Nederlands Platform voor Farmaceutisch Onderzoek

Het Nederlands Platform voor Farmaceutisch Onderzoek (NPFO) presenteert onderzoek in de farmaceutische wetenschappen, zoals medicatieveiligheid, patiëntenzorg, formulering, (bio)analyse, (klinische) farmacologie en casuïstiek.

Interactie tussen valproïnezuur en meropenem: waarde van de vrije concentratie

J.Y.M.N. Derijks-Engwegen a* en L.J.J. Derijks b

Lees abstract

Interaction between valproic acid and meropenem: significance of the free concentration

INTRODUCTION

Meropenem (MER) is a carbapenem antibiotic used in The Netherlands in critically ill patients. A clinically relevant interaction with valproic acid (VPA) has been described, potentially resulting in subtherapeutic levels of VPA. The combination is therefore discouraged.

DESCRIPTION

A 50-year-old patient in the intensive care unit was treated with intravenous (i.v.) VPA 800 mg twice daily and MER 1000 mg three times a day. Phenytoin 75 mg i.v. twice daily was added to prevent therapeutic failure due to interaction of MER and VPA. A sharp decline in total VPA levels to < 0.5 mg/ml was seen. After stopping MER, total VPA levels remained subtherapeutic and VPA dose was increased. No convulsions occurred during subtherapeutic anti-epileptic levels. Retrospectively, we measured unbound VPA concentrations in remaining samples. Free VPA levels after cessation of MER were all therapeutic or above.

DISCUSSION

The mechanism of interaction between carbapenems and VPA is unclear. Although declines in total blood levels of VPA have been seen, these did not always result in therapeutic failure. In most reports, no information is given on free VPA concentrations or albumin levels. Here we show that in hypoalbuminaemia, total VPA levels are misleading in evaluating the combination of MER and VPA and this may inadvertently lead to overdosing of VPA.

CONCLUSION

Due to hypoalbuminaemia in critically ill patients, VPA and its interaction with MER should be monitored based on free concentrations, to prevent overdosing of VPA or unnecessary switching to other anti-epileptics.

Rubriek: Casuïstische mededeling
Identificatie: 2018;3:a1665
Datum: 5 februari 2018

Groene verkleuring van de urine bij een intensivecarepatiënt

Kelly L. Niggebrugge-Mentink *, Charlotte van Kesteren, Serife Ozkal en Marieke M. Beex-Oosterhuis

Lees abstract

Green discolouration of urine from an intensive care patient

INTRODUCTION

Several case reports describe a green discolouration of urine during the use of the anaesthetic propofol. This side effect of propofol is described in the summary of product characteristics and is classified as very rare. For diagnosis, an overview of all possible causes of green discolouration would be useful. Since this is not available in literature, we provide it here.

DESCRIPTION

We describe a 29 year old man who was treated at our intensive care unit and whose urine turned green after four days of treatment with propofol. An overview of the possible causes of urine turning green is presented here.

DISCUSSION

We performed a literature search including several relevant terms and after selecting the articles we screened the references. In summary, we found endogenous and exogenous agents that could cause green urine. Rare cases describe microbiological or other causes. In addition, the propofol infusion syndrome and the relation with green urine is discussed.

CONCLUSION

This case describes a very rare but benign and reversible side effect of propofol. When this phenomenon is not known by the practitioners, this could lead to excessive diagnostics and concerns. Before diagnosing propofol-induced green urine, the other possibilities of green urine should be excluded.

Rubriek: Casuïstische mededeling
Identificatie: 2018;3:a1663
Datum: 5 februari 2018

Associatie tussen HTR2C-polymorfismen en gewichtsverlies bij patiënten met obesitas

Arne J. Risselada ab*, Eibert R. Heerdink bc, Rob K. Gonera d, Toine C.G. Egberts bc en Hans Mulder ab

Lees abstract

Association between HTR2C polymorphisms and weight loss in obese patients

OBJECTIVE

To investigate whether the HTR2C rs1414334 and 759 C/T polymorphisms are associated with weight loss in an anti-obesity programme.

DESIGN AND METHODS

A longitudinal observational follow-up study was used to assess the association between HTR2C genotypes and weight loss during a nine month programme in an obesity clinic. Caucasian patients aged 18 years or older were included. Data were extracted from the patients’ medical records. In total, 128 patients were included (29 males).

