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Biomedical subjects

G M Simpson

Publications and source records attributed to G M Simpson.

At least 91 records · Page 5Linked to original sources

Pharmacokinetics of lithium carbonate in children.

The pharmacokinetics in both serum and saliva of a single oral dose of lithium carbonate 300 mg was investigated in nine children aged 9 to 12 years. The serum and saliva concentration-time curves were parallel and biexponential, with a fast distribution phase after the peak at the second hour and a slow elimination phase starting from the 12th hour. The fast phase half-life was 6.0 +/- 1.8 hour in the serum, and 5.8 +/- 1.9 hour in the saliva. The slow phase half-life was 17.9 +/- 7.4 hour in the serum and 15.6 +/- 8.2 hour in the saliva. Lithium was 2.84 +/- 0.86 times higher in the saliva than in the serum, with a saliva/serum r coefficient of correlation of 0.93. A relatively large error was found in predicting serum levels from saliva. There were significant intersubject differences in the saliva/serum ratio, which point to the need for individual ratios in clinical use. On the whole, the pharmacokinetics of lithium in children had the same features as in adults, with a trend toward a shorter elimination half-life and higher total clearance.

Child↗

Plasma levels and therapeutic response with trimipramine treatment of endogenous depression.

In a 6-week, double-blind study involving 34 endogenously depressed patients, plasma trimipramine levels of two dosage groups, 75-mg/day and 150-mg/day, were compared with regard to clinical efficacy as determined by scores on the Hamilton Rating Scale for Depression, the Clinical Global Impressions scale, and the Zung Self-Rating Depression Scale. Both dosage levels of trimipramine produced prompt, consistent, and progressive antidepressant effects. No correlation between plasma levels and clinical efficacy was found.

Adult↗

Changing from oral to depot fluphenazine.

Many of the problems that occur when patients are changed from oral to depot fluphenazine are caused by the high dosages resulting from the formulas used for dose conversion. The authors propose a new method based on recent information on the pharmacokinetics of fluphenazine decanoate, low-dose treatment strategies in schizophrenia, and their own clinical experience.

Administration, Oral↗

Neuroleptic-induced extrapyramidal symptoms with fever. Heterogeneity of the 'neuroleptic malignant syndrome'.

From 39 reported cases of the "neuroleptic malignant syndrome," three groups were identified: those with concurrent medical problems that could cause fever that accompanied the extrapyramidal symptoms; those with medical problems less clearly related to fever; and those without other medical disorders. Dehydration, infection, pulmonary embolus, and rhabdomyolysis were the common complications of untreated extrapyramidal symptoms. Three patients died, all with medical complications. In 14 cases, no medical cause of fever was identified. Hypotheses about mechanisms for fever include psychiatric illness, disruption of dopaminergic aspects of thermoregulation, and peripheral and central effects on muscle contraction leading to excess heat production. Neuroleptic-induced rigidity should be treated vigorously, with prompt discontinuation of neuroleptic therapy and administration of dopamine agonists in severe cases with or without fever. The cases of extrapyramidal symptoms with fever are too heterogeneous to justify the assumption of a unitary and "malignant" syndrome.

Adolescent↗

Neuroleptic dosage for Asians: a failure to replicate.

Retrospective chart review of 30 Asian patients and 30 matched Caucasian patients failed to replicate a previous report's finding that Asian patients require lower doses of neuroleptic medications than do Caucasian patients.

Adult↗

An update on tardive dyskinesia.

The authors review recent research on definition, diagnosis, neuropathophysiology, treatment, management, and factors that increase risk of tardive dyskinesia, a severe and often unremitting movement disorder associated with neuroleptic treatment. Supersensitivity of dopamine receptors is believed to be the cause of tardive dyskinesia, and treatment strategies have consisted of pharmacologic blockade of dopamine receptors, depletion of dopamine, and restoration of the balance between the dopaminergic system and the neurotransmitter systems that regulate it. Several experimental neuroleptics that do not appear to cause tardive dyskinesia may be approved for use in the United States, but for now preventive measures, such as wise prescription and gradual tapering of neuroleptics, as well as careful monitoring for symptoms of tardive dyskinesia are the clinician's best defense.

Antipsychotic Agents↗

Anticholinergic agents for prophylaxis of neuroleptic-induced dystonic reactions: a prospective study.

