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Therapeutics 4 > Exam 5 > Flashcards

Exam 5 Flashcards

1
Q

Donepezil brand and class

A

Aricept

Acetylcholinesterase inhibitor

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2
Q

Memantine brand and class

A

Namenda

NMDA receptor antagonist

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3
Q

Alzheimer’s disease characteristics

A

Insidious onset
Neurocognitive deficits prominent
60-80% of cases

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4
Q

Alzheimer’s disease treatment options

A

Acetylcholinesterase inhibitors

NMDA receptor antagonist

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5
Q

Vascular dementia characteristics

A

Deficits occur in correlation with cerebrovascular accident.
Attention deficits prominent.

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6
Q

Vascular dementia treatment options

A

Modifying risk factors

Less evidence for cognitive enhancers

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7
Q

Dementia with Lewy bodies characteristics

A 
Insidious onset
Core features (motor features and hallucinations)
Suggestive features (sleep behaviors, sensitivity to antipsychotics)
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8
Q

Dementia with Lewy bodies treatment options

A

AChEIs, NMDA antagonist

Dopamine agonists or antagonists, based on sx

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9
Q

Dementia with Lewy bodies treatment options

A

AChEIs, NMDA antagonist

Dopamine agonists or antagonists, based on sx

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10
Q

Frontotemporal dementia characteristics

A

Younger age of onset

Umbrella diagnosis for significant behavioral, social, or language symptoms

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11
Q

Frontotemporal dementia treatment options

A

Antidepressants

Antipsychotics

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12
Q

Potential reversible causes of dementia

A 
Drugs
Eyes/ears
Metabolic disorders
Emotional
Nutritional/Electrolytes
Tumors/ trauma/ thyroid
Infection
Alcohol
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13
Q

Drugs that may cause cognitive dysfunction

A 
TCAs
Diphenhydramine
Muscle relaxants
Benzodiazepines 
Eszoplicone, zaleplon, zolpidem
Barbiturates
Promethazine
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14
Q

Alternative options to TCAs that do not cause cognitive dysfunction

A

SSRIs (avoid paroxetine)
SNRIs
Bupropion

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15
Q

Alternative options to diphenhydramine that do not cause cognitive impairment

A

Cetirizine, fexofenadine, loratadine

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16
Q

Alternative options to muscle relaxants that do not cause cognitive impairment

A

APAP, NSAIDs, heat, ice

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17
Q

Alternative options to benzodiazepines (for anxiety) that do not cause cognitive impairment

A

Buspirone, SSRI (avoid paroxetine), SNRI

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18
Q

Alternative options to eszopiclone, zaleplon, zolpidem that do not cause cognitive impairment

A

Low dose trazodone, low dose doxepin, ramelteon, melatonin

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19
Q

Alternative options to barbiturates that do not cause cognitive impairment

A

Low dose trazodone, low dose doxepin, ramelteon

Use lowest effective dose

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20
Q

Alternative options to promethazine that do not cause cognitive impairment

A

Dolasetron, granisetron, ondansetron

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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
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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

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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

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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

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25
Q

Risk factors of Alzheimer’s disease

A 
Dyslipidemia
Obesity
Diabetes
HTN
Smoking
Depression
Trisomy 21
TBI
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26
Q

AD timeline

A

Early brain changes
Subtle decline in thinking
Memory changes, confusion
Loss of activities in daily living (ADLs)
Loss of communication and social recognition

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27
Q

Screening of AD

A

US preventive Services Task Force: insufficient evidence to recommend for or against routing screening for dementia
Cognitive assessments- MINI-COG, Mini-mental state exam

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28
Q

Mini-Cog

A 
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
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29
Q

Mini-Mental State Exam (MMSE)

A 
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

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30
Q

Montreal Cognitive Assessment (MoCA)

A

AD scale
Score 0-30, lower numbers indicate greater impairment
>26 is considered normal cognition

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31
Q

Saint Louis University Mental Status Examination (SLUMS)

A

AD scale
Score 0-30, lower numbers indicate greater impairment
>27 is considered normal cognition

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32
Q

Slowing and managing progression of AD

A

Medications- pharmacological management
Avoiding cognitive dysfunction promoters.
Disease states- BP, lipid, glucose management
Education- pt and family support, expectations, legal/financial planning

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33
Q

AD treatment strategy

A

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

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34
Q

Nonpharm management for AD

A 
Patient-centered focus
Create a low stress environment
Simple activities and exercise
Therapy animals
Avoid challenging beliefs/memories ("arguing" may be distressing
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35
Q

