Exam 5 Flashcards
1
Q
Donepezil brand and class
A
Aricept
Acetylcholinesterase inhibitor
2
Q
Memantine brand and class
A
Namenda
NMDA receptor antagonist
3
Q
Alzheimer’s disease characteristics
A
Insidious onset
Neurocognitive deficits prominent
60-80% of cases
4
Q
Alzheimer’s disease treatment options
A
Acetylcholinesterase inhibitors
NMDA receptor antagonist
5
Q
Vascular dementia characteristics
A
Deficits occur in correlation with cerebrovascular accident.
Attention deficits prominent.
6
Q
Vascular dementia treatment options
A
Modifying risk factors
Less evidence for cognitive enhancers
7
Q
Dementia with Lewy bodies characteristics
A
Insidious onset Core features (motor features and hallucinations) Suggestive features (sleep behaviors, sensitivity to antipsychotics)
8
Q
Dementia with Lewy bodies treatment options
A
AChEIs, NMDA antagonist
Dopamine agonists or antagonists, based on sx
9
Q
Dementia with Lewy bodies treatment options
A
AChEIs, NMDA antagonist
Dopamine agonists or antagonists, based on sx
10
Q
Frontotemporal dementia characteristics
A
Younger age of onset
Umbrella diagnosis for significant behavioral, social, or language symptoms
11
Q
Frontotemporal dementia treatment options
A
Antidepressants
Antipsychotics
12
Q
Potential reversible causes of dementia
A
Drugs Eyes/ears Metabolic disorders Emotional Nutritional/Electrolytes Tumors/ trauma/ thyroid Infection Alcohol
13
Q
Drugs that may cause cognitive dysfunction
A
TCAs Diphenhydramine Muscle relaxants Benzodiazepines Eszoplicone, zaleplon, zolpidem Barbiturates Promethazine
14
Q
Alternative options to TCAs that do not cause cognitive dysfunction
A
SSRIs (avoid paroxetine)
SNRIs
Bupropion
15
Q
Alternative options to diphenhydramine that do not cause cognitive impairment
A
Cetirizine, fexofenadine, loratadine
16
Q
Alternative options to muscle relaxants that do not cause cognitive impairment
A
APAP, NSAIDs, heat, ice
17
Q
Alternative options to benzodiazepines (for anxiety) that do not cause cognitive impairment
A
Buspirone, SSRI (avoid paroxetine), SNRI
18
Q
Alternative options to eszopiclone, zaleplon, zolpidem that do not cause cognitive impairment
A
Low dose trazodone, low dose doxepin, ramelteon, melatonin
19
Q
Alternative options to barbiturates that do not cause cognitive impairment
A
Low dose trazodone, low dose doxepin, ramelteon
Use lowest effective dose
20
Q
Alternative options to promethazine that do not cause cognitive impairment
A
Dolasetron, granisetron, ondansetron
21
Q
Alzheimer’s disease
A
60-80% of dementia Cognitive defects which impact social or occupational functioning Diagnosis of exclusion Memory loss is predominant Patient often unaware of symptoms
22
Q
What is the difference between a healthy brain and a brain with Alzheimer’s?
A
A brain with Alzheimer’s has plaques and a diseased and tangled neuron
23
Q
Neurotransmitters involved in Alzheimer’s disease
A
Multiple neuronal pathways are destroyed, mass neurotransmitter deficits
Loss of choline acetyltransferase and acetylcholinesterase.
In moderate to severe AD- excessive glutamate which enhances cellular death
24
Q
Genetic risk factors of Alzheimer’s disease
A
Family history- 1st degree relative increases risk
Apolipoprotein E (APOE)*4 Gene
-Everyone inherits *2, *3, or *4 from each parent. *4 increases late-onset AD risk
Early onset AD- presenilin 1 and 2 (PSEN1), Amyloid precursor protein (APP)
Routine testing not recommended at this time
25
Risk factors of Alzheimer's disease
```
Dyslipidemia
Obesity
Diabetes
HTN
Smoking
Depression
Trisomy 21
TBI
```
26
AD timeline
Early brain changes
Subtle decline in thinking
Memory changes, confusion
Loss of activities in daily living (ADLs)
Loss of communication and social recognition
27
Screening of AD
US preventive Services Task Force: insufficient evidence to recommend for or against routing screening for dementia
Cognitive assessments- MINI-COG, Mini-mental state exam
28
Mini-Cog
```
AD scale
Score of 3, 4, or 5 indicated low likelihood of dementia
Components:
1.) Repeat 3 unrelated words directly.
