ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02581.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Conditions in which antidepressants have been used include diabetic neuropathy, postherpetic neuralgia, headaches, arthritis, chronic back pain, cancer, thalamic pain, facial pain, and phantom limb pain. Although much of the available information is derived from inadequately controlled trials, it seems that antidepressants provide analgesia in many of these disorders. The analgesic effects tend to be independent of antidepressant effects, and doses of heterocyclic antidepressants used for analgesia seem to be lower than those considered effective in the treatment of depression. Doses should be started low and gradually increased until the patient reaches the highest tolerable dose. Onset of analgesia is variable, ranging from 1 day to 10 weeks. Common side effects include dry mouth, drowsiness, urinary retention, orthostatic hypotension, and constipation. Optimum dosages and schedules have not been established.

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02582.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The traditional role of theophylline as a bronchodilator has been expanded by recent findings that suggest this drug has more than smooth muscle relaxant properties. Several investigators indicate that theophylline has an inotropic effect on respiratory muscle, causing enhanced muscular contraction and prevention of muscle fatigue. In animal studies, the drug enhanced respiratory muscle contraction by 15–20%, with levels in the upper end of the therapeutic range (15–20 mg/L). Results of studies in healthy volunteers and patients with lung disease, however, are conflicting. Five clinical trials demonstrated increased diaphragmatic contractility, whereas seven trials showed no effect, with five referring to the diaphragm and the remaining two to the sternomastoid muscle. Disparity in outcomes may be attributed to differences in patient populations, study designs, and techniques used to determine diaphragmatic contractility. Few long‐term trials exist that document significant clinical benefit. Theophylline may prove to be of value in selected populations, such as adults with hypercapnic obstructive lung di

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02583.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Liver function can be assessed by administering an exogenous substance to quantify changes in hepatic blood flow, uptake, biotransformation, and excretion. Characterization of drug half‐life, clearance, and product formation rates are possible methods for measuring hepatic efficiency. Allopurinol and caffeine have been used to measure metabolite formation followed by renal elimination of both parent substance and metabolite. Sorbitol, a substance with high intrinsic clearance, can reflect liver blood flow, while trimethadione, a low‐extraction drug, has been used to measure liver enzyme capacity. Metabolites from lidocaine, methacetin, and aminopyrine have been measured in serum, urine, and breath tests. Salivary clearance measurements of caffeine and antipyrine are reported as suitable for routine use. Genetic diversity of isoenzymes and the many metabolic processes used by hepatocytes make it extremely difficult to quantify functional changes with one substance. Combinations of model substrates have been suggested to assess the many hepatic proces

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02584.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

An effective and well‐tolerated transdermal β‐adrenergic blocker that could be applied once weekly would facilitate compliance. The pharmacokinetics and pharmacodynamics of a once‐weekly formulation of transdermal timolol, a β‐blocker, were evaluated in healthy males. One (n = 6), two (n = 5), and three (n = 5) patches (97.5 mg base/12.58‐cm2patch) were applied at weekly intervals to the subjects' inner arm for 48 hours (part A) and two patches were applied for 7 days (part B). In part A, mean exercise (bicycle ergometry) heart rate (beats/min, bpm) was suppressed from baseline at 48 hours after the patch (p<0.05) in each case (1 patch 167 vs 131 bpm; 2 patches 165 vs 120 bpm; 3 patches 159 vs 120 bpm). Mean plasma timolol concentrations at 48 hours after the patch for one, two, and three patches were 5, 11, and 14 ng/ml, respectively. For part B, mean exercise heart rate at baseline, 24, and 168 hours was 161, 113, and 130 bpm (p<0.05), and mean plasma timolol concentrations at these times were 0, 23, and 4 ng/ml. The relationship between suppression of exercise heart rate and plasma timolol concentrations within subjects was well described by an inhibitory EMAXmodel, where EMAXranged from a suppression of 42–65 bpm associated with a 50% inhibitory (IC50) concentration that ranged from 2–4 ng/ml. Transdermal timolol was associated with significant B blockade for up to 7 days, and caused only minimal

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02585.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

This pilot clinical investigation was conducted to compare a home therapeutic drug‐monitoring (TDM) method for theophylline blood levels and a traditional TDM method with respect to various patient outcome factors. Outpatients with chronic obstructive pulmonary disease (COPD) or asthma who were receiving long‐term theophylline therapy were randomized to one of two groups: home TDM or traditional TDM (controls). Patients in the former group monitored their serum theophylline levels at home over 6 months. Patients in both groups completed survey instruments, including questionnaires, visual analog scales, and other psychosocial measures, at designated times throughout the study period. Pulmonary function tests and dyspnea index scores were evaluated at each clinic visit. Results indicated a significantly lower (p<0.05) number of changes in concomitant drug therapy in the home TDM group compared with controls. Other indicators that showed a trend toward more favorable outcomes in the home TDM group included symptomology, percentage of levels within the therapeutic range, patient attitudes regarding participation in health care management, and pulmonary function test results. Home monitoring prevented unnecessary clinic visits in several instances when theophylline dosage adjustments were based on telephone reports from patients. The utility of a home TDM method for theophylline has not been reported previously despite potential for broad applications. Findings from this preliminary study may support the use and feasibility of state‐of‐the‐art methodologies in carefully selected subpopulations outside the confines of the hospital or clini

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02586.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Infections in the cerebrospinal fluid (CSF) occur in an area of impaired host defenses; therefore, bactericidal antibiotics that reach adequate concentrations in the CSF are necessary for treatment. Measurements of antibiotic penetration into the CSF include CSF inhibitory and bactericidal titers, the absolute antibiotic concentration in the CSF, and the CSF: serum concentration ratio. We present the case of a patient withListeria monocytogenesmeningitis who failed to respond clinically to standard therapy, and whose organism demonstrated tolerance to Ampicillin (MBC: MIC = 258: 1) that successfully responded to trimethoprim‐sulfamethoxazole (TMP‐SMX). The CSF peak bactericidal titer to TMP‐SMX was 1:8, corresponding to that reported as necessary for successful outcome in patients with meningitis. The CSF peak: MBC ratios for TMP and SMX were less than 3:1 and equal to 3:1, respectively. These individual ratios are lower than those suggested for successful treatment of meningitis; however, the recommended ratios were established using single agents and did not account for synergistic activity with a drug combination such as TMP‐SMX. The failure of standard therapy in this patient underscores the importance of MIC/MBC testing when tolerance is suspected or when CSF penetration of antibiotics is relatively poor. In addition, measurements of CSF inhibitory and bactericidal titers, which incorporate the antibiotic concentration in the CSF, susceptibility of the infecting microorganism, and host defense factors, may be useful in monitoring patients with men

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02587.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The detailed pharmacokinetics of fluconazole in serum and cerebrospinal fluid (CSF) were studied in a patient with acquired immunodeficiency syndrome and cryptococcal meningitis, after an intravenous dose of 400 mg. Fluconazole exhibited a serum elimination half‐life of 34.2 hours, distribution volume of 0.56 17kg, and clearance of 0.19 ml/min/kg. Peak CSF concentration occurred at 4 hours after the dose. Overall penetration of fluconazole based on the ratio of areas under the curve of CSF to serum was 70%. The drug exhibited an excellent pharmacokinetic profile for treatment of central nervous system fungal infection

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02588.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02589.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY