CASE 7CASE 7

CHEN,CHUN-HUANG(ALEX)CHEN,CHUN-HUANG(ALEX)

Juanita is 45 years old and has been admitted Juanita is 45 years old and has been admitted at the Half Way Center(a psychiatric center) fat the Half Way Center(a psychiatric center) for seven time.She had been diagnosed as a caor seven time.She had been diagnosed as a case of schizophrenia.She has a number of medise of schizophrenia.She has a number of medication namely:cation namely:

Chlorpromazine(Thorazine)50mg.b.i.d. Chlorpromazine(Thorazine)50mg.b.i.d. Flurazepam(dalmane)30mg.h.s. Flurazepam(dalmane)30mg.h.s. Fluphenazine decanoate(phlufdek)25mg.IM twice a Fluphenazine decanoate(phlufdek)25mg.IM twice a monthmonth

SchizophreniaSchizophrenia

is a psychiatric is a psychiatric diagnosis diagnosis that describes a that describes a mental disorder characterized by mental disorder characterized by impairments in the perception or impairments in the perception or expression of reality and by significant expression of reality and by significant social or occupational dysfunction. A social or occupational dysfunction. A person experiencing schizophrenia is person experiencing schizophrenia is typically characterized as demonstrating typically characterized as demonstrating disorganized thinking, and as experiencing disorganized thinking, and as experiencing delusions or hallucinations, in particular delusions or hallucinations, in particular auditory hallucinations.auditory hallucinations.

DiagnosisDiagnosis

the diagnosis of schizophrenia is based the diagnosis of schizophrenia is based upon the behavior of the person being upon the behavior of the person being assessed. There is a list of criteria that assessed. There is a list of criteria that must be met for someone to be so must be met for someone to be so diagnosed. These depend on both the diagnosed. These depend on both the presence and duration of certain signs presence and duration of certain signs and symptoms. and symptoms.

The most commonly used The most commonly used criteria for diagnosing criteria for diagnosing schizophrenia are from the schizophrenia are from the

American Psychiatric Association's American Psychiatric Association's Diagnostic Diagnostic

Statistical Manual of Mental Disorders Statistical Manual of Mental Disorders (DSM) (DSM)

World Health Organization's International World Health Organization's International Statistical Classification of Diseases Statistical Classification of Diseases

Related Health Problems (ICD) Related Health Problems (ICD)

Characteristic symptomsCharacteristic symptoms

delusionsdelusions hallucinationshallucinations disorganized speech disorganized speech grossly disorganized behavior grossly disorganized behavior negative symptoms negative symptoms Social/occupational dysfunction Social/occupational dysfunction Duration: Continuous signs of the Duration: Continuous signs of the

disturbance persist for at least six months. disturbance persist for at least six months.

Only one Criterion A symptom is required Only one Criterion A symptom is required if delusions are bizarre or hallucinations if delusions are bizarre or hallucinations consist of hearing one voice participating consist of hearing one voice participating in a running commentary of the patient's in a running commentary of the patient's actions or of hearing two or more voices actions or of hearing two or more voices conversing with each otherconversing with each other

These depend on both the presence and These depend on both the presence and duration of certain signs and symptoms. duration of certain signs and symptoms.

Data from a Data from a PETPET suggests that the less the suggests that the less the frontal lobesfrontal lobes are activ are activated (red) during a ated (red) during a working memoryworking memory task, the greater the increa task, the greater the increase in abnormal se in abnormal dopaminedopamine activity in the activity in the striatumstriatum (green), thoug (green), thoug

ht to be related to the ht to be related to the neurocognitiveneurocognitive deficits deficits in schizophrenia. in schizophrenia.

Brain functionBrain function

functional differences in brain activity have functional differences in brain activity have shown that differences seem to most comshown that differences seem to most commonly occur in the frontal lobes, hippocammonly occur in the frontal lobes, hippocampus, and temporal lobes.These differences pus, and temporal lobes.These differences are heavily linked to the neurocognitive defare heavily linked to the neurocognitive deficits which often occur with schizophrenia, icits which often occur with schizophrenia, particularly in areas of memory, attention, particularly in areas of memory, attention, problem solving, executive function and soproblem solving, executive function and social cognition. cial cognition.