Complementary alternative options for AD

A

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)

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36
Q

Prevagen

A

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

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37
Q

Vitamin E

A

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

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38
Q

Ginkgo Biloba

A

Proposed mechanism: improve brain blood flow and mitochondrial function
Does not improve cognitive decline or AD
Publication bias likely
ADRs: bleeding risk, dizziness, diarrhea

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39
Q

Pharmacotherapy for cognitive symptoms of AD

A

Amyloid-beta antibody (Aducanumab )
Acetylcholinesterase inhibitors (Donepezil, Rivastigmine, Galantamine)
NMDA receptor antagonist- memantine
Combo- memantine/donepezil

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40
Q

Aducanumab-avwa

A

Approved in 2021 ONLY for patients with mild cognitive impairment or mild dementia
Very controversial- studies demonstrate reduction in amyloid buildup, however effectiveness unclear

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41
Q

Aducanumab dose and monitoring

A

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

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42
Q

Aducanumab ADR

A

HA, fall, angioedema, urticaria

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43
Q

How are AChEIs thought to decrease symptom progression of AD?

A

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.

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44
Q

How is Namenda XR believed to delay symptom progression of AD?

A

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.

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45
Q

Which FDA approved AD therapy is used for mild to moderate disease?

A

Adacanumab
Donepezil
Galantamine
Rivastigmine

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46
Q

Which FDA approved AD therapy is approved for moderate to severe disease?

A

Donepezil
Rivastigmine
Memantine
Memantine/Donepezil

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47
Q

Donepezil MOA and indication

A

Acetylcholinesterase inhibitor

Indicated for mild to severe AD

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48
Q

Donepezil dosing/admin

A

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

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49
Q

Donepezil interactions

A

Monitor for clinical response or ADR change in strong CYP3A4 inducers/ inhibitors

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50
Q

Rivastigmine MOA and indication

A

Acetylcholinesterase inhibitor

Indicated in mild to moderate AD (oral), mild to severe AD (patch) and Parkinsons dementia

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51
Q

Rivastigmine dosing/admin

A 
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%
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52
Q

Galantamine MOA and indication

A

Acetylcholinesterase inhibitor

Indicated for mild to moderate AD

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53
Q

Galantamine dosing/admin

A

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

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54
Q

Galantamine DDI

A

Monitor for toxicity in 2D6/ 3A4 inhibitors

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55
Q

AchEI ADRs: GI

A

NVD, anorexia, weight LOSS

Peptic ulcer disease/GI bleed

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56
Q

AchEI monitoring

A

Monitor for GI complaints, weight loss, bleeding, NSAID use

Monitor for dizziness, falls, HR, BP

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57
Q

AchEI ADRs: CNS/CV

A

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

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58
Q

Memantine MOA and indication

A

NMDA receptor antagonist

Indicated for moderate to severe AD (NOT mild)

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59
Q

Memantine dosing/admin

A

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

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60
Q

Memantine interactions

A

Urine alkalinizers decrease clearance of memantine if urinary pH 8 or more

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61
Q

Memantine ADR

A

CNS- HA, confusion, dizziness, hallucinations

GI- diarrhea, constipation

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62
Q

Memantine monitoring

A

Monitor dizziness or falls, hallucinations

Monitor bowel movements

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63
Q

Memantine/Donepezil MOA and indication

A

Combo of NMDA receptor antagonist and AchEI

Indicated for moderate to severe AD in patients stabilized on memantine and donepezil

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64
Q

Memantine/Donepezil dosing/admin

A

Take at bedtime w/o regard to food
May be sprinkled on applesauce
If CrCl <29, use memantine ER 14mg formulation

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65
Q

Monitoring for AD

A

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

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66
Q

Supportive therapy for noncognitive symptoms of AD

A

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

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67
Q

Behavioral and Psychological Symptoms of Dementia (BPSD)- how common

A

Experienced by up to 90% of pts

More common in later stages of disease

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68
Q

BPSD

A

Delusions, hallucinations, depression, anxiety, euphoria, sexually inappropriate behavior, aggression, apathy, irritability, disinhibition, wandering, sleep disturbances

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69
Q

BPSD behavioral models:

A

Patient with need, unmet or unnoticed by caregiver, acting out behavior
Environmental stressor, diminished stress-tolerance, behavior

