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Biomedical subjects

C L DeVane

Publications and source records attributed to C L DeVane.

At least 73 records · Page 4Linked to original sources
PubMed1993

Treatment of aggressive children with clonidine: results of an open pilot study.

Seventeen aggressive children (14 boys and 3 girls) aged 5 to 15 years, who were characterized by cruel behavior to others and destruction of property, entered an open pilot study using clonidine to evaluate its efficacy and safety and drug-induced changes in plasma gamma aminobutyric acid (GABA). Aggression decreased in 15 children with minimal side effects. In five cases, GABA increased from 105.4 +/- 15.2 ng/mL at baseline to 125.2 +/- 10.8 ng/mL at follow-up (p < 0.01). A sixth patient was noncompliant. These findings suggest that GABA may be correlated with childhood aggressiveness and may be a useful marker of drug compliance. Pharmacotherapy with clonidine should be further assessed for the control of aggression.

Adolescent↗
PubMed1993

Prescribing attitudes of different physician groups regarding fluoxetine.

OBJECTIVE: To determine the attitudes and prescribing patterns of family medicine and psychiatric physicians regarding fluoxetine. DESIGN: A three-part questionnaire was distributed to the Departments of Family Medicine and Psychiatry. The survey included topics associated with fluoxetine use that have received broad professional attention, such as drug-induced suicidal and aggressive behavior. SETTING: The Family Practice Medical Group and the Department of Psychiatry at the University of Florida. PARTICIPANTS: Mailing lists from both above departments were used to distribute surveys to residents, fellows, and attending/faculty members of each department. Eighty-seven surveys were mailed. MAIN OUTCOME MEASURES: Survey questions were divided into three sections to help determine current attitudes of prescribing fluoxetine: eight short cases, 16 statements, and demographic data. RESULTS: The return rate was 69 percent following a mailing and a hand-delivered copy. Responses were dichotomized to agree or disagree and were analyzed by Fisher's exact test. Psychiatrists were much more likely than family practitioners to prescribe fluoxetine for obsessive-compulsive disorder (OCD), and more likely to prescribe for a patient with a history of substance abuse or seizure disorder. Psychiatrists were more aware of safety issues; however, drug-interaction knowledge was weak in both groups. CONCLUSIONS: Family practitioners, being the most predominant of medical specialists, appeared equally comfortable with prescribing fluoxetine in most circumstances compared with psychiatrists. However, there is a need for pharmacists to provide up-to-date drug information on fluoxetine to all healthcare professionals.

Depressive Disorder↗
PubMed1993

The assessment and clinical implications of haloperidol acute-dose, steady-state, and withdrawal pharmacokinetics.

In order to evaluate comprehensively haloperidol pharmacokinetics under fixed-dose treatment conditions, psychiatric patients were studied after treatment with an acute dose, during maintenance therapy, and after withdrawal from haloperidol following steady-state conditions. After single doses, haloperidol appeared rapidly in serum, achieving peak concentration at a mean of 4.5 hours. The range of observed elimination half-life was broad, between 8.5 and 66.6 hours, with a mean of 19.5 hours. Under conditions of chronic dosing, serial measurements of steady-state serum concentration revealed intrapatient coefficients of variation between 2 and 72%. The mean for all patients was 26.4%. Body clearance decreased nonsignificantly, and elimination half-life increased significantly after chronic dosing compared with kinetic parameters determined after a single dose. The concentration of haloperidol in serum obtained at 8 hours after a single dose correlated most strongly (r = 0.73; p < 0.0001) with steady-state concentration resulting from chronic dosing. A value of 4 ng/ml or lower determined 8 hours after a single oral dose of 0.2 mg/kg identified patients who did not accumulate haloperidol during chronic dosing of 0.4 mg/kg per day above a presumed therapeutic range for haloperidol of 5 to 15 ng/ml. The implications of these data for the clinical use of haloperidol are discussed.

Adult↗
PubMed1992

Panic disorder. Recognizing and managing the 'real thing'.

