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Unit 3: Pharm - Liza > Neuroleptic (Antipsychotic) Drugs > Flashcards

Neuroleptic (Antipsychotic) Drugs Flashcards

1
Q

How do all of the first generation antipsychotics act?

A

They produce a state of “artificial hibernation” or “clinical serendipity” aka catalepsy (trance, muscle rigidity, lack of voluntary movement)

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2
Q

What are the names of all of the first generation phenothiazine antipsychotics?

A

Chlorpromazine, thioridazine, fluphenazine, perphenazine, trifluoperazine

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3
Q

What are the therapeutics of all of the first generation phenothiazine antipsychotics?

A

treat the positive psychotic symptoms of schizophrenia (hallucinations, delusions); all have little effect on the negative symptoms

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4
Q

What are the common side effects of all first generation antipsychotics?

A

neuroleptic malignant syndrome, extrapyramidal syndrome, tardive dyskinesia, hyperprolactinemia, sedation

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5
Q

Which of the first generation drugs is a “butyrophenone”

A

Haloperidol

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6
Q

Which of the first generation drugs is a”dibenzoxazepine”

A

Loxapine

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7
Q

Which of the first generation drugs is a “thioxanthine”

A

Thiothixene

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8
Q

Which of the first generation drugs also cause weight gain in addition to other side effects?

A

Chlorpromazine

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9
Q

Which of the first generation drugs cause hypotension and anticholinergic effects?

A

fluphenazine, haloperidol, chlorpromazine

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10
Q

Which of the first generation drugs cause less sedating and less EPS effects?

A

perphenazine, loxapine

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11
Q

Which of the first generation drugs cause more EPS effects?

A

fluphenazine, haloperidol

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12
Q

Which of the first generation drugs can also be used to treat Huntingon’s movement disorders?

A

chlorpromazine, haloperidol

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13
Q

What are some of the effects of Extra Pyramidal Syndrome?

A

acute dystonia (muscular spasms), akathisia (motor restlessness), akinesia/bradykinesia, pseudoparkinsonism, severe tardive dyskinesia

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14
Q

What is tardive dyskinesia? What drug helps to treat this and how does it work?

A

involuntary assymetrical movements of muscles, facial “tics”. treated with Tetrabenzine which is a dopamine-depleting drug and VMAT inhibitor

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15
Q

What are some side effects of tetrabenzine?

A

depression, increased suicidal tendencies?

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16
Q

What is Neuroleptic Malignant Syndrome?

A

muscle rigidity, cramps, tremors, malignant hyperthermia, autonomic instability, cognitive changes, elevated CK and WBC, rhabdomyolysis, myoglobinemia, catatonia, stupor, diaphoresis…

VERY SERIOUS!!

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17
Q

What are the causes of Neuroleptic Malignant Syndrome

A

dopamine receptor blockade, reduced D2 receptor function, neuroleptic drugs, sudden reduction of dopamine activity

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18
Q

Which of the first generation anti-psychotics possess higher risk of NMS?

A

haloperidol, chlorpromazine

19
Q

What are the treatments to prevent NMS?

A

stop drug, control fever, tx w/dantrolene (muscle relaxant) or bromocriptine to provide Dopamine agonism, benzodiazepines for agitation, hydration

20
Q

What is hyperprolactinemia caused by?

A

reduced dopamine levels in hypothalamus affecting pituitary secretion of prolactin (dopamine normally suppresses prolactin secretion)

21
Q

What are the second generation tricyclic antipsychotics? What is their mechanism of action?

A

Clozapine, Olanzapine, Quetiapine

MOA: D2 receptor antagonist anad 5HT2 receptor antagonist

22
Q

What are some of the benefits to the drug Clozapine?

A

no catalepsy so no EPS, no tardive dyskinesia, akathesia rare, effective against tx-resistant psychoses, decreased suicide risk, **can be used during pregnancy

23
Q

What are some limitations to taking Clozapine?

