Fortnightly review: drug treatment of epilepsy.
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Acetates↗
Biomedical subjects
M Feely
Publications and source records attributed to M Feely.
Prescribing of anti-epileptic drugs in the northern and Yorkshire region: 1992-1995.
Epilepsy is a condition for which regular drug treatment is normally prescribed. We have examined the primary care prescribing rates for anti-epileptic drugs (AEDs) in a region of northern England with a population of 6.8 million. Over the 4-year period 1992-1995 the number of AED prescription items issued rose by 15%. A third of this rise is accounted for by increased prescribing of the new anticonvulsants, vigabatrin, lamotrigine and gabapentin, which are primarily indicated for adjunct use. Prescribing of phenytoin and barbiturates fell over the same period, but this reduction was more than compensated for by increased prescribing of carbamazepine and sodium valproate. There were notable differences in both the overall volume and the choice of AEDs used in different health authority areas and these are probably attributable to the influence of the local secondary-care sector on the therapeutic regimens adopted by general practitioners in the area.
Anticonvulsants↗
Once a day is best: evidence or assumption? The relationship between compliance and dosage frequency in older people.
To rationalise medication in the elderly, physicians often change multiple dose regimens to once daily in the belief that this improves compliance. Effective methods for measuring compliance have only come into use during the last decade. Partly as a result of this, high quality studies comparing once daily with other regimens in the elderly, are lacking. What evidence there is, from investigations which used suboptimum methods and/or mixed (elderly/younger) patient groups, does not justify the widely held view that 'once a day is best', particularly when compared with twice daily regimens.
Aging↗
Initial evaluation of low-dose phenobarbital as an indicator of compliance with antimalarial drug treatment.
Since poor compliance with antimalarial therapy is often suspected but difficult to prove, this study attempted to establish a model for predicting the plasma concentration of phenobarbital (given in low doses in conjunction with the drug) as an indicator of compliance. Phenobarbital was chosen because its value had been demonstrated as a marker of compliance in long-course therapies, any significant departure from steady-state concentrations (achieved with full compliance) indicating one or more missed doses. Therapy for uncomplicated malaria varies from 5 days with artesunate to 7 days with quinine + tetracycline. Volunteers with confirmed falciparum malaria were randomized into 5 groups and given malaria therapy as well as phenobarbital daily for 3-7 days. Plasma samples for determination of phenobarbital concentrations were taken just prior to the daily dose of phenobarbital. Although there was a clear and predictable individual pattern of blood concentrations following each dose of phenobarbital, inter-individual variation in blood levels was significant and reduced their predictive value beyond the second day's dose. The cause of the variations is not clear; it could be attributable to different sources of the drug, previous intake of phenobarbital by the patient, or differences in drug absorption and disposition in malaria patients. Results for the 5-day artesunate regimen suggest that phenobarbital may be useful as a marker of compliance if the patient stops medication after 3 days; clear differences were evident at the end of the course of treatment between plasma phenobarbital concentrations in individuals completing the 5-day course and those who stopped after 3 days. For the quinine-tetracycline regimen, results suggest that it may be possible to discriminate between subjects where there is a 3-day difference in treatment. Phenobarbital is a better discriminant when dosing is every 24 hours as with artesunate, rather than the 8-hourly regimen for quinine-tetracycline. When measuring compliance for malaria treatment, if it is important to know what proportion of patients reach 3, 5 or 7 days of compliance, then phenobarbital might have a role to play in this assessment, but further investigations in more patients would be required. Alternatively, different markers could be used for the doses to be given on these days and, as long as the patient does not mix the doses for the different days, sequential doses and determination of compliance could be based on an "all or none" detection of the marker rather than on drug levels.
Adolescent↗
Steady-state clearance rates of warfarin and its enantiomers in therapeutically dosed patients.
Previous studies to identify the pharmacokinetics of R- and S-warfarin have not used steady-state area under the curve (AUC) data during therapeutic doses of racemic warfarin. Instead they have used high single doses of either racemic warfarin or a single enantiomer in volunteers or have taken a single blood sample from anticoagulated patients and assumed full compliance and a steady-state status. In this study, a series of steady-state racemic warfarin, R-warfarin, and S-warfarin serum concentrations, during a 24 h dosage interval, was measured in 10 compliant patients (5 females and 5 males) taking racemic warfarin. The anticoagulation status of all 10 patients according to the International Normalised Ratio (INR) was stable. Their mean (SD) age and weight were 67.0 (9.9) yr and 63.9 (15.4) kg. The mean (SD) clearances derived from steady-state AUC values, following therapeutic dosing, for racemic warfarin, R-warfarin, and S-warfarin were 2.40 (0.82), 2.30 (0.65), and 2.80 (1.17) ml/h/kg, respectively. The mean (SD) ratio of S-warfarin clearance was 1.24 (0.40). Comparison of the clearance measured from the AUC, of these patients, to one point determinations assuming steady state for the samples drawn at either 6, 15, or 20 h after dosage (during the dosing interval) showed some statistical differences. Most single point determinations of warfarin clearance assume that a sample of 12 h postdose is equivalent to that of the steady-state concentration, but in this study the steady-state concentration of only 6 patients occurred between 6 and 15 h postdate. This could explain why these studies demonstrate differences in the clearance of R- and S-warfarin compared to the values we have derived from steady-state AUC data using patients with proven compliance and therapeutic doses.
Administration, Oral↗
The pharmacokinetics of methadone in healthy subjects and opiate users.
AIMS: There is some evidence that monitoring methadone plasma concentration may be of benefit in dosage adjustment during methadone maintenance therapy for heroin (opiate) dependence. However, the kinetics of oral methadone are incompletely characterized. We attempted to describe the latter using a population approach combining intensive 57 h sampling data from healthy subjects with less intensive sparse 24 h data from opiate users. METHODS: Single oral doses of rac-methadone were given to 13 drug-naive healthy subjects (7 men and 6 women) and 17 opiate users beginning methadone maintenance therapy (13 men and 4 women). Plasma methadone concentrations were measured by h.p.l.c. Kinetic analysis was performed using the P-Pharm software. RESULTS: Comparison of kinetic models incorporating mono- or biexponential disposition functions indicated that the latter best represented the data. The improvement was statistically significant for the data from healthy subjects whether the full 57 h or truncated 24 h profiles were used (P<0.031 and P<0.024, respectively), while it was of borderline significance for the more variable data from opiate users (P=0.057) or for pooled (healthy subjects and opiate users) data (P=0.066). The population mean oral clearance of methadone was 6.9+/-1.5 s.d. l h(-1) (5.3+/-1.2 s.d. l h(-1) using 0-24 h data) in the healthy subjects. The results of separate analyses of the data from opiate users and healthy subjects were in contrast with those obtained from pooled data analysis. The former indicated a significantly lower clearance for opiate users (3.2+/-0.3 s.d. l h(-1), P<0.001); 95% CI for the difference = -3 to -6 l h(-1) and no difference in the population mean values of V/F (212+/-27 s.d. l and 239+/-121 s.d. l, P=0.15), while according to the latter analysis addiction was a covariate for V/F but not for oral clearance. A slower absorption of methadone in opiate users was indicated from the analysis of both pooled and separate data. The median elimination half-life of methadone in healthy subjects was 33-46 h depending on the method used to calculate this parameter. CONCLUSIONS: Estimates of the long terminal elimination half-life of methadone (33-46 h in healthy subjects and, possibly, longer in opiate users) indicated that accurate measurement of this parameter requires a duration of sampling longer than that used in this study. Our analysis also suggested that parameters describing plasma concentrations of methadone after a single oral dose in healthy subjects may not be used for predicting and adjusting dosage in opiate users receiving methadone maintenance therapy unless coupled with feedback concentration monitoring techniques (for example Bayesian forecasting).
Adolescent↗
Hepatitis and hepatitis immunisation.
