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Biomedical subjects

L Hendeles

Publications and source records attributed to L Hendeles.

At least 145 records · Page 8Linked to original sources
PubMed1976

Need for "counter-detailing" antibiotics.

Selected antibiotic advertisements in medical journals are discussed to illustrate the misleading information that is often disseminated to physicians by the pharmaceutical industry. Laboratory and clinical data are presented to question the validity of selected advertisements which (1) encourage the use of Keflex for severe respiratory infections in children, (2) recommend the use of Keflex for the treatment of bacterial bronchitis, (3) suggest that high tissue penetration is a unique property of Vibramycin, (4) present pooled susceptability data which do not reflect microbial resistance patterns in the patient's hospital, (5) recommend twice-daily administration of Ancef for urinary tract infections but do not clearly state the potential danger of this regimen for other infections, (6) suggest that gentamicin should be given to adults in only two dosage sizes for the treatment of serious Gram-negative infections, and (7) lead the reader to assume that only women need to be treated for Trichomonas infections. It is suggested that as antibiotics are marketed, hospital therapeutics committees should evaluate their advantages and permit formulary additions for only those agents demonstrating increased efficacy, decreased toxicity or decreased cost. Pharmacists who monitor drug therapy can provide information to the physician which will increase his awareness of optimal antibiotic therapy.

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PubMed1976

Pharmacotherapy of asthma.

The pharmacological management of asthma is reviewed. Drugs discussed include: (1) sympathomimetic amines, (2) theophylline, (3) cromolyn sodium and (4) corticosteroids. Aspects of treatment discussed include: initial evaluation, therapy for acute symptoms, and chronic asthma.

Acute Disease↗
PubMedDate not supplied

Theophylline. A "state of the art" review.

Theophylline is a bronchodilator and respiratory stimulant that is effective in the treatment of acute and chronic asthma, Cheyne-Stokes respirations, and apnea/bradycardia episodes in newborns. It is also used as an adjunct in the treatment of congestive heart failure and acute pulmonary edema, but it has no established efficacy in patients with chronic irreversible airways obstruction. Benefits and risks from theophylline relate directly to serum concentration, which is a function of both dose and elimination characteristics of the drug in an individual patient. When used to treat acute symptoms, an initial loading dose based on a mean volume of distribution is required to rapidly obtain maximum bronchodilator effect. Because of large interpatient differences in elimination, constant intravenous infusion rates for continued therapy must be guided by monitoring serum theophylline concentration at intervals until a steady-state serum concentration is reached within the 10-20 micrograms/ml therapeutic range. Intravenous, oral or rectal solutions and plain uncoated tablets are appropriate for acute therapy, while reliably absorbed slow-release formulations offer therapeutic advantages for the management of chronic asthma, particularly in patients with rapid elimination. Dosage for long-term therapy is determined by starting with low doses that allow virtually complete acceptance of the medication followed by gradual increases, if tolerated, at three day intervals until mean age-specific doses are reached. Subsequent adjustment in dosage regimens are then based upon serum concentration measurements. Most clinical laboratories now measure theophylline, and newer systems have been developed to provide emergency results within minutes at a reasonable cost. In cases of theophylline poisoning, the drug must be rapidly removed to prevent life-threatening toxicity. When serum concentrations are in excess of 60 micrograms/ml charcoal hemoperfusion dialysis may be indicated, even in the absence of obvious signs of toxicity.

Absorption↗
PubMedDate not supplied

Theophylline views.

Explore the source record for details and available documents.

Child↗
PubMedDate not supplied

A clinical and pharmacokinetic basis for the selection and use of slow release theophylline products.

