Antipsychotic drugs-Kirkpatrick Flashcards
What are appropriate uses for antipsychotics?
Psychosis
Non-psychotic mania
Autism
Adjunct to antidepressants
What are other common uses for antipsychotics?
Behavioral problems in patients with dementia (2nd or 3rd line only)
Delirium ((2nd or 3rd line only)
What is the dopamine theory of schizophrenia?
Psychosis=schizophrenia=dopamine dysregulation
Antipsychotic meds are all dopamine (blank) or (blank) and dopamine receptor binding has a strong correlation with (blank).
anatagonists
partial agonists
clinical dose
T or F
Patients’ responses to antipsychotics are highly variable; some don’t respond at all
T
Psychotic symptoms have a transient increase with infusion of low doses of what three things?
Ketamine (an NMDA antagonist)
MCPP (a sertonin agonist)
Cannabis
What are the 2 dopamine pathways?
When you give block dopamine receptors how does it effect these pathways?
mesocorticolimbic-antipsychotic efficacy
nigrostrital- extrapyramidal side effects
what are the functions of the dopamine pathway?
- reward (motivation)
- pleasure, euphoria
- motor function (fine tuning)
- compulsion
- Perservation
What are the functions of the serotonin pathways?
- mood
- memory processing
- sleep
- cognition
What are the commonly use first generation drugs antipsychotics?
Which ones have a depot formulation?
- fluphenazine
- perphenazine
- trifluoperazine
- haloperidol (haldol)
Haloperidol and fluphenazine
What are the five most commonly used 2nd generation antipsychotics?
Which ones have a depot formulation?
Aripiprazole Olanzapine Quetiapine Risperidone Ziprasidone
-aripiprazole olanzapine, risperidone
What is the mechanism of action of all antispychotics except for one? Which one is the exception and how does it work?
They are all dopamine antagonists
Aripiprazole (abilify)-> partial dopamine agonist
Why dont you use the depot formulation of olanzapine?
Because it causes hypotension
Which 2 antipsychotics cause the most weight gain?
Clozapine and olanzapine
T or F
all of the 2nd generation drugs have superior efficacy, especially for negative symptoms
FALSE
-improvement in neg sx is due to improvement in other psychiatric symptoms and/or motor side effects
T or F
2nd generation drugs have no risk of EPS
False!!
it varies by drug and is dose related
T or F
If a patient’s psychotic symptoms havent responed you should raise the dose
F
T or F
if a patient has particularly severe psychotic symptoms, he or she needs a higher dose
F
T or F
If a patient has symptoms in the grey zone b/w odd experiences and clearcut psychosis, you should give a lower dose than usual
F
How do all antipsychotics look on a dose-response curve?
they have an exponential increase and then plateau (efficacy does not increase past this point, in fact it drops)
What antipsychotic is th e most effective but has the most side effects?
Clozapine
What is the class I antipsychotic?
Clozapine
What is the class II antipsychotic?
Risperidone and Olanzapine
What is the class III antipsychotic?
Everything else (zotepine, amisulpride, aripiprazole, sertindole, quietiapine, ziprasidone, remoxipride)
What is the major side effect of clozapine? Is this reversible? When will it most likely occur? How do you keep an eye out for it?
Agranulocytosis (bone marrow suppression)
Yes
in the first year (about 1%)
Blood draws
What are all the SEs of clozapine?
- agranylocytosis
- sustained tachycardia
- weight gain
- orthostatic hypotension
- hypersalivation
- sedation
What are extrapyramidal side effects?
- Rigidity
- Tremor
- Bradykinesia
- Hypersalivation
- Neuroleptic Malignant Syndrome
- Akathisia
What is the treatment for EPS?
decrease dose, change medication Anticholinergic drug: -diphenydramine (benadryl) -trihexiphenidyl (artane) -benzotropine (cogentin) Amantadine
These will remedy everything except for akathisia
What is the only symptom of EPS that cannot be remedied by amantadine or anticholinergic drugs?
akathisia
How do you treat akathisia?
