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Biomedical subjects

R P Iafrate

Publications and source records attributed to R P Iafrate.

15 recordsLinked to original sources
PubMed1993

Provision of pharmaceutical care in the intensive care unit.

The highly specialized knowledge and skills necessary to care for critically ill patients requires a team approach involving physicians, nurses, pharmacists, and other health care providers. The role of the pharmacist in the intensive care unit is evolving rapidly to a new responsibility for ensuring definite drug therapy outcomes that improve the patient's quality of life. The provision of pharmaceutical care by pharmacists involves identifying, resolving, and preventing drug-related problems. Many medication errors, adverse drug reactions, drug interactions, and inappropriate therapies can be avoided, which will certainly benefit the patient as well as the nursing professions.

Humans↗
PubMed1990

Rifampin relieves pruritus in children with cholestatic liver disease.

Chronic cholestatic liver disease in children frequently results in severe intractable pruritus. Current forms of therapy, including cholestyramine, are usually ineffective. Therefore, a 6-wk, double-blind, crossover study was designed to test the ability of rifampin to relieve pruritus in children with chronic cholestasis. Rifampin proved effective in alleviating pruritus in all five children tested compared with a placebo-treated group. After the 6-wk study period, rifampin was continued for 6 mo, and its effectiveness was maintained. No complications resulted from rifampin use. This study and a similar study in older patients with primary biliary cirrhosis suggest that a highly effective form of therapy is available for treatment of severe pruritus in patients with chronic cholestasis. These patients must be carefully selected and frequently monitored.

Adolescent↗
PubMed1987

Individualizing gentamicin dosage in patients with cystic fibrosis: limitations to pharmacokinetic approach.

Gentamicin serum concentrations were measured in 15 children and seven adults with cystic fibrosis and in eight children with other diseases. Potentially toxic trough concentrations occurred in three of the first nine patients studied, in whom the dose and a 4-hour dosing interval were prescribed on the basis of one-compartment pharmacokinetic calculations (Sawchuck-Zaske method). In contrast, final concentrations were within the accepted target ranges for the remaining 13 patients with cystic fibrosis, in whom the dose and interval were adjusted empirically on the basis of a single pair of "peak" and trough values. The mean +/- SD final dosage required to achieve target concentrations was 13.8 +/- 2.9 mg/kg/d for children and 11.8 +/- 1.1 mg/kg/d for adults (P greater than 0.05), generally divided into four doses at 6-hour intervals. Mean half-life and incremental increase in serum concentration from previous trough to subsequent "peak," an indirect measurement of volume of distribution, were not significantly different between children or adults with cystic fibrosis and pediatric control subjects; there was little interpatient variability in these values. Thus the high dosage requirements were related more to the higher target concentrations than to altered pharmacokinetic disposition in patients with cystic fibrosis. We conclude that the initial dose of gentamicin to achieve a peak of 8 to 12 micrograms/mL and a trough of less than 2.0 micrograms/mL in patients with cystic fibrosis should be 3 mg/kg administered every 6 hours in children and every eight hours in adults. Subsequent dosage adjustment should be made on the basis of a pair of peak and trough serum concentration measurements obtained after the fifth dose. Dosing intervals in this patient population generally should be no shorter than every 6 hours, even if the initial trough concentration is less than 1 microgram/mL.

Adolescent↗
PubMed1986

Current concepts in clinical therapeutics: asthma.

The epidemiology, etiology, pathophysiology, diagnosis, and treatment of asthma are reviewed, and the major drugs used in treating asthma are discussed in depth. In terms of morbidity, mortality, and economic impact, asthma is a serious disease. About nine million Americans suffer from it, and in a recent year nearly 2000 people died from it. The underlying mechanism of asthma appears to be a hyperreactivity of the airways to certain stimuli, including environmental irritants, exercise, and psychological factors. The symptoms of asthma are caused by spasm of airway smooth muscle, increased mucus secretion, and inflammation. Asthma may be classified as intermittent (patients with extended symptom-free periods) or chronic (patients with frequent exacerbations). Diagnosis of asthma relies heavily on a comprehensive patient history confirmed with objective physiologic data. Acute or intermittent asthma should be treated first with inhaled beta 2 agonists such as albuterol or terbutaline. Corticosteroids should be started if the response to the beta 2 agonists is inadequate, and theophylline may be used while waiting for the steroids to exert an effect. Adequate hydration, correction of metabolic acidosis, and oxygen are essential supportive measures. Theophylline appears to be the best noncorticosteroid for chronic asthma, although cromolyn is an acceptable alternative. Sympathomimetic bronchodilator therapy and corticosteroids may be needed adjunctively. Immunotherapy is indicated in patients with chronic asthma caused by specific allergens and poorly controlled on theophylline or cromolyn. Asthma is best managed using multiple pharmacologic agents in response to specific events and symptoms, making optimal therapy difficult to achieve and sometimes difficult to define.

Adrenal Cortex Hormones↗
PubMed1985

Measurement of tobramycin concentrations in saliva.

