Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopamine (DA) D2, D3, and D4 receptors are targets for antipsychotic drugs. The recent cloning, deoxyribonucleic acid sequencing, and brain location of these receptors provide new insight on the DA hypothesis of schizophrenia, particularly for the basis of antipsychotic therapy of schizophrenia. In schizophrenia brain tissue, D2 receptors are elevated and have lost the link to D1 receptors. Brain positron-emission tomography studies of patients may also reveal elevated D2, depending on the method used. Hallucinations and positive symptoms are blocked when about 70% of the D2 receptors are occupied by neuroleptic drugs. An analysis of the literature indicates that therapeutic concentrations of antipsychotic drugs (in the patient's cerebrospinal fluid or plasma water) act primarily at D2 receptors, with the exception of clozapine, which acts at D4 receptors.
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PMID:Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4. 136 57

A 63 year old female, who was admitted to a psychiatric hospital for schizophrenia, was referred to our emergency room because of sudden loss of consciousness and convulsions. On arrival, she was drowsy and hypoxemic. Her chest X-ray showed cardiomegaly with pulmonary edema. ECG showed marked ST depression in precordial leads and serum chemistry revealed marked elevation of CPK, GOT and LDH along with hyponatremia and hypochloremia. She was immediately admitted to CCU on suspicion of acute non-transmural myocardial infarction complicated with congestive heart failure. After fluid restriction and intravenous infusion of dopamine she passed large amount of urine, and her consciousness level, electrolyte imbalance and ECG change, improved gradually. Although serum CPK level increased as high as 32,307 IU/ml, there were no signs of left ventricular asynergy on UCG and CPK isozyme analysis performed later revealed more than 99% of serum cCPK was MM-type. We concluded that water intoxication was the cause of the ECG change and the elevated serum CPK, GOT and LDH levels. There are few reports on elevated CPK level in association with water intoxication, in which rhabdomyolysis is speculated as the cause of CPK elevation. But there is no report on ECG change complicated with water intoxication. In our case, electrolyte imbalance caused by water intoxication seemed to play a major role in ST depression and QT prolongation. Although water intoxication is a rare disorder in the general population, it is not infrequent among patients with psychiatric diseases. Care must be taken when such patients present ECG change and serum enzyme elevation mimicking ischemic heart disease.
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PMID:[A water intoxication patient who showed remarkable ST depression and suspected ischemic heart disease]. 152 80

Many mentally ill patients, particularly those with schizophrenia, have idiopathic or medication-induced disorders of water balance, which include excessive water intake, excessive water excretion, and impaired water excretion. Patients with these disorders manifest polydipsia and polyuria with or without symptomatic hyponatremia (low serum sodium concentration). Other serious sequelae include life-threatening water intoxication. The author reviews the physiology of normal water balance and the mechanism, causes, clinical presentation, and diagnosis of disorders of water balance. Interventions must first focus on identifying reversible factors. Medication-induced water imbalance can usually be reversed without compromising treatment of the underlying psychiatric disorder. A fully effective treatment for idiopathic polydipsia has not been found, although providing optimal treatment for the underlying psychiatric disorder often helps. Monitoring changes in body weight, in conjunction with measures of serum sodium, prevents water intoxication.
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PMID:A rational approach to disorders of water balance in psychiatric patients. 157 22

Dopamine receptors belong to the family of G protein-coupled receptors. On the basis of the homology between these receptors, three different dopamine receptors (D1, D2, D3) have been cloned. Dopamine receptors are primary targets for drugs used in the treatment of psychomotor disorders such as Parkinson's disease and schizophrenia. In the management of socially withdrawn and treatment-resistant schizophrenics, clozapine is one of the most favoured antipsychotics because it does not cause tardive dyskinesia. Clozapine, however, has dissociation constants for binding to D2 and D3 that are 4 to 30 times the therapeutic free concentration of clozapine in plasma water. This observation suggests the existence of other types of dopamine receptors which are more sensitive to clozapine. Here we report the cloning of a gene that encodes such a receptor (D4). The D4 receptor gene has high homology to the human dopamine D2 and D3 receptor genes. The pharmacological characteristics of this receptor resembles that of the D2 and D3 receptors, but its affinity for clozapine is one order of magnitude higher. Recognition and characterization of this clozapine neuroleptic site may prove useful in the design of new types of drugs.
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PMID:Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. 184 Jun 45

