Neuroleptic (Antipsychotic) Drugs

Question 1

How do all of the first generation antipsychotics act?

Answer 1

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

Question 2

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

Answer 2

Chlorpromazine, thioridazine, fluphenazine, perphenazine, trifluoperazine

Question 3

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

Answer 3

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

Question 4

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

Answer 4

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

Question 5

Which of the first generation drugs is a “butyrophenone”

Answer 5

Haloperidol

Question 6

Which of the first generation drugs is a”dibenzoxazepine”

Answer 6

Loxapine

Question 7

Which of the first generation drugs is a “thioxanthine”

Answer 7

Thiothixene

Question 8

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

Answer 8

Chlorpromazine

Question 9

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

Answer 9

fluphenazine, haloperidol, chlorpromazine

Question 10

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

Answer 10

perphenazine, loxapine

Question 11

Which of the first generation drugs cause more EPS effects?

Answer 11

fluphenazine, haloperidol

Question 12

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

Answer 12

chlorpromazine, haloperidol

Question 13

What are some of the effects of Extra Pyramidal Syndrome?

Answer 13

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

Question 14

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

Answer 14

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

Question 15

What are some side effects of tetrabenzine?

Answer 15

depression, increased suicidal tendencies?

Question 16

What is Neuroleptic Malignant Syndrome?

Answer 16

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

VERY SERIOUS!!

Question 17

What are the causes of Neuroleptic Malignant Syndrome

Answer 17

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

Question 18

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

Answer 18

haloperidol, chlorpromazine

Question 19

What are the treatments to prevent NMS?

Answer 19

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

Question 20

What is hyperprolactinemia caused by?

Answer 20

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

Question 21

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

Answer 21

Clozapine, Olanzapine, Quetiapine

MOA: D2 receptor antagonist anad 5HT2 receptor antagonist

Question 22

What are some of the benefits to the drug Clozapine?

Answer 22

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

Question 23

What are some limitations to taking Clozapine?

Answer 23

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

Question 24

What are the benefits to the drugs Olanzapine and Quetiapine?

Answer 24

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

Question 25

What are the common side effects between Olanzapine and Quetiapine?

Answer 25

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

Question 26

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

Answer 26

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

Question 27

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

Answer 27

Risperidone, Ziprazidone, Paliperidone, Aripiprazole

Question 28

What are the benefits to treating with Risperidone and Ziprazidone?

Answer 28

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

Question 29

What are the side effects of Risperidone?

Answer 29

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

Question 30

What are the side effects of Ziprazidone?

Answer 30

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

Question 31

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

Answer 31

1) Risperidone | 2) possible QTc prolongation

Question 32

What is metabolic syndrome?

Answer 32

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

Question 33

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

Answer 33

65-80% striatal D2 receptor occupancy

Question 34

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

Answer 34

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

Question 35

Are D1 and D2 receptor families excitatory or inhibitory?

Answer 35

D1 - excitatory; D2 - inhibitory

Question 36

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

Answer 36

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

Question 37

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

Answer 37

most: clozapine, chlorpromazine least: risperidone

Question 38

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

Answer 38

partial D2 agonist, partial 5HT1A and 5HT2C agonism, 5HT2A and 5HT7 antagonism (not as effective as the other atyipcals and typicals at treating schizophrenia)

Question 39

What are the three recent atypical antipsychotics?

Answer 39

Asenapine, Lurasidone, Iloperidone

Question 40

What does Asenapine treat and what are the side effects?

Answer 40

Tx: bipolar 1, schizophrenia, stuttering Side effects: akathisia, somnolence, weight gain, sedation, insomnia, EPA, tardive dyskinesia, NMS

Question 41

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

Answer 41

Tx: low risk of weight gain, hyperlipidemia, diabetes, QTc prolongation Side Effects: akathisia, somnolence, parkinsonism, weight gain

Question 42

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

Answer 42

Tx: low risk of EPS and hyperprolactinemia Side Effects: orthostatic hypotension, weight gain, diabetes, QTc prolongation, somnolence, dizziness, dry mouth

Question 43

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

Answer 43

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