Antipsychotics Flashcards
Of the four dopamine tracks, which is responsible for psychosis?
Mesolimbic
Which neurotransmitter is thought to play a role in psychosis?
Dopamine (increased levels lead to psychosis)
How does dopamine binding affinity affect the clinical anti-psychotic effects?
D2 receptor antagonist binding affinity strongly correlates with anti-psychotic effects. This supports the evidence that dopamine mediates psychosis
You can also convert meds based off dosing equivalents
Name the prototype/original phenothiazine/FGA
Chlorpromazine
List the side effects/relative prevalence of side effects associated with FGA’s and dopamine binding
extra-pyramidal symptoms, increased prolactin, sexual dysfunction, infertility, decreased bone density…
Fairly common
List the side effects/relative prevalence of side effects associated with FGA’s and muscarinic binding
Anticholinergic –> blurred vision, urinary retention, dry mouth, constipation
Very common
List the side effects/relative prevalence associated with FGA’s and adrenergic receptor binding
Increased orthostasis, increased risk of falls
Very common
List the side effects/relative prevalence associated with FGA’s and Histamine receptor binding
Sedation, weight gain
Very common
Name the three most important high potency FGAs
Haloperidol
Fluphenazine
Trifluoperazine
What is the advantage of high potency FGAs over low potency FGAs in terms of side effects? Disadvantages?
High potency FGAs bind primarily to dopamine receptors, which means there are no appreciable muscarinic/adrenergic/histamine receptor side effects.
Disadvantages: increased extra-pyramidal symptoms
What percentage of patients on high potency antipsychotics develop tardive dyskinesia?
20-50%
List a few of the classic tardive dyskinesia movements
lower facial and tongue movements- blinking, chewing grimacing, lip puckering/smacking,
These movements are permanent
Dopamine antagonism in the tuberoinfundibular tract leads to which side effects?
Increased prolactin
Galactorrhea, lactation, gynecomastia
Decreased GnRH –> decreased LH and FSH –> irregular menstruation and infertility
*Osteopenia –> increased risk of fractures
What side effect differentiates FGAs from SGAs?
extrapyramidal- SGAs do not have extrapyramidal side effects.
Second generation antipsychotics block which two receptors?
Dopamine
Presynaptic serotonin 5HT
Generally speaking, which class of antipsychotics cause more weight gain vs less weight gain?
More: -apines
Less- idones
Describe the partial agonist properties of aripiprazole in low and high dopamine environments
Low: acts as an agonist
High: acts as an antagonist
How do the partial agonist properties of aripiprazole stabilize the dopamine-serotonin stabilization?
Keeps >65% activated, but less than 80% activated..
Gets enough agonism for benefit without activating side effecfts
When is clozapine indicated?
3rd line treatment - for use after failure of 2 other antipsychotics
Describe the benefits of clozaprine
Greater efficiency with overall psychopathology in patients non-responsive to psychotherapy
Greater efficacy in treatment of negative symptoms of schizophrenia
Lowers risk of suicide in patients with a history of attempted suicide
What are the potential negative side effects that make clozapine a 3rd line treatment option?
Very sedating, weight gain, metabolic syndrome, anti-cholinergic
Rare, serious: Agranulocytosis, myocarditis and lowered seizure threshold
Neuroleptic malignant syndrome is a rare side effect of what class of drugs?
First generation antipsychotics
What are the symptoms of neuroleptic malignant syndrome?
Mental status change
Rigidity: increased CPK and tremor
Fever: > 40 common
Dysautonomia: increased HR, changes in BP, increased RR and hypoxia
Sudden death is a side effect of FGAs and SGAs in what patient population?
elderly patients with dementia w/ psychosis
What is the half life of most of the SGAs? What is the major exception?
20-24 hours.
Aripiprazole is much longer (75 hours)
Which drug is the prototype atypical (SGA) antipsychotic?
Clozapine
What is the range of dopamine receptors needed to achieve positive effects without inducing all of the negative side effects?
65-80%
What is the only treatment for tardive dyskinesia?
Clozapine-
It can help, but not necessarily cure it
Why is risperidone always paired with palliperidone when discussing drug pharmacokinetics and pharmacodynamics?
Risperidone is metabolized to palliperidone
What is a major difference between risperidone and palliperidone/
Palliperidone is 80% excreted renally- good for use in patients with liver issues
Which two SGAs need to be taken with food?
Ziprasidone and Lurasidone
