Transcript CASE 7 - Caangay.com

CASE 7
CHEN,CHUN-HUANG(ALEX)
Juanita is 45 years old and has been
admitted at the Half Way Center(a
psychiatric center) for seven time.She
had been diagnosed as a case of
schizophrenia.She has a number of
medication namely:
Chlorpromazine(Thorazine)50mg.b.i.d.
Flurazepam(dalmane)30mg.h.s.
Fluphenazine decanoate(phlufdek)25mg.IM
twice a month
Schizophrenia
 is a psychiatric diagnosis that describes a
mental disorder characterized by
impairments in the perception or
expression of reality and by significant
social or occupational dysfunction. A
person experiencing schizophrenia is
typically characterized as demonstrating
disorganized thinking, and as
experiencing delusions or hallucinations,
in particular auditory hallucinations.
Diagnosis
 the diagnosis of schizophrenia is based
upon the behavior of the person being
assessed. There is a list of criteria that
must be met for someone to be so
diagnosed. These depend on both the
presence and duration of certain signs
and symptoms.
The most commonly used
criteria for diagnosing
schizophrenia are from the
 American Psychiatric Association's
Diagnostic
 Statistical Manual of Mental Disorders
(DSM)
 World Health Organization's International
Statistical Classification of Diseases
 Related Health Problems (ICD)
Characteristic symptoms
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delusions
hallucinations
disorganized speech
grossly disorganized behavior
negative symptoms
Social/occupational dysfunction
Duration: Continuous signs of the
disturbance persist for at least six months.
 Only one Criterion A symptom is required if
delusions are bizarre or hallucinations
consist of hearing one voice participating
in a running commentary of the patient's
actions or of hearing two or more voices
conversing with each other
 These depend on both the presence and
duration of certain signs and symptoms.
Data from a PET suggests that the less the frontal lobes
are activated (red) during a working memory task, the
greater the increase in abnormal dopamine activity in the
striatum (green), thought to be related to the
neurocognitive deficits in schizophrenia.
Brain function
 functional differences in brain activity
have shown that differences seem to
most commonly occur in the frontal lobes,
hippocampus, and temporal lobes.These
differences are heavily linked to the
neurocognitive deficits which often occur
with schizophrenia, particularly in areas
of memory, attention, problem solving,
executive function and social cognition.
Neurochemical
 "dopamine hypothesis of schizophrenia“ proposed that a
malfunction involving dopamine pathways was therefore
the cause of (the positive symptoms of) schizophrenia.
This theory is now thought to be overly simplistic as a
complete explanation, partly because newer antipsychotic
medication (called atypical antipsychotic medication) can
be equally effective as older medication (called typical
antipsychotic medication), but also affects serotonin
function and may have slightly less of a dopamine blocking
effect. In addition dopamine pathway dysfunction has not
been reliably shown to correlate with symptom onset or
severity.
mesolimbic pathway :
Particular focus has been placed upon
the function of dopamine in the
mesolimbic pathway of the brain. This
focus largely resulted from the accidental
finding that a drug group which blocks
dopamine function, known as the
phenothiazines, , could reduce psychotic
symptoms.
NMDA glutamate receptor:
This has largely been suggested by
abnormally low levels of glutamate
receptors found in postmortem brains of
people previously diagnosed with
schizophreni
and the discovery that the glutamate blocking drugs
such as phencyclidine and ketamine can mimic the
symptoms and cognitive problems associated with
the condition.
The fact that reduced glutamate function is linked
to poor performance on tests requiring frontal lobe
and hippocampal function and that glutamate can
affect dopamine function, all of which have been
implicated in schizophrenia, have suggested an
important mediating role of glutamate pathways in
schizophrenia.
Chlorpromazine
was the first antipsychotic drug, used during
the 1950s and 1960s. Used as
chlorpromazine hydrochloride and sold under
the tradenames Largactil® and Thorazine®,
it has sedative, hypotensive and antiemetic
properties as well as anticholinergic and
antidopaminergic effects. It also has
anxiolytic (alleviation of anxiety) properties.
Today, chlorpromazine is considered a typical
antipsychotic.
Mechanism of action
Central
Chlorpromazine acts as an antagonist
(blocking agent) on different postsynaptic
receptors .
1. opaminergic-receptors: D1, D2, D3 ,D4
2. serotonergic-receptors:5-HT1 and 5-HT2
3. histaminergic-receptors:H1-receptors
4. alpha1/alpha2-receptors
5. muscarinic (cholinergic): M1/M2-receptors
Peripheral
1. Antagonist to H1 receptors
2. H2 receptors (reduction of forming of gastric
juice)
3. M1/M2-receptors (dry mouth, reduction in
forming of gastric juice)
4. 5-HT receptors (different antiallergic/gastrointestinal actions).
The use of chlorpromazine has been primarily
replaced by newer generation of atypical
antipsychotics which have an improved side effect
profile. Treatment of both acute and chronic
psychoses, including schizophrenia and the manic
phase of manic depression as well as amphetamineinduced psychoses.
Dosage
 A wide range is covered from 25 mg oral
or intramuscular for mild sedation, every
8 hours, up to 100 mg every 6 hours for
severely ill patients. Different qualified
sources give 800 mg/day to 1,200
mg/day as highest dose.
Side effects
 Side effects of chlorpromazine are typical
of early generation neuroleptics. They
include extrapyramidal side effects such
as tardive dyskinesia and akathisia. A
particularly severe side effect is the
neuroleptic malignant syndrome which
occurs in approximately 0.05% and can
be fatal .
Flurazepam
 (marketed under the brand names
Dalmane® and Dalmadorm®) is a drug
which is a benzodiazepine derivative. It
possesses anxiolytic, anticonvulsant,
sedative and skeletal muscle relaxant
properties.
Has the longest half-life of all of the
benzodiazepines (40-250 hours), and may stay in
the bloodstream for up to four days.
It is used for short-term treatment of patients with
insomnia.
The most common adverse effects are dizziness,
drowsiness, lightheadedness and ataxia.
Fluphenazine
 typical antipsychotic drug used for the
treatment of psychoses such as
schizophrenia and acute manic phases of
bipolar depression. It belongs to the
piperazine class of phenothiazines and is
extremely potent; more potent than
haloperidol and around fifty to seventy
times the potency of chlorpromazine.
Pharmacokinetics
 Fluphenazine has an incomplete oral
bioavailability of 40% to 50% (due to
extensive first pass metabolization in the
liver). Its half life is 15 to 30 hours.
Side effects
 Most common are extrapyramidal side
effects, including tardive dyskinesia. The
frequency and severity of extrapyramidal
side effects are direct proportional to the
dose given and the duration of treatment.
 (sedation, hypotension, anticholinergic
effects like dry mouth, blurred vision etc.)
also vary with the dose given.
THANKS