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Biomedical subjects

B R Parks

Publications and source records attributed to B R Parks.

At least 19 recordsLinked to original sources
PubMed2001

Pediatric patients with undetectable anticonvulsant blood levels: comparison with compliant patients.

Undetectable anticonvulsant blood levels indicate sustained noncompliance (several consecutive doses missed). We compared 91 consecutive outpatients with epilepsy and undetectable anticonvulsant blood levels to 100 patients seen during the same time period, verified as compliant by acceptable serum levels. We hypothesized that pay status, application for Supplemental Security Income, patient age, history of missed appointments, and functional status would differ between compliant and noncompliant patients. We were surprised to find large differences between clinic and insurance patients and between Caucasian and non-Caucasian patients. The 100 compliant patients included 44 Caucasian and 56 non-Caucasian patients, whereas only 9 of 91 noncompliant patients were Caucasian, and only 9 had insurance, compared to 32 compliant patients. Applications for Supplemental Security Income and history of missed appointments were significantly associated with noncompliance, but patient age, seizure type, and seizure control were not. Uninsured Caucasians were more often compliant than non-Caucasians were. Many noncompliant patients had mild epilepsy, which was reportedly doing well. Race and pay status were closely correlated. Several noncompliant females became pregnant, whereas no compliant patients did. Compliant patients were much more likely to be accompanied by a parent or caretaker on clinic visits than noncompliant patients. Noncompliant patients had at least one acceptable subsequent serum level, although 2 patients with intractable epilepsy had undetectable serum levels on three or more occasions. Noncompliance may respond to discussion and advice. We reviewed 124 episodes of undetectable drug levels in the 91 noncompliant patients. Eighteen of these resulted in hospitalization, but in 25 cases, we were told that there had been no seizures since the preceding visit. Many noncompliant patients have infrequent seizures, even if they take little or no medication. Socioeconomic status influences health, life expectancy, and educational success, but it has been claimed to be irrelevant to compliance and adherence issues in epilepsy. Our data and the experience of other centers with childhood diabetes suggest that socioeconomic, racial, and family factors influence compliance or adherence to treatment for many chronic conditions. Educational efforts and support for parents at the start of anticonvulsant treatment may improve compliance. Uninsured patients missed more appointments and were much more likely to be noncompliant than insured patients. Attention to the special problems of Medicaid and minority children is needed.

Adolescent↗
PubMed2000

Anticonvulsant blood levels: historical review with a pediatric focus.

Epilepsy is heterogeneous and its treatment is often complicated by variable drug responses. Buchtal et al reported a close correlation between serum phenytoin levels, electroencephalographic findings, and clinical status in 1960. They suggested that physicians adjust dosage to attain a "therapeutic level." The concept was enthusiastically received. "Therapeutic serum levels" were proposed for most anticonvulsant drugs, and by 1975, most authorities believed that pharmacokinetic factors explained individual differences in drug response. However, Froscher found that measuring levels did not improve patient outcome. More recently, Schumacher's double-blind study found no correlation between phenytoin levels and seizure control or adverse effects. Pharmacodynamic variables (differences in drug responsiveness) are more important than pharmacokinetic factors for many drugs, especially receptor-active drugs. Pharmacokinetic variables were studied first, and led to a simplistic model. They are less significant than pharmacodynamic factors in the case of warfarin anticoagulation. Anticonvulsant levels can reveal noncompliance and pharmacokinetic differences. They say nothing about pharmacodynamics. Reports of "subtherapeutic levels" imply a need to increase dosage, but this is not supported by outcome data. We still lack evidence that specific drug levels are a valid intermediate target 40 years after Buchtal's paper. Responses to some anticonvulsants could depend primarily on pharmacokinetic factors, while pharmacodynamic factors could be supreme for others.

Anticonvulsants↗
PubMed1998

Quality of life assessment by community pharmacists: an exploratory study.

Implicit in the evolving role of pharmacy is that its practitioners embrace the concept of quality of life (QoL). In recent years there has been an increased interest in incorporating health-related quality of life (HRQoL) measures into clinical practice, primarily focusing on the physician as the user of this information. Pharmacists may be able to use these instruments in their practices to provide better pharmaceutical care. To explore the feasibility of such an undertaking, questionnaires were mailed to a national sample of community pharmacies. In addition to the questionnaire, the respondents were provided with examples of two instruments: the Duke Health Profile and the QOLIE-10. A definition of HRQoL was provided to the respondents. After two mailings and a reminder postcard, a usable response rate of 27.2% was achieved. The results revealed that over 80% of the respondents currently discuss HRQoL issues with their patients. In addition, 66% reported that they attempt to assess the HRQoL of their patients, albeit usually on a subjective, informal basis. After viewing examples of HRQoL instruments, over three-quarters of the respondents reported a willingness to use HRQoL assessment tools in their practices. However, only 53.7% of the respondents were familiar with the concept of HRQoL. Less than 5% reported familiarity with formal instruments. The self-reported knowledge of pharmacists concerning HRQoL was low and the respondents recognized a significant gap between their current knowledge and the level of knowledge needed to assess the HRQoL of their patients formally. The results suggest a possible role for the pharmacist in HRQoL assessment. However, the use of HRQoL instruments in community pharmacies will require further training and education on the part of pharmacists concerning the concept of HRQoL, the issues involved in its measurement and how they can use HRQoL information in their practices. In addition, a number of unanswered questions must be addressed through the research process in order for HRQoL questionnaires to become clinical tools in the practice of pharmacy.

