Gibbs Antipsychotics Flashcards
positive symptoms
delusions
hallucinations
disorganized speech
unusual behavior
psychomotor agitation
negative symptoms
flat affect
poverty of speech (alogia)
lack of energy
lack of interest
social withdrawal
avolition (inability to follow through with activities)
anhedonia (lack of pleasure)
cognitive symotoms
attention
memory
executive dysfunction
skill acquisition
mood symptoms
depression
anxiety
aggression
hostility
hopelessness
suicidality
occupational and social dysfunction
social isolation
unemployment
poor relationships
poor self care
schizophrenia definition
a debilitating disease of neuronal connectivity and function in which patients experience and interpret reality abnormally
schizophrenia epidemiology
no gender, racial differences
strong genetic component
difference of age onset in males vs females
males 17-27
females 20-37
schizophrenia cost to society
very high
mostly indirect costs
initial diagnostic presentation of schizophrenia
positive symptoms
early onset means ___ prognosis
worse
women tend to have ___ onset and ___ prognosis
later onset, better prognosis
life expectancy schizophrenia
may be reduced 20-30 years
DSM-V diagnostic criteria for schizophrenia
at least two of the following for over a month: delusion, hallucination, disorganized speech, disorganized behavior, negative symptoms
ONE OF THE TWO MUST INCLUDE DELUSION, HALLUCINATION, DISORGANIZED SPEECH
must cause social dysfunction
symptoms for at least 6 months
rule out schizoaffective, mood disorder, substance use
1 cause of premature death in schizophrenia
suicide
suicide risk is ___ higher than the general population
50X
schizophrenia therapeutic phases
acute, stabilization, maintenance
goals of acute phase
reduce acute symptoms, reduce threat to self or others
goals of stabilization phase
minimize, prevent symptom relapse
optimize therapeutic dose & minimize side effects
goals of maintenance phase
improve functioning, QOL
monitor for prodrome and adverse effects
promote medication compliance
classes of FGAs
phenothiazines, thioxanthenes, butyrophenones
phenothiazines
chlorpromazine, promazine
trifluopromazine
fluphenazine
perphenazine
thioridazine
mesoridazine
chlorpromazine dose
200-900 mg/day
LOW POTENCY
chlorpromazine side effects
sedation, hypotension due to alpha1 adrenergic blockade
EPS due to dopamine D2 receptor blockade in basal ganglia
thioxanthenes
thiothixene
flupentixol
butyrophenones
haloperidol
droperidol
benperidol
haloperidol dose
5-40 mg/day
HIGH POTENCY
haloperidol side effects
significant EPS
all of the FGAs mechanistically act as ___
antagonist at dopamine receptors
also bind with varying degrees of potency to 5HT, cholinergic, histamine receptors
antipsychotic binding to __ receptors correlates with clinical potency
D2
dopamine hypothesis
excessive dopaminergic activity underlies schizophrenia
3 key points to know for FGAs
1) efficacy correlates w/ D2 blockade
2) alleviate mainly positive symptoms
3) high risk of EPS and tardive dyskinesia with high dose, long term use
modified dopamine hypothesis
schizophrenia is associated with hyperdopamine function in the subcortical regions of the brain (positive symptoms) and hypodopamine function in the prefrontal cortex (negative symptoms)
serotonin hypothesis
hallucinogens (LSD) are 5HT2a agonists
atypical antipsychotics are inverse 5HT2a agonists
5HT2a receptors modulate DA release
risperidone/olanzapine (5HT2a blocking activity) have greater efficacy for treating NEGATIVE SYMPTOMS/produce fewer EPS
glutamate hypothesis
NMDAR antagonists (PCP, ketamine) produce sensory hallucinations
changes in glutamate receptor binding found in brains of subjects with schizophrenia
reduced NMDA receptor binding in med-free patients (chronic overactivation of the receptors)
4 defining features of SGAs
1) block more than one type of receptor
2) greater affinity for serotonin receptors
3) more effective at alleviating negative symptoms than FGAs, improve cognitive function
4) less movement disordersS
SGAs (drug names)
clozapine
risperidone
olanzapine
quetiapine
ziprasidone
paliperidone
asenapine
iloperidone
clozapine is associated with
significant risk of neutropenia (loss of neutrophils) which can develop into agranulocytosis (loss of WBCs)
requires extensive blood monitoring
third generation agent?
aripiprazole
aripiprazole mechanism
acts as D2 partial agonist (instead of antagonist)
stabilizes dopamine hyperactivity and hypoactivity
aripiprazole is an antagonist where ___
DA levels high (limbic regions)
aripiprazole is an agonist where ___
DA levels low (prefrontal cortex)
aripiprazole is also involved in serotonin receptors how
partial agonist 5HT1a
antagonist 5HT2a
many side effects of antipsychotics
EPS
metabolic
cardiac
endocrine
adrenergic
anticholinergic
antihistaminergic
akathisia
neuroleptic malignant syndrome
EPS
parkinsonism, dystonias, tardive dyskinesia
metabolic effects
weight gain, hyperglycemia, dyslipidemia, diabetes
cardiac effects
QT prolongation
endocrine effects
hyperprolactinemia
gynecomastia men, amenorrhea women
adrenergic effects
orthostatic hypotension
anticholinergic effects
dry eye, dry mouth, constipation, blurred vision, cognitive impairment
antihistaminergic effects
weight gain, sedation
akathisia
feeling of internal restlessness
neuroleptic malignant syndrome
muscular rigidity, fever, severe EPS, potentially fatal
definition of extrapyramidal side effects
movement disorders caused by D2 receptor blockage in the extrapyramidal motor system
referred to as pseudoparkinsonism
tardive dyskinesia definition
severe abnormal movements, typically involve face, neck, tongue
