Antipsychotics Flashcards
All antipsychotics carry the risk of _____________.
QT prolongation
What are the 2 classes of antipsychotics?
- Typical/conventional (1st generation, FGA)
2. Atypical (2nd generation, SGA)
What is EPS? What can EPS turn into?
Extra-pyramidal Symptoms from increase in ACh (Parkinsonian sx) - reversible movement disorders, such as tremor, rigidity, drooling, masked fascies, akinesia.
Can turn into tardive dyskinesia, which is irreversible.
Explain the balance of DA and ACh.
When the body has too much DA, this decreases the amount of ACh. Anti-psychotic drugs decrease DA, thereby increasing ACh and inducing EPS.
What is the father of the typical antipsychotics?
Chlorpromazine - it was an antihistamine that had antipsy properties
What other binding properties do FGA have (other than D2)?
- H1 blocking- Antihistamine - weight gain
- Alpha-1 blocking - orthostatic hypotension
- M1 blocking - Anticholinergic - anti-SLUDGE
FGA are sometimes referred to as _______ or _______.
Neuroleptics, sedatives
FGA drugs differ in degree of potency. Potency refer to binding capacity of __________ receptors.
Dopaminergic
Most FGA have short/long half lives.
Long
What is first dose phenomenon? How do you treat it?
Acute dystonic rxn
IV benztropine.
What are the ways that you can treat EPS?
- Decrease dose
- Switch to a SGA
- Switch to a low potency agent with high anticholinergic properties
- Add an anticholinergic (Trihexyphenidyl, benztropine, diphenhydramine)
Neuromuscular Malignant Syndrome is hallmarked by what 4 symptoms?
- Hyperpyrexia (103-104)
- Rigidity
- Hyperactive
- Increase in CPK from rhabdo
How do you treat NMS?
D/C antipsychotic and consider dantrolene (muscle relaxer) and/or bromocriptine (DA agonist)
What are the cons of the FGA?
- EPS
- Negative symptoms not treated well
- Decreased adherence
- Greater risk for tardive dyskinesia if on for prolonged period of time
What are the pros of FGA?
- Cheap
2. Multiple dosage forms
Name a high potency FGA. What are 2 pros and 2 cons?
Haloperidol - Vitamin H
1. Highly potent sedative, used for agitation or sedation - calming effect without significant resp depression
2. Can clear quickly, good for elderly. (unlike benzos)
CON:
1. May lower sz threshold
2. QT prolongation
Typical agents block the D2 receptor. Atypical agents are also called SGA. They block ____ and _____, which helps blunt ______ and treats ______ symptoms.
DA and 5HT2a
blunts EPS
treats negative
What are the concerns raised over for SGA?
Metabolic adverse effects - weight gain, DM, dyslipidemia.
$$$$
SGAs have more or less affinity for different receptors than FGAs.
MORE
What are the pros of SGAs?
Improved adherance
reduced EPS in general
treats negative symptoms
starting to see different dosage forms
Quetiapine (Seroquel) treats what 3 issues at what doses?
“Quiet”
Low dose (50) - sleeping pill (hypnotic or sedation) Medium dose (300)- depression High dose (800) - antipsychotic
Quetiapine has a very low risk of ______ and _________, thereby making it a go-to SGA for this reason.
EPS
hyperprolactinemia (least risk)
What SGA can be used for bipolar disease?
Quetiapine
Risperidone
What are the pros and cons of Olanzapine?
Cons: Significant risk for metabolic effects Pros: Pretty good with negative symptoms Low risk of EPS
Olanzapine is son of _________.
Clozapine, first SGA antipsychotic
________ is considered the gold standard for SGA, but it has 5 Black Box Warnings, so it is NOT first line.
Clozapine
What are the major pros/cons of Clozapine?
Pros: Low incidence of EPS, TD Very effective vs negative sx Cons: Risk of agranulocytosis 5 BBW
What do you need to monitor with Clozapine?
CBC for agranulocytosis- qweek for 1st 6mo, then every other week.
max risk is 4-18 weeks after initiation of therapy
Name the 5 BBWs for Clozapine.
- Agranulocytosis
- Orthostatic hypotension
- Seizures
- Myocarditis/cardiomyopathy
- Increased mortality in elderly with dementia related psychosis
What is the newer agent that could replace Clozapine because it has no risk of agranulocytosis?
Olanzapine (Zyprexa)
T or F. Risperidone and Paliperidone have similar characteristics. Why?
T
Paliperidone is a metabolite of Risperidone, so it carries the same risk of hyperprolactinemia
Does risperidone have a high or low risk for the following:
EPS
Metabolic abnormalities
Hyperprolactinemia (sexual dysfunction, bone density)
Higher risk of EPS at higher doses
Low risk of metabolic abnormalities
SIGNIFICANT risk for hyperprolactinemia
Describe Lurasidone’s risk for sedating/metabolic effects and EPS. Why is that way?
Low metabolic risk and Less sedating (L is for low)
Greater risk for EPS
***Lack of anticholinergic properties = less sedation, more EPS
Aripiprazole has a lower/higher incidence of EPS, weight gain, prolactinemia, sedation and dyslipidemia.
What else is it approved to treat?
- LOWER risk
- Augmenting SSRI/SNRIs for resistant major depressive disorder
What drug is a mood stabilizer that also has an indication for bipolar?
Lithium
T or F. Lithium has a high therapeutic index.
False - low - meaning it can become toxic easily
Lithium is a ______ with rapid absorption. What does this mean in regards to using charcoal in OD?
Metallic ion
CANNOT use charcoal
Lithium has an inverse relationship with Na. what does this mean?
Increased Na wasting will increase Li levels (and vice versa) - diuretics that waste Na will retain lithium level
What is the therapeutic level of Lithium? when do you check it?
0.4-1 mmol/L
AM trough
What are the 6 AEs of lithium? What is the heralding sign of too much lithium?
- fine tremor***
- Polys - uria, dipsia
- Hypothyroidism (follow TSH to see if it gets high)
- Weight gain
- metallic taste
- Rash
VPA is another mood stabilizer. What do you need to monitor (in general and in patients who develop lethargy, AMS, vomiting, hypothermia)
LFTs for hepatotoxicity (#1 AE)
Ammonia levels
What can you add in refractory cases of SZP or agitation?
VPA
What are the 4 Pearls?
- ** SGAs Elderly >65 = higher risk of death from heart issues**
- SGAs - Metabolic syndrome, esp in >65
- Avoid in pregnancy, esp 3rd trimester
- Aripiprazole is not a PPI.
What is the relationship between DA and prolactin?
DA hates prolactin. So some antipsychotics can cause hyperprolactinemia (decreased DA = increased prolactin)
Which SGAs carry the highest and lowest of hyperprolactinemia?
Highest - Risperidone, Paliperidone
Lowest - Quetiapine
Which SGAs have the highest and lowest risk of EPS?
Highest - Lurasidone (little anticholinergic properties) Higher risk at higher doses - R and P Low Risk - COQA Clozapine Olanzapine Quetiapine Aripiprazole
Which SGAs have the highest and lowest risk of metabolic AEs - weight gain, DM, dyslipidemia?
High risk - Clozapine, Olanzapine
Mild risk - Quetiapine, R and P
Low risk - Lurasidone, Aripiprazole
What are the other 2 SGA that we did not discuss?
Ziprasidone
Asenapine
