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Biomedical subjects

J D Robinson

Publications and source records attributed to J D Robinson.

At least 109 records · Page 6Linked to original sources
PubMed1982

Investigation of a dosage regimen for intravenous theophylline.

A study was designed to evaluate the validity of the dosage guidelines for theophylline recommended by Hendeles and Weinberger. A total of seven asthmatic smokers and non-smokers were entered and studied. Theophylline serum concentrations were determined prior to the start of therapy and at intervals following initiation of an infusion. The mean theophylline concentration attained for all subjects was 10 micrograms/ml, however, five of the six patients completing the study did not achieve the predicted serum theophylline concentration. Further study of higher dosage designed to achieve a concentration of 12 micrograms/ml is suggested.

Adult↗
PubMed1982

Prediction of theophylline dosage regimens from limited serum sampling.

Intravenous aminophylline was administered to 13 subjects (6 normal, 7 with chronic obstructive pulmonary disease), and multiple blood specimens were drawn over an 8-hour period for theophylline analysis. Half of the samples were obtained during the distribution phase of the drug and the remainder during the elimination phase. These data were entered into a computer program that both calculates and graphically displays individual two-compartment pharmacokinetic data, and recommends a dosing regimen. Analysis of these data demonstrates wide variability in the theophylline volume of distribution, half-life, and predicted dosage regimen. Dosage regimens can be individualized by obtaining two specimens for theophylline analysis during the elimination phase after intravenous administration of the drug; these regimens correlate extremely well (r2 = 0.95) with those designed using all the data points.

Drug Administration Schedule↗
PubMed1982

A pharmacy student searches for psychological predictors of patient compliance.

Pharmacists are becoming more involved in patient counseling and dosage regimen design in an attempt to improve patient compliance. A study was designed and implemented by an undergraduate pharmacy student in an attempt to gain experience in research methodology and to enhance individual clinical involvement. Forty patients, randomly selected at a community pharmacy and a family practice clinic, were administered a Myers-Briggs Type Indicator exam to assess the patient's degree of systematic preference. Refill dates for each patient's hypertensive medications were examined for six months in order to infer compliance. Results of the psychological exam did not accurately predict patient compliance or noncompliance. The student working with only minimal faculty guidance was able to design, implement, analyze, and describe the study. Colleges of pharmacy are encouraged to implement similar clinical research training projects for undergraduate students.

Adult↗
PubMed1982

Antibiotic prescribing in a family medicine residency program.

A total of 227 ambulatory patients who received prescriptions for antibiotics in a family practice residency program was studied. The common infections treated were urinary tract infections, upper respiratory tract infections, impetigo, nonspecific vaginitis, and bronchitis. Cultures obtained in 21.1 percent of the patients were usually considered to be appropriate. Urinary tract infections were usually treated with co-trimoxazole or other drugs containing sulfonamides; upper respiratory tract infections with amoxicillin, ampicillin, or penicillin; impetigo with penicillin; nonspecific vaginitis with vaginal creams; and bronchitis with ampicillin or erythromycin. Most prescriptions (86 percent) were written generically at an approximate savings of $2 per prescription. A review panel audited the prescribing practices and often (32.2 percent) disagreed among themselves, yet they did determine 65.4 percent of the prescriptions to be appropriate. The rate of appropriate antibiotic prescribing practices among the residents was found to decrease as the level of supervision decreased (P less than 0.01).

Adult↗
PubMed1982

Prediction of serum concentrations of digoxin in a family practice center.

Physicians and clinical pharmacists were compared in their ability to predict serum digoxin concentrations and to discriminate among patients who were subtherapeutic, therapeutic or toxic. Physicians correctly predicted patients having therapeutic serum digoxin concentrations 77 percent of the time, but they were unable to reliably identify subtherapeutic and toxic patients. By incorporating more compliance and pharmacokinetic data into their assessment, pharmacists proved to be more accurate than physicians both in the prediction of serum digoxin concentrations (P less than .01) and in therapeutic classifications (P less than .001). The clinical pharmacist can be a valuable aid to the physician in the prediction and interpretation of serum digoxin concentrations.

Adult↗
PubMed1981

Substituting manganese for magnesium alters certain reaction properties of the (Na+ + K+)-ATPase.

MnCl2 was partially effective as a substitute for MgCl2 in activating the K+- dependent phosphatase reaction catalyzed by a purified (Na+ + K+)-ATPase enzyme preparation from canine kidney medulla, the maximal velocity attainable being one-fourth that with MgCl2. Estimates of the concentration of free Mn2+ available when the reaction was half-maximally stimulated lie in the range of the single high-affinity divalent cation site previously identified (Grisham, C.M. and Mildvan, A.S. (1974) J. Biol. Chem. 249, 3187--3197). MnCl2 competed with MgCl2 as activator of the phosphatase reaction, again consistent with action through a single site. However, with MnCl2 appreciable ouabain-inhibitable phosphatase activity occurred in the absence of added KCl, and the apparent affinities for K+ as activator of the reaction and for Na+ as inhibitor were both decreased. For the (Na+ + K+)-ATPase reaction substituting MnCl2 for MgCl2 was also partially effective, but no stimulation in the absence of added KCl, in either the absence or presence of NaCl, was detectable. Moreover, the apparent affinity for K+ was increased by the substitution, although that for Na+ was decreased as in the phosphatase reaction. Substituting MnCl2 also altered the sensitivity to inhibitors. For both reactions the inhibition by ouabain and by vanadate was increased, as was binding of [48V] -vanadate to the enzyme; furthermore, binding in the presence of MnCl2 was, unlike that with MgCl2, insensitive to KCl and NaCl. Inhibition of the phosphatase reaction by ATP was decreased with 1 mM but not 10 mM KCl. Finally, inhibition of the (Na+ + K+)-ATPase reaction by Triton X-100 was increased, but that by dimethylsulfoxide decreased after such substitution. These findings are considered in terms of Mn2+ at the divalent cation site being a better selector than Mg2+ of the E2 conformational states of the enzyme, states also selected by K+ and by dimethylsulfoxide and reactive with ouabain and vanadate; the E1 conformational states, by contrast, are those selected by Na+ and ATP, and also by Triton X-100.

Animals↗
PubMed1981

Clinical pharmacokinetics of chlordiazepoxide in patients with alcoholic hepatitis.

The clearance of chlordiazepoxide from the systemic circulation was studied in 20 subjects which included 15 patients with alcoholic hepatitis and 5 normal volunteers. The half-life for the appearance of the drug in the systemic circulation was found to increase exponentially with age (r = 0.73, P less than 0.0005) and was independent of the presence of alcoholic hepatitis. The metabolic clearance of chlordiazepoxide was significantly lower in the patients than in the normal subjects (7.6 compared to 13.8 ml/kg-h, P less than 0.005). Linear regression analysis revealed a significant correlation between clearance and albumin (r = 0.77, P less than 0.00005). However, the predictive value of this relationship was shown to be minimal. Multiple regression analysis produced only a slight improvement in the correlation when both albumin and lactate dehydrogenase were used as variables (r = 0.83, P less than 0.00005). In six of the patients, a second clearance study was conducted three weeks following their initial one. All repeat subjects showed improvement both clinically and as reflected by their laboratory tests for liver injury, but there was not a significant change in their clearance of chlordiazepoxide. Multiple regression analysis of the clearance data on the initial and repeat subjects showed a significant correlation between clearance and the variables age, albumin and lactate dehydrogenase (r = 0.91, P less than 0.0025). This relationship suggests that over a short period of time (where age can be considered constant) changes in albumin and lactate dehydrogenase could be potentially useful in predicting clearance changes in a single individual.

Adult↗
PubMed1981

Vanadate binding to the (Na + K)-ATPase.

A particulate (Na + K)-ATPase preparation from dog kidney bound [48V]-ortho-vanadate rapidly at 37 degrees C through a divalent cation-dependent process. In the presence of 3 mM MgCl2 the Kd was 96 nM; substituting MnCl2 decreased the Kd to 12 nM but the maximal binding remained the same, 2.8 nmol per mg protein, consistent with 1 mol vanadate per functional enzyme complex. Adding KCl in the presence of MgCl2 increased binding, with a K0.5 for KCl near 0.5 mM; the increased binding was associated with a drop in Kd for vanadate to 11 nM but with no change in maximal binding. Adding NaCl in the presence of MgCl2 decreased binding markedly, with an I50 for NaCl of 7 mM. However, in the presence of MnCl2 neither KCl nor NaCl affected vanadate binding appreciably. Both the nonhydrolyzable, beta, gamma-imido analog of ATP and nitrophenyl phosphate, a substrate for the K-phosphatase reaction that this enzyme also catalyzes, decreased vanadate binding at concentrations consistent with their acting at the low-affinity substrate site of the enzyme, the presence of KCl increased the concentration of each required to decrease vanadate binding. Oligomycin decreased vanadate binding in the presence of MgCl2, whereas dimethyl sulfoxide and ouabain increased it. With inside-out membrane vesicles from red blood cells vanadate inhibited both the K-phosphatase and (Na + K)-ATPase reactions; however, with the K-phosphatase reaction extravesicular K+ (corresponding to intracellular K+) both stimulated catalysis and augmented vanadate inhibition, whereas with the (Na + K)-ATPase reaction intravesicular K+ (corresponding to extracellular K+) both stimulated catalysis and augmented vanadate binding.

Animals↗
PubMed1981

Vanadate inhibition of brain (Ca + Mg)-ATPase.

