Antipsychotics Flashcards
How many categories of antipsychotics exist?
2; 1st generation created before Clozapine, 2nd generation created after Clozapine
Why were the 2nd generations made?
1st generations have too many issues with movement disorders (tardive dyskinesia)
What are the 3 main categories represented by extrapyramidal side effects of 1st generation antipsychotics?
- MC akathisia (restlessness)
- Parkinsonian syndrome (shuffling gate, bradykinesia, tremor, rigidty)
- Dystonia
What monitoring schedule is important for antipsychotics?
Weekly until dose is stable for AT LEAST 2 weeks; 2x a week after dose increase
What is important information about tardive dyskinesia in antipsychotic use?
- Worse with first generation use
- Tardive dyskinesia is permanent even if D/C meds
What are tardive dyskinesia symptoms?
- Sucking/ smacking of lips
- lateral jaw movements
- Facial grimacing
- Choreoathetoid movements of the tongue, trunk, or extremities
What is Valbenazine (Ingrezza) significance?
1st drug to treat tardive dyskinesia
What are metabolic effects of antipsychotic drugs?
- Weight gain 2. DM 3. HLD 4. HTN
What are other significant ADRs of antipsychotic drugs?
- Seizures most can cause
- Orthostatic hypotension
- Neuroleptic malignant syndrome
- QT prolongation
- Myocarditis and Cardiomyopathy
- Sudden death
- Hyperprolactinemia (women galactorrhea and menstrual disturbances) (men sexual dysfunction and gynecomastia)
- Temperature regulation (dehydration, ACH properties, strenuous activity, heat exposure)
What disease should antipsychotics not be used to treat?
Dementia in elderly due to increased mortality
What drugs have the highest risk of causimg neuroleptic malignant syndrome?
First generation antipyschotics
What are risk factors for NMS?
- higher dosage
- switch from one agent to another
- parenteral administration
What is the tetrad of sx in NMS?
- Mental status change (intial sx) agitated, delirium confusion
- Muscle rigidity
- Hyperthermia
- Autonomic dysfunction
What labs are helpful in Dx of NMS?
Serum CK elevation (>1000 IU/L)
How to tx pts with NMS?
- Stop causative agent (antipsychotics)
- Also top lithium, anticholinergics, serotonergics
- Supportive care
- Admit to ICU for cardiopulmonary care
- BZDs if agitated
- Last line Electroconvulsive therapy
How to restart neuroleptic drugs post-NMS?
- Allow for a 2 week minimum “cleanse” before resuming therapy from when sx stop
- Use lower rather than higher potency drugs
First generation antipsychotics drugs that are high potency
- Haloperidol (haldol)
- Fluphenazine (Prolixin)
- Perphenazine
What are ADRs associated with high potency FGAs?
- High risk of EPS
- Prolactinemia
What are low potency FGA drugs?
- Chlorpromazine (Thorazine)
- Thioridazine
What ADRs exist with the low potency FGAs?
- High histamine and muscarinic activity
- Increased sedation
- Prolactinemia
What FGAs are aviailable as injectables? What types?
- Haloperidol and Fluphenazine (both are high potency)
- Long acting injectable (dosed 2-6 weeks) a d immediate release
What PK issues exist for FGAs?
- PO absorption is erratic
- Highly protein/ tissue bound
- Long 1/2 lifes
- All metabolized by CYP450 with many having active metabolites
What is the MOA of FGA drugs?
Strong antagonism of dopamine D2 receptors
What is MOA of second generation antipsychotics?
Higher affinity for blocking serotonin 2 receptors
What are some of the second generation antipsychotics (atypicals)?
- Aripiprazole (Abilify)
- Clozapine
- Olanzapine
- Quetiapine
- Risperadone
What is Clozapine indicated for?
Refractory psychosis
What drug has the highest risk for EPS in SGAs?
Risperadone
What drugs have the highest risk for metabolic effects?
Olanzapine and Clozapine
What SGAs have the lowest risk of EPS and tardive dyskinesia?
- Quetiapine
- Iloperidone
- Clozapine
What generation of antipsychotics have better control over negative symptoms?
SGAs
QT interval prolongation is mild in SGAs, what drugs should be avoided in high risk pts?
Iloperidone and Ziprasidone
What SGA has a FDA warning for DRESS syndrome?
Olanzapine
What SGA has a warning for agranulocytosis and must be checked every month?
Clozapine
How should treatment be administered when treating with antipsychotics?
Titrate as quickly as possible from low dose to therapeutic dose
What is the typical titration with antipsychotics?
5/ 7 days- weeks
What is important about response times with antipsychotic use?
Response occurs within 4-6 weeks with the most improvements in the 1st 2 weeks
When can the current drug treatment of an antipsychotic be termed ineffective?
After a stable dose of a drug has been administered for 2-6 weeks
When is it helpful to switch antipsychotics?
When poor response of drug is related to ADRs
When is changing antipsychotics less beneficial? What to use?
- When drug has poor efficacy
- Clozapine
When can psychosis be considered refractory?
Response remains inadequate after trying 2 different antipsychotics for at least 6 weeks
Switching to Clozapine requires what?
- Close monitoring
- Patient/ family agree to adhere to therapy and monitoring
- Absolute neutrophil count >= 150 cell/microliter
What is one of the biggest problems with refractory psychosis?
Pt drug adherence
