Microprocessor-assessed adherence with once- or twice-a-day dosing with Sulfonylurea--no difference.
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Diabetes Mellitus↗
Biomedical subjects
S G Jue
Publications and source records attributed to S G Jue.
Polyarthralgia associated with prazosin use.
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Adrenergic alpha-Antagonists↗
Probable terfenadine-fluoxetine-associated cardiac toxicity.
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Adult↗
Dose-dependent inhibition of theophylline metabolism by disulfiram in recovering alcoholics.
The influence of disulfiram on theophylline metabolism was studied in 20 recovering alcoholics. Ten of the patients, who were selected at random, received 250 mg of disulfiram daily. The other 10 patients received 500 mg of disulfiram daily. Two single-dose studies of theophylline kinetics were performed--one as a baseline control and the other after 1 week of treatment with disulfiram. With disulfiram pretreatment, the plasma clearance of theophylline was decreased from 105.7 +/- 10.2 (mean +/- SEM) to 83.1 +/- 8.1 ml/kg per hour (p less than 0.001) in the 250 mg group and from 94.3 +/- 13.3 to 65.4 +/- 10.7 ml/mg per hour (p less than 0.001) in the 500 mg group. The elimination half-life was prolonged significantly in both groups. The percent reduction in theophylline clearance was greater in the 500 mg group (32.5 +/- 3.1; range, 21.6 to 49.6) than it was in the 250 mg group (21.2 +/- 1.7; range, 14.6 to 29.6; p less than 0.01). Disulfiram decreased the formation of all theophylline metabolites in smokers in both treatment groups. In each group, the hydroxylation pathway was affected more than the demethylation pathway. These data indicate that at therapeutic doses disulfiram exerts a dose-dependent inhibitory effect on theophylline metabolism. Depending on the dose of disulfiram, a dose reduction of theophylline by as much as 50% may be necessary to minimize the risk of toxicity.
Adult↗
Problems in the use of anticancer drugs in the elderly.
The elderly represent a special challenge to the physician in providing effective cancer chemotherapy. Though they represent the majority of the patients who eventually will need such therapy, until recently little information was available on its use in this population. There are variable age changes in pharmacokinetics, particularly in renal elimination of drug and metabolites, which may necessitate dosage amendment. Concomitant renal impairment or hepatic disease may further alter drug disposition. Other common pre-existing conditions in the elderly also may increase susceptibility to adverse drug effects. For example, the risk of toxicity from doxorubicin and vincristine can be increased in the presence of pre-existing cardiac disease or peripheral neuropathy, respectively. Because of the variability of the ageing process and the effects of concomitant disease, each patient must be assessed on an individual basis. Furthermore, in treatment planning, not only age and health status but also the patient's attitude and the tumour type are important considerations. Chemotherapy for most malignancies appears beneficial and well tolerated in the elderly, and there is little evidence that age per se is a determinant of chemotherapy regimen selection and dosing. The exceptions may be the curable haematological malignancies for which chemotherapy seems less efficacious and more toxic in geriatric than younger patients. The complications of chemotherapy such as vomiting, mucositis and bone marrow depression must be anticipated, diagnosed early and managed aggressively in aged patients. Guidelines are provided to help manage these problems. Chemotherapy in the elderly is still at a relatively early stage of development. Further research is required to establish optimal regimens for use in this population, in particular for curable haematological neoplasms.
Aged↗
Bromperidol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in psychoses.
Bromperidol is a close structural analogue of haloperidol. Both agents possess similar pharmacodynamic properties which are consistent with central antidopaminergic activity. The available clinical data from non-comparative and comparative trials have shown that bromperidol possesses antipsychotic activity. Its overall efficacy was slightly greater than chlorpromazine and perphenazine, and similar to or slightly better than haloperidol in a small number of comparative studies. Bromperidol frequently displayed a faster onset of action than these comparative agents and there have been reports of bromperidol causing an activating effect. However, extrapyramidal side effects occurred with similar frequency and severity after bromperidol compared with the 3 reference drugs. Data from additional controlled clinical trials are required to confirm the comparative antipsychotic efficacy of bromperidol and to assess whether it possesses any advantages in certain sub-types of schizophrenia.
