CASE 7 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  delusions delusions  hallucinations 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. PETfrontal lobesworking memorydopamine striatum neurocognitive deficitsPETfrontal lobesworking memorydopamine striatum neurocognitive deficits

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 : 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. 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: 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 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. antagonist 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 anti- allergic/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 amphetamine- induced 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 ( 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. piperazinephenothiazines piperazinephenothiazines

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. extrapyramidaltardive dyskinesiaextrapyramidaltardive dyskinesia  (sedation, hypotension, anticholinergic effects like dry mouth, blurred vision etc.) also vary with the dose given. anticholinergic

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