BMC Clinical Pharmacology - Latest articles

How often do physicians review medication charts on ward rounds?

Khang Li Looi and Peter N Black — 2008-09-29

Background: Prescribing errors are common in hospital settings. Regular review of medication charts is recommended as a way to reduce errors but it is not clear how often this happens. The aim of this study was to determine the frequency with which specialist physicians reviewed medication charts during ward rounds. Methods: An observer noted how often consultant physicians at Auckland City Hospital reviewed medication charts during ward rounds. The physicians were not aware that they were being observed. Results: Twenty-one physicians were observed over a 26 week period. The general physicians reviewed the medication charts on 77% of occasions (range: 45% - 100%) during routine ward rounds and 65% of the time (range: 41% - 80%) on post admission rounds. Subspecialty physicians who did not see more than 8 patients on their rounds reviewed medication charts more frequently (88%) than those specialties where more than 8 patients were seen on average (61%). Conclusion: The physicians did not review medication charts on all ward rounds and there was considerable variation in how often they did this. There is some evidence that the frequency with which charts are reviewed decreases as the number of patients seen increases. More efforts should be made to encourage regular review of medication charts.

Use of and attitudes towards the prescribing guidelines booklet in primary health care doctors

Magnus AB Axelsson, Malin Spetz, Anders Mellén and Susanna M Wallerstedt — 2008-09-22

Background: In the region of Västra Götaland in Sweden, prescribing guidelines, drawn up by 24 expert groups and determined by the regional board for drugs, are since 2006 available in the form of an annually published booklet. This study investigates, for the first time, the use of and attitudes towards this publication. Methods: A questionnaire was administered to doctors working in primary health care in the region of Västra Götaland in Sweden. Questions included characteristics of the responding doctor and use of the prescribing guidelines booklet, as well as attitude questions constructed as statements to which the responder should grade his level of agreement from 1 (total disagreement) to 6 (total agreement). Results: Totally 603 filled-in questionnaires were returned (estimated response rate 60%). The majority of the doctors (n = 571, 97%) responded that they use the prescribing guidelines booklet, and when prescribing a drug for a new diagnosis, a drug from the booklet is chosen in most cases [median (25th – 75th percentile) 80 (75–90)]. However, at renewal of a drug prescription, active change to a drug from the prescribing guidelines booklet occurs less often [median (25th – 75th percentile) 50 (20–70)]. The booklet also includes short therapy advice sections, which 231 doctors (42%) use every day and 191 (34%) use every week. The attitudes towards the prescribing guidelines booklet were generally positive. Doctors in privately run primary health care units and doctors running their own business were generally more negative and judged themselves to be less adherent to the prescribing guidelines booklet compared with doctors in publicly run primary health care units. Conclusion: The prescribing guidelines booklet is frequently used and is generally appreciated, though differences exist between subgroups of users.

Long-term platinum retention after treatment with cisplatin and oxaliplatin

Elke EM Brouwers, Alwin DR Huitema, Jos H Beijnen and Jan HM Schellens — 2008-09-17

Background: The aim of this study was to evaluate long-term platinum retention in patients treated with cisplatin and oxaliplatin. Methods: 45 patients, treated 8–75 months before participating in this study, were included. Platinum levels in plasma and plasma ultrafiltrate (pUF) were determined. In addition, the reactivity of platinum species in pUF was evaluated. Relationships between platinum retention and possible determinants were evaluated. Results: Platinum plasma concentrations ranged between 142–2.99 × 103 ng/L. Up to 24% of plasma platinum was recovered in pUF. No platinum-DNA adducts in peripheral blood mononuclear cells (PBMCs) could be detected. Ex vivo incubation of DNA with pUF of patients revealed that up to 10% of the reactivity of platinum species was retained. Protein binding proceeded during sample storage. Sodium thiosulfate (STS) appeared to release platinum from the plasma proteins. Platinum levels were related to time, dose, STS co-administration, and glomerular filtration rates (GFR). Conclusion: Our data suggest that plasma platinum levels are related to time, age, dose, GFR, and STS use. Platinum in plasma, probably, represent platinum eliminated from regenerating tissue. Platinum species in pUF were partly present in a reactive form. The effects of the reactivity on long-term consequences of Pt-containing chemotherapy, however, remains to be established.

