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Biomedical subjects

J L Browne

Publications and source records attributed to J L Browne.

At least 19 recordsLinked to original sources
PubMed1989

A comparison of pharmacokinetic versus empirical lithium dosing techniques.

Three methods for estimating maintenance dosage requirements of lithium carbonate were retrospectively evaluated in 20 inpatients who met criteria of the Diagnostic and Statistical Manual, Third Edition, for "bipolar disorder, manic phase." Dosing methods evaluated included a pharmacokinetic method, the single-point method of Perry et al.; a population-based nomogram approach, the Zetin et al. method; and a physician-based empirical dosing procedure. The ability of each dosing procedure to produce dosing recommendations that resulted in a targeted steady-state serum lithium concentration was evaluated. The empirical dosing procedure demonstrated a significant tendency (bias) to underestimate the dose necessary to produce a desired steady-state serum lithium concentration. Comparison of the predictive accuracy of the various dosing methods failed to demonstrate any statistically significant differences among the dosing procedures. There was a strong trend, however, for the Perry method to produce predictions of steady-state lithium levels that were more frequently within 0.2 mEq/L of actual levels.

Adolescent↗
PubMed1989

Bayesian forecasting of serum lithium concentrations. Comparison with traditional methods.

Twelve pharmacokinetic methods of estimating lithium maintenance dosage requirements were compared in 21 patients with bipolar illness. Methods which were compared included the single- and multiple-point methods of Perry, 4 non-linear regression and 6 Bayesian methods. The REVOL algorithm was employed for converging on to estimates of clearance and apparent volume of distribution for the non-linear regression and Bayesian methods. Data analysis was based on an evaluation of prediction error as a measure of bias, and absolute prediction error as a measure of precision. In a direct comparison, there were no statistically significant differences in bias or precision between any of the methods.

Adolescent↗
PubMed1988

Comparison of pharmacokinetic procedures for dosing lithium based on analysis of prediction error.

Five pharmacokinetic methods for estimating maintenance dosage requirements of lithium carbonate were compared retrospectively in 20 inpatients with acute bipolar illness. Specific pharmacokinetic methods tested included the method of Cooper, the multiple-point method of Perry, the single-point method of Perry, the method of Zetin, and the method of Pepin. Data analysis was based on evaluation of prediction error or the difference between the predicted steady-state lithium concentration and the measured steady-state lithium concentration at equivalent daily doses. Each dosing method was assessed in regard to accuracy and bias of predicted steady-state serum lithium concentrations. Bias was assessed by comparison of the median value of the prediction error with zero. The dosing recommendation based on the Cooper nomogram resulted in a significant positive bias (p less than or equal to 0.05). Intermethod accuracy was assessed by comparison of the absolute prediction errors of each dosing method. Significant differences in accuracy were observed between the method of Pepin when compared with the single-point method of Perry (p less than or equal to 0.05, k-sample sign test). All other comparisons were nonsignificant.

Adolescent↗
PubMed1986

Effects of smoking on nortriptyline plasma concentrations in depressed patients.

The pharmacokinetic parameters of half-life, volume of distribution, and steady-state nortriptyline plasma concentration normalized to a 100-mg/day maintenance dose were calculated in nine smokers and 15 nonsmokers. The mean normalized total nortriptyline concentration for the smokers of 118 +/- 33 ng/ml was significantly lower than the nonsmokers' mean value of 158 +/- 35 ng/ml. The mean normalized free plasma concentrations for the smokers of 11.4 +/- 3.5 ng/ml was not different from the nonsmokers' mean concentrations of 11.5 +/- 2.6 ng/ml. The smokers had a slightly higher percentage free drug values of 10.2 +/- 4.0% (p = 0.08) as contrasted to 7.4 +/- 1.5% free nortriptyline for the nonsmokers. The nortriptyline half-life figures for both the free and total drug concentrations did not differ. Multiple linear regression analysis utilizing age, smoking status, sex, liver function, and the presence or absence of enzyme-inducing or -inhibiting drugs as the potential independent variables and percentage free nortriptyline or total nortriptyline concentration as the dependent variable, found that smoking status explained 21% of the variation in the percentage free nortriptyline in the patients and 26% of the variation in the total nortriptyline concentrations. These preliminary data suggest that smokers ideally should be dosed at the lower end of the nortriptyline therapeutic range, whereas nonsmokers should be dosed at the upper end to maximize the antidepressant effect and minimize adverse effects.

Adolescent↗
PubMed1986

A review of alprazolam withdrawal.

A cumulative review of case reports in the literature describing withdrawal reactions secondary to alprazolam is presented. In four of eight reports, the primary withdrawal manifestations were grand mal seizures. One case was characterized by painful myoclonus. In the remaining three cases, the major complications consisted of rebound anxiety with psychotic features. Despite tapering of the daily dosage according to manufacturer guidelines, a withdrawal syndrome was precipitated in three of the cases. As a result of alprazolam's atypical pharmacodynamic profile, the issue is raised as to whether alprazolam is pharmacologically cross-tolerant with other benzodiazepines.

Alprazolam↗
PubMed1986

Hyperalgesia produced by intrathecal opioid antagonists depends on receptor selectivity and noxious stimulus.

