Antipsychotics Flashcards
Typical antipsychotics mechanism
Da antagonists
Atypical antipsychotics mechanism
Da and 5HT2A antagonists
Four dopaminergic pathways and their function
Nigrostriatal –extrapyramidal motor function
Mesolimbic – reward and emotional behavior
Mesocortical - cognition
Tuberoinfundibular – inhibits the secretion of prolactin
Classification of the typical antipsychotics by potency
Low Potency (High Ach, M1, A1 blockade) Chlorpromazine Perphenazine (Mid level) Fluphenazine Haloperidol High potency (low Ach, H1, A1 blockade)
Therapeutic use of the typical antipsychotics
Schizophrenia, schizoaffective disorder, delusional disorder, brief psychotic disorder.
Mood disorders: bipolar and mdd with psychotic features
Delirium
Violent behavior/agitation
Which two typical antipsychotics have a decanoate preparation?
Haloperidol and fluphenazine
Typical antipsychotic side effects
Extrapyramidal movements
Negative symptom increase
Prolactin levels rise (gynecomastia)
Which antipsychotics carry the greatest risk of EPS, TD, and neuroleptic malignant syndrome?
High potency (haloperidol and Fluphenazine)
How to treat EPS from typical antipsychotics
antimuscarinics (trihexylphenadyl, DA agonists)
Acute dystonia
Happens from typical antipsychotics, treat with anticholinergics
Akathisia, treatment
Subjective feeling of inner restlessness, give beta blockers, benzodiazepines, anticholinergics
Tardive dyskinesia, treatment
In 5% of patients on antipsychotics chronically. Continuous writing movements of tongue mouth fingers hands and sometimes feet. Common with high potency antipsychotics. Treat by stopping or switching the antipsychotic, increasing dose will help temporarily.
Neuroleptic malignant syndrome
Life threatening reaction from antipsychotics that can cause eps along with autonomic symptoms. Increased WBC, CPK, LFT. Happens more in young males.
Blockade of A1 receptors causes
Orthostatic hypotension, dizziness, priapism
Cardiac effects of antipsychotics
Can prolong the QT interval, cause PVCs, and sudden death
Atypical antipsychotic mechanism
Serotonin and dopamine antagonists. D2 antagonists with rapid dissociation D2 partial agonists Serotonin partial agonist at 5HT1A Serotonin antagonist at 5HT2A
How do 5HT2A antagonists stimulate DA release
They prevent serotonergic activation of Gaba interneurons that usually inhibit DA release, so there is a better balance of Dopamine released, so EPS aren’t bad
Why are atypical antipsychotics better than typicals?
because they don’t any extrapyramidal side effects, thanks to the inhibition of gabaergic interneurons, so more better balance of DA.
Also, reduced risk of hyperprolactinemia
cognitive enhancement
improved adherence
D2 antagonists with rapid dissociation
Hit and run, so the block isn’t too long lasting.
Aripiprazole
D2 partial agonist
5HT1a partial agonist
5HT2A antagonist
really tunes control of dopamine
Clozapine
More effective than all other antipsychotics, so it’s the drug of choice for treatment-resistant schizophrenics. Low D2 antagonism, but causes metabolic syndrome the most by blocking 5HT2C receptors in the hypothalamus and can cause agranulocytosis
Risperidone
At therapeutic doses, occupies close to 100% of the 5HT2 receptors, but only 65% of the D2 receptors. Highest risk of the atypicals to cause extrapyramidal side effects
Highest risk of EPS among atypical antipsychotics
Risperidone
Biggest adverse effects of typicals vs atypicals
EPS and TD vs Weight gain, diabetes, CVD, dyslipidemia
Metabolic syndrome
Visceral Obesity
Insulin Resistance
Dyslipidemia (high triglycerides, low HDL)
Hypertension
Atypicals that cause the most weight gain
Clozapine and olanzapine
Which atypical causes agranulocytosis?
ANC <500, clozapine – must increase gradually and check a CBC weekly
Atypical antipsychotics that we need to know
Aripiprazole, Risperdone, Clozapine, Olanzapine, Quetiapine, Ziprasidone
Atypical antipsychotics off label use
For dementia related psychosis (this can increase mortality in elderly)
What type of symptoms are atypicals best for?
Negative symptoms
Which drug is used to treat agitation in the medically sick?
Haloperidol
First line, second line
First line: Atypicals (aripiprazole, quetiapine, ziprasidone, risperdone)
Second line : Clozapine and olanzapine
Thirdline: typicals