Antihypertensive drug class and impaired fasting glucose: a risk association study among Chinese patients with uncomplicated hypertension

Martin CS Wong, Johnny Y Jiang, H Fung, Sian Griffiths and Stewart Mercer — 2008-09-10

Background: There is a scarcity of studies addressing the factors associated with impaired fasting glucose in Chinese patients with uncomplicated hypertension. We included 1,218 patients newly prescribed a single antihypertensive drug in the public primary healthcare setting in Hong Kong, where their fasting glucose levels were measured 6–7 weeks after the first-ever antihypertensive prescription. Methods: The odds ratios of having above borderline (≥ 6.1 mmol/l) and adverse (≥ 7.0 mmol/l) glucose levels, respectively, were studied according to patient age, gender, socioeconomic status, clinic types and antihypertensive drug classes by multivariable regression analyses. Results: The fasting glucose levels were statistically similar (p = 0.786) among patients prescribed thiazide diuretics (5.48 mmol/l, 95%, 5.38, 5.59), calcium channel blockers (5.46 mmol/l, 95% C.I. 5.37, 5.54), β-blockers (5.42 mmol/l, 95% C.I. 5.34, 5.51) and drugs acting on the renin angiotensin system (RAS) [5.41 mmol/l, 95% C.I. 5.20, 5.61]. Multivariate analyses reported no significant associations between antihypertensive drug class and impaired fasting glucose. Elderly patients and male gender were significantly more likely to present with above borderline and adverse readings respectively. Conclusion: Clinicians should be aware of the increased risk of impaired fasting glucose in these groups, and use of thiazides should not in itself deter its use as a first-line antihypertensive agent among ethnic Chinese patients.

Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: The effect of water and timing of meal intake on oral delivery of Salmon Calcitonin

Morten A Karsdal, Inger Byrjalsen, Bente J Riis and Claus Christiansen — 2008-09-09

Background: To investigate the influence of water intake and dose timing on the pharmacokinetic and pharmacodynamic parameters of an oral formulation of salmon calcitonin (sCT). Methods: The study was a randomized, partially-blind, placebo-controlled, single dose, exploratory crossover phase I study. 56 healthy postmenopausal women were randomly assigned to receive five treatments. The treatments comprised a combination of study medication (SMC021 (0.8 mg sCT + 200 mg 5-CNAC), SMC021 placebo, or 200 IU Miacalcic® NS nasal spray), water volume given with the tablet (50 or 200 ml water), and time between dosing and meal (10, 30, or 60 minutes pre-meal). Plasma sCT levels and changes in the bone resorption (C-terminal telopeptide of collagen type I) was investigated. Trial regristration Results: Oral delivery of 0.8 mg of sCT with 50 ml of water compared to that with 200 ml water resulted in a two-fold increase in maximum concentration (Cmax and AUC0–4) of plasma sCT but comparable time to reach maximum concentration (Tmax). The sCT AUC0–4 with 50 ml of water was 4-fold higher than that obtained with nasal calcitonin. The increased absorption of sCT resulted in increased efficacy demonstrated by AUC of the relative change of serum CTX-I measured in the 6 hours post dosing. Conclusion: 0.8 mg sCT with 50 ml of water taken 30 and 60 minutes prior to meal time resulted in optimal pharmacodynamic and pharmacokinetic parameters. The data suggest that this novel oral formulation may have improved absorption and reduction of bone resorption compared to that of the nasal form.

The Clinical Pharmacology of Intranasal l-Methamphetamine

2008-07-21

Background: We studied the pharmacology of l-methamphetamine, the less abused isomer, when used as a nasal decongestant. Methods: 12 subjects self-administered l-methamphetamine from a nonprescription inhaler at the recommended dose (16 inhalations over 6 hours) then at 2 and 4 (32 and 64 inhalations) times this dose. In a separate session intravenous phenylephrine (200 μg) and l-methamphetamine (5 mg) were given to define alpha agonist pharmacology and bioavailability. Physiological, cardiovascular, pharmacokinetic, and subjective effects were measured. Results: Plasma l-methamphetamine levels were often below the level of quantification so bioavailability was estimated by comparing urinary excretion of the intravenous and inhaled doses, yielding delivered dose estimates of 74.0 ± 56.1, 124.7 ± 106.6, and 268.1 ± 220.5 μg for ascending exposures (mean 4.2 ± 3.3 μg/inhalation). Physiological changes were minimal and not dose-dependent. Small decreases in stroke volume and cardiac output suggesting mild cardiodepression were seen. Conclusion: Inhaled l-methamphetamine delivered from a non-prescription product produced minimal effects but may be a cardiodepressant.