Neurochemical Neurochemical "dopamine hypothesis of schizophrenia“ "dopamine hypothesis of schizophrenia“ proposed that a mproposed that a m

alfunction involving dopamine pathways was therefore the alfunction involving dopamine pathways was therefore the cause of (the positive symptoms of) schizophrenia. This thcause of (the positive symptoms of) schizophrenia. This theory is now thought to be overly simplistic as a complete eeory is now thought to be overly simplistic as a complete explanation, partly because newer antipsychotic medication xplanation, partly because newer antipsychotic medication (called atypical antipsychotic medication) can be equally ef(called atypical antipsychotic medication) can be equally effective as older medication (called typical antipsychotic mefective as older medication (called typical antipsychotic medication), but also affects serotonin function and may have dication), but also affects serotonin function and may have slightly less of a dopamine blocking effect. In addition dopaslightly less of a dopamine blocking effect. In addition dopamine pathway dysfunction has not been reliably shown to cmine pathway dysfunction has not been reliably shown to correlate with symptom onset or severity. orrelate with symptom onset or severity.

mesolimbic pathway :mesolimbic pathway :

Particular focus has been placed upon thParticular focus has been placed upon the function of dopamine in the mesolimbic e function of dopamine in the mesolimbic pathway of the brain. This focus largely rpathway of the brain. This focus largely resulted from the accidental finding that a esulted from the accidental finding that a drug group which blocks dopamine functidrug group which blocks dopamine function, known as the phenothiazines, , could on, known as the phenothiazines, , could reduce psychotic symptoms. reduce psychotic symptoms.

NMDA glutamate receptor:NMDA glutamate receptor:

This has largely been suggested by abnorThis has largely been suggested by abnormally low levels of glutamate receptors foumally low levels of glutamate receptors found in postmortem brains of people previound in postmortem brains of people previously diagnosed with schizophrenisly diagnosed with schizophreni

and the discovery that the glutamate bland the discovery that the glutamate blocking drugs such asocking drugs such as phencyclidine phencyclidine and and ketamineketamine can mimic the symptoms and can mimic the symptoms and cognitive problems associated with the cognitive problems associated with the condition.condition.

The fact that reduced glutamate functioThe fact that reduced glutamate function is linked to poor performance on tests n is linked to poor performance on tests requiring frontal lobe and hippocampal requiring frontal lobe and hippocampal function and that glutamate can affect function and that glutamate can affect dopamine dopamine function, all of which have befunction, all of which have been implicated in schizophrenia, have suen implicated in schizophrenia, have suggested an important mediating role of ggested an important mediating role of glutamate pathways in schizophreniaglutamate pathways in schizophrenia..

ChlorpromazineChlorpromazine

was the first antipsychotic drug, used during twas the first antipsychotic drug, used during the 1950s and 1960s. Used as chlorpromazinhe 1950s and 1960s. Used as chlorpromazine hydrochloride and sold under the tradename hydrochloride and sold under the tradenames es Largactil®Largactil® and and Thorazine®Thorazine®, it has sedati, it has sedative, hypotensive and antiemetic properties as ve, hypotensive and antiemetic properties as well as anticholinergic and antidopaminergic well as anticholinergic and antidopaminergic effects. It also has anxiolytic (alleviation of aneffects. It also has anxiolytic (alleviation of anxiety) properties. Today, chlorpromazine is coxiety) properties. Today, chlorpromazine is considered a typical antipsychotic. nsidered a typical antipsychotic.

Mechanism of actionMechanism of action

CentralCentralChlorpromazine acts as an Chlorpromazine acts as an antagonistantagonist (block (block

ing agent) on different postsynaptic recepting agent) on different postsynaptic receptors .ors .

1. opaminergic-receptors: D1, D2, D3 ,D4 1. opaminergic-receptors: D1, D2, D3 ,D4 2. serotonergic-receptors:5-HT1 and 5-HT2 2. serotonergic-receptors:5-HT1 and 5-HT2 3. histaminergic-receptors:H1-receptors 3. histaminergic-receptors:H1-receptors 4. alpha1/alpha2-receptors 4. alpha1/alpha2-receptors 5. muscarinic (cholinergic): M1/M2-receptors 5. muscarinic (cholinergic): M1/M2-receptors

PeripheralPeripheral1. Antagonist to H1 receptors1. Antagonist to H1 receptors2. H2 receptors (reduction of forming 2. H2 receptors (reduction of forming of gastric juice)of gastric juice) 3. M1/M2-receptors (dry mouth, 3. M1/M2-receptors (dry mouth, reduction in forming of gastric reduction in forming of gastric juice) juice) 4. 5-HT receptors (different anti-4. 5-HT receptors (different anti-

allergic/gastrointestinal actions).allergic/gastrointestinal actions).

