)

1
Q

EPS cause

A

exposure to dopamine antagonist med

blocks D2 receptors means inhibiting dopamine and blocking ACH

this leads to more ACH release which turns into EPS

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2
Q

4 EPS symptoms

A

Dystonia
Akathesia
Parkinsonism
Tardive Dyskinesia

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3
Q

Dystonia sx

A

torticollis
sustained muscular contraction
oculogyric crisis

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4
Q

Dystonia tx

A

anticholinergic med

benztropine***
biperiden
diphenhydramine

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5
Q

Akathesia sx

A

restless
tapping
pacing

can’t sit still – psychomotor restlessness

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6
Q

Akathesia tx

A

Treatment (beta blocker) – propranolol***

mirtazapine
cyproheptadine
BZDs

i. Avoid polypharm or rapid dose increases to avoid akathisia

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7
Q

Parkinsonism sx

A

bradycardia
postural instability
tremor
rigidity
shuffling gait

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8
Q

Parkinsonism tx

A

Treatment (anticholinergic med) –

reduce dose or switch to lower risk med

***benzotropine (caution in elderly),

amantadine (good for elderly)

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9
Q

Tardive Dyskinesia sx, MOA

A

chronic manifestation

– involuntary movements of lower face, limbs, trunk –

reversibly inhibits VMAT2

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10
Q

Tardive dyskinesia risk factors

A

early presence of EPS

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11
Q

Tardive Dyskinesia tx

A

stop Rx

Valbenazine, deutetrabenazine, clozapine,
gingko biloba

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12
Q

serotonin syndrome vs NMS

onset

A

SS more rapid

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13
Q

serotonin syndrome vs NMS

which is deadly

A

NMS

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14
Q

serotonin syndrome vs NMS

3 similar sx

A

fever
Tachy
HTN

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15
Q

serotonin syndrome vs NMS

reflexes

A

SS: Clonus (hyperreflexia 4+)

NMS: rigidity

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16
Q

serotonin syndrome vs NMS

SS sx not in NMS

A

diarrhea

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17
Q

serotonin syndrome vs NMS

identifying labs

A

not SS

But NMS: inc CK, WBC, rhabdo

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18
Q

serotonin syndrome vs NMS

rx associations

A

SS: SSRI/SNRI, MAOI, linezolid, triptins, analgesics, cough med, St John wort, tryptophan

NMS: Antipsychotics though 1st gen more

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19
Q

serotonin syndrome TX

A

support flux BP and P,

avoid restraints

BZDs
cyproheptadine, olanzapine

DO NOT USE: propranolol, dantrolene, bromcriptine

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20
Q

NMS tx

A

DC med

Dantrolene, bromocriptine, amantadine
(too much DA is blocked, give some back)

Cooling measures (tyl & ibu ineffective)

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21
Q

SS to avoid

A

use wash out of 2 wk between SSRIs to TCAs unless it is fluoxetine, then it is 5 wks

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22
Q

NMS risk for recurrence

A

30% - start low and slow

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23
Q

SS acronym

A

Shits – diarrhea

Shivering
Hyperreflexia
Increased Temp
Vital signs instability Encephalopathy Restlessness
Sweating

