Exam 3 - Schizophrenia (Watts/Ott) Flashcards
what are the positive symptoms
hallucinations
delusions
bizarre behavior
thought disorders
what are the negative symptoms
blunted emotion
poor self care
social withdrawal
poverty in speech
Cognitive symptoms involve ______ receptors and _____ receptors
D1 receptors; Glutamate Receptors
what neurotransmitters are to be involved in schizophrenia
dopamine
serotonin
glutamate
do positive or negative symptoms respond better to drug therapy
positive!
negative has like no response
what 5HT receptor is known as the mediator for hallucinations
5HT 2A
5HT2A receptors modulate _______ release in the cortex, limbic region, and striatum
dopamine
5HT2A receptors modulate dopamine release in what area?
cortex, limbic region, and striatum
5HT2A receptors modulate _______ release and ______ receptors
glutamate; NMDA
what kind of agents can exacerbate symptoms of schizophrenia
dopaminergic
L-DOPA, Amphetamine, Bromocriptine
what is the major receptor antagonized by antipsyhchotics
dopamine!
MAINLY D2
newer antipsychotics also antagonize what receptor?
serotonin
what are other (aka minor) receptors that antipsychotics antagonize?
NE, ACh, Histamine
most antipsychotic drugs are (agonist, partial agonist, or antagonist?)
Antagonist!!
D1 or D2 receptors have more correlation b/w binding potency and clinical effectiveness
D2!!
when D2 antagonism occurs in the basal ganglia — what effects are seen?
EPS/motor effects
what are symptoms of EPS
dystonia
pseudoparkinsonism
tremor
aktahisia
what is akathisia
restlessness
what is dystonia
increase muscle tone
are EPS symptoms form antipsychotics reversible?
yes
when do EPS symptoms occur when an antipsychotic is started
days to weeks
early on!
what are symptoms of tardive dyskinesia?
rhythmic involuntary movements
irregular purposelessness
athetoid (worm like)
axial hyperkinesias (to and fro)
are tardive dyskinesia symptoms form antipsychotics reversible?
no!
when do tardive dyskinesia symptoms occur when an antipsychotic is started
later!
months to a year
what is NMS side effect from antipsychotic?
neuroleptic malignant syndrome
serious/rapid (fatality)
(EPS + Fever)
Antipsychotic drugs take about how long for effectiveness?
2- 3 weeks
Antipsychotic drugs take about how long for maximal effectiveness
6 weeks to 6 months…
ADE’s of Antipsychotics: Autonomic
when Muscarinic cholinoreceptors are blocked what are the manifestations?
dry mouth
difficulty urinating
constipation
loss of accommodation (eye)
ADE’s of Antipsychotics: Autonomic
when alpha adrenergic blockade occurs what are the manifestations?
orthostasis hypotension
impotence
failure to ejaculate
ADE’s of Antipsychotics: CNS
when dopamine receptor blockade occurs — what are the manifestations?
parkinson’s syndrome
aktahasia
dystonia
ADE’s of Antipsychotics: CNS
if supersensitvity of dopamine receptors occur — what is the manifestation?
tardive dyskinesia
ADE’s of Antipsychotics: CNS
if muscarinic blockade happens - what is the manifestation? (CNS!!*)
toxic - confusional state
ADE’s of Antipsychotics: CBS
if histamine receptors are blocked - what is the clinical manifestation?
sedation
ADE’s of Antipsychotics: Endocrine System
what is the manifestation when dopamine receptors are blocked (causing hypoerprolactonemia)
ameorrhea
galactorhea
infertility
impotence
ADE’s of Antipsychotics:
when combined H1 and 5HT(2C) blockade occurs — what is the manifestation
weight gain
which drug was the first typical antipsychotic?
chlorpromazine
Key Points for Chlorpromazine?
Watts Table
1st antipsychotic
antihistamine side effects
Key Points for Promethazine
Watts Table
antihistamine
antiemetic
Key Points for Thioridazine
Watts Table
Anticholinergic
sedation
sexual dysfunction
cardiovascular
Key Points for Fluephenazine
Watts Table
EPS
Key Points for Prochlorperazine
Watts Table
Antiemetic
Key Points for Perphenazine
Watts Table
CATIE Studies =
Combo w/ anticholinergic vs newer agents
Key Points for Thiothixene
Watts Table
modest EPS
Key points for haloperidol
Watts Table
EPS
Key Points for Molindone
Watts Table
moderate EPS
Key Points for Pimozide
Watts Table
used for tourette’s disease, suppress motor and vocal tics
what drug was the first atypical antipsychotic
clozapine
biggest side effect with clozapine
agranulocytosis
Clozapine & Agranulocytosis
occurs when?
1 -2 % get it first 6 mos
why is aripiprazole’s MOA so different?
partial agonist at 5HT(1A) (and D2?)
aka a receptor involved in depression
what drugs are partial D2/D3 agonist
Brexpiprazole
Cariprazine
key points for clozapine (watts table)
1st atypical antipsychotic
agranulocytosis
risk of diabetes
key points for Olanzapine (watts table)
weight gain
risk of diabetes
key points for quetiapine (watts table)
metabolite w/ antidepressant activity
hypotension
sedation
key points for risperdone (watts table)
5HT2A/D2 receptor antagonist
key points for ziprasidone (watts table)
5HT2A/D2/alpha1 affinity
prolongs QT interval
key points for Lurasidone (watts table)
5HT2A/D2
reduced metabolic effects
rapid titration
key points for Aripiprazole (watts table)
high 5HT2A/D2 affinity
partial agonist activity
Key Features that define psychotic disorders
delusions hallucinations disorganized thinking disorganized abnormal motor behavior negative
what drugs can hasten the onset of schizophrenia/exacerbate symptoms, AND reduce time to relapse
marijuana
cocaine
amphetamines
oral antipsychotic therapy or IM depot drug treatment is first line?
oral is first line
Aripiprazole: long or short half life?
long
Aripiprazole - P450 interactions?