Panic disorder is a severe anxiety disease frequently encountered in primary care. Although it is associated with potentially serious medical and psychiatric complications and is often difficult to diagnose, the condition is highly treatable. Initial pharmacotherapy may include alprazolam (Xanax), imipramine hydrochloride (Janimine, Tofranil), or phenelzine (Nardil). Correct diagnosis and treatment can alleviate much suffering and expense and promote both mental and physical health.

Diagnosis, Differential↗
PubMed1992

A review of cyclic antidepressant-induced blood dyscrasias.

OBJECTIVE: To review the literature for cases of blood dyscrasias associated with cyclic antidepressants. Several types of blood dyscrasias are discussed. DATA SOURCES: All references were selected through the use of MEDLINE. Indexing terms were blood, abnormalities, dyscrasias, antidepressants, agranulocytosis, and eosinophilia. The only constraints were English language and human subjects. STUDY SELECTION: All cases were included except for letters to the editor of various journals when pertinent data such as doses and additional medications were omitted. DATA SYNTHESIS: The review provides a table listing the different blood dyscrasias and the drug the patient was receiving. The table also includes time of onset, time to recovery, and several symptoms for each patient. CONCLUSIONS: Common symptoms of various blood dyscrasias are discussed. The chemical structures of the antidepressants are related to phenothiazines, which are also implicated in causing blood dyscrasias. Recommendations for treatment of both the dyscrasia and depression are discussed.

Adult↗
PubMed1992

Pharmacokinetics of the selective serotonin reuptake inhibitors.

The pharmacokinetic properties of the newer specific serotonin (5-HT) reuptake inhibitors are reviewed. Fluoxetine, paroxetine, sertraline, and fluvoxamine show kinetic characteristics similar to those of the older tricyclic antidepressants. They are well absorbed orally but exhibit an extensive first-pass extraction in the liver. They are widely distributed in body tissues and highly bound to plasma proteins. The clearance of these drugs by the body is accomplished almost entirely by hepatic metabolism. Fluoxetine and sertraline both produce a pharmacologically active metabolite, although insufficient data are available to evaluate the clinical significance of desmethylsertraline. With the exception of fluoxetine, which has an elimination half-life of 2 to 3 days, the other drugs have half-lives of about 1 day. Available data indicate that paroxetine and fluvoxamine achieve steady state within 4 to 14 days of chronic dosing, whereas for fluoxetine, and particularly norfluoxetine, steady state is not reached for weeks. The pharmacokinetics of these drugs are characterized by marked intersubject variability. Only preliminary data are available on steady-state plasma concentrations achieved during treatment and correlations to therapeutic or adverse effects.

1-Naphthylamine↗
PubMed1991

Determination of cocaine, benzoylecgonine and ecgonine methyl ester in plasma by reversed-phase high-performance liquid chromatography.

A combined assay is described for cocaine and its major metabolites, benzoylecgonine and ecgonine methyl ester. The method uses electrochemical and ultraviolet detectors in series. A non-silica column is used with high-pH mobile phase. The three compounds are completely separated from other cocaine metabolites. The assay has been suitable for pharmacokinetic studies of cocaine disposition in animal studies.

Animals↗
PubMed1991

Effect of electroconvulsive therapy on serum concentration of alpha-1-acid glycoprotein.

Recent studies have shown significant alterations in serum alpha-1-acid glycoprotein (AGP) concentration in epileptic patients, the major protein to which basic drugs bind in serum. To date, there have been no reports in the literature investigating the effects of generalized seizures as a result of repeatedly administered electroconvulsive therapy (ECT) on this serum protein. As the cyclic antidepressants are basic drugs that bind avidly to AGP, an alteration of AGP concentration by ECT could represent a mechanism of interaction between two somatic treatments for depression. We therefore determined the serial AGP concentrations of 10 patients undergoing repeated ECT. AGP concentrations were determined by radial immunodiffusion on serum samples obtained at each treatment session (course of treatment ranged from 4 to 12 sessions over 8 to 32 days). The mean (SD) AGP concentrations prior to and at the end of ECT were 88.7 (18.3) mg/dl and 97.8 (24.8) mg/dl, respectively. Variability in AGP concentration was observed over the course of treatments with no consistent trend (intrapatient coefficients of variation averaged 11.5%). These data suggest that serial ECT does not produce consistent, significant changes in serum AGP concentrations and should have limited effects on altering the serum protein binding and, therefore, pharmacological effects of concurrently administered cyclic antidepressants.