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24
Q

Dopamine Pathways

A

Mesocortical
Mesolimbic
Nigrostriatal
Tuberinfundibular

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25
mesocortical pathway
neg sx of schiz dec d2 activity impaired cognitions and flattening affect
26
mesolimbic pathway
pos sx of schiz brain responds to dec D2 by inc activity in mesolimbic
27
Nigrostriatal pathway
regulates coordination and movement major dec in parkinsons which is why antipsych can cause parkinsonism
28
tuberoinfundibular pathway
responsible for actions of pituitary (prolactin) If Da is dec then inc prolactin --causing galactorrhea, amenorrhea which means dec FSH
29
Dopamine made in the
VTA
30
5HT made in the
raphe nuclei
31
NE made in the
Locus Ceruleus
32
Ach regulated by the
parasympathetic nervous system (side effect: dry mouth, itchy eyes, blurry vision, urinary retention, memory impairment, elevated temp)
33
NT on and off switch
on is glutamate--excitatory off is GABA--inhibitory
34
dopamine hypothesis
D2 receptor presynaptic autoreceptors (gatekeepers) occupancy provides negative feedback. Diseases or meds that ↑ DA will enhance or produce positive symptoms. AntiΨ that ↓ DA activity will ↓ or stop psychoses.
35
how AntiΨ = ↓ DA
= mesolimbic – improve + symptoms = mesocortical – may worsen negative sympomts = nigrostriatal – risk EPS inducing movement disorders = tuberinfundibular – risk of galactorrhea, amenorrhea
36
defining characteristic of schiz
psychosis
37
psychosis associated with
schiz mania depression cognitive disorders
38
psychosis definition
Set of symptoms which a person’s mental capacity, affective response capacity to recognize reality communicate, relate to others is impacted
39
Schizophrenia dx to know
Disorganized speech Negative sx PLUS hallucinations delusions and/or disorganized speech 6+ mo with at least 1 mo of : 1. Delusions 2. Hallucinations 3. Disorganized speech or behavior 4. Catatonic behavior 5. Negative symptoms
40
target of most meds for schiz
positive sx
41
negative sx (5)
a. Alogia – reduced speech b. Affective blunting - ↓emotional response c. Asociality -↓social drive, limited eye contact d. Anhedonia - ↓interest in pleasurable things e. Avolution - ↓motivation, poor grooming
42
mesolimbic pos or neg
positive
43
mesocortical pos or neg
neg
44
antipsychotic neurotransmitters
DA 5HT NE His Ach
45
Antipsych 1st vs 2nd NT focus
1st: D2 antagonist 2nd: D2/5HT2A antagonist
46
Antipsych 1st AE diff from 2nd
High EPS and NMS rates 2nd has lower affinity on D2 so lower risk of EPS
47
Antipsych 1st receptors and what they cause
D2 Alpha 1 (orthostasis, hypotension, priapism) histamine 1 (wt gain, sedation), muscarinic (dry mouth, vision changes, constipation, difficulty urinating)
48
AIMS
used to assess for AE of antipsych
49
2 high potency 1st gen antipsych
Haloperidol Fluphenazine
50
1 low potency 1st gen antipsych
Chlorpromazine
51
Haloperidol notes to know
highest rate of EPS QT prolongation, torsades less wt gain/metabolic
52
2nd gen antipsych AE
wt gain so risk of: inc cholesterol DMII
53
Clozapine 4 points to know
REMS reporting for tx resistant frequent labs for agranulocytosis watch for constipation
54
antipsych with highest rate of increased prolactin
risperidone
55
active metabolite of risperidone
paliperidone
56
2nd gen antipsych good for bipolar depression
lurasidone
57
common antipsych for peds
risperidone, aripiprazole
58
Antipsych rx SL
asenapine
59
Antipsych that cause sedation and which are less
PINES less in pip, rip, done
60
Antipsych that cause wt gain and which are less
PINES less in pip, rip, done
61
antipsych that cause anticholinergic
Pines
62
antipsych that cause EPS
DONES less in pines
63
antipsych that cause hypotension
Pines and dones
64
antipsych that cause QTc
Pines and dones less in pip, rip, zole
65
MDD patho
dysregulation of emotion in response to stress dysregulation of 5HT, NE, DA stress= release glucocorticoids, corticotropin, cytokines which all interfere with the NT more
66
MDD monoamine hypothesis
mood improved with adding MAOI and TCA =deficiency 5HT, NE, and/or DA
67
MDD tx approach if partialk or no response
assess adherence inc dose as tolerated after 8 wks can inc dose, switch alternative, augment with antiD/atypical, psychotherapy
68
AE for MDD tx options
elderly: hyponatremia SS discontinuation syndrome: flu like SI Sex dys dec Sz threshold: Buproprion
69
SSRI MOA
inhibition of presynaptic 5HT receptors by interfering with intracellular 5HT transporters inhibits reuptake of 5HT which ↑ amount of 5HT active and available in synaptic cleft leading to increase 5HT in synaptic cleft
70
SSRI AE
HA, wt gain, GI upset, sexual dysfunction, agitation/anxiety when starting
71
SNRI MOA
inhibits presynaptic 5HT and NE transporters leading to ↑5HT and HE in synaptic cleft
72
SNRI AE
same as SSRIs plus HTN, nausea/diarrhea, sweating, dry mouth, dizziness, fatigue
73
TCA reserved for
Tx resistant depression les tolerable and more deadly in OD due to cardiac
74
TCA MOA
inhibition of presynaptic 5HT and NE reuptake by inhibition of these transporters leading to ↑5HT and NE in synaptic cleft and antagonizes Ach and His, also Na and Ca channel inhibitor (may result in some mood stabilization effects), also binds to α and muscarinic receptors
75
TCA alt use
pain
76
TCA AE
more sedation, anticholinergic effects of confusion, constipation, wt gain Tertiary amines – more sedation and anticholinergic effects (amitriptyline, imipramine, clomipramine, doxepin) Secondary amines – more cardiac effects (nortriptyline, desipramine, amoxapine)
