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Antipsychotic Drugs Flashcards

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1
Q

FDA approved indications for anti-psychotics

A

Schizophrenia
Bipolar disorder
Agitation
Autism

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2
Q

Common uses for anti-psychotics

A 
Schizophrenia and other psychotic disorders
Bipolar disorder
Major depression with psychosis
Delirium/Dementia
Substance induced psychosis 
Tourette/OCD?
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3
Q

Which tract in the brain causes psychosis?

A

Mesolimbic tract (DA)

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4
Q

Which tract in the brain do antipsychotics work on?

A

Mesolimbinc tract (DA)

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5
Q

What are the 4 DA tracts in the brain?

A

Mesolimbic
Mesocortical
Nigrostriatal
Tuberoinfundibular

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6
Q

Dopamine binding affinity is strongly correlated with clinical anti-psychotic effects: the higher the affinity, the ____ the dose needed for anti-psychotic effects

A

Smaller

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7
Q

100 mg Chlorpromazine= __ mg Haloperidol

A

2 mg

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8
Q

Haloperidol is a ___ potency drug ( ___ binding affinity)

A

High

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9
Q

Chlorpromazine is a ___ potency drug ( ____ binding affinity)

A

Low

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10
Q

What are the limitations of the dopamine hypothesis?

A
  • FGA tx of schizo was more effective against + symptoms
  • 35% of treated patients relapse
  • 20-40% patients do not respond adequately
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11
Q

Other names for FGA

A

Neuroleptics
Major Tranquilizers
Conventional anti-psychotics
Typical anti-psychotics

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12
Q

What are the 3 Phenothiazines (FGA) and relative potencies?

A

Chlorpromazine- low
Thioridazine- low
Perphenazine- moderate

all end in “azine”

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13
Q

What is the 1 Thioxanthine (FGA) and relative potency?

A

Thiothixene - moderate

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14
Q

Describe the ideal therapeutic window for anti-psychotics (including tracts and % of D2 receptors bound)

A

Block >60-65% of D2 receptors in mesolimbic tract (anti-psychotic)
Block

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15
Q

What are the effects of low potency FGAs on dopamine receptors?

A

Antipsychotic effect and SE
-Extrapyramidal (EPS/TD)
(Due to decreased dopamine and increased Ach)
-Increased prolactin

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16
Q

What are the effects of low potency FGAs on muscarinic receptors?

A

= anti-cholinergic
blurred vision, urinary retention, dry mouth, constipation
“Can’t see, can’t pee, can’t spit, can’t shit”
“Self treating” for EPS

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17
Q

What are the effects of low potency FGAs on adrenergic receptors?

A

Orthostasis, increased fall risk

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18
Q

What are the effects of low potency FGAs on histamine receptors?

A

Sedation, weight gain

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19
Q

First Aid Chlorpromazine SE

A

Corneal deposits

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20
Q

First Aid Thioridazine SE

A

Retinal deposits

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21
Q

What are the 2 phenothiazines that are high potency FGA?

A

Fluphenazine
Trifluoperazine

“Azines”

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22
Q

What is the 1 Butyrophenone high potency FGA?

A

Haloperidol

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23
Q

High potency FGA Side Effects

A

Dopamine: extrapyramidal, increased prolactin (gynecomastia, galactorrhea, sexual dysfunction, menstrual irregularity/infertility), decreased bone density

No effects on muscarinic, adrenergic, or histamine receptors

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24
Q

What receptor(s) do high potency FGA act on?