Adolescent↗
PubMed1991

Disposition and pharmacodynamics of methamphetamine in pregnant sheep.

To determine the placental transfer of methamphetamine, its subsequent fetal disposition, and its hemodynamic effects, we administered methamphetamine intravenously to 15 pregnant ewes 3 days after placement of maternal and fetal vascular catheters. Methamphetamine crossed the placenta within 30 seconds of its administration. Although the ewes had higher peak concentrations, the fetuses' longer elimination half-life ultimately led to higher fetal than maternal methamphetamine concentrations. The ratio of fetal tissue to plasma drug concentration 2 hours after administration was highest in the lung, followed by the placenta, kidney, intestine, liver, brain, and heart. Methamphetamine caused a 54% to 63% rise in maternal blood pressure, a 20% to 37% increase in fetal blood pressure, and a drop in fetal oxyhemoglobin saturation and arterial pH. We conclude that methamphetamine, in doses at or below what is commonly abused, has effects that could be detrimental to the health of the mother and her fetus.

Animals↗
PubMed1991

Inhalational administration of cocaine in sheep.

A pipe for administration of inhaled cocaine and its pyrolytic products in laboratory animals was developed and tested. In-vitro trials showed 30.0 +/- 5.2% (mean +/- SE) recovery of cocaine in solvent. Five non-pregnant ewes were instrumented with tracheal T-tubes and vascular catheters. After surgical recovery, ewes received three doses of cocaine (free base) in a randomized fashion; 2 mg/kg and 4 mg/kg both by inhalation, and 2 mg/kg intravenously. Arterial blood samples were collected and assayed for cocaine and its major metabolites by high performance liquid chromatography. Blood pressure and heart rate were continuously recorded. Cocaine administered by inhalation was eliminated with a half-life of 1.6 +/- 0.5 min (mean +/- SE) compared to 3.4 +/- 0.9 following intravenous administration (p less than 0.03). Likewise, clearance values were greater following inhalation, 5532 +/- 1756 ml/min/kg, than following intravenous administration, 163 +/- 20.6 ml/min/kg (p less than 0.04). Both routes of administration led to significant elevations in blood pressure, 7.5% increase after smoking vs 20% increase after intravenous administration. No correlation was found between inhalational dose of cocaine and peak plasma cocaine concentration.

Administration, Inhalation↗
PubMed1991

Influence of menstrual cycle and gender on alprazolam pharmacokinetics.

The effects of menstrual cycle phases and gender on alprazolam pharmacokinetics were evaluated in normal volunteers. Alprazolam (1 mg) was administered to seven women during the late follicular and luteal phases of the menstrual cycle and to eight men on one occasion. No difference in alprazolam pharmacokinetic parameters was observed during the menstrual cycle phases. Mean alprazolam clearance (+/- SD) was 0.0037 +/- 0.0009 ml/hr during the follicular phase and 0.0036 +/- 0.001 ml/hr during the luteal phase (p greater than 0.05, difference not significant). With use of weight as a covariant, there was no difference in alprazolam pharmacokinetic parameters between women and men. Mean alprazolam clearance (+/- SD) was 0.0036 +/- 0.0009 ml/hr in women compared with 0.0041 +/- 0.0006 ml/hr in men (p greater than 0.05, difference not significant). Although alprazolam metabolism was similar on the 2 days tested, alterations may occur at other times during the menstrual cycle. Further investigation is needed to understand the effects of menstrual cycle phases and gender on drug metabolism.

Adult↗
PubMed1991

Pharmacokinetic and dynamic correlates of intravenous alprazolam challenge.