Vanadate was a potent inhibitor of the membrane-bound (Ca + Mg)-ATPase from rat brain, the concentration required for 50% inhibition under conditions optimal for enzymatic activity being 3 mu M. Vanadate inhibition increased with the MgCl2 concentration, half-maximal inhibition occurring at 2 mM MgCl2, near the MgCl2 concentration required for half-maximal activation of the ATPase activity. MnCl2 could substitute for MgCl2, and at concentrations of 1 mM (Ca + Mn)-ATPase activity was greater than (Ca + Mg)-ATPase activity, although sensitivity to vanadate was less. Vanadate inhibition increased also with the KCl concentration, half-maximal inhibition occurring at 8 mM, again near the concentration required for half-maximal activation of ATPase activity. By contrast, NaCl stimulated (Ca + Mg)-ATPase activity without potentiating vanadate inhibition. These effects of cations on ATPase activity and vanadate inhibition resemble properties of certain transport ATPases and thus suggest mechanistic and functional similarities.

Animals↗
PubMed1981

Severe diarrhea secondary to propranolol.

Although propranolaol is effective and widely used for many disorders, there are reports of it causing side effects severe enough to warrant its discontinuance. A 71-year-old female is reported to have experienced diarrhea and weight loss from the use of propranolol 20 mg qid. On discontinuing the drug, the diarrhea quickly resolved. On rechallenge with 10 mg qid the patient displayed no problems; however, when the dosage was increased to 20 mg qid, the diarrhea returned. When the drug was discontinued the second time, the diarrhea stopped again. The occurrence of diarrhea in any patient receiving propranolol should cause consideration of an adverse drug reaction.

Aged↗
PubMed1981

Pharmacokinetics service for ambulatory patients.

The use of an EMIT-based serum analysis and clinical pharmacokinetics service at a family practice medical group was evaluated. The baseline level of serum drug concentration (SDC) requests per month was determined in a six-month analysis. After the purchase of the EMIT equipment and the initiation of the service, records were maintained to evaluate the cost of providing the service and its effect on the number of assays performed. This study also determined: (1) how often the pharmacist's recommendations were followed by the physicians, (2) whether the pharmacist's predicted SDC corresponded with the actual concentration, and (3) the effect of an inservice pharmacokinetics educational program on physicians' knowledge, as determined by pre- and post-testing. The requests for SDCs were found to increase from monthly average of 18 to 47 during the first year of the program's operation. The service was found to be financially self-supporting. Family practitioners concurred with the pharmacists' recommendations 97% of the time. Through the use of pharmacokinetic equations and compliance data, the pharmacists were able to predict SDC, with 91% accuracy for compliant patients. The physicians' test scores improved from 59% to 79% after the educational program. The SDC assay service (independent of the consultation service provided by faculty members and students) was self-supporting. Assessment of compliance appears to be a necessary part of an ambulatory pharmacokinetics service in accurately predicting SDC values.

Ambulatory Care↗
PubMed1980

Sensitivity of the (Na+ + k+)-atpase to state-dependent inhibitors. Effects of digitonin and Triton X-100.

Treatment of a purified (NA+ + 5+)-ATPase preparation from dog kidney with digitonin reduced enzymatic activity, with the (Na+ + k+)-atpase reaction inhibited more than the K+-phosphatase reaction that is also catalyzed by this enzyme. Under the usual assay conditions oligomycin inhibits the (Na+ + k+)-atpase reaction but not the K+-phosphatase reaction; however, treatment with digitonin made the K+-phosphatase reaction almost as sensitive to oligomycin as the (Na+ + k+)-atpase reaction. The non-ionic detergents, Triton X-100, Lubrol WX and Tween 20, also conferred sensitivity to oligomycin on the K+-phosphatase reaction (in the absence of oligomycin all these detergents, unlike digitonin, inhibited the K+-phosphatase reaction more than the (Na+ + k+)-atpase reaction). Both digitonin and Triton markedly increased the K0.5 for K+ as activator of the K+-phosphatase reaction, with little effect on the K0.5 for K+ as activator of the (Na+ + k+)-ATpase reaction. In contrast, increasing the K0.5 for K+ in the K+-phosphatase reaction by treatment of the enxyme with acetic anhydride did not confer sensitivity to oligomycin. Both digitonin and Triton also increased the inhibition of the K+-phosphatase reaction by ATP and increased the inhibition by inorganic phosphate and vanadate. These observations are interpreted as digitonin and Triton favoring the E1 conformational state of the enzyme (manifested by sensitivity to oligomycin and a greater affinity for ATP at the low-affinity substrate sites), as opposed to the E2 state (manifested by insensitivity to oligomycin, greater sensitivity to phosphate and vanadate, and a lower K0.5 for K+ in the K+-phosphatase reaction). In addition, digitonin blocked activation of the phosphatase reaction by Na+ plus CTP. This effect is consistent with digitonin dissociating the catalytic subunits of the enzyme, the interaction of which may be essential for activation by Na+ plus nucleotide.

Animals↗