77
TCA toxicity
Toxic levels reached at 7x/therapeutic dose. Monitor for QRD widening (tell tale sign of TCA OD)
78
TCA toxicity tc
Treatment is Sodium bicarb
79
MAOI MOA
irreversibly inhibits monoamine oxidase preventing metabolism of NE< 5HT, and DA which Allows the levels to increase
80
MAOI AE
HTN crisis – avoid aged cheese, wine, soy, draft beer as well as amphetamines, carbamazepine, decongestants, ephedrine, cough meds
81
MAOI use
tx resistant MDD
82
SSRI 1srt sx to improve
sleep problems
83
SSRI function of 5HT
Depression Obsession Migraines Anxiety Intestines Nausea Sexual
84
SSRI longest half life
fluoxetine good for if you forget meds but careful with switch to another SSRI cuz of 5 wk washout need
85
Fluoxetine careful when switching to another SSRI due to
need of 5 wk washout
86
SSRI worst AE sex
paroxetine due to rapid absorption
87
Paroxetine contraindication
pregnant
88
SSRI most GI AE
Sertraline so take with food
89
SSRI safe from pregnancy
Sertraline
90
SSRI high tolerability and lack enzyme interactions
citalopram and escitalopram
91
citalopram and escitalopram AE
Qtc EKG yearly get genetic testing
92
citalopram interaction
omeprazole inhibits metabolism
93
SSRI approved for OCD
fluvoxamine high number of interactions though
94
SNRI 2 common rx
venlafaxine and duloxetine
95
TCA rx for depression
Amitriptyline & Nortriptyline – Tertiary amine
96
TCA used for sleep
doxepin
97
Amitriptyline & Nortriptyline which for elderly
Nortriptyline less sedating so less fall risk and less hypotension
98
3 atypical antidepressants
Mirtazapine Buproprion Trazadone
99
Mirtazapine MOA
↑synaptic concentration of 5HT & NE through presynaptic α2 Antagonism – also 5HT2a and 5HT3 antagonists (better tolerability) and His antagonist.
100
Mirtazapine AE
Sedation wt gain agranulocytosis
101
Bupropion MOA
boosts DA & NE but lacks 5HT involvement. Inhibits DA & NE transporters = ↑DA and NE in synapse
102
Bupropion contraindication
bulimia can cause sz
103
Trazadone MOA
5HT antagonist and reuptake inhibitor. Weak inhibition of 5HT and NE reuptake, 5HT2a antagonist, weak α-1 antagonist and His antagonist
104
Trazadone AE
priapism
105
MAOI combo with SSRI/SNRI
can cause SS needs 2 wk washout 5 wks for fluoxetine
106
5 Antidepressants with superior efficacy:
Escitalopram Mirtazapine Sertraline Venlafaxine Citalopram
107
MDD tx avoid if worried about wt gain
avoid mirtazapine
108
MDD tx avoid if worried about sex AE
SSRI
109
when to augment MDD tx
after 2+ antidepressants AE issues with effect that can be targeted
110
augmentation options for MDD
lithium thyroid hormone Antipsych: aripiprazole, quetiapine stimulants: ritaline/adderall ECT
111
MDD tx duration of therapy for 1st, 2nd, 3rd episode
6+ mo 12+ mo lifetime
112
MDD tx with pain issue
SNRI
113
MDD tx with concentration issue
Bupropion duloxetine fluoxetine
114
Bipolar disorder etiology
Genetic Neurological: NTs etc Prenatal infxn
115
Bipolar DDX
SUD rx induced thyroid other psych (schiz) remember to r/o Bipolar in those with depression
116
Bipolar risk factors
abuse/neglect psych stress SUD
117
Bipolar patho (need to know?)
alterations in GABA, glutamate, and monoamines (NE, DA, 5ht) transmission Ca dysregulation - ↑intracellular calcium signaling DA hypothesis – intrinsic dysregulation in homeostatic regulation of dopaminergic functions Hypothalmic-pituitary axis dysregulation - ↑glucocorticoids, ↓glucocorticoid receptor sensitivity Autonomic dysregulation - ↑sympathetic activity, ↓parasympathetic activity Monoamine hypothesis - ↓NE, DA, 5HT = depression Monoamine receptor hypothesis - ↓NE, DA, 5HT = ↑receptors = depression Glutamate –major excitatory neurotransmitter GABA – major inhibitory neurotransmitter 5HT1A – agonism of receptor = ↑DA – antagonism of receptor = ↓DA 5HT2A – agonism of receptor = ↓DA – antagonism of receptor = ↑DA ↑amines = mania Autoreceptors – regulate the release of the monoamine that acts on it – in the presence of the monoamine, will turn off release of that monoamine NE: α2 receptor DA: D2 5HT: 5HT1A, 5HT1B and D
118
Bipolar goals of tx
eliminate episode prevent reoccurrence minimize AE pt compliance
119
BP1 DSM
mania+psychosis elevated, expansive, or irritable mood most of the day 1+ wk with 3+ sx w/wo psychotic episode
120
BP rapid cycling
rapid switch from mania to depression and back – mania recurs 4+/yr
121
BPII DSM
hypomania+ depression elevated, expansive, or irritable mood most of the day 4+ days 3+ sx at least 1+ hypomanic episode and 1+ major depressive episode
122
cyclothymia DSM
(hypomania + dysthymia) cyclic disorder Brief episodes of hypomania and dysthymia No full manic or major depressive episodes chronic
123
cyclothymia sx
Distractibility Irritability Grandiosity Flight of ideas Activity increased Sleep - ↓need Talkativeness
124
Bipolar tx options
1st: antipsychotics Mood stabilizers anti sz
125
BP tx options that need close monitoring
lithium VPA
126
BP tx mania vs depression
All antipsychotics work for mania. For depression: quetiapine, lurasidone, olanzapine-fluoxetine
127
BP tx for depression
quetiapine, lurasidone, olanzapine-fluoxetine
128
BP med choices
1. Lithium – effective for manic episodes and maintenance of reoccurrence 2. Quetiapine 3. Lamotrigine – preferred for bipolar depression 4. Lurasidone 5. Cariprazine
129
BP tx preferred for depression
lamotrigine
130
BP tx valproate vs lithium
Valproate better for rapid cycling
131
BP and carbamazepine