In order to achieve the greatest chance for maximum benefit from theophylline in the management of chronic asthma, the serum concentration should be maintained in the therapeutic range of 10 to 20 micrograms/ml. Conventional rapid release formulations produce excessive fluctuations in serum concentrations that can result in variability in clinical response between doses. In contrast, slow release formulations have the potential to achieve relatively constant serum concentrations with 12-hour dosing intervals, thus providing around-the-clock stabilisation of the hyper-reactive airways that characterise chronic asthma. Furthermore, the decreased frequency of dosing with these formulations can improve patient compliance. However, significant differences in rate and extent of absorption exist between the available formulations. Single-dose bioavailability studies comparing a slow release product with an oral solution or plain uncoated tablet in a crossover design permit examination of the rate and extent of absorption. Comparison of a slow release product with an oral reference following multiple doses at steady-state permits examination of the extent but generally not rate of absorption. The mean fraction absorbed-time profile, calculated from a modification of the Wagner-Nelson equation, is a process-independent method of comparing rates of absorption of different products after single doses. A prospective study in 14 children with chronic asthma has demonstrated that this modified equation, when rearranged to iteratively solve for serum concentrations, can accurately predict steady-state serum concentrations for different dosing intervals in patient populations with different rates of elimination. When slow release products are compared in this manner at 8- or 12-hour dosing intervals for patients with slow elimination, clinically relevant differences between brands are not apparent. However, in patients with rapid elimination, i.e. children, cigarette smokers, and 25% of non-smoking adults, application of this method shows that only some formulations (i.e. 'Slo-Bid Gyrocaps' and 'Theo-Dur', which is also marketed under different brand names names such as 'Sustaire', 'Pulmi-Dur' and 'Theolin Retard') can maintain serum concentrations within the therapeutic range for an entire 12-hour dosing interval. More rapidly absorbed slow release products must be administered at 8-hour dosing intervals in patients with rapid elimination, despite promotional claims to the contrary. Current products promoted for once-a-day administration are clinically inadequate because of incomplete and erratic absorption, and/or excessive serum concentration fluctuations.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMedDate not supplied

Selecting a decongestant.

Antihistamines and decongestants often are used interchangeably and in combination for a variety of upper respiratory illnesses ranging from allergic rhinitis to the common cold; yet, these two classes of drugs have distinct therapeutic actions. When administered alone, antihistamines are of no value in reducing nasal stuffiness. Therefore, many allergy products also contain decongestants. Conversely, cough-cold remedies often contain antihistamines despite their lack of efficacy in these conditions. Nasal congestion, on the other hand, regardless of its cause, responds quite well to decongestants. The topical route provides a faster and more intense decrease in nasal airway resistance, but has a shorter duration and the potential to produce rebound congestion in patients with allergic rhinitis, whereas oral agents do not. Phenylpropanolamine, pseudoephedrine, and phenylephrine are the most common decongestants. Although all are sympathomimetic amines, their efficacy varies. In particular, phenylephrine is subject to first-pass metabolism and therefore is not bioavailable in currently recommended doses. In addition, phenylpropanolamine and pseudoephedrine, but not phenylephrine, are effective decongestants. Slow-release formulations allow a longer dosing interval, especially during the night. However, most formulations available in the United States are manufactured and sold without Food and Drug Administration scrutiny. Since the in vitro dissolution of many of these products differs, it is possible that some of the generic formulations are not bioequivalent to established brand-name products. Therefore, pharmacists should not substitute formulations without discussing the matter with the prescriber.

Administration, Oral↗
PubMedDate not supplied

Therapeutic equivalence of a generic slow-release theophylline tablet.

STUDY OBJECTIVE: To evaluate the relative bioavailability and clinical efficacy of two slow-release theophylline products. DESIGN: Randomized, double-blind, crossover trial. SETTING: A university-affiliated clinical research center. PATIENTS: Fourteen adults with asthma. INTERVENTIONS: The patients received a generic slow-release theophylline tablet or Theo-Dur at bedtime for 5 nights. MEASUREMENTS AND MAIN RESULTS: Serum drug concentrations were measured after the last dose. Attenuation of exercise-induced bronchospasm (EIB) was included as a surrogate for efficacy. There was no significant difference in extent of absorption. The mean differences between the generic product and Theo-Dur in area under the curve was -13.9 micrograms/ml.hr-1 (95% CI -41 to 12.9, p = 0.3) and in peak concentration (Cmax), -0.5 microgram/ml (95% CI -1.7 to 2.7, p = 0.6). In contrast, the generic product was absorbed more rapidly; the mean differences in the time to peak concentration (Tmax) was -3.0 hours (95% CI -4.3 to -1.7, p = 0.0003), in trough concentration (Cmin), -0.9 microgram/ml (95% CI -1.9 to -0.01, p = 0.05), and in fluctuation between Cmax and Cmin, +128% (95% CI 40 to 217, p = 0.008). Neither product effectively attenuated EIB, since mean serum concentrations during the exercise challenges were unexpectedly below 10 micrograms/ml after both products. CONCLUSION: These two products are not bioequivalent, but the difference in absorption rates is unlikely to be clinically important in most patients (i.e., they are therapeutic equivalents).

Absorption↗