A

agranulocytosis, granulocytopenia, can be lethal, seizure risk, weight gain, diabetes, hyperlipidemia, GI hypomotility, myocarditis

24
Q

What are the benefits to the drugs Olanzapine and Quetiapine?

A

no EPS, no tardive dyskinesia, no agranulocytosis, effective against positive symptoms and modest improvement against negative symptoms

25
Q

What are the common side effects between Olanzapine and Quetiapine?

A

weight gain, hyperglycemia, postural hypotension, constipation, somnolence, dizziness

26
Q

What are some additional side effects that Olanzapine has (that Quetiapine doesn’t)?

A

type 2 diabetes, increased hepatic transaminases, EPS, hyperprolactinemia, akathesia possible

27
Q

What are names of the second generation non-tricyclic antipsychotics?

A

Risperidone, Ziprazidone, Paliperidone, Aripiprazole

28
Q

What are the benefits to treating with Risperidone and Ziprazidone?

A

effective against positive symptoms, modest improvement against negative symptoms and fewer metabolic complications

29
Q

What are the side effects of Risperidone?

A

postural hypotension, constipation, dizziness, insomnia, hyperprolactinemia, weight gain, hyperglycemia, EPS at larger doses

30
Q

What are the side effects of Ziprazidone?

A

mild to moderate somnolence, higher incidence of cardiac arrhythmias, QT prolongation, possible EPS

31
Q

What is Paliperidone an active metabolite of and what is an additional side effect of taking this drug?

A

1) Risperidone

2) possible QTc prolongation

32
Q

What is metabolic syndrome?

A

3 of the following 5 factors: waistline/BMI large, HTN, low HDL/high LDL, elevated triglycerides, hyperglycemia

33
Q

What’s the therapeutic window for the antipsychotic drugs so they don’t produce EPS but are still effective?

A

65-80% striatal D2 receptor occupancy

34
Q

The dopaminergic neurons from SNpc, VTA and hypothalamus form which pathways?

A

1) SNpc–>nitrostriadal
2) VTA–>mesolimbocortical
3) Hypothalamus–>tuberoinfundibular

35
Q

Are D1 and D2 receptor families excitatory or inhibitory?

A

D1 - excitatory; D2 - inhibitory

36
Q

What does the fast-off D2 receptor hypothesis have to say about atypical antipsychotics vs traditional antipsychotics?

A

the atypical (i.e. second generation) dissociate from D2 receptor more rapidly and thus may be more accommodating to physiological DA transmission

**note that other studies found opposing evidence for this and D2 receptor occupancy is not the sole basis for MOA

37
Q

Which of the antipsychotics have the highest risk of seizure and which have the least?

A

most: clozapine, chlorpromazine
least: risperidone

38
Q

What is the MOA of Aripiprazole and what does it tx?

A

partial D2 agonist, partial 5HT1A and 5HT2C agonism, 5HT2A and 5HT7 antagonism

(not as effective as the other atyipcals and typicals at treating schizophrenia)

39
Q

What are the three recent atypical antipsychotics?

A

Asenapine, Lurasidone, Iloperidone

40
Q

What does Asenapine treat and what are the side effects?

A

Tx: bipolar 1, schizophrenia, stuttering

Side effects: akathisia, somnolence, weight gain, sedation, insomnia, EPA, tardive dyskinesia, NMS

41
Q

What are the benefits to treating with Lurasidone and what are the side effects?

A

Tx: low risk of weight gain, hyperlipidemia, diabetes, QTc prolongation

Side Effects: akathisia, somnolence, parkinsonism, weight gain

42
Q

What are the benefits to treating with Iloperidone and what are the side effects?

A

Tx: low risk of EPS and hyperprolactinemia

Side Effects: orthostatic hypotension, weight gain, diabetes, QTc prolongation, somnolence, dizziness, dry mouth

43
Q

What is the proposed reason for the metabolic effects associated w/second generation antipsychotics?

A

H1 Receptor activation which activates hypothalamic AMP-kinase–>increases phospho-AMPK

Unit 3: Pharm - Liza (14 decks)

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