We reported a case of acute water intoxication from compulsive water-drinking, who showed triphasic waves on EEG. The patient was a 50-year-old man who had been undergoing medical treatment in a mental hospital since he was suffering from schizophrenia diagnosed at the age of 35. He had sometimes had a tendency to drink a large amount of water since 45 years old. He began to drink water compulsively since three days ago. He vomited just after he drank excessive water with his mouth directly to the tap for several minutes, and soon fell into loss of consciousness. He was transmitted to our hospital because of acute consciousness disturbance on the next day. On neurological examination, he was profoundly comatose with miosis and conjugate deviation to the right side. His extremities showed decorticate posturing. On admission, serum sodium level was 101 mEq/l, and plasma osmolality was 208 mOsm/l. Serum enzymes derived from muscle and myoglobin were markedly elevated. But there was no laboratory evidence of the other metabolic disorders such as hepatic or renal disease. Computed tomography of the brain disclosed severely diffuse swelling with largely obliterated sulci and narrowed ventricles. EEG showed triphasic waves predominantly over centro-parieto-occipital portion, behind which there was slow wave activity with a loss of normal alpha wave activity. Immediately, treatment began by a combination of saline and glyceol infusion for the purpose of correcting severe hyponatremia, subsequently removing brain edema. As serum sodium level gradually returned to normal, the brain CT findings were getting better.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of acute water intoxication showing triphasic waves on EEG]. 193 65

A cross-sectional survey of the drinking habits of 877 mentally handicapped in-patients revealed 31 patients (prevalence 3.5%) who, in the opinion of nurses, drank five litres or more daily. Low urine specific gravity was a less useful indicator of polydipsia. Polydipsia appeared to be significantly associated with a borderline level of handicap and with a diagnosis of schizophrenia, autism or severe personality/behaviour disorder. Of five cases of water intoxication associated with polydipsia, one was fatal. In two cases excess drinking improved with increased neuroleptic medication. Lithium and demeclocycline were used in two cases to prevent hyponatraemic episodes.
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PMID:Intoxicated by water. Polydipsia and water intoxication in a mental handicap hospital. 175 59

The review presents evidence that 5-HT3 receptors within the brain may contribute to the control of behavior. 5-HT3 receptor antagonists GR38032F, zacopride, ICS 205-930 and other agents are very potent in reducing mesolimbic dopamine hyperactivity caused by the injection of amphetamine or infusion of dopamine into the rat nucleus accumbens and amygdala, and the ventral striatum of the marmoset. Such actions are distinguished from those of neuroleptic agents by a failure to reduce normal levels of activity or to induce a rebound hyperactivity after discontinuation of treatment. Indeed, the 5-HT3 receptor antagonists can prevent the neuroleptic-induced rebound hyperactivity. Further evidence that 5-HT3 receptors moderate limbic dopamine function is shown by their ability to reduce both the behavioral hyperactivity and changes in limbic dopamine metabolism caused by DiMe-C7 injection into the ventral tegmental area. The 5-HT3 receptor antagonists also have an anxiolytic profile in the social interaction test in the rat, the light/dark exploration test in the mouse, the marmoset human threat test and behavioral observations in the cynomolgus monkey. They differ from the benzodiazepines by an absence of effect in the rat water lick conflict test and a withdrawal syndrome. Importantly, the 5-HT3 receptor antagonists are highly effective to prevent the behavioral syndrome following withdrawal from treatment with diazepam, nicotine, cocaine and alcohol. Intracerebral injection techniques in the mouse indicate that the dorsal raphe nucleus and amygdala may be important sites of 5-HT3 receptor antagonist action to inhibit aversive behavior. Studies with GR38032F indicate an additional effect in reducing alcohol consumption in the marmoset. The identification and distribution of 5-HT3 receptors in the brain using a number of 5-HT3 receptor ligands, [3H]65630, [3H]zacopride and [3H]ICS 205-930 correlates between studies, and the 5-HT3 recognition sites in cortical, limbic and other areas meet the criteria for 5-HT3 receptors to mediate the above behavioral effects. Thus the use of 5-HT3 receptor antagonists reveals an important role for 5-hydroxytryptamine in the control of disturbed behavior in the absence of effect on normal behavior. The profile of action of the 5-HT3 receptor antagonists has generated a major clinical interest in their potential use for schizophrenia, anxiety and in the control of drug abuse.
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PMID:The psychopharmacology of 5-HT3 receptors. 220 69