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Adverse Drug Reaction Reporting Systems↗
Out in the open--the reality of suicide and parasuicide.
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Humans↗
Defining the concept of care in the community.
Care in the community has meant many different policies at different times. Recent policies have changed definitions but have done little to improve the lot of people affected by mental illness.
Community Mental Health Services↗
Hand-in-hand to the same goal. Quality assurance and research in nursing.
1. The provision of good quality care is a right for all patients and the responsibility of all who deliver it. 2. Care based on knowledge that is validated by research can lead to improved practice and the further development of the service. 3. Patients now question the care they receive and expect an assurance of the quality of care they will receive when in hospital. 4. Quality assurance and the utilisation of research findings can enhance and improve patient care.
Humans↗
Know your patient. The importance of assessment in care delivery.
Assessment is the first part of the nursing process, and thus forms the basis of the care plan. The essential requirement of accurate assessment is to view patients holistically and thus identify their real needs.
Clinical Competence↗
The influence of an academic representative on prescribing by general practitioners.
1. The effect of providing information about medicines by a short 'sales' interview between individual general practitioners and an 'academic representative' on prescribing was investigated. 2. The promotional campaign was designed to encourage a rational approach to prescribing of non-steroidal anti-inflammatory agents in an intervention group of 101 general practitioners selected at random from the Leeds Family Practitioner Committee (FPC). The remaining general practitioners in the Leeds FPC acted as a reference group. 3. The prescribing data for each group for 5 months immediately prior to and 5 months following intervention were compared. 4. Intervention produced a significant increase (P less than 0.005) in the prescribing cost of ibuprofen, the non-steroidal promoted as first choice agent, which was sustained for at least 5 months. 5. Prescribing of the second choice agent, piroxicam, decreased in the reference group but not in the intervention group. 6. There was a decrease in the average prescribing cost of pounds 6.60 per doctor per month in the intervention group compared with the reference group.
Costs and Cost Analysis↗
A strategy to regain control: helplessness and depressive illness in women.
The feelings of helplessness which accompany depression in many women have known psychological, physiological and sociological causes. By including patients in the decision-making process, nurses can help them begin to take control over their lives.
Depressive Disorder↗
Comparison of lisinopril versus atenolol for mild to moderate essential hypertension.
The antihypertensive effects and safety profiles of lisinopril (10 to 40 mg) and atenolol (50 to 100 mg) were compared in a randomized, double-blind, parallel group trial in 144 patients with essential hypertension. After 8 weeks of therapy, seated blood pressure (BP) decreased by 26/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. Lisinopril produced a greater reduction (p less than 0.05) in sitting systolic BP than did atenolol. Standing BP decreased by 25/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. No important changes in hematologic and biochemical profiles were seen with either drug. Eleven patients, 7 receiving lisinopril and 4 receiving atenolol, were withdrawn because of adverse experiences; another 3 patients defaulted during treatment, 1 in the lisinopril group and 2 in the atenolol group. Both drugs were well-tolerated and are therefore suitable for first-line therapy in essential hypertension.
Antihypertensive Agents↗
Measuring compliance in methadone maintenance patients: use of a pharmacologic indicator to "estimate" methadone plasma levels.
A quantitative indicator of compliance is not available for methadone--the drug of choice for the treatment of opioid addiction. We successfully used low-dose phenobarbital (a valid pharmacologic indicator) to measure compliance by incorporating the drug into the methadone medication of patients attending an addiction unit. Plasma phenobarbital and methadone concentrations were measured in 20 (11 clinic-based and 9 community-based) patients receiving long-term treatment with the phenobarbital level-to-dose ratio, together with interviews, to validate methadone measurements and to monitor compliance. Patients attending the unit on a daily basis and who consumed their medication in the clinic were substantially more compliant than community-based patients. Laboratory measurements of phenobarbital and methadone helped to identify the use of illicit methadone, as well as incorrect self-administration, such as the consumption of several days' dosage at one time.