Evaluation of safe and effective administration of nitrous oxide after a postgraduate training course

2008-06-11

Background: Conscious sedation is used in dentistry to improve access and quality of care in patients who have difficulty coping with treatment. The aim of this prospective study was to describe a postgraduate training course in conscious sedation for dentists, with specific evaluation of the safe and effective administration of a 50% nitrous oxide in oxygen premix. Methods: 45 practitioners were trained between 2002 and 2004. They carried out 826 sessions of inhalation sedation in 662 patients. The clinical competency of this group was compared with an expert group. Results: There was no difference between trainees and experts in ability to complete the planned dental treatment under sedation (89.6% vs 93.2%). Trainees were less successful than experts for patients with intellectual disability (87.4% vs 94.2%, p < 0.01). For both groups, the degree of cooperation improved between initial induction and each perioperative step (Wilcoxon test, p < 0.01). However, for trainees, Venham behaviour scores varied with the type of patient (Kruskal Wallis test, p < 0.001). No major adverse effects were recorded. Trainees reported more minor adverse effects than experts (13% vs. 5.3% respectively, Fisher exact test, p < 0.001) Conclusion: The trainee practitioners provided effective and safe inhalation sedation. This challenges the current French restriction of the 50% nitrous oxide in oxygen premix to the hospital setting. Further emphasis is required on the teaching of behaviour management skills for patients with intellectual disability.

Renal safety of zoledronic acid with thalidomide in patients with myeloma: a pharmacokinetic and safety sub-study

2008-03-31

Background: Cases of impaired renal function have been reported in patients who had been treated with both zoledronic acid and thalidomide for myeloma. Hence, we conducted a safety study of zoledronic acid and thalidomide in myeloma patients participating in a trial of maintenance therapy. Methods: Twenty-four patients who were enrolled in a large randomized trial of thalidomide vs no thalidomide maintenance therapy for myeloma, in which all patients also received zoledronic acid, were recruited to a pharmacokinetic and renal safety sub-study, and followed for up to 16 months. Results: No significant differences by Wilcoxon rank-sum statistic were found in zoledronic acid pharmacokinetics or renal safety for up to 16 months in patients randomized to thalidomide or not. Conclusion: In myeloma patients receiving maintenance therapy, the combination of zoledronic acid and thalidomide appears to confer no additional renal safety risks over zoledronic acid alone.

Individual case safety reports in children in commonly used drug groups – signal detection

Gertrud Brunlöf, Carina Tukukino and Susanna M Wallerstedt — 2008-03-17

Background: Due to few paediatric drug safety studies, knowledge on risks of drug treatment in children is limited. The knowledge needs to be increased to make proper risk-benefit analyses possible when treating paediatric patients with drugs. The aim of the present study was to investigate drug groups commonly used in children concerning type and frequency of individual case safety reports in children. Methods: Number and type of individual case safety reports in the 30 groups of drugs (5th level ATC-code) most sold (number of defined daily doses) in outpatient treatment to children (<15 years old) during 2005 were obtained. Descriptive analyses of the adverse drug reactions reported in children were performed. Results: The number of individual case safety reports per million defined daily doses in children varied in the groups of drug between 0 and 24. The largest number was found in the drug group R03DC, the leukotriene receptor antagonist montelukast; the majority of the children being <5 years old and experiencing psychiatric adverse drug reactions. Conclusion: The number of individual case safety reports per million defined daily doses varies in different groups of drugs. A possible signal for montelukast and psychiatric adverse drug reactions was found, which should be further explored.

Aspects of statin prescribing in Norwegian counties with high, average and low statin consumption – an individual-level prescription database study

2007-12-05

Background: A previous study has shown that variations in threshold and intensity (lipid goal attainment) of statins for primary prevention contribute to regional differences in overall consumption of statins in Norway. Our objective was to explore how differences in prevalences of use, dosing characteristics, choice of statin and continuity of therapy in individual patients adds new information to previous results. Methods: Data were retrieved from The Norwegian Prescription Database. We included individuals from counties with high, average, and low statin consumption, who had at least one statin prescription dispensed during 2004 (N = 40 143).1-year prevalence, prescribed daily dose (PDD), statin of choice, and continuity of therapy assessed by mean number of tablets per day. Results: The high-consumption county had higher prevalence of statin use in all age groups.Atorvastatin and simvastatin were dispensed in 79–87% of all statin users, and the proportion was significantly higher in the high-consumption county.The estimated PDDs were higher than the DDDs, up to twice the DDD for atorvastatin. The high-consumption county had the highest PDD for simvastatin (25.9 mg) and atorvastatin (21.9 mg), and more users received tablets in the upper range of available strengths. Continuity of therapy was similar in the three counties. Conclusion: Although differences in age-distribution seems to be an important source of variation in statin consumption, it cannot account for the total variation between counties in Norway. Variations in prevalences of use, and treatment intensity in terms of PDD and choice of statin also affect the total consumption. The results in this study seems to correspond to previous findings of more frequent statin use in primary prevention, and more statin users achieving lipid goal in the highest consuming county.