Adult↗
PubMed1994

Drug therapy for epilepsy.

Epilepsy, a chronic brain disorder characterized by recurrent seizures, affects 1 to 3 percent of the U.S. population. In addition to six drugs classically used either alone or in combination to control epilepsy, three new agents have recently become available. The choice of therapy for each patient must be individualized, based on an accurate determination of the type of epilepsy, an understanding of drug pharmacokinetics, interactions and side-effect profiles, and issues related to patient acceptability and compliance. Approximately 70 percent of patients currently achieve good control of epilepsy, and it is hoped that new agents and improved therapeutic management can substantially increase this percentage.

Acetates↗
PubMed1991

Intraosseous administration of antibiotics: same-dose comparison with intravenous administration in the weanling pig.

STUDY OBJECTIVES: To assess the reliability of the intraosseous route of administration for delivery of a loading dose of broad-spectrum antibiotics in a pediatric animal model. DESIGN: Serum levels achieved within 90 minutes of equivalent intraosseous (IO) and IV bolus dosing of ceftriaxone, cefotaxime, and a combination of ampicillin and gentamicin were compared in the weanling pig. SUBJECTS: Twelve female weanling pigs were studied in the Animal Facilities Laboratory at the University of Mississippi Medical Center. INTERVENTIONS: Through a proximal tibial IO catheter, each anesthetized animal received one of the following: 50 mg/kg ceftriaxone, 50 mg/kg cefotaxime, or 300 mg/kg ampicillin followed immediately by 2.5 mg/kg gentamicin. Venous blood was obtained for antibiotic assay at 15, 30, 45, 60, and 90 minutes after IO injection. The animals were allowed to recover, and, after a one-week washout period, each received the same antibiotic and dose as before through a peripheral IV. Levels were assayed at the same intervals and IO versus IV were compared. MEASUREMENTS AND MAIN RESULTS: Comparable serum levels of all four antibiotics were achieved by the two routes. Gentamicin levels were statistically indistinguishable IO versus IV at all assay intervals. Ampicillin and cefotaxime levels achieved by the two routes were equivalent within one hour of dosing. Serum levels of ceftriaxone after IO administration paralleled those after IV dosing but remained significantly lower at all time intervals. CONCLUSIONS: In the weanling pig model, the IO route was used to deliver serum levels of broad-spectrum antibiotics comparable to those attained after IV administration. The data support the use of standard parenteral doses for IO administration. To overcome potential avid protein binding of ceftriaxone in the bone marrow, we recommend using ceftriaxone at its highest recommended IO loading dose. Consistent with many other medications that have been similarly tested, these data indicate that initial or empiric antibiotic coverage in hypodynamic and shock states in infants and young children need not await the establishment of traditional IV access.

Ampicillin↗
PubMed1991

Toxicity with dextromethorphan-containing preparations: a literature review and report of two additional cases.

Dextromethorphan-containing cold/cough preparations are frequently prescribed and bought over the counter for use in children. Although generally considered safe, dextromethorphan has been shown to cause CNS side effects, including hyperexcitability, increased muscle tone, and ataxia. Two deaths have been reported with intentional dextromethorphan overdose. A literature review, brief review of pharmacology, and report of two cases of adverse reactions to dextromethorphan-containing preparations are presented.

Child, Preschool↗
PubMed1991

Metabolism and disposition of indomethacin in preterm infants.

38 preterm infants with symptomatic patent ductus arteriosus received indomethacin intravenously. Plasma samples were collected at 2, 4, 6 or 8 and 12 h after each of 3 doses. Indomethacin, demethylindomethacin and p-chlorobenzoic acid were determined in plasma and urine along with acid-labile metabolites using HPLC. Fifty-eight percent of the infants demethylated indomethacin; half of the unchanged and demethylated drug was found as conjugates in urine; 14% deacylated the drug. Shorter elimination half-life, smaller area under the plasma concentration-time curves and increased plasma clearance were associated with demethylation. Postnatal age greater than 2 weeks correlated with both demethylation and failure of indomethacin to effect ductal closure.

Birth Weight↗
PubMed1988

Elevated serum iron levels following administration of cisplatinum.

An increase in serum iron levels and a decrease in serum unsaturated iron binding capacity (uIBC) were noted following the administration of cisplatinum to 9 children with malignancies. The mean serum iron concentration increased from a pretreatment level of 75.7 +/- 30.5 micrograms/ml to a posttreatment level of 162.1 +/- 65.3 micrograms/ml with the first cisplatinum treatment course (p less than 0.004). The uIBC concomitantly decreased from 181.9 +/- 33.7 micrograms/ml to 86.4 +/- 44.6 micrograms/ml (p less than 0.0005). A cumulative effect was noted following subsequent courses. The levels returned to baseline values within 2-4 months following cessation of therapy in 6 children in whom follow-up data were available. It is possible that this reversal of the iron/uIBC ratio is the result of cisplatinum competition for iron binding sites to proteins.