for acute mania and maintenance
132
BP mania tx
lithium, valproic acid, carbamazepine 2nd line – quetiapine, risperidone, olanzapine, ziprasidone, aripiprazole, asenapine
133
BP tx maintenance
lithium valproic acid quetiapine
134
1st line tx for mania
lithium, quetiapine, valproate, asenapine, aripiprazole, paliperidone >6mg, risperidone, Cariprazine
135
1st line x for acute mgmt of BP1 depression
quetiapine, lurasidone + lithium/valproate, lithium, lamotrigine, lurasidone, lamotrigine adjunct
136
1st line x for acute mgmt of BPII depression
quetiapine
137
1st line tx for maintenance for bipolar depression
lithium, quetiapine, valproate, lamotrigine, quetiapine + lithium/valproate, asenapine, aripiprazole (daily or monthly), aripiprazole + lithium/valproate
138
how to take lithium
with food
139
lithium AE
Lithium – monitor levels Movement – toxicity = tremor Nephrotoxicity – resolved with hydration and dialysis hypOthyroidism – with long term use (6-18mo)– can be treatment with levothroid Pregnancy – teratogen – can cause low implanted tricuspid valve
140
Lithium drug drug interactions
caffeine and theophylline = ↓levels HCTZ, NSAIDs, ACE inhibitors = ↓renal clearance = ↑effects of lithium
141
lithium monitoring
TSH, renal function, calcium, lithium levels, UA, CBC w/ diff, wt, pregnancy
142
lithium MOA
Inhibits GSK preventing cell death and creating neuroprotection
143
VPA MOA
Inhibits voltage-gated Na channels (anticonvulsant component) ↑amount of GABA (benzo like sedation)
144
VPA tx and prevents:
manic episodes
145
VPA AE
nausea, drowsiness, skin changes, wt gain, hair loss, dizziness In women: PCOS, hyperandrogenism, menses changes Teratogen in Pregnancy – neural tube defects (due to folate deficiency) – not recommended In women of childbearing age At high levels: vomiting, sedation, cognitive dulling
146
lithium and VPA clearance
renal hepatic
147
VPA monitor
VPA level LFT CBC pregnancy tests
148
Lamotrigine helps with
bipolar depression with little effect on mania
149
Lamotrigine MOA
blocking α unit of VSSC
150
Starting lamotrigine
slow and titrate over weeks to avoid SJS
151
lamotrigine AE
10% widespread itchy rash (1% turn into SJS) sedation, HA, dizziness, ataxia, nausea
152
Lamotrigine drug drug
Valproate = ↑serum lamotrigine levels by double Carbamazepine and phenytoin = ↓lamotrigine levels OCPs and estrogens = ↓lamotrigine levels
153
Carbamazepine used for
tx and prevent manic episodes also sz
154
Carbamazepine MOA
inhibits voltage-gated sodium channels and augments GABA transmission
155
Carbamazepine monitor
Agranulocytosis and SJS genetic test asias for HLA CBC, retic, Fe, fast cop
156
Carbamazepine AE
GI, rash, sedation, anticholinergic effects, dizziness, transient elevated LFTs Serious side effects: diplopia, ↓Na, birth defects, SJS, aplastic anemia, agranulocytosis
157
Anxiety NT
5HT
158
Anxiety sx
1st symptom of anxiety is fear and 2nd is worry ↓concentration, sleep changes, fatigue, arousal, irritability, muscle tension, compulsions, phobic avoidance, panic attacks
159
Anxiety patho
Amygdala (fear) – integrates sensory and cognitive information to determine fear response – emotions, motor response, endocrine response, autonomic responses, anxiety CSTC Loops (worry) – cortico-striato-thalamo-cortical loops --Regulates recurrent thoughts --Involved 5HT, GABA, NE, DA, glutamate, voltage-gated ion channels --↓COMT activity = ↑DA in circuits --↑DA activity and ↓efficiency of info process under stress = worry and anxiety --GABA – main inhibitory neurotransmitter Main target for BZDs, barbiturates, sedative hypnotics, ETOH --5HT and NE – 5HT regulates fear and worry Excess NE creates nightmares, hyperarousal, flashbacks, panic attacks
160
Anxiety tx BZD MOA
enhance GABA actions to dec anxiety
161
Anxiety tx Buspirone MOA
– no withdrawal effects, no sedation – can take weeks to level off – not for PRN use – can counteract sexual side effects from SSRI
162
Anxiety tx prazosin
most common a1 inhibitor
163
Anxiety tx propranolol
βblocker and low doses – crosses blood-brain barrier
164
Anxiety tx SSRI/SNRI to know
at start of SNRI, anxiety may worsen – needs time for post synaptic receptors to down regulate and desensitize = ↓fear and worry in the long-term Start low and slow
165
PTSD rx tx is based on
increasing GABA and decreasing Glutamate
166
acute stress disorder timing
sx <1 mo
167
Acute PTSD timing
1mo to 40+ yrs
168
Chronic PTSD timing
6 mo to 40+ yrs
169
Broad DSM def of PTSD
must have traumatic event with psych distress sx exposure presence of 1+ intrusion sx assoc with event persistent avoidance negative alteration in cognition or mood marked alteration in arousal and reactivity 1+ mo sx
170
PTSD tx 1st line generally
SSRI/SNRI
171
PTSD tx for combat
fluoxetine better than sertraline
172
PTSD SSRI?SNRI options for tx
fluoxetine, paroxetine, sertraline, venlafaxine
173
PTSD alt tx for chronic nightmares
prazosin
174
PTSD tx for psychosis
antipsychotics augment with olanzapine, quetiapine, or risperidone
175
why no BZD for PTSD
potentiate effect of GABA – AVOID – may worsen outcomes
176
catatonia s/sx
catalepsy (gesture held against gravity) agitation posturing grimacing resistance to movement stupor mutism mannerisms, negativism mimicking speech, mimicking movements, repetitive movements
177
catatonia as comorbidity
30% w/ schiz 43% with bipolar may also be seen in autism, OCD, PTSD, withdrawal from ETOH, BZD
178
catatonia patho
dysfunction or interference in frontal cortex-basal ganglia circuitry ↓in GABA and DA activity Localized seizures in frontal lobe and anterior limbic system
