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Pharm > Antipsychotic Drugs > Flashcards

Antipsychotic Drugs Flashcards

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
Q

What are some features of EPS?

A

Parkinsonian (resting tremor, bradykinesia, stiffness/rigidity)
Dystonia
Akathesia

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26
Q

What percentage of patients will develop EPS from taking high potency anti-psychotics?

A

50-90%

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27
Q

What is Tardive Dyskiensia (TD), what % of patients will develop?

A

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%

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28
Q

Effects on which DA tract cause the extra-pyramidal side effects (EPS)?

A

Nigrostriatal tract

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29
Q

What is acute dystonia?

A

Sustained abnormal posture
Occurs within a couple weeks of someone starting the meds
Made worse by activity
Patient may report as “allergic reaction”

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30
Q

Who is at risk for EPS-dystonia?

A

Young males

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31
Q

What is acute akathesia?

A

Inner sense of restlessness and need to move?

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32
Q

Who is at risk for acute akathesia?

A

Women- 2x > men

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33
Q

Effect on which DA tract causes the increased prolactin?

A

Tuberoinfundibular tract

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34
Q

Increased prolactin causes what other symptoms?

A

Galactorrhea/lactation
Gynecomastia
Irregular menstruation, fertility issues
Osteopenia

35
Q

What was the first SGA developed?

36
Q

List the SGA:

A

Clozapine

Risperidone
Paliperidone
Ziprasidone
Lurasidone
Iloperidone

Olanzapine
Quetiapine
Asenapine

Aripiprazole

37
Q

Describe the relative binding affinity of Clozapine for serotonin and dopamine receptors

A

Binding affinity for serotonin receptor is roughly 10x stronger than that for dopamine receptor

38
Q

Describe the relative binding affinity for Onlazapine/Quietapine for serotonin and dopamine receptors

A

Both have relatively similar binding affinities for dopamine and serotonin receptors

39
Q

Describe the relative binding affinity for Risperidone and ziprasidone for the serotonin and dopamine receptors

A

Receptor binding affinity for serotonin is higher than that for dopamine

40
Q

What is the MOA of SGA?

A

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
Q

Which SGA is not going to have significant anti-histaminic side effects?

A

Risperidone

42
Q

Which 2 SGAs are not going to have significant anti-muscarinic (anti-cholinergic) side effects?

A

Risperidone and Ziprasidone

43
Q

Which SGA will not have anti alpha-adrenergic side effects?

A

TRICK! They all have some amount of anti-alpha adrenergic SE

44
Q

List in order the likelihood that SGAs will cause EPS/TD and increased prolactin

A 
Risperidone
Ziprasidone/Olanzapine
Quetiapine
Clozapine (none)
45
Q

List in order the likelihood that SGAs will cause Alpha 1 related orthostasis

A

Clozapine
Olanzapine/Quetiapine/Risperidone
Ziprasidone

46
Q

List in order the likelihood that SGAs will cause M1-anticholinergic SE

A

Clozapine
Olanzapine
Quetiapine
Risperidone/Ziprasidone (none)

47
Q

List in order the likelihood that SGAs will cause Histamine related sedation

A

Clozapine/Olazapine
Quetiapine
Ziprasidone
Risperidone (none)

48
Q

List in order the likelihood that SGAs will cause metabolic syndrome (weight gain, lipids, glucose intolerance)

A

Clozapine/Olanzapine
Quetiapine/Risperidone
Ziprasidone

49
Q

Which class of SGAs are worse for weight gain- the “apines” or the “idones”

A

“apines”

50
Q

What is the effect of Aripiprazole on weight?

A

Weight neutral

51
Q

What is the effect of Ziprasidone on weight?

A

Weight neutral

52
Q

Which SGA causes the most weight gain

A

Clozapine, followed closely by Olanzapine

53
Q

SGA Partial Agonist MOA

A

Can have an antagonist or agonist effect depending on the level of dopamine in the env
less dopamine = agonist
more dopamine = antagonist

54
Q

What are the indications for clozapine?

A

Pts non-responsive to other anti-psychotics
Treatment of negative symptoms of schizophrenia
Lowers the risk of suicide

55
Q

What are the common SE of clozapine?

A 
Sedating
Weight gain
Metabolic syndrome
Anti-cholinergic
Anti- alpha adrenergic
56
Q

What are the rare/serious SE of clozapine?

A

Agranulocytosis
Myocarditis
Decreased seizure threshold

57
Q

Neuroleptic Malignant Syndrome (NMS)

A

Seen with SGAs or FGAs, rare

Dopamine system goes haywire

58
Q

What are the symptoms of Neuroleptic Malignant Syndrome?

A

Mental status change
Rigidity- increased CPK, tremor
Fever >40 C
Increased HR, inc/dec BP, inc RR

59
Q

Treatment of NMS (neuroleptic malignant syndrome)

A

Stop DA blocker
Supportive therapy
FA: dantrolene, D2 agonists-bromocriptine

60
Q

Sudden Death

A

Increased mortality in elderly patients with dementia psychosis
Stroke and related disorders
Increased risk with CVD
FGAs and SGAs

61
Q

Recommendation for anti-psychotics in the elderly w/ dementia

A

Conservative use- low dose, minimize treatment length, alternative tx when available

62
Q

What route of administration of the anti-psychotics provides the best bioavailability?

63
Q

Anti-psychotics protein binding

A

90% protein bound, unbound crosses BBB

64
Q

Which SGA has the longest half life?

A

Aripiprazole

65
Q

Low potency FGA affect which receptors?

A

Dopamine, muscarinic, alpha-adrenergic, histamine

66
Q

High potency FGA affect which receptors?

A

Dopamine 2

67
Q

Side effects of low potency FGA correlated with receptors:

A

Dopamine: EPS/TD, inc prolactin
Muscarinic: treats EPS, anti-cholinergic SE
Adrenergic: dizziness, orthostasis, fall risk
Histamine: sedation, weight gain

68
Q

Side effects of high potency FGA correlated with receptors:

A

Dopamine: EPS/TD

69
Q

What is the only treatment for tardive dyskinesia?

70
Q

Side effects of Clozapine (SGA) correlated with receptors:

A

Muscarinic: v anti-cholinergic
Adrenergic: orthostasis
Histamine: v sedating
Weight gain, serotonin syndrome

71
Q

What is the one side effect of Lurasidone?

72
Q

In Risperidone and Paliperidone, there is a dose dependent risk for ____ and ____?

A

EPS and increased prolactin

73
Q

Which SGA carries an increased risk for increased qTC interval?

A

Ziprasidone

74
Q

What are you options for Rx of patient with poor compliance

A

Long acting injectables!

75
Q

What are the four long acting SGA injectables

A

Risperidal Consta
Invega Sustenna
Zyprexa
Abilift maintena

76
Q

What form is asenapine available in?

A

Sublingual

77
Q

What is the side effect of Aripiprazole?

78
Q

What are the two long acting FGA injectables?

A

Haldol

Fluphenazine

79
Q

Risperidone is metabolized to _______

A

Palliperidone

80
Q

How is palliperidone excreted?

81
Q

Indications for palliperidone?

A

Use in pt w/ liver dises

82
Q

Contraindication for palliperidone?

A

Renal clearance issues

83
Q

Important note about absorption of Ziprasidone and Lurasidone?

A

take with food! 50% better absorption!

Pharm (20 decks)

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