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Biomedical subjects

L Hendeles

Publications and source records attributed to L Hendeles.

At least 109 records · Page 6Linked to original sources
PubMed1981

Pharmacologic prophylaxis of allergic rhinitis: relative efficacy of hydroxyzine and chlorpheniramine.

The efficacy of hydroxyzine and chlorpheniramine in preventing exacerbations of ragweed allergic rhinitis was compared in a double-blind, randomized manner. Ninety-five subjects with positive skin tests, a history of two previous symptomatic seasons, and discontinuation of immunotherapy for at least 1 yr received either hydroxyzine 150 mg/day, chlorpheniramine 24 mg/day, or placebo during the 1978 ragweed season. Subjects in the placebo group experienced annoying or disabling sneezing 50% of days during the period of highest pollen counts whereas those in the chlorpheniramine and hydroxyzine groups experienced this symptom with equal severity only 22% and 12% of days, respectively. Suppression of rhinorrhea and itchy nose was similar although less dramatic. Both antihistamines were more effective than placebo in altering conjunctivitis, but neither decreased the frequency or severity of nasal stuffiness. Skin tests to ragweed decreased in diameter during the season by 38%, 13%, and 3% among patients receiving hydroxyzine, chlorpheniramine, and placebo, respectively. Frequent drowsiness occurred initially in subjects taking both antihistamines but did not persist. Thus, prophylactic antihistamine therapy effectively prevents most symptoms of seasonal allergic rhinitis without persistent drowsiness. These data further suggest a therapeutic advantage for hydroxyzine over chlorpheniramine in the doses used.

Adolescent↗
PubMed1981

Relationship of formulation and dosing interval to fluctuation of serum theophylline concentration in children with chronic asthma.

Completeness of absorption and fluctuations in serum, theophylline concentration were examined in 14 children, 8 to 17 years of age (mean 12.4), with chronic asthma treated in variable sequence with a slow-release formulation at eight- and 12-hour intervals, and plain tablets every six hours. The total fraction absorbed for the slow-release formulation was 0.98 +/- 0.07 (mean +/- SEM) during the eight-hour and 0.99 +/- 0.04 during the 12-hour regimens. Observed fluctuations in serum concentration were closely approximated by predictions determined from absorption of single doses in adult volunteers. Available single-dose absorption data then were used to compare predicted fluctuations in serum concentration among nine formulations (18 brand names) for eight- and 12-hour dosing in an average child and adult (elimination half-lives of 3.7 and 8.2 hours, respectively). Although predicted peak concentrations were less than twice the trough for all products when given at 12-hour intervals to an average nonsmoking adult, only two of the nine formulation (both from the same manufacturer) were likely to maintain predicted fluctuations within the 10 to 20 micrograms/ml therapeutic range during 12-hour dosing intervals in an average child. Most children and those adults with rapid elimination generally will require eight-hour dosing with the other products.

Adolescent↗
PubMed1980

Dose-dependent kinetics for theophylline: observations among ambulatory asthmatic children.

In order to assess the clinical impact of dose-dependent kinetics for theophylline, the relationship between serum concentration and daily dosage among patients under the care of the University of Iowa Pediatric Allergy and Pulmonary Service was examined. Dosage was titrated clinically, with the final adjustment based on a serum theophylline measurement. Of 200 charts initially reviewed, 42 patients were found in whom at least two peak serum concentrations had been measured at different doses of the same theophylline preparation. In 30 (15% of initial 200) of these 42 patients, the percent change in serum concentration exceeded the percent change in dose by at least 50%. Subsequently, 300 additional charts were reviewed to identify a total of 26 patients with three steady-state serum concentrations at three different doses. Only five of these patients demonstrated a linear relationship between dose and serum concentration; the other 21 demonstrated disproportionate changes compatible with parallel first-order and dose-dependent kinetics. Thus, clinically important dose-dependent kinetics for theophylline occur in at least 15% of children, and theophylline dosage therefore must be adjusted in small increments in order to avoid disproportionately large changes in serum concentration with consequent risks of toxicity during continuous therapy.

Adolescent↗
PubMed1980

The reliability of serum theophylline determinations from clinical laboratories.

Three aliquots of pooled serum containing theophylline and disguised as patient specimens were sent, one at a time, on different days, to 29 community hospital and referral laboratories serving Iowa. The mean +/- SEM concentration of 65 replications for the same serum pool was 15.7 +/- 0.1 microgram/ml. Twenty-eight per cent of the 85 measurements reported by the clinical laboratories were outside the acceptable range of 13.2 to 18.1 microgram/ml established by the 95% confidence limits of the assayed pool. Reliability of the results was not related to the type of facility, method of measurement, or fee charged. Therefore, variation in clinical laboratory performance was a result of technician error in handling or analyzing the specimens. We conclude that measurements of serum theophylline can only be relied on to adjust dosage when the accuracy of the laboratory has been established with blinded samples.