179
catatonia test
Bush-Francis Catatonia Rating Scale – score of 2+ = positive finding
180
catatonia tx 1st line
BZD- Ativan trial
181
Other catatonia tx
ECT Antipsychotics – depends on pt Zolpidem (GABA agonist) – alternative to lorazepam challenge Dopamine Agonist – Amantadine, memantine Supportive Care
182
Wake promoters r/t sleep
Ach, corticotropin factors, DA, His, NE, Orexin, Substance P
183
Sleep promoters
Adenosine, GABA, melatonin
184
Insomnia criteria
difficulty falling asleep, staying asleep, waking early 3+ nights for 3+ months Not explained by another medical condition or SUD Needs to cause clinical distress
185
Insomnia 1st line tx
CBT-I and sleep hygiene – try before meds
186
Insomnia rx tx options
Melatonin and valerian Diphenhydramine, unisom, hydroxyzine BZDs NonBZDs – z-meds Belsomra, Dayvigo (orexin receptor antagonist) – avoid ETOH and CNS depressant (opioid) Antidepressants: Elavil, doxepin, mirtazapine, trazodone – good for BZD avoidance Gabapentin, tiagabine Antipsychotics – quetiapine (insomnia assoc w/ schiz, bipolar, depression), olanzapine
187
ADHD 1st line tx 4-5 6-12 12-18yo
4-5 yo – PTBM, classroom interventions (these are for all ages) 6-12 yo – Methylphenidate, amphetamines 12-18 yo – FDA approved meds w/ collaborative agreement with pt
188
methylphenidate MOA
selectively blocks/inhibits presynaptic reuptake of DA and NE (more NE & DA Available in synapse = ↑action)
189
psych rx in pregnancy and lactation needs dose adjustment because (4)
bodily changes inc in free drug levels serum concentrations can drop up to 50% some liver enzymes can go up or downn or not change
190
body changes in pregnancy mostly occur ___ and reverse ___
2nd and 3rd tri 1-2 wks post partum
191
major congenital malformations happen when
1st tri up to 14 wks
192
most fetal anomaly deaths come from
structural anomalies
193
VPA and pregnancy
Neural tube defect
194
functional defect definition
altered function with no change in structure
195
when do learning problems and functional deficits and hearing loss issues occur during pregnancy
2nd and 3rd tri
196
risk of untreated mental illness to pregnancy
poor compliance with tx which risks later fetal/baby issues SUD and misuse impaired bonding suicide and infanticide psychiatric relapse (BP, MDD, Schiz, Anx etc)
197
risk of relapse with d/c of antidepressant
75%
198
risk of mood episodes with d/c of mood stabilizer
85%
199
risk of relapse with d/c of schiz rx tx
50%
200
The body's response to untreated anxiety in pregnancy
vasoconstrictive stress hormone = reduced placenta blood flow = problems with nutrient and o2 delivery
201
% chance of major congenital malformation in gen pop
3%
202
if on psychotropic rx when initially pregnant, avoid___ and consider
abrupt d/c past responses, exposures, med risk/benefit
203
if poss change in meds should be done ___ pregnancy
before
204
ideally wait for stabilization ___ months before trying to conceive
3
205
FDA pregnancy categories
Pregnancy, Lactation, and Females and Males of reproductive potential
206
RID and definition
relative infant dose Quantifies risk of Rx use in breastfeeding
207
relative infant dose equation
drug ingested by infant during exclusive breastfeeding/kg
208
RID % probably safe
<10%
209
2 antidepressants not ideal in pregnancy and why
fluvoxamine and paroxetine high number of drug interactions
210
preferred SSRI in pregnancy
sertraline and paroxetine
210
probably safe rx in pregnancy
nortriptyline, imipramine, escitalopram, duloxetine, doxepin, amitriptyline
210
bupropion and pregnancy
low in breast milk but potential for sz
211
Characteristics that change rx placental transfer and transfer into breastmilk
high protein bound= less transfer to milk Increased lipophilicity - <800 Dalton crosses into milk Low molecular weight - <500 Dalton=readily diffuse across the placenta Decreased protein binding - Rx protein bound do not cross placenta or epithelia – only free unbound drug is able to cross cell membranes longer half lives Poorly ionized drugs diffuse readily across placenta – a degree of ionization depends on PK and pH of maternal blood Weak acids are ionized and held in maternal plasma – since fetal plasma and amniotic fluid are more acidic than maternal pH, weak bases, free drug becomes ionized. and trapped in fetal circulation and amniotic fluid
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most common psych rx that affect pregnancy and lactation are those that
affect the CNS as they can inc the free rx concentration Also those that cause sedation, lethergy, apnea, seizures, tremors, irritability, resp depression, hypotonia ---Caused by opioids, BZDs, antiepileptics, antipsychotics
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Antidepressants and pregnancy
no confirmed birth defect but 1st tri paroxetine did should poss cardiac modest risk of miscarriage early slight inc risk of persistent pulm HTN in newborn poor neonatal adaptation syndrome 3rd tri
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BZD and pregnancy
highly lipid soluable and unionized – causes rapid and complete diffusion across placenta but no teratogenesis - possible cleft palate during 1st trimester (avoid during 1st trimester) Not CI but can cause sedation, poor wt gain, apnea, irritability in infants short acting preferred: lorazepam, oxezapam
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maternal sedation does not equal
infant sedation