2.) Draw a clock face showing 11:10
3.) Recall previous 3 unrelated words
```
29
Mini-Mental State Exam (MMSE)
```
AD scale
Score 0-30, lower numbers indicate greater impairment
>27 considered normal
Score 9-0= severe
Score 23-18= Mild
```
Tests orientation to time, place, registration repeat, serial 7s or spell "world backwards, registration recall, Gnosia (recognition), repetition, complex commands
30
Montreal Cognitive Assessment (MoCA)
AD scale
Score 0-30, lower numbers indicate greater impairment
>26 is considered normal cognition
31
Saint Louis University Mental Status Examination (SLUMS)
AD scale
Score 0-30, lower numbers indicate greater impairment
>27 is considered normal cognition
32
Slowing and managing progression of AD
Medications- pharmacological management
Avoiding cognitive dysfunction promoters.
Disease states- BP, lipid, glucose management
Education- pt and family support, expectations, legal/financial planning
33
AD treatment strategy
Start low and go slow
Success= decline in MMSE of <2points/year
-If decline is >3 points after 1 year, use alternative treatment
Consider washout period of 1 week if alternating agents
34
Nonpharm management for AD
```
Patient-centered focus
Create a low stress environment
Simple activities and exercise
Therapy animals
Avoid challenging beliefs/memories ("arguing" may be distressing
```
35
Complementary alternative options for AD
Prevagen (Apoaquorin)
Vitamin E
Ginkgo biloba
Caprylic acid
Huperzine A
Omega-3 fatty acids (linked to reduction in cognitive decline)
Axona (medical food that forms ketone bodies to reduce glucose use in brain)
36
Prevagen
Proposed mechanism is to protect neuronal cells from calcium-mediated toxicity by promoting calcium homeostasis.
High rate of publication bias
10mg in 90 days appears safe, may improve cognitive function in older adults without dementia
ADR- HA, dizziness, nausea
37
Vitamin E
Proposed mechanism: protects against oxidative stress and free radicals
No-low efficacy
ADR: bleeding risk, nausea, diarrhea, fatigue
Doses >400 IU/day associated with increased risk of prostate cancer, HF, mortality, hemorrhagic stroke
38
Ginkgo Biloba
Proposed mechanism: improve brain blood flow and mitochondrial function
Does not improve cognitive decline or AD
Publication bias likely
ADRs: bleeding risk, dizziness, diarrhea
39
Pharmacotherapy for cognitive symptoms of AD
Amyloid-beta antibody (Aducanumab )
Acetylcholinesterase inhibitors (Donepezil, Rivastigmine, Galantamine)
NMDA receptor antagonist- memantine
Combo- memantine/donepezil
40
Aducanumab-avwa
Approved in 2021 ONLY for patients with mild cognitive impairment or mild dementia
Very controversial- studies demonstrate reduction in amyloid buildup, however effectiveness unclear
41
Aducanumab dose and monitoring
IV infusion every 4 weeks
Monitoring: recent MRI prior to tx
F/U MRI prior to 7th and 12th infusion
Reason: microhemorrhages and/or focal superficial siderosis
Monitor ARIA (amyloid related imaging abnormalities)
-Edema, microhemorrhage, superficial siderosis
42
Aducanumab ADR
HA, fall, angioedema, urticaria
43
How are AChEIs thought to decrease symptom progression of AD?
AD is associated with neuronal death, resulting in reduced promotion of ACh. AChEIs are thought to slow the breakdown of ACh to compensate for the loss.
44
How is Namenda XR believed to delay symptom progression of AD?
AD causes sustained activation of NMDA receptors which may lead to excessive calcium influx, neuronal dysfunction, and cell death.
Namenda XR is believed to block sustained activation of NMDA receptors caused by abnormal glutamatergic activity.
45
Which FDA approved AD therapy is used for mild to moderate disease?
Adacanumab
Donepezil
Galantamine
Rivastigmine
46
Which FDA approved AD therapy is approved for moderate to severe disease?