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70
Q

Assessment of BPSD

A

Ensure the patient and staff/caregiver are safe
Compare behaviors to baseline
Investigate reversible causes- delirium, ADR, other
Evaluate for precipitating factors

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71
Q

Assessment of BPSD

A

Ensure the patient and staff/caregiver are safe
Compare behaviors to baseline
Investigate reversible causes- delirium, ADR, other
Evaluate for precipitating factors

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72
Q

Nonpharm for BPSD

A

First line
Psychosocial approach- activities of interest, social interactions, comfort
CBT- milder disease and comorbid depression

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73
Q

Antipsychotics for BPSD

A

Haloperidol, aripiprazole, risperidone all have most evidence
Olanzapine, Quetiapine alternatives
Shortest duration, lowest effective dose, monitor closely

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74
Q

BBW for all antipsychotics for BPSD

A

risk of death

75
Q

Antipsychotics in the elderly

A

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
Q

Antipsychotics in BPSD take home messages

A

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
Q

Neurotransmitter systems and psychosis theories

A

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
Q

Typical antipsychotics major classes

A

Phenothiazines- chlorpromazine, fluphenazine
Thioxanthenes- thiothixene
Butyrophenones-haloperidol, benperidol

79
Q

Atypical antipsychotics agents

A

2nd gen

Clozapine, olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole

80
Q

Pharmacology of early antipsychotics (1st gen)

A 
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
Q

Neuroleptic syndrome

A

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
Q

How many D2 receptors need to be blocked for 1st gen antipsychotics to be effective?

A

> 60% D2 receptors needed for clinical improvement

Differences in potency but not in efficacy

83
Q

Effects of 1st gen antipsychotics on DA function

A

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
Q

Nigrostriatal DA pathway

A

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
Q

Mesolimbic DA pathway

A

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
Q

Mesocortical DA pathway

A

Function: hypofunction may be related to impaired cognition
Drug effect: DA receptor blockade may worsen negative symptoms
Terminates in frontal cortex

87
Q

Tuberoinfundibular DA pathway

A

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
Q

AE of typical antipsychotics

A

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
Q

Valbenazine and Deutetrabenezine

A

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
Q

Antipsychotic agents: Other receptor effects

A 
alpha1
D2
H1
M1
5-HT2C
91
Q

What is the AE associated with alpha 1 receptor blockade?

A

Dizziness, orthostatic hypotension, reflex tachycardia

92
Q

What is the AE associated with D2 blockade?

A

Extrapyramidal side effects, increased prolactin levels

93
Q

What are the AE associated with H1 receptor blockade?

A

Sedation, weight gain

94
Q

What are the adverse effects associated with M1 receptor blockade?

A

Blurred vision, constipation, dry mouth

95
Q

What are the AE associated with 5-HT2C receptor blockade?

A

Weight gain

96
Q

Atypical antipsychotics vs typical antipsychotics

A

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
Q

Pneumonic for remembering second gen antipsychotics

A

Pines, dones, and a rone, two pips and a rip

98
Q

Major groups of second generation agents

A

5-HT2A/D2 antagonists (pines, dones, and a rone)

DA2/5-HT1A partial agonists (two pips and a rip)

99
Q

5-HT2A/D2 antagonists

A

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
Q

DA2/5-HT1A partial agonists

A

Two pips and a rip

Aripiprazole, Brexipiprazole, Cariprazine

101
Q

Effect of typical antipsychotics on DA neurotransmission presynaptic

A

Short term- activated neurons

Long-term= inactivated neurons- depolarization inactivation

102
Q

Effect of typical antipsychotics on DA neurotransmission postsynaptic

A

Short term- receptor blockade- motor AE

Long term- receptor super-sensitivity, tardive dyskinesia

103
Q

alpha 1 receptor blockade AE

A

dizziness, orthostatic hypotension, reflex tachycardia

104
Q

D2 receptor blockade AE

A

EPS, increased prolactin levels

105
Q

H1 receptor blockade AE

A

Sedation, weight gain

106
Q

M1 receptor blockade AE

A

Blurred vision, constipation, dry mouth

107
Q

5-HT2C receptor blockade AE

A

weight gain

108
Q

5-HT1 regulation of DA

A

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
Q

Aripiprazole

A

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
Q

Preclinical profile of 2nd gen antipsychotic agents

A

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
Q

Clinical profile of 2nd gen (atypical) antipsychotics

A

Low EPS
Low tardive dyskinesia
Less hyperprolactinemia (except risperidone)
Doesnt worsen (may improve) negative symptoms

112
Q

Olanzapine weight gain

A

Recent studies show that concomitant treatment with the opioid antagonist samidorphan lessens weight gain with olanzapine

113
Q

Pimavanserin

A

5-HT2A inverse agonist
No D2 blockade
Approved for tx of hallucinations/ delusions in psychosis in PD, in trials for schizophrenia

114
Q

What is schizophrenia?

