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Biomedical subjects

T B Cooper

Publications and source records attributed to T B Cooper.

At least 235 records · Page 13Linked to original sources
PubMed1982

Cardiovascular effects of phenelzine and amitriptyline in depressed outpatients.

Blood pressure and ECG changes were monitored in depressed outpatients treated for 6 weeks with amitriptyline, 150 mg/day, or phenelzine, 60 mg/day, as part of an ongoing double-blind study. Phenelzine produced significant decreases in blood pressure and a significant increase in orthostatic fall in pressure. Amitriptyline produced little overall change in blood pressure. The degree of MAO inhibition in phenelzine-treated patients was significantly correlated with blood pressure. Tricyclic plasma concentrations were also related to some blood pressure measures. Reported dizziness/faintness did not correlate with blood pressure changes in either group. Amitriptyline significantly increased heart rate, while phenelzine produced slowing. Amitriptyline was associated with significant prolongation of QRS and QTc but not PR intervals. Phenelzine produced significant shortening of the QTc interval.

Adult↗
PubMed1982

Fluphenazine blood levels and clinical response.

The radioreceptor assay for neuroleptics (NRRA) holds out great theoretical promise as a method for monitoring blood neuroleptic levels, but its practical value is yet to be established. In the present study, 12 psychotic patients were followed longitudinally during treatment with oral (n = 9) and/or depot (N = 7) fluphenazine. Neuroleptic blood levels were determined both by the NRRA and by high performance liquid chromatography utilizing an electrochemical detector (HPLC). Clinical status was monitored by the Brief Psychiatric Rating Scale. Although blood levels were near the limits of sensitivity, the NRRA was able to detect the drug in most samples. HPLC was able to detect fluphenazine in less than 20% of the samples. Detectable blood levels by HPLC were associated with high blood levels by the NRRA. There was a significant correlation between blood levels as measured by the NRRA and clinical improvement. This correlation appears to be independent of the dose or route of administration of fluphenazine. Many patients were followed for several months and a few for over a year. A remarkable constancy of blood levels was found, particularly with depot administration. Given these findings, the NRRA may be an important clinical tool for monitoring patients receiving fluphenazine.

Chromatography, High Pressure Liquid↗
PubMed1981

Simultaneous determination of imipramine, desipramine, and their 2-hydroxy metabolites in plasma by ion-pair reversed-phase high-performance liquid chromatography with amperometric detection.

An ion-pair reversed-phase high-performance liquid chromatographic (HPLC) method, using an electrochemical detector, is presented for the simultaneous and rapid quantitation of imipramine desipramine, and their 2-hydroxylated metabolites in plasma. The drugs are extracted from 1 ml of plasma at pH 9.7 with ether, back-extracted into 0. M HCl, and reextracted into ether following alkalinization. An efficient electrochemical oxidation reaction at the detector electrode affords a low detection level of approximately 5 ng/ml in a mobile phase of acetonitrile--acetate buffer (40:60) containing 0.005 M heptanesulfonate. Patient data are presented as correlations between the plasma level of each hydroxy metabolite and its respective parent compound. The method is applicable to the laboratory experienced in HPLC.

Chromatography, High Pressure Liquid↗
PubMed1981

Clozapine: plasma levels and prolactin response.

Serial plasma clozapine levels and serum prolactin levels were determined in two schizophrenic patients receiving clozapine, a novel antipsychotic drug. Despite marked therapeutic response and substantial clozapine blood levels, prolactin levels obtained 11--12 h after the last oral dose were unaffected or only minimally elevated. This confirms previous evidence of clozapine's unusual characteristics.

Adult↗
PubMed1981

Prediction of steady state plasma and saliva levels of desmethylimipramine using a single dose, single time point procedure.