2D6 and 3A4 substrate
T or F: LAIs of Aripriprazole need dosing adjustment if given with 2D6/3A4 inhibitors or 3A4 inducers
truuuue
T or F: Aripiprazole does not need oral overlap with LAI?
FALSE!! need overlap the Ability Maintena and Aristada
Aripiprazole Oral/LAI Overlap:
Abilify Maintena needs ______ overlap
and
Aristada needs _____ overlap
(how long of overlap?)
Maintena: 2 - weeks
Aristada: 3 - weeks
Asenapine:
what formulation only?
sublingual
Asenapine: P450 interaction?
1A2
Asenapine: Clinical Considerations?
QT prolonging
metallic tasta/unit dose packaging
smoking decrease concentration
caffeine can increase concentration
Brexpiprazole: once or twice daily dosing?
once
Brexpiprazole or Aripiprazole?
which one has a higher incidence of akathisia
Aripiprazole
Brexpiprazole: P450 interactions?
2D6 and 3A4 substrate
just like aripiprazole
Brexpiprazole Clinical Considerations?
P450 2D6 or 3A4 substrates
once daily dosing
Max Dose 4 mg (or 3mg if severe hepatic dysfunction or CrCl < 60 mL/min)
Cariprazine: P450?
3A4 substrate
Cariprazine: Max dose?
6 mg QD
Cariprazine: higher doses mean higher risk of _______ but not _______
akathisia risk increases
higher doses does NOT lead to more efficacy
Cariprazine: dose adjustments?
not recommended in severe hepatic impairment or CrCl < 30 mL/min
Side Effects of Clozapine?
AGRANULOCYTOSIS cardiomyopathy hypersalivation hypotension metabolic syndrome QT prolongation constipation sedation
which drugs has to have REMS program
Clozapine
what is the monitoring requirements for Clozapine
ANC weekly x 6 mos
ANC biweekly x 6 mos
then
every 4 weeks forever
Iloperidone ADEs?
boxed warning for QT prolongation
orthostatic hypotension!!
slow dose titration
Iloperidone: once or twice daily dosing?
TWICE Daily!!
Iloperidone P450 interactions?
2D6 and 3A4 substrate
Lurasidone: once or daily dosing?
once daily
usual max dose of Lurasidone
160 mg
for Lurasidone dosing: if moderate hepatic impairment or CrCl < 50 mL/min: max dose?
80 mg
for Lurasidone dosing: if severe hepatic impairment what is the max dose?
40 mg
Olanzapine: once or twice daily dosing?
both..
Olanzapine: best time to take the medication?
bedtime — because sedation
ADEs of olanzapine?
sedation
hyperglycemia/hyperlipidemia
metabolic syndrome
anticholinergic ADEs at higher doses
P450 of Olanzapine?
1A2 substrate
what two meds MUST be taken with food (to improve bioavailability)
Lurasidone
Ziprasidone
what drugs are 1A2 substrates
Olanzapine
Asenapine
Clozapine
which drugs have renal or hepatic dosing adjustments
brexpiprazole
cariprazine
lurasidone
(paliperidone - is renal only)
what drug will have a ghost capsule?
Paliperidone
Paliperidone — what are the IM formulations available?
Invega Sustenna
Invega Trinza
Paliperidone —-
Invega Sustenna given IM every _____ weeks
Invega Trinza given IM every _____ weeks
sustenna: q 4 weeks
trinza: q 12 weeks
Paliperidone —
can only do Invega Trinza if ???
patient has been stable Invega Sustenna 4 stable maintenance doses
Risperidone: has higher risks of what?
EPS and hyperprolactinemia
P450 interaction for risperdone?
2D6
which drug has 2D6 interactions only?
risperidone
Ziprasidone usually ______ dosing but can be ___
usually twice; can be once
Clinical Considerations of Ziprasidone?
twice daily
MUST TAKE WITH FOOD
QT prolongation
Dress warning
what is the drug Pimavanserin used for?
“antipsychotic” for parkinson patients having hallucinations
ADEs for pimavanserin
peripheral edema
confusional states
nausea
rare angioedema
Clozapine and REMS:
patients can start the drug if their ANC level is greater than ________
1500 /uL
what IM drugs are oil based
Fluphenazine
Haloperidol
what drug has to be refrigerated and reconstituted
Risperdal Consta
what drug can have PDSS from IM injection
Zyprexa Relprevv
what is PDSS
post dose delirium sedation syndrome
monitor for 3 hours after dose
4 main types of EPS
Acute Dystonia
Drug Induced Parkinson’s
Akathisia
Tardive Dyskinesia (
how to treat acute dystonia
IM anticholinergic now
can do 50 mg of benadryl
who is at highest risk for acute dystonia
young, black, male
how to treat akathisisa
beta blocker (propranolol) BZD - prn dosing Oral anticholinergic (not too effective) try to lower dose of antipsychotic if possible
how to treat tardive dyskinesia
lower antipsychotic dose if possible,
DO NOT GIVE ANTICHOLINERGICS