A

Psychiatric disorder with persistent psychosis, impaired social functioning, and impaired occupational functioning.

115
Q

Schizophrenia characteristics

A

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
Q

Clinical course of schizophrenia

A

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
Q

Known/suspected causes of schizophrenia

A

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
Q

Schizophrenia DSM-5 diagnostic criteria

A

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
Q

Positive symptoms of schizophrenia

A

Hallucinations, hostility, excitability, delusions, suspiciousness/persecution, conceptual disorganization, grandiosity

120
Q

Schizophrenia diagnosis exclusions

A

Schizoaffective/mood disorder

121
Q

Key features of psychosis

A

Delusions
Hallucinations
Disorganized thinking
Motor behaviors

122
Q

Motor behaviors in psychosis

A

Catatonia- alterations in environmental reactivity

Abnormal motor movements

123
Q

Disorganized thinking in psychosis

A

Inferred from speech communication

Difficulty communicating due to lack of ability for the listener to understand the individual’s thought expression

124
Q

Delusions in psychosis

A

Fixed, false beliefs
Persecutory, grandiose, somatic
Remain despite contrary evidence

125
Q

Hallucinations in psychosis

A 
Perceptive experience (any of the senses)
Exist despite a lack of external stimulus
126
Q

Negative symptoms of schizophrenia

A 
Avolition
Affective flattening
Anhedonia
Asociality
Alogia
127
Q

Structural brain changes in schizophrenia

A

Enlarged ventricles
Reductions in total brain volume
Loss of gray matter in frontal cortex/temporal lobes

128
Q

Other neuronal involvement in schizophrenia

A

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
Q

Treatment recommendations in schizophrenia

A

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
Q

Nonpharm options for schizophrenia

A 
CBTp
Physcoeducation
Employment support, family support, and assertive community treatment
ECT
rTMS
131
Q

1st generation/typical antipsychotics MOA

A

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
Q

1st generation antipsychotics agents

A 
Chlorpromazine
Fluphenazine
Haloperidol
Loxapine
Perphenazine
Trifluoperazine
Thioridazine
Thiothixene
133
Q

2nd generation antipsychotics MOA

A

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
Q

Which 2nd gen antipsychotics are partial agonists at the D2 receptors

A

Aripiprazole, brexpiprazole and cariprazine

135
Q

Which atypical antipsychotics is the most typical?

A

Risperidone

136
Q

D-HAMS

A 
Dopaminergic
Histaminic
Adrenergic
Muscarinic
Serotonergic

Receptors for schizophrenia

137
Q

What is the effect of dopaminergic receptors?

A

Therapeutic effects
EPS
Hyperprolactinemia

138
Q

What are the effects of histaminic receptors?

A

sedation, weight gain

139
Q

What are the effects of adrenergic receptors?

A

Postural hypotension and reflex tachycardia

140
Q

What are the effects of muscarinic receptors?

A

Antihcolinergic- dry mouth, constipation, urinary retention, blurred vision, decreased cognition

141
Q

What are the effects of serotonergic receptors?

A

Reduced EPS, weight gain, modulation of dopamine release

142
Q

Which 1st gen antipsychotics are high potency?

A

Haloperidol
Fluphenazine
Thiothixene
Trifluoperazine

Increase prolactin, lost of EPS (DA effects)
Lower sedation AE

143
Q

1st generation mid-low potency agents

A

Perphenazine
Loxapine
Chlorpromazine
Thioridazine

Dry mouth, hypotension, sedation

144
Q

Which 1st gen antipsychotics have injections?

A

Chlorpromazine, fluphenazine, haloperidol, thiothixene

145
Q

Which 1st gen antipsychotic has an aerosol powder formulation?

A

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
Q

Which antipsychotics must be taken with food?

A

Lurasidone, Ziprasidone, lumateperone

147
Q

Antipsychotics: depot injections (LAI-APs)

A

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
Q

What are the formulations of asenapine?

A

SL tablet, transdermal

149
Q

Which atypicals are affected by CYP2D6 metabolizers?