Child↗
PubMed1988

Serum alpha-tocopherol concentrations in preterm infants receiving less than 25 mg/kg/day alpha-tocopherol acetate supplements.

Alpha-tocopherol (aT) concentrations were determined in 52 preterm infants receiving less than 25 mg/kg/day alpha-tocopherol acetate (aTA) supplements through intravenous hyperalimentation solutions, lipid, and oral aTA. One fourth of the study infants had aT concentrations greater than 3.5 mg/dl at least once, and an association between concentrations greater than 3.5 mg/dl and necrotizing enterocolitis was demonstrated. In contrast, another one fourth of the infants' concentrations remained less than 0.5 mg/dl through the first postnatal week. The highly variable serum tocopherol concentrations correlated with total serum lipid content but not with plasma aTA hydrolysis activity.

Humans↗
PubMed1982

Indomethacin and the preterm infant with a patent ductus arteriosus: relationship between plasma concentration and ductus closure.

The relationship of indomethacin pharmacokinetics to clinical and echocardiographic evidence of closure of the patient ductus arteriosus (PDA) is described in 9 preterm infants. PDA closures occurred in 4 infants when peak indomethacin plasma concentrations were 0.71-1.10 micrograms/ml, mean 0.93 +/- 0.16 microgram/ml. With partial or no PDA response to oral treatment, the peak concentrations were 0.20-0.69 microgram/ml, mean 0.57 +/- 0.08 microgram/ml, p less than 0.01. The left atrial size in the study infants correlated inversely with the indomethacin peak concentrations, r = 0.75. The plasma apparent terminal half-life correlated with postnatal age, r = 0.75. All patients with peak concentrations greater than 0.50 microgram/ml had transient oliguria. This study suggests that a minimum indomethacin concentration may be needed to promote PDA constriction.

Bacterial Infections↗
PubMed1982

Gentamicin disposition in asphyxiated newborns: relationship to mean arterial blood pressure and urine output.

The purpose of this study was to investigate the effects of changes in renal function on gentamicin disposition following perinatal asphyxia. Gentamicin pharmacokinetics, renal function, mean arterial pressure (MAP) and five-minute Apgar scores were determined in 80 preterm infants admitted to two neonatal intensive care units over an 18 month period. A 2.5 mg/kg dose of gentamicin was infused intravascularly over 20 to 30 minutes in a retrograde fashion. The gentamicin half-life and clearance were prolonged in asphyxiated infants. For the asphyxiated infants gentamicin half-life increased and urine output decreased with a significant correlation (r = -0.66, p less than 0.05). Gentamicin clearance and urine output in the asphyxia group correlated with MAP (r = +0.67, p = 0.07). In non-asphyxia infants no such correlation was seen. This study does not distinguish between asphyxia-induced or gentamicin-induced nephrotoxicity following gentamicin therapy. We suggest that gentamicin concentrations be closely monitored in asphyxiated newborns who demonstrate compromised renal function.

Asphyxia Neonatorum↗
PubMed1980

Aldosterone-induced hypertension: effects of a kininase inhibitor.

A synthetic orally active angiotensin I converting enzyme inhibitor Captopril (Squibb), (D-2-methyl-3-mercaptopropanoyl-L-Proline), was administered to three groups of hypertensive animals. The animals were made hypertensive by uninephrectomy, daily injections of 5 ug/100 g body weight d-aldosterone (Sigma) in wheat germ oil and substitution of 0.9% NaCl for the drinking water. Captopril was given to pregnant and nonpregnant animals during the developmental phase of hypertension and to nonpregnant animals with established (4 weeks of treatment) hypertension. The agent attenuated the hypertension in both the pregnant and nonpregnant animals when given while hypertension was developing. Captopril was effective in reducing established aldosterone-NaCl hypertension to normotensive levels.

Aldosterone↗
PubMed1980

Effect of indomethacin on desoxycorticosterone acetate-sodium chloride-induced renal lesions in the pregnant rat and her offspring.

To explore the effects of inhibition of prostaglandin synthesis on renal lesions, 37 female rats were made hypertensive and of these, 22 were treated with indomethacin. The blood pressure (207 +/- 5 mm Hg) in the indomethacin group was significantly (p < 0.01) higher than the blood pressure (191 +/- 7 mm Hg) in the control group. Weight changes were not significantly different. Renal lesions of varying severity were noted in mothers and offspring of both groups. The lesions ranged from thickening of the basement membranes to glomerular congestion, some with nearly complete eradication of glomerular architecture. Although the lesions appeared to be more marked in the indomethacin-treated group, no specific pattern of lesion location nor significant differences in the severity of the lesions was demonstrated. These data suggest that the lesions noted were the result of the hypertension. However, exacerbation by indomethacin could not be excluded.

Animals↗