Opioid antagonists selective for delta-, kappa- and mu-receptor subtypes were administered intrathecally in rats prior to determination of response thresholds to noxious heat, pressure and chemical visceral stimulation. All antagonists induced hyperalgesia differentially with two or more stimuli but delta- and mu-blockade failed to alter writhing activity. Thus, the extent of involvement of an opioid receptor subtype in antinociception depends on the type of noxious stimulation.

Analgesia↗
PubMed1986

Exacerbation of tardive dyskinesia by Joseph disease.

A 76-year-old patient is described in whom a severe, life-threatening tardive dyskinesia developed after oral administration of approximately 2 mg of haloperidol per day for 4 weeks. The patient's strong genetic predisposition for Joseph disease may have potentiated both the development and the severity of the tardive dyskinesia. Withdrawal of neuroleptic agents accompanied by aggressive treatment with reserpine resulted in a complete recovery over 5 weeks. The clinical and pathologic characteristics of Joseph disease and tardive dyskinesia are compared.

Aged↗
PubMed1985

Relationship of free nortriptyline levels to therapeutic response.

The relationship between the free plasma concentration of nortriptyline and therapeutic response was examined. Eighteen depressed inpatients were treated for 21 days with steady state total nortriptyline plasma concentrations between 50-150 ng/ml. Steady state free nortriptyline concentrations were measured. The therapeutic nortriptyline response was measured by administering the Hamilton and the Carroll Rating scales at day zero and day 21. Statistical relationships between free levels of drug and clinical response were found to be insignificant. Qualitative assessment of the data suggest that free serum levels of nortriptyline in excess of 10 ng/ml may have an inhibitory effect on clinical response.

Adolescent↗
PubMed1984

Tussive activity of inhaled PGD2 in the cat and characterisation of the receptor(s) involved.

Prostaglandin D2 (PGD2) and some naturally occurring and synthetic prostaglandin (PG) analogues were evaluated for irritant/ tussive activity in cats. PGD2, PGF2 alpha and ICI81008 were potent tussive agents when inhaled, producing both an early and late phase of coughing. In addition all three prostaglandins decreased respiratory rate. In contrast PGE2, PGE1 and PGA1 were 100-1000 times less potent than PGF2 alpha as irritants and weakly stimulated respiratory rate. The PGE class of compounds only produced an early phase of coughing. The rank order of early phase tussive activity was ICI81008 greater than PGF2 alpha greater than PGF2 beta much greater than PGE1 = PGE2 = PGA1. This rank order is similar to that characterising the prostanoid 'X' contractant or class II receptor(s).

Aerosols↗
PubMed1984

Nortriptyline capacity-limited metabolism: a case report.

A case report of a 62-year-old patient is presented with apparent dose-dependent kinetics for nortriptyline following the administration of therapeutic doses of the drug. Twelve-hour measurements of total plasma nortriptyline following steady state administration of the drug at 10 mg every other day, 10 mg daily, and 25 mg daily were 38, 86, and 647 ng/ml and while free plasma nortriptyline concentrations were 0.37, 0.9, and 6.6 ng/ml, respectively. Half-lives calculated from samples collected at 12, 24, and 36 hours status after administration of steady state 10 mg every other day, 10 mg daily, and 25 mg daily maintenance doses were 30.4, 36.7, and 64 hours, respectively. Toxicity did not occur despite excessive total plasma tricyclic antidepressant concentrations as a result of abnormally increased plasma protein binding of nortriptyline. The case is contrasted to the usual pharmacokinetic characteristics for the tricyclic antidepressants.

Blood Proteins↗
PubMed1983

Effects of naloxone and Mr 1452 on stress-induced changes in nociception of different stimuli in rats.

The effects of naloxone and Mr 1452 on nociceptive responding to heat and pressure following restraint stress were examined. Thresholds for heat and pressure were determined using standard tail immersion and paw pressure tests. Restraint produced significant analgesia to heat but hyperalgesia to pressure. Naloxone reduced this heat analgesia but had no effect on stress-induced hyperalgesia to pressure. Mr 1452 also attenuated the heat analgesia but in contrast to naloxone it potentiated the hyperalgesia to pressure. These results suggest a differential involvement of mu- and k-opioid systems in the mediation of stress-induced changes in nociception.

Animals↗
PubMed1982

Amoxapine neurotoxicity: a case report with long-term follow-up.

At this time, because of the lack of knowledge and experience in the treatment of amoxapine toxicity, it is impossible to formulate any conclusions concerning this drug's true toxic potential and capabilities. In toxic situations, amoxapine appears to produce some of the expected sequelae associated with TCAs. Neurotoxicity appears to be amoxapine's greatest toxic liability; the drug seems to have the ability to produce unusual neurological alterations, as well as a tendency to induce severe seizure activity. Procedures generally utilized for treatment of TCA or neuroleptic overdoses may prove inappropriate for dibenzoxazepine overdoses. It appears that intervention should include combating initiation of seizure activity and maintaining functional acid-base status. It has yet to be determined whether amoxapine or other dibenzoxazepine derivatives have a greater potential than other TCAs for inducing metabolic acidosis in toxic situations. However, observations from cases presented here would indicate this to be a distinct possibility.

Adult↗