Paired serum and saliva specimens were obtained from 16 patients and three volunteers who had received tobramycin. In addition, saliva was collected from ten controls who had not taken any drugs in the previous week. Tobramycin concentrations were measured in duplicate by the Emit assay modified to obtain precise results at concentrations greater than 0.25 microgram/ml. The drug was undetectable in 32 of 34 saliva specimens and only trace amounts were present in the other two, even though corresponding steady-state serum concentrations were greater than or equal to 4.0 micrograms/ml for 29 of 34 specimens. Tobramycin values were zero for all ten saliva specimens from controls. These results probably can be extrapolated to other aminoglycoside antibiotics since most are hydrophilic and ionized at physiologic pH, which disfavors penetration into saliva. We conclude that saliva cannot be used as a noninvasive indirect method of measuring aminoglycoside serum concentrations to guide dosage adjustments.

Adolescent↗
PubMed1984

Evaluation of a rapid immunoassay for monitoring serum pentobarbital concentrations.

A modification of the EMIT-Tox qualitative serum barbiturate assay (Syva Company, Palo Alto, CA) was evaluated for measuring pentobarbital concentrations. Pentobarbital calibrator solutions were substituted for the secobarbital calibrators provided with the assay kit, and control solutions of pentobarbital were used to determine the modified assay's precision and accuracy. Specificity for pentobarbital with respect to other barbiturates and assay interference from other drugs were evaluated in vitro. Serum samples obtained from 49 patients receiving intravenous pentobarbital sodium to treat intracranial hypertension were assayed by gas-liquid chromatography (GLC) and by the modified EMIT procedure. Samples from patients who were receiving both phenobarbital and pentobarbital (9 of 49) were assayed for both drugs, interference curves were plotted, and the corrected pentobarbital concentrations were compared with GLC values. The modified assay method provided an accurate measurement of serum pentobarbital concentrations of 1-30 micrograms/ml. Significant cross-reactivity with the pentobarbital assay was present for secobarbital, butabarbital, allobarbital, and phenobarbital. Dexamethasone, dopamine, phenytoin, cimetidine, lidocaine, diazepam, morphine, and several other drugs at concentrations of 1000 micrograms/ml did not interfere with the assay. There was a strong correlation between the GLC reference method and the modified EMIT assay (r = 0.96). Clinically important cross-reactivity with phenobarbital was found; the corrected pentobarbital concentrations for patients who had received phenobarbital strongly correlated with GLC results (r = 0.98). The modified assay appears to be sufficiently reliable for determination of pentobarbital serum concentrations.

Chromatography, Gas↗
PubMed1982

Computer-simulated conversion from intravenous to sustained-release oral theophylline.

A computer equipped with a pharmacokinetic program was used to theoretically determine the proper time to administer the first dose of a commonly prescribed, sustained-release oral theophylline product (Theo-Dur) in patients maintained on a continuous intravenous aminophylline infusion. Four conversion methods were tested. They included giving the first oral dose (1) immediately upon discontinuation of the iv infusion, (2) two hours after discontinuing the iv infusion, (3) four hours after discontinuing the iv infusion, and (4) two hours before discontinuing the iv infusion. Each of the four methods was simulated in three groups of patients: smokers, nonsmokers, and patients with cirrhosis. Results showed that, in most situations, given the first oral dose immediately upon discontinuation of the intravenous infusion provided minimal deviation from eventual steady-state levels. In addition, this computer simulation suggests that the initial 12-hour maintenance dose recommended by the FDA may result in toxicity in certain patient groups.

Administration, Oral↗
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

Effect of dose and ointment application technique on nitroglycerin plasma concentrations.

Each of ten non-smoking, healthy male volunteers between the ages of 20 and 30 and within 10% of their ideal body weight received four nitroglycerin ointment (NTG-O) treatments: 1/2" NTG-O over 3.94 in2 and 7.88 in2, and 1" NTG-O over 3.94 in2 and 7.88 in2 in a randomized order. Eleven blood samples and 22 determinations of heart rate and blood pressure were obtained over each 6-hour study period. Nitroglycerin plasma concentrations were determined by gas-liquid chromatography with electron capture detection. Area under the nitroglycerin plasma concentration-time curve (AUC), peak plasma concentration (Cmax), and time to peak concentration (Tmax) were determined for each study. Cmax and AUC values were corrected for the actual dose applied. Differences between AUC, Cmax and Tmax were tested using repeated measures analysis of variance. Change in surface area had no statistically significant effect on AUC, Cmax and Tmax. Mean AUC for the 1/2" and 1" doses differed (648 vs 2003 ng.ml-1 min, p = 0.016), as did Cmax (4.6 vs 12.4 ng.ml-1, p = 0.022); however, there was no correlation between individual doses and AUCs. Generally, NTG plasma concentrations within the proposed therapeutic range of 1.2-11.1 ng.ml-1 were detectable throughout each study interval. These data suggest that continuous absorption occurred throughout the 6-hour dosing interval, that a trend toward increased AUC and Cmax occurred with the larger surface area, and that, in general, doubling the dose of NTG-O doubles the AUC.

Adult↗