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Biomedical subjects

C L DeVane

Publications and source records attributed to C L DeVane.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Disposition of cocaine in pregnant sheep. I. Pharmacokinetics.

Cocaine abuse by pregnant women is increasingly recognized as causing serious health consequences for mother and newborn. To assess the placental transfer and fetal effects of cocaine, we studied its pharmacokinetics following intravenous administration to the pregnant ewe and fetus. Following bolus doses of 0.5-4.0 mg/kg to ewes, cocaine appeared within 30 s in fetal circulation, with peak concentrations occurring in 4-5 min. The disappearance of cocaine in the fetal plasma paralleled that in maternal plasma, suggesting that a rapid equilibrium of cocaine occurred between maternal and fetal compartments. The mean half-life of cocaine in the fetus across doses (4.4-5.0 min) was similar to that in the ewe (4.0-5.6 min). Plasma clearance of cocaine in the ewe did not appear to vary according to dose. The fetal exposure to cocaine, as indicated by the area under the fetal plasma concentration versus curve, was a linear function of maternal cocaine dose (r = 0.96, p less than 0.01). These results demonstrate rapid placental transfer of cocaine after maternal administration in an animal model and rapid metabolism by mother and fetus.

Animals↗
PubMed1991

Disposition of cocaine in pregnant sheep. II. Physiological responses.

We studied maternal and fetal blood pressure, heart rate, arterial blood gases and fetal behavioral state alterations in response to maternally administered cocaine hydrochloride in 11 pregnant sheep. Cocaine administration to the ewe caused a dose-dependent increase in maternal blood pressure and heart rate and in fetal blood pressure, and a decrease in fetal arterial oxygen tension. In the ewe, blood pressure changes corresponded linearly to dose administered (r = 0.88, p less than 0.001). Blood pressure changes were correlated to peak plasma cocaine concentration in the ewe (r = 0.52, p less than 0.01) and in the fetus (r = 0.43, p = 0.05). In addition, in 7 of 8 fetuses which had entered rapid eye movement (REM) sleep within 5 min of maternal cocaine administration, REM sleep was abruptly terminated either by the cocaine, fetal hypoxia or some other nonspecific event caused by the maternal cocaine administration. Maternal cocaine administration causes maternal and fetal hemodynamic alterations that have potential adverse effects in pregnancy.

Animals↗