Double-Blind Method↗
PubMed1980

Medical management of noninfectious rhinitis.

Noninfectious rhinitis and the clinical pharmacology of drugs used in its treatment, including specific treatment recommendations, are reviewed. Characterized by hyperreactivity of the nasal mucosa to a variety of stimuli, noninfectious rhinitis can be classified either as seasonal or perennial allergic rhinitis (when antigens can be identified) or as vasomotor or nonallergic rhinitis (when antigens are not identifiable). However, noninfectious rhinitis is probably better viewed as a continuum between these extremes rather than as definitive categories. Treatment measures include removal of offending agents when possible, and injection of allergenic extracts to decrease sensitivity to inhalant allergens. Among the pharmacologic alternatives, the classical H1 antihistamines competitively inhibit the action of mast-cell histamine at its receptor sites and thus decrease sneezing, nasal pruritus, rhinorrhea, and conjunctivitis. Orally bioavailable alpha-adrenergic agents such as pseudoephedrine and phenylpropanolamine decrease nasal congestion that responds poorly to antihistamines. Topical vasoconstrictors are contraindicated in chronic rhinitis because of the complications of rebound congestion. Systemic corticosteroids are effective but rarely appropriate for chronic rhinitis. Potent topical corticosteroids such as intranasal beclomethasone dipropionate are useful for severe nasal congestion. Cromolyn sodium, an inhibitor of histamine release from mast cells, appears to have some efficacy in suppressing symptoms of allergic rhinitis and conjunctivitis when used topically. Anticholinergics have occasionally been recommended to reduce rhinorrhea, but little data on their efficacy are available.

Adolescent↗
PubMed1980

Experience with theophylline for the management of chronic asthma.

Even with the availability of new and exciting antiasthmatic drugs, theophylline is emerging as one of the most useful noncorticosterioid agents available for suppressing symptoms in the patient with chronic asthma. Maximal benefit, however, requires appreciation of recent developments related to the pharmacodynamics and pharmacokinetics of theophylline. Serum theophylline concentrations between 10 and 20 microgram/ml are most likely to result in benefit without toxicity. A wide range of doses is required to attain these serum concentrations as a function of individual variability in the rate of drug elimination. Sustained-release theophylline preparations, when reliably and completely absorbed, offer major therapeutic advantage by minimizing fluctuations in serum concentrations and consequent variation in effect between doses. Moreover, this stabilization of the airway hyperreactivity of asthma can be attained with 12-hour dosing for most patients with one of the newer formulations. Initiation of therapy with low doses and determination of final dosage by measurement of serum theophylline concentration is essential for safe and effective use of this drug. Based upon cumulative frequency distributions, a simple and efficient dosing schedule had been developed that virtually eliminates problems of intolerance to the drug. About 99% of children and almost as many adults tolerate theophylline without adverse effects when used in this manner and most patients can be maintained virtually free of asthmatic symptoms with theophylline as the only chronic medication.

Adrenal Cortex Hormones↗
PubMed1980

Avoidance of adverse effects during chronic therapy with theophylline.

Recent definition of the pharmacodynamics and pharmacokinetic characteristics of theophylline and readily available, specific assays have increased the therapeutic benefits from this drug while decreasing the risk of toxicity. Once familiarity is achieved with the various factors that alter clearance, such as age, smoking habits, physiological abnormalities, and concurrent drug therapy, initial dosage can be appropriately individualized. Careful product selection, the slow progressive titration of dose over nine days, and the accurate measurement and interpretation of serum theophylline concentration prevent adverse effects and interactions. However, long-term therapy with theophylline should probably be avoided when other alternatives are available in patients with cor pulmonale, liver dysfunction, cardiac decompensation, migraine headaches, and seizure disorders.

Drug Interactions↗
PubMed1980

Role of dialysis in the management and prevention of theophylline toxicity. Commentary.

Various methods have been described for the extracoporeal removal of theophylline from the body. Charcoal hemoperfusion appears to be the most efficient means while peritoneal dialysis does not even match normal metabolic clearance. None have been unequivocally associated with clinical benefit in the presence of severe theophylline toxicity, although the use of efficient means that increases theophylline elimination may be of value prior to the onset of seizures if serum concentrations are over 60 micrograms/ml. While the treatment of life-threatening symptoms from theophylline overdose remains poorly defined, toxicity during clinical use is avoidable. Mean pharmacokinetic indices and dose requirements can be used to asses risk, and measurement of serum levels further allows appropriate individualized dosage.

Charcoal↗