Antipyschotics Flashcards
what are the four dopamine pathways in the brain
- mesolimbic pathway
- nigrostriatal pathway
- mesocortical pathway
- tuberoinfundibular pathway
explain the mesolimbic and nigrostriatal pathway in terms of schizophrenia
- hyperactivity in the mesolimbic pathway account for the positive psychotic symptoms so blocking D2 receptors alleviates the positive psychotic symptoms
- nigrostriatal pathway controls motor movement –> blocking D2 receptors –> extrapyramidal reactions –> acute dystonia, akathisia (uncontrollable restlessness), parkinsonian like symptoms (bradykinesia, tremors, rigidity)
explain the mesocortical and tuberoinfundibular pathway
- reduced activity in mesocortical –> negative psychotic symptoms –> blockade of D2 receptors in this pathway –> cause or worsen negative symptoms such as emotional blunting and cognitive problems
- dopamine released from tuberoinfundibular pathway inhibits prolactin secretion –> blockade of D2 receptors –> increase in prolactin –> galactorrhea
what are the classical antipsychotics and how are they sub classified
high potency: Haloperidol and Fluphenazine
low potency: Chlorpromazine and Thioridazine
what does it mean to be a high potency and low potency antipsychotic
- high potency: haloperidol and fluphenazine are more likely to produce extrapyramidal symptoms because of higher affinity for D2 receptors
- low potency: Chlorpromazine and Thioridazine are less likely to produce extrapyramidal symptoms and more likely to produce sedation and postural hypotension
what are the atypical antipsychotics
CROAQ
Clozapine Risperidone Olanzapine Aripiprazole Quetiapine
mechanism of classical antipsychotics (name them)
high: haloperidol and fluphenazine
low: chlorpromazine and thioridazine
block dopamine receptors in the brain and in the periphery
what are the D1-like and D2-like dopamine receptors and what type of G proteins do they use for their mechanism
D1 like dopamine receptors: D1 and D5 –> Gs and they activate adenylyl cyclase
D2 like dopamine receptors: D2, D3, D4 –> Gi and they inhibit adenylyl cyclase
receptors does clozapine have a high affinity towards
D1, D2, D4, 5HT-2, muscarinic, and alpha adrenergic
receptors does risperidone have a high affinity towards
higher affinity towards 5-HT2 than D2
what are common properties of atypical antipsychotics
- dual antagonism for 5-HT2A and D2
- exert part of their action by antagonizing 5-HT
- less likely to have extrapyramidal reactions than the classical agents
- less likely to have tardive dyskinesia
- less likely to increase prolactin
- more effective at treating negative symptoms
- effective in treatment of refractory population
mechanism of action of Aripiprazole
- partial agonist at 5-HT1A and D2
- antagonist at 5-HT2A
How do most of the antipsychotics have anti emetic effect and what are the exceptions
- anti emetic effect due to blockade of D2 receptors
- exception is Aripiprazole (agonist at D2) and Thioridazine
what antipsychotics are used to treat outpatients and individuals who are not compliant with medication
Fluphenzine decanoate
Risperidone decanoate
Haloperidol decanoate
they are all slow releasing formulations
why are low potency classical agents less likely to have extrapyramidal reactions (name them)
Chlorpromazine and Thioridazine
less affinity for D2 receptors and have stronger anti cholinergic effects (hence why they are more likely to have sedation and postural hypotension)
what can the parkinsonism seen as side effects of anti psychotics be treated with
Benztropine and Trihexyphenidyl
-together with diphenhydramine and amantadine
what should not be used to treat parkinsonism
levodopa
what can acute dystonia be treated with
benztropine, trihexyphenidyl, diphenhydramine
what is used to manage akathisia (uncontrolled restlessness)
- reduced dosage of anti pyschotics
- Clonazepam
- Propanolol
Used to treat patients with tardive dyskinesia who require antipsychotics
Clozapine
steps taken when tardive dyskinesia is diagnosed/seen in patient taking anti psychotics
First, this is due to upregulation of dopamine receptors due to its blockade
- discontinue antipsychotics
- stop anti cholinergic drugs
- stop anti parkinsonism drugs
- stop TCAs
AE of antipsychotics
NESS
Neuroleptic Malignant Syndrome
Extrapyramidal reactions
Seizures
Sedation
What is neuroleptic malignant syndrome
- results from excessively rapid blockade of dopamine receptors
- characterized by severe rigidity, tremor, hyperthermia, altered mental status, autonomic instability, elevated WBC, elevated serum creatine kinase
what can be used to treat neuroleptic malignant syndrome
Dantrolene
Bromocriptine
which of the antipsychotics is associated with agranulocytosis and how is it monitored
Clozapine
patients must get weekly blood count for first 6 months of treatments then every 3 weeks thereafter
endocrine side effects of antipsychotics
hyperglycemia and diabetes
only antipsychotic to cause retinal deposit resembling retinitis pigmentosa
Thioridazine
other AE of antipsychotics
Drowsiness
Jaundice
Poikilothermia
uses of anti psychotics
Schizophrenia Bipolar Disorder Tourette's disorder Alzheimer's Treatment resistant major depression Psychotic depression
non psychiatric uses of anti psychotics
nausea and vomiting (blockade of D receptors)
Neuroleptanesthesia (droperidol)
drug of choice for psychotics and why
atypical drugs preferred due to benefit for negative symptoms, less EPR, less tardive dyskinesia, less increase in prolactin increase
what is Clozapine reserved for and why
Refractory patients due to agranulocytosis