Donepezil
Rivastigmine
Memantine
Memantine/Donepezil
47
Donepezil MOA and indication
Acetylcholinesterase inhibitor
| Indicated for mild to severe AD
48
Donepezil dosing/admin
Take at bedtime without regard to food.
Aricept 23mg tab- do not crush or chew
ODT- dissolve on tongue and follow with water
May increase from 5mg to 10mg after 1 month
49
Donepezil interactions
Monitor for clinical response or ADR change in strong CYP3A4 inducers/ inhibitors
50
Rivastigmine MOA and indication
Acetylcholinesterase inhibitor
| Indicated in mild to moderate AD (oral), mild to severe AD (patch) and Parkinsons dementia
51
Rivastigmine dosing/admin
```
Take WF
<6mg PO= 4.6 mg patch
6-12 mg PO= 9.5mg patch
Adjust every 2-4 weeks, retitrate if 3+ day interruption
Nicotine increases clearance by 23%
```
52
Galantamine MOA and indication
Acetylcholinesterase inhibitor
| Indicated for mild to moderate AD
53
Galantamine dosing/admin
Take WF
Oral solution: mix with 3-4 oz of any nonalcoholic beverage and drink immediately
Titrate monthly and retitrate if 3+ day interruption
Avoid if CrCl <9mL/min
If CrCl 9-59= max dose 16mg/d
54
Galantamine DDI
Monitor for toxicity in 2D6/ 3A4 inhibitors
55
AchEI ADRs: GI
NVD, anorexia, weight LOSS
| Peptic ulcer disease/GI bleed
56
AchEI monitoring
Monitor for GI complaints, weight loss, bleeding, NSAID use
| Monitor for dizziness, falls, HR, BP
57
AchEI ADRs: CNS/CV
Dizziness, syncope, bradycardia, atrial arrhythmias, MI, seizures, SA and AV block, QT prolongation
Abnormal dreams, sleep disturbances
Routing HR checks at baseline, monthly during titration, and then Q 6 months
58
Memantine MOA and indication
NMDA receptor antagonist
| Indicated for moderate to severe AD (NOT mild)
59
Memantine dosing/admin
Take without regard to food
Oral solution- slowly squirt into corner of mouth, do NOT mix with any other liquid, ER cap may be sprinkled on applesauce
Titrate weekly
If CrCl <29 mL/min, IR up to 5 mg BID, ER up to 14mg/day
60
Memantine interactions
Urine alkalinizers decrease clearance of memantine if urinary pH 8 or more
61
Memantine ADR
CNS- HA, confusion, dizziness, hallucinations
| GI- diarrhea, constipation
62
Memantine monitoring
Monitor dizziness or falls, hallucinations
| Monitor bowel movements
63
Memantine/Donepezil MOA and indication
Combo of NMDA receptor antagonist and AchEI
| Indicated for moderate to severe AD in patients stabilized on memantine and donepezil
64
Memantine/Donepezil dosing/admin
Take at bedtime w/o regard to food
May be sprinkled on applesauce
If CrCl <29, use memantine ER 14mg formulation
65
Monitoring for AD
Baseline cognitive status, physical status, functional performance, behavior
Monitor 2 and 3 months after therapy initiation (if 3 months on max tolerated AChEI ineffective, consider switch)
Monitor at least q 6 months thereafter
Treatment duration unclear
66
Supportive therapy for noncognitive symptoms of AD
Noncognitive symptoms- depression, psychosis
Treatment of psychotic or behavioral symptoms should include environmental interventions and meds only if necessary
Asses underlying causes- meds, medical illness, environment, abuse, unmet needs
67
Behavioral and Psychological Symptoms of Dementia (BPSD)- how common
Experienced by up to 90% of pts
| More common in later stages of disease
68
BPSD
Delusions, hallucinations, depression, anxiety, euphoria, sexually inappropriate behavior, aggression, apathy, irritability, disinhibition, wandering, sleep disturbances
69
BPSD behavioral models:
Patient with need, unmet or unnoticed by caregiver, acting out behavior
Environmental stressor, diminished stress-tolerance, behavior
70
Assessment of BPSD
Ensure the patient and staff/caregiver are safe
Compare behaviors to baseline
Investigate reversible causes- delirium, ADR, other
Evaluate for precipitating factors
71
Assessment of BPSD
Ensure the patient and staff/caregiver are safe
Compare behaviors to baseline
Investigate reversible causes- delirium, ADR, other
Evaluate for precipitating factors
72
Nonpharm for BPSD
First line
Psychosocial approach- activities of interest, social interactions, comfort
CBT- milder disease and comorbid depression
73
Antipsychotics for BPSD
Haloperidol, aripiprazole, risperidone all have most evidence
Olanzapine, Quetiapine alternatives
Shortest duration, lowest effective dose, monitor closely
74
BBW for all antipsychotics for BPSD
risk of death
75
Antipsychotics in the elderly
Risk of movement disorders-pseudoparkinsonism, tardive dyskinesia, dystonia, akathisia, risperidone, haloperidol, quetiapine, olanzapine
Risk of QTc prolongation and CV events- IV haloperidol
Risk of hypotension and syncope
76
Antipsychotics in BPSD take home messages
Always try nonpharm first
Reserve for cases where behavioral disturbances put pt or caregiver at risk.