-change meds
-beta blockers (propranolol)
-maybe high doses of B6
-maybe clonazepam
NOT ANTICHOLINERGICS
A study was done comparing the rate of antipsychotic medication discontinuation with 1st generation vs 2nd generation antipsychotics, which class was discontinued more and why?
both were discontinued equally due to SEs
What is this:
syndrome of involuntary choreo-athethoid movements, not just the mouth and face
tardive dyskinesia
Tardive dyskinesia is a SE of (blank) generation antipsychotics and is (blank and blank)-related
first
dose and time
What ethinicity and gender is most susceptible to tardive dyskinesia?
Male gender, AA
If you stop the medication that is inducing tardive dyskinesia what will happen?
you will get transient worsening and then you may or may not get improvement
What movement disorder may be a risk factor for tardive dyskinesia?
Akathesia
Which is drug puts you at higher risk of developing tardive dyskinesia; haloperidol or olanzapine?
Haloperidol
What is the only antipsychotic drug that caused weight loss?
Olindone (moban)
Weight gain in schizophrenics is iatrogenic (caused by physicians) cuz that antipsychotics make you gain weight! How do we know this?
cuz schizophrenia is associated with smaller BMI, shorter and skinner people w/out tx
How do you treat weight gain?
- change meds
- decrease dose
- exercise
- nutritional counseling
- metformin
If you block D2 receptors, what are the side effects?
EPS, prolactin elevation
If you block M1 receptors, what are the side effects?
Cognitive deficits, dry mouth, constipation, increased heart rate urinary retention, blurred vision
If you block H1 receptors what are the side effects?
sedation, weight gain, dizziness
If you block the alpha 1 receptors what are the side effects?
hypotension
If you block the 5-HT2A receptors what are the side effects?
anti-EPS
If you block the 5-HT2c receptors what are the side effects?
satiety blockade
Why are secondary generation drugs considered better than first generation drugss?
cuz they block the 5-HT2A receptor thus inducing ANTI-EPS side effects YAY
What is the QT interval?
What happens if the interval is increased?
measure of the time between the start of the Q wave and the end of the T wave in EKG
-the electrical depolarization and repolarization of the ventricles
-its a risk factor for ventricular tachyarrhytmias (especially torsades de pointes) AND sudden death
A normal QT wave depends on a (blank). How do you correct a QT wave for differences in heart rate?
What is a normal QTc?
- heart rate
- The QTC (estimates QT interval at a heart rate of 60bpm)
- less than 400 ms
There is a risk of sudden death with a QTc of.... Borderline for males? Abnormal for males? Borderline for females? Abnormal for females?
431-450
>450
451-470
>470
What are risk factors for increased QTc?
- hypokalemia
- hypomagnesemia
- hypocalcemia
- medications
What 2 antipsychotics can cause increased QTC and by how much?
4 ms for risperidone
30 ms for thioridazine
In dementia what are some behavioral problems associated with it?
psychosis, agitation, suspiciousness, irritability
How do you treat dementia often times?
How well does this work?
-antipsychotics and benzodiazepines
short term-> may work
Long term-> danger and ineffective
Treating dementia with Benzos can result in what two serious side effects?
How should you treat dementia instead?
increased confusion
falls
-psychosocial interventions, especially managing environmental cues (including social interactions) should be the first step
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of (blank). (blank) is not approved for the tx of patients with dementia-related psychosis
death.
Olanzapine (zyprexa)
What is a drug you should use instead of a antipsychotic in the treatment of dementia related psychosis and why? When cant you use this
citalopram -> has equal efficacy to risperidone
May not work in vascular dementia
IV Haloperidol increases the risk of (blank).
QTc prolongation
Drug-induced long QT and arrhythmia propensity substantially increase when specific psychotropic drugs are administered to patients with (blank X 4)
hypokalemia, abnormal T wave morphology, HCV infection, and HIV infection.
What atypical antipsychotic results in a lot of sedation and how is this drug taken?
asenapine-> sublingually
does lurasidone effect the QT interval?
no
Among antipsychotics, (blank) remains the agent most associated with QTc prolongation; intravenous (blank) also appears to carry an increased risk. Of the atypical antipsychotics, (blank) appears most likely to prolong the QTc interval.
Which SSRI causes prolonged QTc?
thioridazine
haloperidol
ziprasidone
Citalopram