RESULTS

There was a significant association between the HTR2C 759 T allele and resistance to weight loss in the first month of the programme. For each T allele present, there was 0.78% (95% confidence interval [95%-CI] 0.19-1.38; P = 0.01) less weight loss (as a percentage of the body weight at start). Patients carrying the variant HTR2C 759 T allele were also less likely to reach > 7% weight loss (odds ratio [OR] 0.23; 95%-CI 0.06-0,85; P = 0.028), and dropped out of the programme sooner (–0.78 months; 95%-CI –1.51- –0.06; P = 0.035; corrected for gender). No associations with the HTR2C rs1414334-genotype and any of the primary endpoints for weight loss or secondary endpoints were found.

CONCLUSION

Patients carrying the HTR2C 759 T allele were more resistant to weight loss and dropped out of the programme sooner. However, these effects were small and only explained a small part of a very complex puzzle. Genotyping HTR2C to predict a patient’s chance of success in an obesity clinic is therefore not warranted.

Rubriek: Oorspronkelijk artikel
Identificatie: 2018;3:a1662
Datum: 5 februari 2018

Risicofactoren voor medicatiefouten na eerdere medicatieverificatie bij electieve opnames

M.M. Ebbens abc*, K.B. Gombert-Handoko b, M. Al-Dulaimy d, P.M.L.A. van den Bemt c en E.J. Wesselink a

Lees abstract

Risk factors for medication erros at admission in preoperatively screened patients

BACKGROUND

Preoperative screening (POS) may help to reduce medication errors at admission (MEA). However, due to the time window between POS and hospital admission, unintentional medication discrepancies may still occur and thus a second medication reconciliation at hospital admission is necessary. Insight into potential risk factors associated with these discrepancies would be helpful to focus the second medication reconciliation on high risk patients.

OBJECTIVE

To determine the occurrence of MEA and to identify risk factors for MEA in preoperatively screened patients.

METHODS

This single-centre observational cross-sectional study included elective surgical patients between 26 October and 18 December 2015. Main inclusion criteria were age ≥18 years and elective non-day care admissions. Medication reconciliation took place at the preoperative screening and was repeated within 30 hours of admission. Unintended discrepancies between the first and second medication reconciliation were defined as MEA. The primary outcome was the occurrence of MEA in preoperatively screened patients. The association of this outcome with potential risk factors was analysed using multivariate logistic regression analysis.

RESULTS

Of the 183 included patients 60 (33%) patients had at least one MEA. In a multivariate model the number of medications at POS (adjusted odds ratio 1.16, 95%-confidence interval [95%-CI] 1.04-1.30), and respiratory disease (odds ratio 4.25, 95%-CI 1.52-11.83) were significantly associated with MEA.

CONCLUSION

In our study MEA occurred in 33% of preoperatively screened patients. Polypharmacy and respiratory comorbidities are risk factors for MEA in preoperatively screened patients.

Rubriek: Korte bijdrage
Identificatie: 2018;3:a1661
Datum: 9 januari 2018

Keuzes van patiënten en apothekers bij medicatiebewaking

Marcel Kooij

Rubriek: Referaat
Identificatie: 2018;3:e1654
Datum: 9 januari 2018

Patiëntgericht communiceren voor apothekers

Marcel Kooij

Rubriek: Referaat
Identificatie: 2018;3:e1653
Datum: 9 januari 2018

Vaccinsurveillance in lage- en middeninkomenslanden

Rogier Klok

Rubriek: Referaat
Identificatie: 2017;2:e1652
Datum: 29 december 2017

Kosteneffectiviteit van farmacogenetica; een voorbeeld van een vroege analyse

Rogier Klok

Rubriek: Referaat
Identificatie: 2017;2:e1651
Datum: 28 december 2017

Het gebruik van thiazidediuretica bij een zeer lage glomerulaire filtratiesnelheid

Harm Geers ab*

Lees abstract

Using thiazide diuretics with a very low glomerular filtration rate

BACKGROUND

Diuretic therapy with thiazides is usually not recommended in chronic kidney disease (CKD, i.e. glomerular filtration rate [GFR] <30 ml/min), because of the supposed low or absent diuretic effect due to lower tubular concentrations of the thiazide. The antihypertensive volume status and sodium excretion effects of thiazide diuretics in patients with CKD and low GFR are investigated in this literature review.