Adult↗
The prediction of steady-state plasma phenobarbitone concentrations (following low-dose phenobarbitone) to refine its use as an indicator of compliance.
1. A model for predicting the steady-state plasma concentration of phenobarbitone following low-dose phenobarbitone used as an indicator of compliance was derived using data for 10 healthy volunteers. 2. Each volunteer was given a single 30 mg oral dose of phenobarbitone and the pharmacokinetics were described. Subsequently, volunteers were given phenobarbitone 2 mg daily for 28 days and a further pharmacokinetic profile determined during and after this period. 3. An initial predicted estimate of steady-state plasma drug concentration was made using each volunteer's demographic details. This estimate was revised by Bayesian analysis using single timed samples (24, 48, 72 or 96 h) following the single dose. 4. The model was tested on a further 10 healthy volunteers given a single 8 mg dose and who were subsequently given 2 mg daily for 28 days. 5. The revised estimate of peak steady-state plasma phenobarbitone concentration utilising the 96 h post-single dose concentration (356 ng ml-1) was least biased (mean prediction error +/- 95% CI = 10.6 +/- 19.8 ng ml-1) and most precise (root mean square error +/- 95% CI = 28.3 +/- 19.0 ng ml-1). In all cases the peak or trough steady-state drug concentration was within 13% of the predicted value. 6. The model reflected compliance accurately in a further eight volunteers with simulated partial (two-thirds) compliance. 7. The use of a predictive model using Bayesian analysis to estimate expected steady-state plasma phenobarbitone concentrations could increase further the usefulness of low-dose phenobarbitone as an indicator of compliance.
Adult↗
What do patients and rheumatologists regard as an 'acceptable' risk in the treatment of rheumatic disease?
A questionnaire designed to ascertain the risk of adverse effects which patients with rheumatic conditions would accept for a particular therapeutic outcome was administered to 50 patients. The same questionnaire together with 'potted' histories of five of the patients was sent to 10 consultant rheumatologists. The willingness of both patients and doctors to risk side-effects varied with both the severity of the side-effect and the potential therapeutic benefit. Doctors were more willing than patients to risk death or serious disability (Wilcoxon, P less than 0.01) for a particular expected benefit. Doctors were also more willing to risk side-effects in treating seropositive rheumatoid arthritis than in treating non-articular rheumatism. No correlation was seen for patients between acceptable risk and diagnosis, pain or smoking habits. The risks which both groups stated they were willing to accept were less than those apparently associated with antirheumatic therapy. The results disagreed markedly with those of a previous study, demonstrating the importance of the methods used in this type of work.
Attitude of Health Personnel↗
A comparison of a short half-life marker (low-dose isoniazid), a long half-life pharmacological indicator (low-dose phenobarbitone) and measurements of a controlled release 'therapeutic drug' (metoprolol, Metoros) in reflecting incomplete compliance by volunteers.
1. Although, long half-life compounds appear to be more appropriate pharmacological indicators of compliance with treatment, short half-life markers or measurements of short half-life therapeutic drugs are frequently used. 2. We have compared the usefulness of low-dose phenobarbitone (a long half-life indicator), low dose isoniazid (a short half-life marker) and controlled release metoprolol (Metros) (a controlled release formulation of a short half-life 'therapeutic' drug) in seven volunteers with simulated partial (two thirds) compliance. 3. Detection of isoniazid metabolites in urine had an 83% sensitivity and 94% specificity for detecting ingestion within the previous 24 h and 100% sensitivity and 82% specificity for detecting ingestion within the past 6 h but gave no indication of the longer term pattern of compliance. 4. At 28 days (a time when steady-state would be obtained for all three drugs) phenobarbitone plasma levels were 70% (66-76%)--median and interquartile range--of the expected steady-state level if compliance had been complete. Corresponding figures for metoprolol were 82% (37-100%). 5. Measurement of phenobarbitone was much superior to isoniazid or metoprolol measurements in reflecting partial compliance over the previous 1 to 4 weeks.
Administration, Oral↗