The use of carbamazepine in psychiatry has widened its scope in the last years. Its efficacy is proven best in manic syndromes, in the prophylaxis of manic-depressive illness and in the treatment of alcohol withdrawal symptoms. Beyond this, carbamazepine has been used successfully in depression, schizophrenia, organic psychoses and intermittent explosive disorder. The manifold therapeutic possibilities should not make forget the side effects. The most severe effects to be expected are impairment of the hematopoietic system and skin reactions. Vegetative and neurotoxic effects most commonly occur in the beginning of therapy, after increasing the dosage and in case of intoxication. Further possible side effects are disturbances of hepatic, thyroid, renal and cardiac function, of immune response, water balance and calcium metabolism. Monitoring of these parameters during therapy with carbamazepine is necessary.
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PMID:[Carbamazepine in the treatment of psychiatric diseases: effects and side effects]. 224 87

In a long-term psychiatric setting, self-induced water intoxication may be a life-threatening situation. At first glance, the symptoms or behaviors of self-induced water intoxication are similar to schizophrenia, i.e., inappropriate behavior, delusions, hallucinations, confusion, and disorientation. In some cases, the symptoms of water intoxication mimic schizophrenia and thus, are disguised as a part of the psychoses. Affected individuals develop polydipsia, which is accompanied by overhydration and dilutional hyponatremia. If untreated, the symptoms may progress from mild confusion to acute delirium, seizures, coma, or death (Ripley, Millson, & Koczapski, 1989). Under normal circumstances there is a delicate balance of water requirement and water intake. If the balance of water is altered, electrolyte imbalance can occur. The recognition of water intoxication or self-induced water intoxication and psychosis among chronic, institutionalized patients may prevent their death or the development of neurological damage (Arieff, 1985). Because self-induced water intoxication often goes unrecognized in its early stages and may have irreversible or fatal complications, early detection is crucial. This article will discuss the etiology, nursing assessment, and interventions associated with patients suffering from self-induced water intoxication.
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PMID:The water-intoxicated patient. 226 Aug 89

Among patients with psychiatric disorders, especially schizophrenia, a pattern of extreme polydipsia and polyuria sometimes emerges, usually without readily identifiable medical causes. Hyponatremia may develop and progress to water intoxication, with symptoms including restlessness, confusion, seizures, or even death. We review the clinical features and pathophysiology of this syndrome and discuss nursing roles in identifying and managing patients with polydipsia and hyponatremia. While the causes of polydipsia and hyponatremia are unclear, relevant factors seem to include a possible dysfunction in central nervous system (CNS) thirst and osmoregulatory centers, the inappropriate secretion of or sensitivity to antidiuretic hormone (ADH), and psychoactive drugs. Management techniques for affected patients concentrate on careful observation, fluid restriction, and the minimization of possible exacerbating factors such as high neuroleptic dosage and cigarette consumption.
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PMID:Polydipsia and hyponatremia in psychiatric patients: challenge to creative nursing care. 235 13


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