Re-evaluate need regularly
Rarely use for >12 weeks
77
Neurotransmitter systems and psychosis theories
DA theory- hyperactive mesolimbic DA and hypoactive mesocortical DA systems. DA releasing agents can cause psychosis
Glutamate theory-NMDA receptor hypofunction. Ketamine and PCP block NMDA receptors and produce psychosis
Serotonin theory: 5-HT2A receptor hyperactivity in cortex. LSD is a 5HT2A agonist and produces psychosis
78
Typical antipsychotics major classes
Phenothiazines- chlorpromazine, fluphenazine
Thioxanthenes- thiothixene
Butyrophenones-haloperidol, benperidol
79
Atypical antipsychotics agents
2nd gen
| Clozapine, olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole
80
Pharmacology of early antipsychotics (1st gen)
```
1st gen (typical) antipsychotics referred to as neuroleptics. They decreased nerve function, major tranquilizer.
MOA- blockage of D2 dopamine receptors. Drugs antagonize the behavioral and biochemical effects of DA.
```
81
Neuroleptic syndrome
Produced by 1st gen antipsychotics
Suppression of spontaneous movements, reduction in initiative and interest, reduced emotion
Patients still are easily aroused and have intellectual faculties
82
How many D2 receptors need to be blocked for 1st gen antipsychotics to be effective?
>60% D2 receptors needed for clinical improvement
| Differences in potency but not in efficacy
83
Effects of 1st gen antipsychotics on DA function
Acute: DA receptor blockade results in blockade of DA mediated effects, receptor blockade results in compensatory increase in DA neuronal firing.
Chronic effects: DA receptor super-sensitivity, depolarization inactivation. Reduction in active DA neurons.
84
Nigrostriatal DA pathway
Function: normal in patients. control of movement
Drug effect: D2 receptor blockade results in extrapyramidal symptoms (parkinsonism) and tardive dyskinesia
EPS is acute, tardive dyskinesia is chronic
Terminates in basal ganglia
85
Mesolimbic DA pathway
Function: hyperactivity related to psychosis and positive symptoms, reward pathway
Drug effect: D2 receptor blockade and depolarization (inactivation) blockade would reduce positive symptoms. But also may cause secondary negative symptoms (apathy, lack of motivation). Blocks reward pathway.
Terminates in nucleus accumbens
86
Mesocortical DA pathway
Function: hypofunction may be related to impaired cognition
Drug effect: DA receptor blockade may worsen negative symptoms
Terminates in frontal cortex
87
Tuberoinfundibular DA pathway
Function: normal in pts. DA inhibits prolactin secretion
Drug effect: D2 receptor blockade would elevate serum prolactin levels. Breast enlargement, fertility issues, milk production
Terminates in hypothalamus
88
AE of typical antipsychotics
Many are related to DA receptor blockade
EPS: parkinsonism, dystonias, akathisia (due to DA blockade in basal ganglia)
Tardive dyskinesia- late occurring oral-facial movements. May be due to DA receptor supersensitivity.
Increased prolactin levels
Neuroleptic malignant syndrome
89
Valbenazine and Deutetrabenezine
Selective inhibitor of the pre-synaptic human VMAT2.
FDA approved for tx of tardive dyskinesia
Impaired VMAT2 leads to reduced DA storage, increased intraneuronal DA metabolism. Resulting in depletion of intraneuronal DA and less release and less receptor activation
90
Antipsychotic agents: Other receptor effects
```
alpha1
D2
H1
M1
5-HT2C
```
91
What is the AE associated with alpha 1 receptor blockade?
