Antipsychotics Flashcards
What is the major dopaminergic tract that is the source of psychosis?
Mesolimbic tract
One theory says that too much dopamine can cause….
Schizophrenia
How does the binding affinity of the antipsychotic drug affect its dosing?
The greater the binding affinity for DA receptors, the smaller dose is needed for the antipsychotic effect
List the Low Potency FGAs
Chlorpromazine
Thioridazine
Perphenazine
Thiothixene
What % of DA receptors need to be blocked to produce a therapeutic effect? What about side effects in the nigrostriatal and tuberoinfundibular tracts?
Therapeutic: block 60-65% of D2 receptors in the mesolimbic tract
Side effects in nigrostriatal and tuberinfundibular tracts: above 80% D2 receptor blockage
Chlorpromazine
Adverse Effects
Dopamine - EPS or Tardive dyskinisia; increased prolactin
Muscarinic- blurred vision, urinary retention, dry mouth, constipation
Alpha 1 adrenergic – orthostasis
H1 - sedation; weight gain
List the High Potency FGAs
Haloperidol
Fluphenazine
Trifluoperazine
High Potency FGAs
Adverse effects
Dopamine- EPS and TD; hyperprolactinemia (galactorrhea, gynecomastia)
No H1, musc, alpha1 side effects!
Excess dopamine blockage in the Nigrostriatal pathway tends to cause…
ExtraPyramidal Symptoms
Tardive dyskinisia
Excess dopamine blockage in the Tuberoinfundibular pathway tends to cause…
Hyperprolactinemia
Gynecomastia, Galactorrhea
Low GnRH
Osteopenia (increased fractures)
List some SGAs
Clozapine
Risperidone Quetiapine Aripiprazole Olanzapine Asenapine Ziprasidone Iloperidone Paliperidone Luraisdone
SGAs
MOA
Dual antagonism of both the presynaptic 5HT-2A and postsynaptic D2 receptors
Blocking the 5HT-2A receptors causes a disinhibition of DA release, thus causing excess DA in the synapse, so SGA DA blockade is not as long lasting
Which SGA is a partial agonist of the DA receptor? Describes its pharmacodynamics
Aripiprazole
Has agonist effects in a low dopamine environment. Has antagonist effects in a high dopamine environment
Positive Results of using Clozapine (a SGA)
Has efficacy in treating negative symptoms of schizophrenia
Helps with TD
Decrease risk of suicide or violence
Helps with treatment resistant schizophrenia
Clozapine is the 3rd line choice for antipsychotics (after 2 others failed). This is due to its adverse effects, including…
Common: Sedating, Weight Gain
Metabolic Syndrome
Anticholinergic
Rare:
AGRANULOCYTOSIS
Myocarditis
Decreased Seizure threshold
All antipsychotics have the potential side effect of NMS. What is that?
NMS = Neuroleptic Malignant Syndrome
Caused by excess dopamine blockade
Dopamine system goes haywire, causing mental status changes, rigidity, tremor, fever, inc HR, low BP, inc RR
What is the recommendation for treating elderly patients with antipsychotics?
Treat with low doses for minimal time
FGAs and SGAs can cause sudden death in elderly patients with dementia
Which SGA has the longest half life?
Aripiprazole (3 days)
Describe the protein binding of Antipsychotics
90% protein bound, unbound portion passes through the BBB
Avg half life for antipsychotics
About 30 hours (so you reach steady state between 4-7 days)
What is the only treatment for Tardive Dyskinisia?
Clozapine
Aripiprazole
Adverse Effects
Dopamine- akathesia
Low risk of weight gain
Musc, Adrenergic, H1– none
What is the relationship between Risperidone and Palliperidone?
Risperidone is metabolized to Palliperidone
Palliperidone
Excretion
Mostly renally excreted, so used in pts with liver disease