In normal volunteer study (20 subjects) where each ingested 75 mg desmethylimipramine (DMI), blood and saliva samples were collected at 1, 2, 3, 4, 5, 7, 12, 24, and 32 h post dose. Each subject then was given DMI 25 mg b.i.d. for 15 days. Blood and saliva samples were collected on days 3, 4, 12, 13, 14, and 15. All samples were analyzed for total DMI content. Strong correlations were found between the blood samples collected 12, 24, and 32 h post dose (r = 0.93, 0.96, 0.95) and saliva samples collected 24 and 32 h post single dose (r = 0.91, 0.84) and the subjects' respective steady states. Although the correlation between blood and saliva levels was weaker (r = 0.7) because of considerable interindividual variation in the saliva/plasma DMI ratio (16-fold variation), this ratio in individual subjects was stable. These data suggest that, as has been shown for other psychotropic drugs, single blood measures at 24 h post ingestion of 75 mg DMI can be used to predict optimal dosage in individual patients. Acceptable predictions of steady state plasma levels were obtained when this technique was applied to patient data available in the literature. It is also suggested that if the saliva/plasma ratio is established for each individual patient, their drug level monitoring may be possible using this noninvasive approach.

Desipramine↗
PubMed1981

Monitoring lithium dose levels: estimation of lithium in blood and other body fluids.

The theoretical basis and practical application of the analytical procedures used to quantitate lithium in biological fluids, i.e., flame emission and atomic absorption, are described in their most simple form in nontechnical language. The clinical relevance of the erythrocyte to plasma ratio, saliva, urine, and spinal fluid lithium measures is discussed. Other topics include acute treatment plasma lithium levels and maintenance treatment plasma levels, pitfalls in sample collection, availability of micro (finger prick) procedures, and laboratory accuracy and evaluation.

Blood Specimen Collection↗
PubMed1981

Prenatal exposure to imipramine alters early behavioral development and beta adrenergic receptors in rats.

Offspring of rats exposed to water or 15 mg/kg/dy of imipramine (IMI) on gestational day 8 through 20 were examined for behavioral and neurochemical development. IMI-treated mothers gained significantly less weight during pregnancy, but the percentage giving birth, length of gestation and litter size were unaffected. Body weights of IMI-exposed offspring were significantly lower than controls until postnatal day 14 and brain weights were lower until day 30. In IMI-exposed pups, eye-opening occurred significantly earlier, development of the surface righting reflex was delayed and development of negative geotaxis was altered. Hypothalamic levels of noradrenaline and adrenaline were unchanged in IMI pups at 7, 14 and 30 days, but dopamine levels, unaffected at 7 and 14 days, were significantly lower than controls at 30 days. The number of cortical beta adrenergic receptors, measured by [3H]dihydroalprenolol binding, was significantly decreased by 18.7% at 14 days and 9.1% at 30 days. Affinity for binding was increased at 30 days. Brain levels of IMI and its metabolite desmethylimipramine were detectable in newborns prenatally exposed to IMI and desmethylimipramine/IMI ratios were 1.8 times those found in adults. The results indicate that prenatal exposure to IMI produces behavioral and neurochemical consequences lasting well past cessation of drug exposure.

Animals↗
PubMed1980

Determination of phenelzine in human plasma with gas chromatography-mass spectrometry using an isotope labeled internal standard.

A quantitative gas chromatographic-mass spectrometric assay was developed for the determination of phenelzine in human plasma. Phenelzine, in aqueous solution or in plasma reacts at room temperature with pentafluorobenzaldehyde to form quantitatively a hydrazone derivative. The derivative has good gas chromatographic characteristics. The assay utilizes selected ion monitoring in a gas chromatographic effluent, the molecular ion generated by electron impact ionization of phenelzine derivative. Phenelzine-d, was synthesized and used as an internal standard. The assay can measure 2 ng/ml of the drug with about 10% precision. The method was used for the determination of steady state levels of phenelzine in the plasma of patients taking a therapeutic dose of the drug.

Deuterium↗
PubMed1980

Effect of antiparkinsonian medication on plasma levels of chlorpromazine.