The use of chlorpromazine has been priThe use of chlorpromazine has been primarily replaced by newer generation of marily replaced by newer generation of atypical antipsychotics which have an iatypical antipsychotics which have an improved side effect profile. Treatment mproved side effect profile. Treatment of both acute and chronic psychoses, inof both acute and chronic psychoses, including schizophrenia and the manic phcluding schizophrenia and the manic phase of manic depression as well as ampase of manic depression as well as amphetamine-induced psychoses.hetamine-induced psychoses.

DosageDosage

A wide range is covered from 25 mg oral A wide range is covered from 25 mg oral or intramuscular for mild sedation, every or intramuscular for mild sedation, every 8 hours, up to 100 mg every 6 hours for 8 hours, up to 100 mg every 6 hours for severely ill patients. Different qualified severely ill patients. Different qualified sources give 800 mg/day to 1,200 sources give 800 mg/day to 1,200 mg/day as highest dose. mg/day as highest dose.

Side effectsSide effects

Side effects of chlorpromazine are typical Side effects of chlorpromazine are typical of early generation neuroleptics. They incof early generation neuroleptics. They include extrapyramidal side effects such as tlude extrapyramidal side effects such as tardive dyskinesia and akathisia. A particuardive dyskinesia and akathisia. A particularly severe side effect is the larly severe side effect is the neuroleptic neuroleptic malignant syndromemalignant syndrome which occurs in appr which occurs in approximately 0.05% and can be fatal .oximately 0.05% and can be fatal .

FlurazepamFlurazepam

(marketed under the brand names (marketed under the brand names DalmaDalmanene® and ® and DalmadormDalmadorm®) is a drug which i®) is a drug which is a benzodiazepine derivative. It possesss a benzodiazepine derivative. It possesses anxiolytic, es anxiolytic, anticonvulsant, sedative ananticonvulsant, sedative and skeletal muscle relaxantd skeletal muscle relaxant properties. properties.

Has the longest half-life of all of the Has the longest half-life of all of the benzodiazepines (40-250 hours), and benzodiazepines (40-250 hours), and may stay in the bloodstream for up to may stay in the bloodstream for up to four days.four days.It is used for short-term treatment of It is used for short-term treatment of patients with insomnia.patients with insomnia.The most common adverse effects are The most common adverse effects are dizziness, drowsiness, lightheadedness dizziness, drowsiness, lightheadedness and ataxiaand ataxia..

FluphenazineFluphenazine

typical antipsychotictypical antipsychotic drug used for the tre drug used for the treatment of psychoses such as schizophreatment of psychoses such as schizophrenia and acute manic phases of bipolar denia and acute manic phases of bipolar depression. It belongs to the pression. It belongs to the piperazinepiperazine clas class of s of phenothiazinesphenothiazines and is extremely pote and is extremely potent; more potent than haloperidol and arount; more potent than haloperidol and around fifty to seventy times the potency of chnd fifty to seventy times the potency of chlorpromazine.lorpromazine.

PharmacokineticsPharmacokinetics

Fluphenazine has an incomplete oral bioFluphenazine has an incomplete oral bioavailability of 40% to 50% (due to extensiavailability of 40% to 50% (due to extensive first pass metabolization in the liver). Itve first pass metabolization in the liver). Its half life is 15 to 30 hours. s half life is 15 to 30 hours.

Side effectsSide effects

Most common are Most common are extrapyramidalextrapyramidal side eff side effects, including ects, including tardivetardive dyskinesiadyskinesia. The fre. The frequency and severity of extrapyramidal sidquency and severity of extrapyramidal side effects are direct proportional to the doe effects are direct proportional to the dose given and the duration of treatment. se given and the duration of treatment.

(sedation, hypotension, (sedation, hypotension, anticholinergicanticholinergic eff effects like dry mouth, blurred vision etc.) alects like dry mouth, blurred vision etc.) also vary with the dose given. so vary with the dose given.

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