A

Aripiprazole

Iloperidone

149
Q

Long acting antipsychotics- 1st generation

A

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
Q

Long-acting antipsychotics long acting injections

A

Risperidone
Paliperidone
Olanzapine
Aripiprazole

152
Q

Risperidone LAI

A

Reconstituted polymer

No oral overlap

153
Q

Paliperidone LAI

A

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
Q

Aripiprazole LAI

A

Maintena- 14 day PO overlap
Aristada- 21 day PO overlap
Initio- initial injection, no oral overlap

155
Q

Olanzapine LAI

A

Must be monitored for 3 hours following each administration for post injection delirium sedation syndrome (PIDSS)
REMS program

156
Q

Lumateperone

A

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
Q

Olanzapine/Samidorphan

A

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
Q

BBW for all antipsychotics

A

Elderly patients, dementia related psychosis

159
Q

Precautions for almost all FGAs

A 
Seizure disorder
Neuroleptic Malignant Syndrome
Movement disorders
Bloody dyscrasias (neutropenia)
Inability to adjust to extreme heat
CV disease
Hyperprolactinemia 
Dysphagia
160
Q

Precautions for almost all FGAa

A 
Seizure disorder
Neuroleptic Malignant Syndrome
Movement disorders
Bloody dyscrasias (neutropenia)
Inability to adjust to extreme heat
CV disease
Hyperprolactinemia 
Dysphagia
161
Q

Precautions for all/most SGAs

A 
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
Q

Which antipsychotics have a BBW of suicidality?

A

Brexpiprazole, aripiprazole, olanzapine/fluoxetine, quetiapine, lurasidone

163
Q

Extrapyramidal AE

A

More commonly seen with typical antipsychotics
DA effects > ACh effects
Acute dystonia, pseudoparkinsonism, akathisia, tardive dyskinesia

164
Q

Acute dystonia

A

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
Q

Pseudoparkinsonism

A

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
Q

Akathisia

A

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
Q

Tardive dyskinesia

A

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
Q

Neuroleptic malignant syndrome

A

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
Q

QTc prolongation

A 
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
Q

Endocrine AE

A

Hyperprolactinemia from hypothalamic DA blockade
Galactorrhea, gynecomastia, amenorrhea, sexual dysfunction
More common with typical antipsychotics, does not happen with partial agonsits

171
Q

Metabolic AE

A 
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
Q

Typicals: misc effects

A

Thioridazone- pigmentary retinopathy (max dose 800mg/day)
Low potency agents- skin discoloration with sun exposure
All agents- transient elevations in LFTs

173
Q

Which atypicals have the highest metabolic risk? Increase sugar and weight

A

Clozapine
Olanzapine
Quetiapine

174
Q

Which atypicals have a medium metabolic risk and are most similar to typicals?

A

Increase prolactin levels
Risperidone
iloperidone
paliperidone

175
Q

Which atyipcals have low metabolic risks and are full antagonists? and have weird admin

A

Asenapine- SL, transdermal
Lorazidone- WF
Ziprasidone= WF

176
Q

Which atypicals are partial agonists, have no hyperprolactinemia, low metabolic risk, and can cause more akathisia?

A

Cariprazine
Aripiprazole
Brexipiprazole

177
Q

Clozapine BBW

A

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
Q

Clozapine REMS

A

For agranulocytosis

Want ANC >1500

179
Q

Which antispychotic needs renal adjustment?

A

Paliperidone

180
Q

Benzodiazepines with clozapine/ olanzapine

A

Increased risk of hypotension
Avoid IM olanzapine with benzodiazepines
Separate by 1 hour at least

181
Q

Pregnancy/ lactation with antipsychotics

A 
Pregnancy- main concern is movement disorders and withdrawal 
Clozapine and lurasidone may have least risk
Lactation- avoid
Partial agonists (CAB) reduce prolactin levels
182
Q

Use of antipsychotics in pediatrics

A

More susceptible to metabolic changes (weight gain)
Schizophrenia rare in pediatrics
Risperidone and aripiprazole can be used in autism

183
Q

Antipsychotic in the elderly

A

Used for BPSD, anxiety, agitation, hypnosis, depression augmentatation
Rare: parkinsons disease psychosis

184
Q

Pimavanserin

A

MOA: inverse agonist of 5-HT2A
Indicated ONLY for PD related psychosis
Being studied for schizophrenia

Therapeutics 4 (8 decks)

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