Neuroleptic (Antipsychotic) Drugs Flashcards
How do all of the first generation antipsychotics act?
They produce a state of “artificial hibernation” or “clinical serendipity” aka catalepsy (trance, muscle rigidity, lack of voluntary movement)
What are the names of all of the first generation phenothiazine antipsychotics?
Chlorpromazine, thioridazine, fluphenazine, perphenazine, trifluoperazine
What are the therapeutics of all of the first generation phenothiazine antipsychotics?
treat the positive psychotic symptoms of schizophrenia (hallucinations, delusions); all have little effect on the negative symptoms
What are the common side effects of all first generation antipsychotics?
neuroleptic malignant syndrome, extrapyramidal syndrome, tardive dyskinesia, hyperprolactinemia, sedation
Which of the first generation drugs is a “butyrophenone”
Haloperidol
Which of the first generation drugs is a”dibenzoxazepine”
Loxapine
Which of the first generation drugs is a “thioxanthine”
Thiothixene
Which of the first generation drugs also cause weight gain in addition to other side effects?
Chlorpromazine
Which of the first generation drugs cause hypotension and anticholinergic effects?
fluphenazine, haloperidol, chlorpromazine
Which of the first generation drugs cause less sedating and less EPS effects?
perphenazine, loxapine
Which of the first generation drugs cause more EPS effects?
fluphenazine, haloperidol
Which of the first generation drugs can also be used to treat Huntingon’s movement disorders?
chlorpromazine, haloperidol
What are some of the effects of Extra Pyramidal Syndrome?
acute dystonia (muscular spasms), akathisia (motor restlessness), akinesia/bradykinesia, pseudoparkinsonism, severe tardive dyskinesia
What is tardive dyskinesia? What drug helps to treat this and how does it work?
involuntary assymetrical movements of muscles, facial “tics”. treated with Tetrabenzine which is a dopamine-depleting drug and VMAT inhibitor
What are some side effects of tetrabenzine?
depression, increased suicidal tendencies?
What is Neuroleptic Malignant Syndrome?
muscle rigidity, cramps, tremors, malignant hyperthermia, autonomic instability, cognitive changes, elevated CK and WBC, rhabdomyolysis, myoglobinemia, catatonia, stupor, diaphoresis…
VERY SERIOUS!!
What are the causes of Neuroleptic Malignant Syndrome
dopamine receptor blockade, reduced D2 receptor function, neuroleptic drugs, sudden reduction of dopamine activity
Which of the first generation anti-psychotics possess higher risk of NMS?
haloperidol, chlorpromazine
What are the treatments to prevent NMS?
stop drug, control fever, tx w/dantrolene (muscle relaxant) or bromocriptine to provide Dopamine agonism, benzodiazepines for agitation, hydration
What is hyperprolactinemia caused by?
reduced dopamine levels in hypothalamus affecting pituitary secretion of prolactin (dopamine normally suppresses prolactin secretion)
What are the second generation tricyclic antipsychotics? What is their mechanism of action?
Clozapine, Olanzapine, Quetiapine
MOA: D2 receptor antagonist anad 5HT2 receptor antagonist
What are some of the benefits to the drug Clozapine?
no catalepsy so no EPS, no tardive dyskinesia, akathesia rare, effective against tx-resistant psychoses, decreased suicide risk, **can be used during pregnancy
What are some limitations to taking Clozapine?
agranulocytosis, granulocytopenia, can be lethal, seizure risk, weight gain, diabetes, hyperlipidemia, GI hypomotility, myocarditis
What are the benefits to the drugs Olanzapine and Quetiapine?
no EPS, no tardive dyskinesia, no agranulocytosis, effective against positive symptoms and modest improvement against negative symptoms
What are the common side effects between Olanzapine and Quetiapine?
weight gain, hyperglycemia, postural hypotension, constipation, somnolence, dizziness
What are some additional side effects that Olanzapine has (that Quetiapine doesn’t)?
type 2 diabetes, increased hepatic transaminases, EPS, hyperprolactinemia, akathesia possible
What are names of the second generation non-tricyclic antipsychotics?
Risperidone, Ziprazidone, Paliperidone, Aripiprazole
What are the benefits to treating with Risperidone and Ziprazidone?
effective against positive symptoms, modest improvement against negative symptoms and fewer metabolic complications
What are the side effects of Risperidone?
postural hypotension, constipation, dizziness, insomnia, hyperprolactinemia, weight gain, hyperglycemia, EPS at larger doses
What are the side effects of Ziprazidone?
mild to moderate somnolence, higher incidence of cardiac arrhythmias, QT prolongation, possible EPS
What is Paliperidone an active metabolite of and what is an additional side effect of taking this drug?
1) Risperidone
2) possible QTc prolongation
What is metabolic syndrome?
3 of the following 5 factors: waistline/BMI large, HTN, low HDL/high LDL, elevated triglycerides, hyperglycemia
What’s the therapeutic window for the antipsychotic drugs so they don’t produce EPS but are still effective?
65-80% striatal D2 receptor occupancy
The dopaminergic neurons from SNpc, VTA and hypothalamus form which pathways?
1) SNpc–>nitrostriadal
2) VTA–>mesolimbocortical
3) Hypothalamus–>tuberoinfundibular
Are D1 and D2 receptor families excitatory or inhibitory?
D1 - excitatory; D2 - inhibitory
What does the fast-off D2 receptor hypothesis have to say about atypical antipsychotics vs traditional antipsychotics?
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
Which of the antipsychotics have the highest risk of seizure and which have the least?
most: clozapine, chlorpromazine
least: risperidone
What is the MOA of Aripiprazole and what does it tx?
partial D2 agonist, partial 5HT1A and 5HT2C agonism, 5HT2A and 5HT7 antagonism
(not as effective as the other atyipcals and typicals at treating schizophrenia)
What are the three recent atypical antipsychotics?
Asenapine, Lurasidone, Iloperidone
What does Asenapine treat and what are the side effects?
Tx: bipolar 1, schizophrenia, stuttering
Side effects: akathisia, somnolence, weight gain, sedation, insomnia, EPA, tardive dyskinesia, NMS
What are the benefits to treating with Lurasidone and what are the side effects?
Tx: low risk of weight gain, hyperlipidemia, diabetes, QTc prolongation
Side Effects: akathisia, somnolence, parkinsonism, weight gain
What are the benefits to treating with Iloperidone and what are the side effects?
Tx: low risk of EPS and hyperprolactinemia
Side Effects: orthostatic hypotension, weight gain, diabetes, QTc prolongation, somnolence, dizziness, dry mouth
What is the proposed reason for the metabolic effects associated w/second generation antipsychotics?
H1 Receptor activation which activates hypothalamic AMP-kinase–>increases phospho-AMPK