Dizziness, orthostatic hypotension, reflex tachycardia
92
What is the AE associated with D2 blockade?
Extrapyramidal side effects, increased prolactin levels
93
What are the AE associated with H1 receptor blockade?
Sedation, weight gain
94
What are the adverse effects associated with M1 receptor blockade?
Blurred vision, constipation, dry mouth
95
What are the AE associated with 5-HT2C receptor blockade?
Weight gain
96
Atypical antipsychotics vs typical antipsychotics
Atypical has low EPS, including tardive dyskinesia. Able to maintain efficacy while decreasing EPS compared to 1st gen.
Mechanistic diff in 5-HT2A receptor antagonism (5-HT2/D2 antagonists, D2/5-HT1A partial agonists)
Clozapine is uniquely effective in treatment resistant schizophrenics
97
Pneumonic for remembering second gen antipsychotics
Pines, dones, and a rone, two pips and a rip
98
Major groups of second generation agents
5-HT2A/D2 antagonists (pines, dones, and a rone)
| DA2/5-HT1A partial agonists (two pips and a rip)
99
5-HT2A/D2 antagonists
Agents have a higher affinity for 5-HT2A vs D2 receptors
pines, dones, and a rone
clozapine, olanzapine, quetiapine, asenapine, ziprasidione, lurasidone, risperidone, iloperidone, palidperidone, lumateperone
100
DA2/5-HT1A partial agonists
Two pips and a rip
| Aripiprazole, Brexipiprazole, Cariprazine
101
Effect of typical antipsychotics on DA neurotransmission presynaptic
Short term- activated neurons
| Long-term= inactivated neurons- depolarization inactivation
102
Effect of typical antipsychotics on DA neurotransmission postsynaptic
Short term- receptor blockade- motor AE
| Long term- receptor super-sensitivity, tardive dyskinesia
103
alpha 1 receptor blockade AE
dizziness, orthostatic hypotension, reflex tachycardia
104
D2 receptor blockade AE
EPS, increased prolactin levels
105
H1 receptor blockade AE
Sedation, weight gain
106
M1 receptor blockade AE
Blurred vision, constipation, dry mouth
107
5-HT2C receptor blockade AE
weight gain
108
5-HT1 regulation of DA
5-HT1A agonism achieves the same outcome as 5-HT2A antagonism, it opposes effects of D2 receptor blockade in striatum and cortex.
Increases nigrostriatal DA release (diminishing EPS)
Increases mesocortical DA release, improving negative symptoms
109
Aripiprazole
DA system stabilizer- in the case of too much DA, acts as an antagonist. In the case of too little DA, acts as an agonist.
Unique MOA- activation of presynaptic DA receptors. D2 antagonist in hyperdopaminergic states and D2 agonist in hypodopaminergic states.
5-HT1A partial agonist, possible 5-HT2B antagonist
110
Preclinical profile of 2nd gen antipsychotic agents
Weak D2 antagonist; stronger 5-HT2 antagonist
D2/5-HT1A partial agonists
Little/No DA receptor super sensitivity with chronic admin
Selective depolarization inactivation of mesolimbic DA neurons.
Fast dissociation from D2 receptors.
Increase DA, ACh, and NE release in cortex
111
Clinical profile of 2nd gen (atypical) antipsychotics
Low EPS
Low tardive dyskinesia
Less hyperprolactinemia (except risperidone)
Doesnt worsen (may improve) negative symptoms
112
Olanzapine weight gain
Recent studies show that concomitant treatment with the opioid antagonist samidorphan lessens weight gain with olanzapine
113
Pimavanserin
5-HT2A inverse agonist
No D2 blockade
Approved for tx of hallucinations/ delusions in psychosis in PD, in trials for schizophrenia
114
What is schizophrenia?
Psychiatric disorder with persistent psychosis, impaired social functioning, and impaired occupational functioning.
115
Schizophrenia characteristics
Prodrome- period before diagnosis with social isolation, lack of energy, worry, inattentiveness
Age- late teens to early 30s for diagnosis
Sex- about equal, but male onset is earlier
116
Clinical course of schizophrenia
Significantly higher mortality rates than general population- CV disease, cancer, accidents, suicides
Higher rates of smoking
Chronic disease requiring life long therapy
Course of relapse and remission varies between patients
117
Known/suspected causes of schizophrenia
Largely unknown
Fetal insults during pregnancy (infection, fetal distress, etc.)