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gabapentin and pregnancy
poss preterm birth in breastmilk
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z meds and pregnancy
no major malformations, preterm delivery possible – zolpidem & zalepion have low milk levels and short halflife (likely OK)
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trazadone and pregnancy
major malformations unlikely – limited data
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insomnia in pregnancy recommendations
sleep hygiene and CBT are 1st line prior to any meds
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antipsychotics and pregnacy
no major congenital some risk with risperidone potential floppy baby with clozapine Risk of GDM and increased wt in mom and baby with clozapine and olanzapine
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placental pressure highest to lowest (4)
1. Olanzapine, 2. haloperidol, 3. risperidone, 4 (lowest) quetiapine
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SGA with most reproductive safety data
Quetiapine, olanzapine, and risperidone
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hyperprolactinemia and pregnancy
can impair fertility in males and females – consider switching to lower risk agent PRECONCEPTION
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highest to lowest risk of hyperprolactinemia and pregnancy
risperidone & paliperidone -> FGAs -> olanzapine ->ziprasidone -> quetiapine -> clozapine -> aripiprazole
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clozapine and pregnancy
appropriate tx should be continued (benefits outweigh risks) with weekly monitoring for severe neutropenia in mom and baby x6 mo post partum
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Long acting injections and pregnancy
continue if benefits outweigh risks
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antipsychotics and lactation
generally compatible with lactation EXCEPT clozapine (neutropenia, seizures) women should continue to breast feed unless on clozapine Monitor infant for sedation, poor feeding, motor abnormalities, neurodevelopmental abnormalities – especially premies who are at greater risk
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low RID antipsych rx
olanzapine and quetiapine
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moderate RID antipsych
risperidone and aripiprazole
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Bipolar in pregnancy rx tx pref
antipsych preferred to mood stabilizers
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carbamazepine and pregnancy
give high dose folate before and during prengnacy potential for neural tube defects, hypospadias, diaphragmic hernia, skelatal/facial abnormalities, neonatal hemorrhage lower risk than valproic acid
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carbamazepine and lactation
safe but monitor for sedation and poor sucking
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lamotrigine and pregnancy
likely no risk of major malformation, poss cleft palate serum concentrations dec significantly in pregnancy so have to monitor monthly and divide dose to reduce peak exposure
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lamotrigine and lactation
consider alternative D/c if skin rash in baby
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lithium and pregnancy
rate but poss ebstein anomaly avoid in 1st tri with 4 wk taper before conception when resume divide doses to limit peak exposure montly monitor x3-6 wks then weekly until delivery reduce/hold 24-48 hrs before labor prepregnancy dose should be resumed post partum
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lithium and lactation
not preferred but monitor levels in mom
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VPA and pregnancy
neural tube and cardiac defects, cleft palate, craniofacial anomalies, cognition/brain volume, hypospadias ---also poss association with autism should NOT be prescribed to women of child-bearing potential or pregnant women unless viable alternatives to not exist taper over 4 wks in planning pregnancy if you have to cont rx, use as monotherapy with lowest effective dose. If combo or higher doses= inc malformation rate need folic acid supp before and during
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VPA and lactation
safe but caution with high doses
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stimulants and pregnancy
not recc due to inc risk for spontaneous abortion/miscarriage/neonatal withdrawal syndrome no major congenital
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stimulants and lactation
not recc, monitor for infant wt gain and AE Methylphenidate/amphetamines may impair milk production via reductions in prolactin levels
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smoking tx and pregnancy
non pharm is 1st line NRT preferred to smoking Bupropion and varenciline not recc
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smoking tx and lactation
NRT pref, may consider bupropion but consider Sz risk no varenciline due to psych AE
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alcohol dependence and pregnancy tx
send for inpatient withdrawals once inpatient: Chlordiazepoxide and diazepam preferred insufficient data on acamprosate, naltrexone, disulfiram
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alcohol dependence and lactation
pharmacotherapy not recommended due to limited data
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BZD dependance and pregnancy