The concentration-effect relationship of alprazolam plasma concentration and growth hormone changes was studied in six healthy volunteers by use of three different intravenous bolus doses of alprazolam (0.003, 0.007, and 0.02 mg/kg) in a random blind order. There was a linear increase in peak concentration (Cmax) and area under the curve (AUC) of alprazolam with increasing dose (r = 0.96). There was no significant correlation between alprazolam Cmax and effect on growth hormone measured as either maximum increase or maximum percentage change from baseline. There was, however, an overall positive correlation (r = 0.58) between the AUC values of alprazolam and growth hormone from 0 to 120 minutes, although the relative degree of increased AUC of growth hormone with increasing AUC of alprazolam varied greatly across individuals. The difficulties of interpreting the mechanisms underlying differential growth hormone responses even when concentration of stimulus is controlled are discussed.

Alprazolam↗
PubMed1991

Immunologic effects of cocaine and related alkaloids.

Because of the national epidemic of cocaine abuse and the increasing prevalence of infectious diseases among drug abusers, we investigated the effects of cocaine and cocaine metabolites on human cellular immune functions. Mononuclear cells (MNC) were isolated from blood of healthy adult volunteers. MNC were stimulated in vitro with mitogens with and without various concentrations of cocaine. Because of cocaine's poor stability in vitro, we found it necessary to replenish cocaine daily to MNC cultures. Under these conditions, cocaine, in a dose response fashion, significantly inhibited MNC proliferation. Metabolites of cocaine did not alter MNC proliferative responses significantly from control cultures. Polymorphonuclear leukocyte chemotaxis was also significantly impaired by cocaine. Our data demonstrate that cocaine is immunosuppressive and that it acts on human MNC during early stages of cellular activation. These data further suggest that illicit cocaine use may compromise the integrity of the immune system.

Chemotaxis, Leukocyte↗
PubMed1991

Pharmacokinetics, pharmacodynamics, and treatment issues of benzodiazepines: alprazolam, adinazolam, and clonazepam.

Alprazolam, adinazolam, and clonazepam share the typical pharmacological effects of benzodiazepines yet are diverse in their pharmacokinetic properties. Alprazolam has an average terminal elimination half-life of 12 hours, whereas adinazolam generates a metabolite responsible for its benzodiazepine effects whose half-life is less than 3 hours. Clonazepam shows a much slower elimination with a half-life of 20 to 80 hours. The rate of decline of plasma benzodiazepine concentration may be an important factor in determining the number of daily doses necessary to maintain optimal anti-panic effects and to minimize rebound anxiety and withdrawal effects. Clonazepam, which has a longer half-life, would be expected to have some advantages over the other drugs. The limited data available do not provide evidence for any substantial advantages of one benzodiazepine over another. The potential disadvantage of the rapid elimination half-life of adinazolam and its metabolite may be offset by formulation in a sustained release capsule. When discontinuing therapy abruptly, a benzodiazepine with a longer half-life may be advantageous; however, when pharmacotherapy is discontinued gradually, the importance of half-life is diminished. Studies of the pharmacodynamics of drug-receptor interactions suggest new approaches to minimizing the adverse effects of discontinuing benzodiazepine therapy. Preliminary data relating plasma alprazolam concentrations to anxiolytic and adverse effects are presented.

Alprazolam↗
PubMed1991

Dosage regimen design for cyclic antidepressants: a review of pharmacokinetic methods.

One of the difficulties in pharmacotherapy of depression is the frequent need to make several dosage titrations before reaching the optimal therapeutic dosage. This problem has led to several experimental approaches for predicting a stable antidepressant maintenance dose from plasma concentration data collected shortly following a test dose. The theoretical basis for these methods is reviewed along with the results of clinical trials. It is concluded that accurate steady-state concentrations of cyclic antidepressants can be predicted from kinetic analysis of plasma concentrations obtained early in therapy. The most applicable drug for prospective dosing methods is nortriptyline with its widely accepted therapeutic plasma concentration range. Other drugs that also have substantial evidence for predicting the optimal dose from an early point in therapy include desipramine and imipramine. Predictive dosing methods are easily applied in the inpatient setting. Multiple data points obtained between 12 and 48 hours after the first dose are likely to give accurate predictions and provide clinically useful information. More widespread application of predictive approaches to dosage regimen design of antidepressant pharmacotherapy may lead to reduced hospitalization and cost savings.

Antidepressive Agents, Tricyclic↗