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Pharm Unit 3 > CNS III- Neuroleptic (Antipsychotic) Drugs > Flashcards

CNS III- Neuroleptic (Antipsychotic) Drugs Flashcards

1
Q

What is the primary use of antipsychotic drugs?

A

Treatment of schizophrenia

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2
Q

What are some of the clinical symptoms of schizophrenia?

A

Positive (psychotic) symptoms - delerium, paranoia, hallucinations (auditory most common)

Cognitive dysfunction - working memory, attention, executive function (abstract thinking, problem solving)

Negative symptoms - apathy, withdrawl, anhedonia (lack of pleasure)

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3
Q

First generation anti-psychotic drugs are not as effective as treating what kind of symptoms?

A

Negative symptoms

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4
Q

What are some adverse effects of 1st gen antipsychotic drugs?

A

-Extra Pyramidal Syndrome (EPS) effects
parkinsonism, dystonia, akathisia (involuntary movements)
-Tardive dyskinesia (severe)-tx with tetrabenzine
-Sexual Dysfunction
-Hypotension
-Hyperprolactinemia-tx with bromocryptine
-Neuroleptic malignant syndrome

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5
Q

What is neuroleptic malignant syndrome defined by?

A
  • Rare, 0.2 to 3% incidence (2:1, ♂:♀)
  • Life-threatening neurological disorder, 10% mortality rate
  • Muscle rigidity, cramps, tremors
  • Fever (malignant hyperthermia)
  • Autonomic instability (unstable BP, hypertensive crisis)
  • Cognitive changes (confusion, delirium, agitation, coma)
  • Elevated serum creatine kinase and white blood cell counts,
  • Rhabdomyolysis, sometimes myoglobinemia,
  • Catatonia, stupor
  • Diaphoresis (excessive sweating)
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6
Q

FEVER and FALTER mnemonics for neuroleptic malignant syndrome

A 
FEVER				
F – Fever			
E – Encephalopathy		
V – Vitals unstable		
E – Elevated enzymes (CPK)	
R – Rigidity of muscles		
FALTER
F – Fever
A – Autonomic instability
L – Leukocytosis
T – Tremor
E – Elevated enzymes (elevated CPK)
R – Rigidity of muscles
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7
Q

Which atypical neuroleptic requires monitoring with weekly blood tests?

A

Clozapine- there is approximately a 1% incidence of agranulocytosis while taking this drug (can be lethal)

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8
Q

Which neuroleptic drug(s) is associated with increased risk of seizures?

A

Clozapine, chlorpromazine

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9
Q

Name the class that the following drugs fall into: Chlorpromazine, Fluphenazine, Trifluoperazine, Perphenazine, Thioridazine, Thiothizene, Loxapine, Haloperidol

A

First generation antipsychotics

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10
Q

What is the mechanism of all of the first generation antipsychotics? (Chlorpromazine, Fluphenazine, Trifluoperazine, Perphenazine, Thioridazine, Thiothizene, Loxapine, Haloperidol)

A

D2 receptor antagonist

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11
Q

Which two first generation antipsychotics generate more EPS than Chlorpromazine? Less?

A

More-Haloperidol and Fluphenazine

Less- Perphenazine, and Loxapine

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12
Q

What is meant by saying that the first generation antipsychotics produce an “artificial hibernation”?

A

These drugs induce catalepsy (trance, muscle rigidity, lack of voluntary movement)

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13
Q

What is the mechanism of action tetrabenazine and what is it used to treat?

A

Depletes dopamine, inhibits VMAT2 (transporter for repackaging monoamines)
Treats-movement disorder in Huntingtons and tardive dyskinesias

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14
Q

What is the mechanism of action of Dantrolene and what is it used to treat?

A

muscle relaxant to treat malignant hyperthermia in NMS

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15
Q

What are the 7 second generation antispsychotics?