The development of acute dystonic reactions was monitored in 202 acute psychiatric patients during initial hospitalization and treatment with various neuroleptic drugs in a prospective study. Data were analyzed to determine the effect of anticholinergic prophylaxis, age, sex, and type and dosage of neuroleptic on the incidence of dystonic reactions. Nearly 90% of dystonic reactions occurred by the third day of treatment. The overall trend favored the prophylactic use of antiparkinsonian drugs with all neuroleptics, and the effect of this prophylaxis with haloperidol was statistically significant. Because anticholinergic prophylaxis was used more often when larger dosages of neuroleptics were prescribed, an added effect in the observed trend for fewer dystonic reactions is suggested.

Adolescent↗

Family management in the prevention of morbidity of schizophrenia. Clinical outcome of a two-year longitudinal study.

Environmental stress may contribute to the clinical morbidity of established cases of schizophrenia treated with optimal neuroleptic drugs. A family-based approach that aimed to enhance the problem-solving capacity of the index patient and his family caregivers was compared with a patient-oriented approach of similar intensity over a two-year period. Thirty-six patients who returned to stressful parental households after florid episodes of schizophrenia (CATEGO and DSM-III) were stabilized with optimal neuroleptics before being randomly assigned to family or individual therapy in a comprehensive community management program. After nine months, family-managed patients had fewer exacerbations of schizophrenia, lower ratings of schizophrenic psychopathology, fewer hospital admissions, and a trend toward lower deficit symptoms and reduced neuroleptic dosage. This reduced clinical morbidity was sustained throughout the second year of less intensive follow-up. The relative efficacy of the family approach in this clinical management study did not appear to be due to prognostic factors, rater bias, stressful life events, or the effectiveness of pharmacotherapy. Definitive tests of these findings with respect to efficacy require further well-designed studies.

Adolescent↗

Mania in two sisters with similar cerebellar disturbance.

The authors describe two sisters who presented with a clinical picture consistent with mania. On further investigation, both had marked vermian and cerebellar cortical atrophy on CAT scans. Their mother also had a history suggestive of cerebellar disease. To the authors' knowledge, this is the first report of familial cerebellar disease with a clinical presentation of mania.

Adult↗

Blood levels of neuroleptics: state of the art.

Difficulties in developing techniques to measure plasma levels of neuroleptic drugs have included the presence of metabolites, as well as cross-reactivity not only between these metabolites and the parent compound but between drugs (e.g., a phenothiazine and a tricyclic). Although newer techniques have minimized some of these problems, interpretation of published data must also recognize such design limitations as variable dose, small sample size, etc. The literature is reviewed on the relationship between therapeutic response and plasma levels of chlorpromazine, thioridazine, thiothixene, fluphenazine, butaperazine, and haloperidol. It is suggested that additional studies, carefully designed, on dosage and plasma levels could help in achieving the lowest possible therapeutic dosage and thus in minimizing side effects.

Antipsychotic Agents↗

Neuroleptic-induced striatal dopamine receptor supersensitivity in mice: relationship to dose and drug.

Clozapine and molindone administered to mice for 21 days did not elevate the density of striatal 3H-spiperone binding sites at doses clinically equivalent to 1.5 mg/kg haloperidol, which elevated binding by 29%. Thioridazine (25 mg/kg) elevated binding by 25%. It appears that clinically equivalent doses of clozapine and molindone have reduced ability to induce striatal D-2 dopamine receptor supersensitivity. These data are discussed in relationship to in vitro potencies and toxicity. The dose-response relationship of chronic haloperidol treatment and specific striatal 3H-spiperone binding was complex, i.e., binding was elevated at all doses, but the dose-response curve was concave upward. These data suggest that supersensitization is a complex interactive phenomenon comprised of elevation of striatal D-2 dopamine receptor density and other compensatory mechanisms.

Animals↗

Critical interpretation of urinary phencyclidine monitoring.

A critical appraisal of issues and problems in monitoring urinary phencyclidine (PCP) is presented. Problems may be related to impurities of ingested material and/or metabolites, and methods that are not sensitive enough to detect PCP in the nanogram/ml amounts which may be present in blood or urine. Possible false positives found with some methods are discussed. Most complicated of all is the unpredictable excretion of PCP which can result in negative urines followed by urines which test positive for PCP without necessity of any further ingestion of PCP. A set of guidelines for use in monitoring and interpreting PCP values is included.

False Negative Reactions↗