Clinical Trials as Topic↗
Aging and drug interactions. II. Effect of phenytoin and smoking on the oxidation of theophylline and cortisol in healthy men.
The effect of age on the induction of theophylline metabolism by phenytoin was examined in healthy young and old male cigarette smokers (greater than or equal to 20 cigarettes/day) and nonsmokers. Two single dose studies of theophylline pharmacokinetics were performed, one as a base-line control and another after a 2-week course of phenytoin. Phenytoin was administered as an i.v. loading dose followed by oral ingestion. The dose was adjusted to achieve total phenytoin plasma concentrations within a low therapeutic range (10-13 micrograms/ml). Free phenytoin concentrations in plasma were slightly higher in old (nonsmokers 0.84 +/- 0.13 micrograms/ml; smokers 0.89 +/- 0.12 micrograms/ml) than in young (nonsmokers 0.75 +/- 0.10 micrograms/ml; smokers 0.72 +/- 0.10 micrograms/ml) subjects, but the differences were not significant. Base-line plasma theophylline clearance was 30% lower in old compared with young nonsmokers (34.0 +/- 2.5 vs. 48.8 +/- 2.6 ml/hr/kg, P less than .001), whereas the small age difference between old and young smokers (86.0 +/- 8.4 vs. 72.4 +/- 8.0 ml/hr/kg) was not significant. Smokers had higher values of theophylline clearance than nonsmokers regardless of age. Half-life was prolonged in old nonsmokers in proportion to decreased clearance, despite a slight decrease in volume of distribution. Phenytoin induced theophylline metabolism to an equal degree in both age groups and in both smokers (young 42.6 +/- 6.5%; old 47.3 +/- 3.6%) and nonsmokers (young 56.3 +/- 8.8%; old 45.4 +/- 6.4%). The magnitude of its induction in smokers was additive to that of cigarette smoking. Old age was associated with a modest selective reduction in N-demethylated metabolic pathways to 3-methylxanthine and 1-methyluric acid, whereas smoking preferentially induced the formation of these products. Phenytoin increased the production of all theophylline primary metabolites to an equal degree in both old and young subjects. The urinary excretion of 6 beta-hydroxycortisol was not influenced significantly by age or smoking and increased 2- to 3-fold in all subject groups with phenytoin. These results confirm earlier observations of a reduction in basal oxidative capacity in elderly nonsmoking males. They also demonstrate that the ability to induce the metabolism of theophylline by smoking or phenytoin and the ability to induce the metabolism of cortisol by phenytoin are maintained in old age.
Adult↗
Cigarette smoking and theophylline metabolism: effects of phenytoin.
The induction of theophylline clearance by phenytoin was investigated in 12 young male subjects (six nonsmokers and six cigarette smokers). Each subject received intravenous theophylline to determine baseline pharmacokinetics. This was followed by an intravenous loading dose of phenytoin sodium and oral maintenance dosing for 2 weeks, after which the intravenous theophylline study was repeated. Phenytoin concentrations were similar in nonsmokers (10.8 +/- 2.0 micrograms/ml) and smokers (11.5 +/- 0.9 micrograms/ml). Control theophylline elimination half-life was 35% less and clearance 88% greater in smokers than in nonsmokers. The proportionate changes in half-life (26.8% +/- 5.6% in smokers and 25.8% +/- 3.5% in nonsmokers) and clearance (48.0% +/- 10.1% in smokers and 39.7% +/- 7.2% in nonsmokers) as the result of phenytoin induction were similar in both groups. These results demonstrate that the induction of theophylline clearance by phenytoin is additive to that caused by cigarette smoking and provide support for the suggestion that theophylline metabolism is influenced by multiple polymorphisms.
Adult↗
Loprazolam. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in insomnia.