Infections and autoimmune inflammatory processes
Cannabis use in youth/adolescence
Higher in urban areas/ low socioeconomic process (may be due to social drift)
Genetic correlation
118
Schizophrenia DSM-5 diagnostic criteria
2 or more symptoms, each present for a significant amount of time during a 1 month period. One of the symptoms must be delusions, hallucinations, or disorganized speech
Social/occupational dysfunction
Duration- continuous signs >6 months, with at least 1 month being positive symptoms
119
Positive symptoms of schizophrenia
Hallucinations, hostility, excitability, delusions, suspiciousness/persecution, conceptual disorganization, grandiosity
120
Schizophrenia diagnosis exclusions
Schizoaffective/mood disorder
121
Key features of psychosis
Delusions
Hallucinations
Disorganized thinking
Motor behaviors
122
Motor behaviors in psychosis
Catatonia- alterations in environmental reactivity
| Abnormal motor movements
123
Disorganized thinking in psychosis
Inferred from speech communication
| Difficulty communicating due to lack of ability for the listener to understand the individual's thought expression
124
Delusions in psychosis
Fixed, false beliefs
Persecutory, grandiose, somatic
Remain despite contrary evidence
125
Hallucinations in psychosis
```
Perceptive experience (any of the senses)
Exist despite a lack of external stimulus
```
126
Negative symptoms of schizophrenia
```
Avolition
Affective flattening
Anhedonia
Asociality
Alogia
```
127
Structural brain changes in schizophrenia
Enlarged ventricles
Reductions in total brain volume
Loss of gray matter in frontal cortex/temporal lobes
128
Other neuronal involvement in schizophrenia
Glutamate- NMDA receptor dysfunction increasing limbic DA release, neurotoxicity
GABA- alterations in the prefrontal cortex affecting cognition
5-HT- transporter density increase, 5-HT2a antagonism increases DA release in prefrontal cortex.
Acetylcholine receptors-
nicotinic and muscarinic
129
Treatment recommendations in schizophrenia
Any antipshychotic could be considered 1st line except clozapine and lumateperone
Adequate trial- 2-6 weeks
After failure- switch to one of the above
Third line: clozapine, trial 12+ weeks
Beyond: augmenting clozapine, multiple agents, ECT
130
Nonpharm options for schizophrenia
```
CBTp
Physcoeducation
Employment support, family support, and assertive community treatment
ECT
rTMS
```
131
1st generation/typical antipsychotics MOA
DA D2 receptor blockade- leads to therapeutic effects and EPS
Muscarinic- M1 receptor blockade
Histaminic- H1 receptor blockade
Alpha- alpha 1 receptor blockade
Agents differ in potency and receptor affinity
132
1st generation antipsychotics agents
```
Chlorpromazine
Fluphenazine
Haloperidol
Loxapine
Perphenazine
Trifluoperazine
Thioridazine
Thiothixene
```
133
2nd generation antipsychotics MOA
Similar to 1st generation antipsychotics
Increase D2 receptor dissociation
Additional serotonin 5HT2a antagonism
Exception: aripiprazole, brexpiprazole, and cariprazine are partial agonists at D2 receptors.
134
Which 2nd gen antipsychotics are partial agonists at the D2 receptors
Aripiprazole, brexpiprazole and cariprazine
135
Which atypical antipsychotics is the most typical?
Risperidone
136
D-HAMS
```
Dopaminergic
Histaminic
Adrenergic
Muscarinic
Serotonergic
```
Receptors for schizophrenia
137
What is the effect of dopaminergic receptors?
Therapeutic effects
EPS
Hyperprolactinemia
138
What are the effects of histaminic receptors?
sedation, weight gain
139
What are the effects of adrenergic receptors?
Postural hypotension and reflex tachycardia
140
What are the effects of muscarinic receptors?
Antihcolinergic- dry mouth, constipation, urinary retention, blurred vision, decreased cognition
141
What are the effects of serotonergic receptors?
Reduced EPS, weight gain, modulation of dopamine release
142
Which 1st gen antipsychotics are high potency?