need inpatient withdrawal consider taper with long acting BZD but may inc fetal exposure taper 20-30% per day as tolerated until d/c
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opioid dependence and pregnancy
1st line: opioid agonist neonatal adaptation syndrome seen w/ buprenorphine and methadone Buprenorphine – no major congenital malformations – inpt detox typically required for exposed infants shorter neonatal abstinence syndrome vs methadone Limited data for buprenorphine/naloxone (switch to buprenorphine) Methadone – historically drug of choice – no major congenital malformation Inpt detox Naltrexone – no major congenital malformations – risk of spontaneous abortion, premature labor, fetal distress may hinder use of pain rx in delivery NOT preferred due to opioid withdrawal and fetal complications at initiation may occur
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opioid dependence and lactation
Breastfeeding encouraged w/ MAT – small amounts of buprenorphine and methadone pass into milk Discourage breastfeeding in women on illicit substances
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BPD etiology
inheritable mixed gene and environment
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BPD sx
affective instability/negative poor coping rumination/anger impulsivity instability in personal relationships sustained behavior and dependent on environmental triggers (unlike bipolar/depression)
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1st line tx for all personality disorders
psychotherapy
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Rx tx options and personality disorder
no rx is FDA approved and should be adjunct and not the sole tx lack of consensus but generally based on domains: Affective instability: SSRI/SNRI Impulsive/self injury: SSRI or mood (lithium/VPA/CBZ) Cognitive/perception disturb: low dose antipsych: FGA (halo), olanzapine, risperidone, clozapine emotional dysregulation: SSRI/mood Impulsivity/aggression: Antipsych (olanzapine), mood
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personality disorders and adherence and comorbidity
adherence is poor comorbid guidelines underdeveloped and many likely face social adversity make response/drop out worse anxiety/SUD, depression more common
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Antisocial personality disorder rx tc
only Rx antipsychotics or sedatives for short-term crisis management
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Schizotypal rx tx
some evidence for SGA (risperidone, olanzapine) and low dose FGA (haloperisol, thiothixene) - no reliable evidence for antidepressants
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avoidant personality disorder rx tx
may consider SSRI, SNRI (venlafaxine), MAOI, gabapentin, pregabalin NO BZDs
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restricted diet and neurotransmitter
less tryptophan so less 5HT
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anorexia nervosa patient presentation
perfectionist obsessed with food ritualized
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Bulimia severity
Mild – 1-3/wk Mod – 4-7/wk Severe – 8-13/wk Extreme – 14+/wk
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Bulimia tx 1st line
CBT
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Bulimia and rx tx
rx shows poor efficacy maybe low dose olanzapine or SSRI with comorbid anx/dep
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Bulimia and rx wt gain
Dronabinol DHEA D-Cycloserine
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Bulimia and rx for binging/purging
high dose fluoxetine is FDA approved with goal to dec # of occurences
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Bulimia patient presentation
driven to restrain food intake loss of control with overeating occurs intermittently extreme fear of wt gain high impulsivity/impulse dysregulation as compared to anorexia – novelty seeking – more likely to have substance abuse issues than anorexia
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Binge eating tx
same as bulimia but may also use amphetamine antiD and topamaz may enhance CBT effective
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OCD assessment
Yale-Brown Obsessive-Compulsive Scale – Gold standard but needs training to perform 2 others reliable
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OCD patho
dysregulate DA, 5HT, Glutamate
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OCD tx mild, mod, severe
Mild – CBT including exposure therapy Mod – SSRI or intensive CBT Severe – SSRI + CBT
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OCD 1st line rx and for how long
SSRI (fluoxetine, fluvoxamine, paroxetine, sertraline) high dose associated with better outcomes max tolerated for 8-12 wks as trial note w/d associate with major relapse risk Cont Rx for 1-2 yrs before tapering with periodic CBT booster sessions for 3-6 mo after acute tx or 12 months after remission
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OCD if SSRI inadequate
switch or augment with SGA
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OCD tx monitoring
suicide ECG with high dose citalopram clomipramine: anticholinergic/arrythmia/Sz
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Body dysmorphic disorder clinical appearance
appearance preoccupations delusionality and referential thinking (poor insight, worse than OCD pts, 50% are deluded) compulsive and safety behaviors (time consuming behaviors to diminish distress) effects males and females equally