Twenty-one chronic schizophrenics were stabilized with chlorpromazine therapy at their therapeutic dosage for one month. Trihexyphenidyl hydrochloride or identical placebo was then added according to a double-blind, split crossover design. The duration of each half of the crossover was 15 days. Steady state blood samples were drawn three times weekly during the experimental period and the amount of chlorpromazine was determined. The results indicated there were no differences in the levels obtained between the trihexyphenidyl and the placebo phases. A two-hour postdrug blood sample was also drawn at the end of each phase and again, there were no differences between the two conditions. The importance of these results is discussed.

Chlorpromazine↗
PubMed1979

Plasma tricyclic drug levels in amitriptyline-treated depressed patients.

In a double-blind phenelzine controlled clinical trial, 49 depressed outpatients were treated with a fixed dose of amitriptyline (AMI) 150 mg/day for 6 weeks. No significant relationships were found between steady-state plasma levels of AMI and its metabolite, nortriptyline, at 4 weeks and therapeutic response at 6 weeks or side effects. In the patient subgroup with more severe endogenous symptoms, there was a general trend for a weak positive association between AMI plasma levels and clinical improvement. Plasma tricyclic determinations appear to have little if any predictive value for antidepressant effect in outpatients treated with AMI.

Adult↗
PubMed1979

Effects of loxapine on the sleep of chronic schizophrenics.

The sleep patterns of four male chronic schizophrenic patients were monitored throughout the various phases of a 1-year therapeutic trial with loxapine succinate, a newly developed neuroleptic. Compared with the initial drug-free baseline, the early drug period was characterized by an increase in REM percentage, REM density, and REM activity. During the drug maintenance period, the increase in REM phasic events was accompanied by an increase in total sleep. Severe insomnia was noted during the initial period of drug withdrawal. The absence of time lag between changes in drug administration schedule and the associated alterations in sleep patterns was in contrast with the time latency of the therapeutic response. This neuroleptic on sleep and on psychopathology are mediated by different mechanisms.

Adult↗
PubMed1979

GLC analysis of loxapine, amoxapine, and their metabolites in serum and urine.

A GLC analysis is presented for loxapine, amoxapine, and their major metabolites in serum and urine. Electron-capture detection is employed for serum analysis, and flame ionization is used for urine analysis. The procedure includes trifluoroacetylation of secondary amine functions, followed by trimethylsilylation of phenolic groups after ethyl acetate extraction of the sample. Urine requires prior enzymatic hydrolysis of conjugates. Data indicating the utility of the procedure in hospitalized patients and normal volunteers are presented.

Amoxapine↗
PubMed1978

Clinical and plasma level characteristics of intramuscular and oral loxapine.

The intramuscular and oral forms of loxapine succinate were compared in their clinical, side effect, and blood level characteristics in ten hospitalized chronic schizophrenic patients. The first phase of the study determined the single dose that produced moderate sedation (i.e., the sedation threshold), and this dose was essentially the same for the two forms. Continuous administration of the two forms using the individualized sedation threshold dosage also failed to indicate any clinical or side effect differences in the two forms. The blood level characteristics, however, did differ between the two forms. The kinetic studies indicated that there was a larger are under the loxapine curve with the intramuscular form than with the oral form, while the 8-OH loxapine area was larger with the oral form. The steady-state studies also showed that the i.m. form had higher loxapine levels than the oral form. The significance of these findings, both clinically and in terms of the relative activity of loxapine and its metabolites, is discussed.

Administration, Oral↗
PubMed1978

Overdrive pacing for supraventricular tachycardia: a review of theoretical implications and therapeutic techniques.

Rapid atrial pacing for treatment of supraventricular arrhythmias has been demonstrated to be safe and effective. Virtually any supraventricular tachycardia with the exception of atrial fibrillation, Type II atrial flutter, and probably sinus tachycardia can be treated successfully with pacing techniques. The recognition of the advantages of cardiac pacing over drug therapy or DC cardioversion has resulted in its widespread use, especially after open-heart surgery. Although the response to overdrive pacing may not reliably identify the underlying mechanism of supraventricular tachycardia, the response of the arrhythmia to pacing (i.e., whether it is interruptable or noninterruptable), is most useful in the approach to management of the individual patient.

Atrial Flutter↗