Haloperidol
Fluphenazine
Thiothixene
Trifluoperazine
Increase prolactin, lost of EPS (DA effects)
Lower sedation AE
143
1st generation mid-low potency agents
Perphenazine
Loxapine
Chlorpromazine
Thioridazine
Dry mouth, hypotension, sedation
144
Which 1st gen antipsychotics have injections?
Chlorpromazine, fluphenazine, haloperidol, thiothixene
145
Which 1st gen antipsychotic has an aerosol powder formulation?
Loxapine
FDA indicated for ACUTE treatment of agitation in schizophrenia/bipolar disorders in adults
BBW and REMS program- potential to cause respiratory distress. Do not use in any underlying respiratory illness.
ONLY use in facilities that can intubate/ventilate patients.
146
Which antipsychotics must be taken with food?
Lurasidone, Ziprasidone, lumateperone
147
Antipsychotics: depot injections (LAI-APs)
Non compliance common- results in relapse, healthcare costs, morbidity
LAI may be effective in relapse prevention, prevention of illness worsening
Data suggests early use of LAI-APs benefit hospitalization and all-cause discontinuation
148
What are the formulations of asenapine?
SL tablet, transdermal
149
Which atypicals are affected by CYP2D6 metabolizers?
Aripiprazole
| Iloperidone
149
Long acting antipsychotics- 1st generation
Haloperidol and fluphenazine
Esterified in sesame oil, can't use in sesame oil allergy.
Absorption slower than elimination.
Haloperidol- loading dose, 20mg x PO dose optional, then 10-15mg PO
Fluphenazine- 12.5mg IM to 10mg PO
151
Long-acting antipsychotics long acting injections
Risperidone
Paliperidone
Olanzapine
Aripiprazole
152
Risperidone LAI
Reconstituted polymer
| No oral overlap
153
Paliperidone LAI
Invega sustenna- 117mg Q 4 weeks
then
Invega Trinza- Q 3 months, start after 4 months on Sustenna
OR
Invega Halfyera- Q 6 months, start after 4 months on Sustenna or 1 cycle of Trinza
Sustenna, Trinza reduced dose in CCl 50-80mL/min, do not use in <50mL/min
Halfyera use not recommended for CrCl <90mL/min
154
Aripiprazole LAI
Maintena- 14 day PO overlap
Aristada- 21 day PO overlap
Initio- initial injection, no oral overlap
155
Olanzapine LAI
Must be monitored for 3 hours following each administration for post injection delirium sedation syndrome (PIDSS)
REMS program
156
Lumateperone
New antipsychotic agent- additional D2 presynaptic partial agonist activity
Administer WF
Low metabolic risk
ADR: Most common somnolence, xerostemia, nausea, dizziness
Place in therapy unclear
157
Olanzapine/Samidorphan
Indicated for schizophrenia and Bipolar I disorder, manic or mixed, and maintenance
Samidorphan is an opioid antagonist- added to help with weight management, no comparative data to metformin
158
BBW for all antipsychotics
Elderly patients, dementia related psychosis
159
Precautions for almost all FGAs
```
Seizure disorder
Neuroleptic Malignant Syndrome
Movement disorders
Bloody dyscrasias (neutropenia)
Inability to adjust to extreme heat
CV disease
Hyperprolactinemia
Dysphagia
```
160
Precautions for almost all FGAa
```
Seizure disorder
Neuroleptic Malignant Syndrome
Movement disorders
Bloody dyscrasias (neutropenia)
Inability to adjust to extreme heat
CV disease
Hyperprolactinemia
Dysphagia
```
161
Precautions for all/most SGAs
```
Seizures
Neuroleptic malignant syndrome
Metabolic abnormalities that can increase CV risk
Hyperprolactinemia
Blood dyscrasias
Orthostasis and syncope
Dysphagia
Inability to adjust to extreme heat
```
162
Which antipsychotics have a BBW of suicidality?