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Body dysmorphic disorder tx 1st line
CBT Rx SSRI (fluoxetine, fluvoxamine for 6-9 wks, citalopram and escitalopram for 5 wks), clomipramine 12-16 wks then switch to another SSRI if no response
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Trichotillomania & Excoriation onset
onset is early puberty then relapsing/remitting
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Trichotillomania & Excoriation tx
CBT poor evidence for SSRI/ other rx CBT much superior
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Hoarding disorder tx
CBT (group and indiv) rx: venlafaxine/paroxetine
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Addiction patho
impulsivity and compulsivity dysregulation PFC inhibits activity of ventral striatum drugs cause mesolimbic to release DA to inc pleasure DA stop responding to drug and instead to conditioned stimulus associated with drug causing cravings and compulsive use
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AUD patho
short term ETOH inc GABA and dec Glut long term: brain tries to restore equilibrium by doing opposite ETOH w/d has no compensation and shift is toward hyperexcitation
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AUD DSM w/d dx
need cessation or dec ETOH and have distress Sx 2+ -insomnia -increased hand tremor -anxiety -seizures -autonomic symptoms (sweating, tachycardia) -nausea/vomiting -psychomotor agitation (tapping, pacing, rapid talking) -hallucinations/perceptual disturbances (auditory, tactile, visual)
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AUD w/d stages
1st stage – fairly mild - within 8 hrs– N/V, stomach pain, tiredness, depression 2nd stage – begins 24 hrs after last drink – HTN, anxiety, irritability, mood swings 3rd stage – severe – can last about 72 hrs – symptoms include stages 1 & 2
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assess acute w/d AUD
CIWA Mild = <10 Mod = 10-18 Severe = >19 Complicated = >19 – includes hallucinations, seizures, delirium
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AUD w/d tx 1st line
BZD- dec w/d including Sz/delirium and agonist at GABA front load with long acting- diazepam - pref for severe CIWA <19
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AUD tx options
Naltrexone acamprosate disulfiram
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AUD and naltrexone patho versions black box monitor
antagonist and multiple receptors dec mesolimbic reward = dec consumption ok if cont to drink LA inject: vivitrol black box for hepatotoxicity monitor LFT before and every 6 mo avoid opioids many stop due to AE N/D
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acamprosate and AUD MOA indication contra AE
MOA: blocks NMDA and inc GABA and dec Glut to restore balance indication for maint of abstinence, ok if hepatic disease or on opioid tx contra: kidney AE: D/anxiety/insomnia but usually well tolerated
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Disulfiram and AUD MOA reaction time AE CI population
MOA: inhibit aldehyde enzyme leading to rapid accumulation and toxic reaction drinks ETOH and gets sick reaction 10-30 min and can last for hours AE: flushing, nausea, thirst, palpitations, CP, hypotension somnolence, metallic after-taste and peripheral neuropathy CI: severe cardiac, severe hepatic, psychotic population: support other rx, mod-sev AUD
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non FDA AUD rx tx
topiramate gabapentin baclofen zofran
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nicotine 5As
ask, advise, assess, assist (create tx plan), arrange (for f/u)
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nicotine behavioral tx model
transtheoretical model
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nicotine 1st line tx
NRT monotherapy consistently (not PRN) Bupropion/chantix can use in combo with NRT
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nicotine tx rx CI
pregnant, smokeless tobacco, light smokers, adolescents MI in last 2 wks, serious arrhythmia, worsening angina
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bupropion for nicotine MOA start Dose CI
MOA: blocks NE/DA reuptake to mimic nicotine Start 7 days prior to quit Dose AM and early PM to avoid insomnia CI: Sz, head injury, eating disorder
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Varenicline for nicotine MOA Start precaution
MOA: nAChR partial agonist/antagonist. Basically some relief while blocking nicotine effect Start 1 wk before quit date precaution: poss inc agitation, SI, mood swings Dose change in renal
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why abuse gabapentin/pregabalin MOA tx
pregabalin 6x more potent and faster peak self tx pain, euphoria can boost cocaine, BZD< opioid, caffeine, ETOH MOA: inc GABA w/d poss, more craving with pregabalin and similar to opioid Tx: taper slow. No BZD. Poss efficacy with haloperidol/benadryl
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types of pain
Nociceptive pain – somatic: well localized, aching, throbbing – bone, skin, soft tissue Visceral – poorly localized, deep aching, cramping, pressure – hollow and solid organs Neuropathic pain – tingling, numbness, radiating pain – due to pathologic damage to nervous system - occurs after disease or traums – fibromyalgia Chronic pain syndrome – Pain for 3+ months and has a psychological impact