Loprazolam is a 1,4-benzodiazepine with hypnotic properties, advocated for use in acute or chronic insomnia. As loprazolam has a half-life of 7 to 8 hours in healthy adults it may have advantages over longer-acting hypnotics, particularly when residual sedative effects on the day after ingestion are undesirable, although at doses greater than 1 mg residual sedation may occur. In addition, it may reduce daytime anxiety, following a hypnotic dose the night before, more effectively than the short-acting drug, triazolam. In short term comparative studies loprazolam was clearly superior to placebo, and was at least as effective as triazolam, flurazepam, nitrazepam, flunitrazepam or temazepam in hastening sleep onset, reducing nocturnal awakenings and increasing total sleep duration and quality. In the small number of patients with chronic insomnia who have received extended treatment with loprazolam, no evidence of tolerance has occurred, although rebound insomnia was evident 3 days after drug withdrawal in several studies. Thus, with its 'intermediate' elimination half-life, loprazolam would appear to have some potential advantages over both long- and short-acting hypnotics in selected patients, although further studies are needed to fully elucidate its place in therapy.
Anti-Anxiety Agents↗
Inservice teaching and adverse drug reactions in a nursing home.
A prospective study was carried out in two skilled nursing facilities (SNFs) to determine: the feasibility of identifying potential adverse drug reactions (ADRs) by monitoring drug order changes; the ADR rate in the elderly in SNFs; the ease of using an algorithm to assess the probability that an adverse event is drug-related; and whether a one-hour inservice lecture could alter the number of drug order changes or the number of ADRs detected. Over three months, 27 of 248 order changes (10.8 percent) were identified as possible ADRs. Fifteen of 248 (six percent) of the orders were probable or definite ADRs. The ADR rates were 9.5 percent and 14.8 percent, for the study and control SNFs, respectively (p greater than 0.05). This method of detecting ADRs depends on recognition of a clinically observable adverse event by the nurse, nurse practitioner, or physician. Therefore, the hypothesis that an inservice lecture on ADRs could increase the recognition of ADRs was tested. More drug order changes were initiated in the control facility that retained a full-time nurse practitioner, but no change in the number of drug order changes or ADR rates was seen after the inservice lecture in the study facility. This method is the first to identify, prospectively, clinically manifest ADRs and to test a method to influence their rate in nursing home elderly.
Aged↗
Ciclopirox olamine 1% cream. A preliminary review of its antimicrobial activity and therapeutic use.
Ciclopirox olamine is a substituted pyridone antimycotic, unrelated to the imidazole derivatives, with activity against a broad spectrum of dermatophytes, yeasts, actinomycetes, molds, other fungi, and a variety of Gram-positive and Gram-negative bacteria. The efficacy of ciclopirox olamine cream has been demonstrated in open and placebo-controlled studies in patients with superficial dermatophyte or yeast infections, and in double-blind comparative trials in patients with dermatomycoses, topical ciclopirox olamine was comparable to or better than clotrimazole in efficacy and caused a similar number of side effects. Ciclopirox olamine penetrates through fingernails and in preliminary studies has been successfully used in onychomycoses. However, further studies are needed to establish the role of ciclopirox in the treatment of onychomycoses and dermatomycoses relative to that of the more recently introduced antigungal agents.
Animals↗
Alprazolam: a review of its pharmacodynamic properties and efficacy in the treatment of anxiety and depression.
Alprazolam is a triazolobenzodiazepine which is related to diazepam and other 1,4-benzodiazepines, and has a similar pharmacological profile. Relative to the newer benzodiazepines, alprazolam has an intermediate half-life of 10 to 12 hours in healthy young subjects. In placebo-controlled and double-blind comparative trials in patients with anxiety, alprazolam was of comparable efficacy to diazepam and generally caused a lower incidence of drowsiness. Alprazolam has antidepressant activity and has been shown to be similar in efficacy to imipramine in the treatment of unipolar depression. Thus, alprazolam may be particularly useful in patients with mixed anxiety/depression. However, its general acceptance as an antidepressant awaits further studies.
Alprazolam↗
Stable isotope methodology in a pharmacokinetic study of the interaction of theophylline and cimetidine.