Brexpiprazole, aripiprazole, olanzapine/fluoxetine, quetiapine, lurasidone
163
Extrapyramidal AE
More commonly seen with typical antipsychotics
DA effects > ACh effects
Acute dystonia, pseudoparkinsonism, akathisia, tardive dyskinesia
164
Acute dystonia
Occurs within 1-3 days
Spastic muscle contraction, usually head + neck
Increased in males, younger, higher doses, higher potency
Manage with IM anticholinergic- diphenhydramine, benztropine
165
Pseudoparkinsonism
Occurs within 1-3 months of initiation
Symptoms resemble PD- gait disturbances, cogwheel rigidity, bradykinesia
Increased in female, elderly, high doses, high potency
Manage by decreasing dose, anticholinergic agents
-Benzotropine, diphenhydramine, trihexyphenidyl
166
Akathisia
Occurs within the first 3 months, sooner in fast titration
Symptoms include subjective restlessness, jitteriness, fidgeting, pacing
Increased in high dose, high potency, fast titration, concomitant stimulant use
Manage by decreasing dose, change agent, pharmacologically
propranolol, lorazepam
167
Tardive dyskinesia
Typicals > atypicals
Symptoms include repetitive involuntary movements generally involving the mouth and face
May be irreversible
Increased in females, elderly, DM, affective disorders, early EPS development, alcohol use
Manage by minimum effective dose, atypical medications
-Valbenazine, Deutetrabenazine
168
Neuroleptic malignant syndrome
Rare but life threatening
Symptoms- fever, lead-pipe rigidity, mental status changes, autonomic dysfunction
Manage with supportive care, d/c antipsychotic- bromocriptine, dantrolene
```
Fever
Arms
Leukocytosis
Tremors
Elevated CPK
Rigidity
```
169
QTc prolongation
```
Caution in pre-existing abnormalities, other QTc prolonging agents, patients with QTc near 500
Baseline ECG may be appropriate
Least: aripiprazole
Most: ziprasidone, thioridazine
BBW: thioridazine
```
170
Endocrine AE
Hyperprolactinemia from hypothalamic DA blockade
Galactorrhea, gynecomastia, amenorrhea, sexual dysfunction
More common with typical antipsychotics, does not happen with partial agonsits
171
Metabolic AE
```
Much more common with atypicals (SGAs)
Central obesity
High BP
High triglycerides
Low HDL cholesterol
Insulin resistance
Consider metformin with antipsychotic induced weight gain and insulin resistance
```
172
Typicals: misc effects
Thioridazone- pigmentary retinopathy (max dose 800mg/day)
Low potency agents- skin discoloration with sun exposure
All agents- transient elevations in LFTs
173
Which atypicals have the highest metabolic risk? Increase sugar and weight
Clozapine
Olanzapine
Quetiapine
174
Which atypicals have a medium metabolic risk and are most similar to typicals?
Increase prolactin levels
Risperidone
iloperidone
paliperidone
175
Which atyipcals have low metabolic risks and are full antagonists? and have weird admin
Asenapine- SL, transdermal
Lorazidone- WF
Ziprasidone= WF
176
Which atypicals are partial agonists, have no hyperprolactinemia, low metabolic risk, and can cause more akathisia?
Cariprazine
Aripiprazole
Brexipiprazole
177
Clozapine BBW
Mortality and psychosis
Seizures- dose dependent, consider seizure prophylaxis (valproate)
Orthostasis, syncope, bradycardia, cardiac arrest- avoid combo with benzos, risk greatest during titration period
Myocarditis and cardiomyopathy- baseline ECG recommended, eosinophilia may be early indicator
Agranulocytosis- strict CBC monitorins, REMS
178
Clozapine REMS
For agranulocytosis
| Want ANC >1500
179
Which antispychotic needs renal adjustment?
Paliperidone
180
Benzodiazepines with clozapine/ olanzapine
Increased risk of hypotension
Avoid IM olanzapine with benzodiazepines
Separate by 1 hour at least
181
Pregnancy/ lactation with antipsychotics
```
Pregnancy- main concern is movement disorders and withdrawal
Clozapine and lurasidone may have least risk
Lactation- avoid
Partial agonists (CAB) reduce prolactin levels
```
182
Use of antipsychotics in pediatrics
More susceptible to metabolic changes (weight gain)
Schizophrenia rare in pediatrics
Risperidone and aripiprazole can be used in autism
183
Antipsychotic in the elderly
Used for BPSD, anxiety, agitation, hypnosis, depression augmentatation
Rare: parkinsons disease psychosis
184
Pimavanserin
MOA: inverse agonist of 5-HT2A
Indicated ONLY for PD related psychosis
Being studied for schizophrenia