A

Clozapine, Olanzapine, Quetiapine, Risperidone, Ziprazidone, Paliperidone (metabolite of risperidone) and Aripiprazole

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16
Q

What is the mechanism of action of the 2nd generation antipsychotics excluding Aripiprazole?

A

D2 and 5HT2 receptor antagonism

17
Q

Which of the following may have limited use due to Agranulocytosis and must be monitored by weekly blood tests? Clozapine, Olanzapine, Quetiapine, Risperidone, Ziprazidone, Paliperidone

A

Clozapine-also has seizure risk, Akathesia, GI hypomotility and myocarditics

18
Q

Which of the following drugs has a higher incidence of cardiac arrythmias from QT prolongation? Clozapine, Olanzapine, Quetiapine, Risperidone, Ziprazidone, Paliperidone

A

Ziprazidone, and Paliperidone

19
Q

What are some of the common side effects of almost all second generation antipsychotics?

A

weight gain, hyperglycemia, postural hypotension, somnolence (except risperidone and paliperdone-insomnia) and constipation

20
Q

What are the side effects of Ziprazidone and Paliperidone in addition to the side effects of other 2nd generation antipsychotics?

A

QT prolongation, insomnia, hyperprolactinemia, dizziness, EPS

21
Q

Which of the following may increase serum hepatic transaminases? Clozapine, Olanzapine, Quetiapine, Risperidone, Ziprazidone, Paliperidone

A

Olanzapine

22
Q

Which of the second generation antipsychotics has less metabolic complications?

A

Risperidone, Ziprazidone, and Paliperidone (non-tricyclics)

23
Q

What is the mechanism of action of Aripiprazole?

A
  • partial D2, D3 and 5HT1a receptor agonist

- 5HT2a antagonist

24
Q

What is Aripiprazole used to treat?

A

Schizophrenia-not as effective as other atypicals
Bipolar
Depression-as adjunct

25
Q

What medications can be used to treat the hyperprolactinemia side effect?

A

dopamine agonists-bromocriptine and pergolide (not in US because of cardiac valve fibrosis)

26
Q

Which pathway of the brain is implicated in the positive symptoms of schizophrenia?

A

mesolimbic

27
Q

Which pathway of the brain is implicated in the negative symptoms of schizophrenia?

A

mesocortical

28
Q

What is the rapid D2 receptor dissociation hypothesis and what is it used to explain?

A

hypothesis-typical antipsychotics bind D2 receptor tight, atypical bind but a released quickly
explains-less dopamine side effects of atypical antipsychotics

29
Q

What is the data against the D2 dissociation hypothesis?

A

D2 is not the only basis for the mechanism of action of the atypical antipsychotics

30
Q

What is the serotonin DA antagonist theory?

A

it is a combination of D2 and 5HT2A receptor antagonism that correlates with the antipsychotic and low EPS effects of the atypical antipsychotics

31
Q

What is the “magic shotgun concept”?

A

clozapine is the gold standard atypical antipsychotic but it has severe and life threatening side effects

32
Q

Which antipsychotics can be used in pregnancy?

A

Clozapine and Lurasidone

33
Q

What are the 3 more recent atypical antipsychotics?

A

Asenapine, Lurasidone, Iloperidone

34
Q

Is the therapeutic window for antipsychotics wide or narrow?

A

narrow (65% receptor occupancy to 80% receptor occupancy)

35
Q

Which receptor type is found at reduced levels in post mortem analysis of schizophrenic patients?

A

mGluR2- normally it directly inhibits 5HT2A receptor

36
Q

Which of the first generation antipsychotics can be used to treat movement disorders of Huntingtons Disease?

A

Chlorpromazine, Fluphenazine and Haloperidol

37
Q

How is NMS treated?

A
  • Stop neuroleptic drug
  • Control fever-cooling blankets
  • Dantrolene
  • Bromocryptine
  • Hydration
  • Benzos for agitation

Pharm Unit 3 (14 decks)

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