A

Dopamine

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25
What are some features of EPS?
Parkinsonian (resting tremor, bradykinesia, stiffness/rigidity) Dystonia Akathesia
26
What percentage of patients will develop EPS from taking high potency anti-psychotics?
50-90%
27
What is Tardive Dyskiensia (TD), what % of patients will develop?
involuntary movements from taking DA blockers tardive= on meds for months - years Classically involves lower facial and tongue movements Does not remit, even after stopping DA antagonist 20-50%
28
Effects on which DA tract cause the extra-pyramidal side effects (EPS)?
Nigrostriatal tract
29
What is acute dystonia?
Sustained abnormal posture Occurs within a couple weeks of someone starting the meds Made worse by activity Patient may report as "allergic reaction"
30
Who is at risk for EPS-dystonia?
Young males
31
What is acute akathesia?
Inner sense of restlessness and need to move?
32
Who is at risk for acute akathesia?
Women- 2x > men
33
Effect on which DA tract causes the increased prolactin?
Tuberoinfundibular tract
34
Increased prolactin causes what other symptoms?
Galactorrhea/lactation Gynecomastia Irregular menstruation, fertility issues Osteopenia
35
What was the first SGA developed?
Clozapine
36
List the SGA:
Clozapine ``` Risperidone Paliperidone Ziprasidone Lurasidone Iloperidone ``` Olanzapine Quetiapine Asenapine Aripiprazole
37
Describe the relative binding affinity of Clozapine for serotonin and dopamine receptors
Binding affinity for serotonin receptor is roughly 10x stronger than that for dopamine receptor
38
Describe the relative binding affinity for Onlazapine/Quietapine for serotonin and dopamine receptors
Both have relatively similar binding affinities for dopamine and serotonin receptors
39
Describe the relative binding affinity for Risperidone and ziprasidone for the serotonin and dopamine receptors
Receptor binding affinity for serotonin is higher than that for dopamine
40
What is the MOA of SGA?
Serotonin -Dopamine Dual Antagonism - block post synaptic D2 receptors - block pre synaptic 5-HT2 receptors (normally inhibit DA release> increased DA release) - allows for
41
Which SGA is not going to have significant anti-histaminic side effects?
Risperidone
42
Which 2 SGAs are not going to have significant anti-muscarinic (anti-cholinergic) side effects?
Risperidone and Ziprasidone
43
Which SGA will not have anti alpha-adrenergic side effects?
TRICK! They all have some amount of anti-alpha adrenergic SE
44
List in order the likelihood that SGAs will cause EPS/TD and increased prolactin
``` Risperidone Ziprasidone/Olanzapine Quetiapine Clozapine (none) ```
45
List in order the likelihood that SGAs will cause Alpha 1 related orthostasis
Clozapine Olanzapine/Quetiapine/Risperidone Ziprasidone
46
List in order the likelihood that SGAs will cause M1-anticholinergic SE
Clozapine Olanzapine Quetiapine Risperidone/Ziprasidone (none)
47
List in order the likelihood that SGAs will cause Histamine related sedation
Clozapine/Olazapine Quetiapine Ziprasidone Risperidone (none)
48
List in order the likelihood that SGAs will cause metabolic syndrome (weight gain, lipids, glucose intolerance)
Clozapine/Olanzapine Quetiapine/Risperidone Ziprasidone
49
Which class of SGAs are worse for weight gain- the "apines" or the "idones"
"apines"
50
What is the effect of Aripiprazole on weight?
Weight neutral
51
What is the effect of Ziprasidone on weight?
Weight neutral
52
Which SGA causes the most weight gain
Clozapine, followed closely by Olanzapine
53
SGA Partial Agonist MOA
Can have an antagonist or agonist effect depending on the level of dopamine in the env less dopamine = agonist more dopamine = antagonist
54
What are the indications for clozapine?
Pts non-responsive to other anti-psychotics Treatment of negative symptoms of schizophrenia Lowers the risk of suicide
55
What are the common SE of clozapine?
``` Sedating Weight gain Metabolic syndrome Anti-cholinergic Anti- alpha adrenergic ```
56
What are the rare/serious SE of clozapine?
Agranulocytosis Myocarditis Decreased seizure threshold
57
Neuroleptic Malignant Syndrome (NMS)
Seen with SGAs or FGAs, rare | Dopamine system goes haywire
58
What are the symptoms of Neuroleptic Malignant Syndrome?
Mental status change Rigidity- increased CPK, tremor Fever >40 C Increased HR, inc/dec BP, inc RR
59
Treatment of NMS (neuroleptic malignant syndrome)
Stop DA blocker Supportive therapy FA: dantrolene, D2 agonists-bromocriptine
60
Sudden Death
Increased mortality in elderly patients with dementia psychosis Stroke and related disorders Increased risk with CVD FGAs and SGAs
61
Recommendation for anti-psychotics in the elderly w/ dementia
Conservative use- low dose, minimize treatment length, alternative tx when available
62
What route of administration of the anti-psychotics provides the best bioavailability?
IM >PO
63
Anti-psychotics protein binding
90% protein bound, unbound crosses BBB
64
Which SGA has the longest half life?
Aripiprazole
65
Low potency FGA affect which receptors?
Dopamine, muscarinic, alpha-adrenergic, histamine
66
High potency FGA affect which receptors?
Dopamine 2
67
Side effects of low potency FGA correlated with receptors:
Dopamine: EPS/TD, inc prolactin Muscarinic: treats EPS, anti-cholinergic SE Adrenergic: dizziness, orthostasis, fall risk Histamine: sedation, weight gain
68
Side effects of high potency FGA correlated with receptors:
Dopamine: EPS/TD
69
What is the only treatment for tardive dyskinesia?
Clozapine
70
Side effects of Clozapine (SGA) correlated with receptors:
Muscarinic: v anti-cholinergic Adrenergic: orthostasis Histamine: v sedating Weight gain, serotonin syndrome
71
What is the one side effect of Lurasidone?
Akathesia
72
In Risperidone and Paliperidone, there is a dose dependent risk for ____ and ____?
EPS and increased prolactin
73
Which SGA carries an increased risk for increased qTC interval?
Ziprasidone
74
What are you options for Rx of patient with poor compliance
Long acting injectables!
75
What are the four long acting SGA injectables
Risperidal Consta Invega Sustenna Zyprexa Abilift maintena
76
What form is asenapine available in?
Sublingual
77
What is the side effect of Aripiprazole?
Akathesia
78
What are the two long acting FGA injectables?
Haldol | Fluphenazine
79
Risperidone is metabolized to _______
Palliperidone
80
How is palliperidone excreted?
80% renal
81
Indications for palliperidone?
Use in pt w/ liver dises
82
Contraindication for palliperidone?
Renal clearance issues
83
Important note about absorption of Ziprasidone and Lurasidone?
take with food! 50% better absorption!

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