Theophylline administered orally and (1,3-15N,2-13C)theophylline administered intravenously in tracer quantities were used to investigate under steady-state conditions the interaction of theophylline with cimetidine in a patient with chronic obstructive pulmonary disease. Both compounds were quantified simultaneously by mass spectral analysis after solvent extraction and high pressure liquid chromatographic purification of plasma samples. The assay is reliable and accurate to a plasma level of 50 ng ml-1 for the stable isotope tracer with a practical lower limit of detection of 10 ng ml-1.
Carbon Isotopes↗
Amoxapine: a review of its pharmacology and efficacy in depressed states.
Amoxapine is an N-demethylated dibenzoxazepine closely related in the neuroleptic loxapine. Its tricyclic structure appears to give it antidepressant properties resembling imipramine and amitriptyline. In uncontrolled trials it was shown to have antidepressant activity in usual doses up to 200 to 400mg daily. In placebo and double-blind controlled studies comparing amoxapine with the standard tricyclic antidepressants imipramine and amitriptyline, it was shown to be comparable in efficacy with a possibly somewhat faster onset of improvement of selected symptoms of depression in some studies. Because of the small study groups and lack of placebo control, many reports do not show statistically significant differences of treatment over standard drugs. To date there have been no studies comparing amoxapine with electroconvulsive therapy. Side effects were qualitatively similar to standard drugs with a suggestion that in standard doses or overdose myocardial effects are mild. However, the final place of amoxapine in the therapy of depressed states is still to be decided.
Amoxapine↗
Assessment of sulfonylurea adherence and metabolic control.
This study was designed to compare sulfonylurea adherence assessment by providers, patients' self-report, pill counts, and a medication event monitoring system (MEMS-3) device, and correlate the estimates of metabolic control by provider, patient, and laboratory. Forty-seven outpatient veterans with fair to poor metabolic control of non-insulin-dependent diabetes mellitus were enrolled and received monthly refills of sulfonylurea in vials with a cap containing an electronic medication monitoring microprocessor. Pill counts and fasting plasma glucoses were measured monthly, and glycohemoglobin and a 24-hour diet recall were obtained at 0 and 60 days. Investigators then asked providers and patients to assess adherence and metabolic control. Forty-seven percent were nonadherent to medication using MEMS-3, 29% using pill counts, 29% using provider assessment, and 31% using self-report. Thirty-one percent of providers and 53% of patients assessed metabolic control differently than laboratory values. Assessment of medication adherence by provider, patient, and pill counts did not explain metabolic control as closely as assessment by MEMS-3.
Diabetes Mellitus, Type 2↗
Pharmacists' interventions using an electronic medication-event monitoring device's adherence data versus pill counts.
OBJECTIVE: To compare adherence data from an electronic medication-event monitoring device (MEMS, Aprex) with pill counts in assisting pharmacists in making recommendations regarding diabetes therapy. DESIGN: Two-month, double-blind, randomized, controlled trial. SETTING: Veterans Affairs Medical Center ambulatory care clinics. PATIENTS: Forty-seven patients with poor to fair metabolic control of diabetes mellitus were enrolled. Patients were excluded if they were receiving insulin, had a concurrent infection, required child-resistant caps or medication remainder devices, or could not return for followup visits. Twenty patients were randomized to the MEMS and 27 to the control group (pill counts). Fasting plasma glucose concentrations were measured monthly and glycohemoglobin concentrations were measured at baseline and 60 days. Thirty-two patients were evaluable: 15 using MEMS and 17 using pill counts. INTERVENTION: Investigators made pharmacologic or educational recommendations to the patient's healthcare provider based on both laboratory data and MEMS readings in the treatment group or laboratory data and pill counts in the control group. MAIN OUTCOME MEASURE: Quantities and types of recommendations regarding diabetes therapy made by pharmacists using adherence data from the two methods were tabulated. RESULTS: In the MEMS group, 47 percent of the recommendations related to patient education compared with 12 percent in the control group (p = 0.028). MEMS data would have changed four recommendations in the control group to involve patient education. CONCLUSIONS: MEMS data resulted in different numbers and types of recommendations than pill counts. Pharmacists then could make specific recommendations regarding patient education before resorting to pharmacologic manipulations.
Aged↗