METHODS

PubMed and EMBASE were searched using “thiazides” and “chronic kidney disease” as key search terms to identify studies on thiazide use in patients with an estimated GFR (eGFR) < 40 ml/min. Extracted from the included studies were effects on: blood pressure, volume status, fractional sodium excretion and side effects. Case reports were excluded. Ten studies were included.

RESULTS

Overall, thiazide diuretics lowered blood pressure, increased fractional sodium excretion and decreased extracellular volume in patients. The mean eGFR ranged from 4 to 40 ml/min. Side effects were usually mild and thiazides were well tolerated.

CONCLUSION

Thiazides are effective in patients with low GFR and can be used more often in these patients. The advice to be restrictive on using thiazides in patients with an eGFR < 30 ml/min needs to be differentiated based on the results of this review. The effectiveness of thiazide diuretics may be caused by adaptive responses of intact nephrons, which leads to increased filtration and increased distal sodium delivery, which increases the effect on sodium excretion of thiazides. In addition the concentration of thiazides at postglomerular capillaries may increase, because more fluid is filtered and upregulation of organic anion transporters may increase active secretion of thiazides into the tubules.

Rubriek: Oorspronkelijk artikel
Identificatie: 2017;2:a1664
Datum: 28 december 2017

Heruitgifte van ongebruikte geneesmiddelen: een kwalitatief onderzoek onder stakeholders

Charlotte L. Bekker ab*, Helga Gardarsdottir bc, Toine C.G. Egberts bc, Marcel L. Bouvy c en Bart J.F. van den Bemt ad

Lees abstract

Redispensing of medicines unused by patients: a qualitative study among stakeholders

BACKGROUND

Medication waste has undesirable economic and environmental consequences. This waste is partly unavoidable but might be reduced by redispensing medicines unused by patients. However, there is little knowledge of stakeholders’ views on the redispensing.

OBJECTIVE

To identify the stakeholders’ views on the redispensing of medicines unused by patients.

DESIGN AND METHODS

Qualitative study in which semi-structured interviews were conducted with 19 Dutch stakeholders from September 2014 until April 2015. The interview guide included two themes: medication waste and redispensing of unused medicines. The latter included qualitative, legal and financial aspects and stakeholder involvement with specific attention for the patient. Interview transcripts were subjected to thematic content analysis.

RESULTS

All stakeholders considered the redispensing of medicines desirable if the implementation is feasible and the requirements for the safe redispensing are met. All of them pointed out that the product quality of redispensed medicines should be guaranteed and that it should be clear who is responsible for the quality of redispensed medicines. The stakeholders stated that transparent communication to patients is essential to guarantee trust in the redispensing system and that patients should be willing to use redispensed medicines. Moreover, the redispensing system’s benefits should outweigh the costs and a minimal economic value of medicines suitable for redispensing should be determined.

CONCLUSION

Redispensing unused medicines could decrease medication waste if several requirements are met. For successful implementation of a redispensing system, all relevant stakeholders should be involved and cooperate as a joint-force.

Rubriek: Korte bijdrage
Identificatie: 2017;2:a1653
Datum: 28 december 2017

Ziekenhuisfarmaciedagen, 9 en 10 november 2017

Lees abstract

De hier opgenomen abstracts vormen de mondelinge presentaties tijdens de Ziekenhuisfarmaciedagen op 9 en 10 november 2017 te Bunnik.

Rubriek: Congresabstracts
Identificatie: 2017;2:a1666
Datum: 15 december 2017

Sederende medicatie bij de geriatrische intensivecarepatiënt

Bart G.J. Dekkers ab, Bert Loef c, Marijn Boer c en Ithamar Brinkman a*

Lees abstract

Sedative drugs in the geriatric intensive care patient

BACKGROUND

The number of elderly patients admitted to Intensive Care Units (ICUs) has increased significantly in recent years. It has been demonstrated that the elderly are more prone to inadequate drug treatment and adverse drug effects.

OBJECTIVE

To perform a literature review on the effects of aging on pharmacokinetic and pharmacodynamic properties of commonly used sedative drugs in Dutch ICUs.

DESIGN AND METHODS

Literature review using PubMed.

RESULTS

Literature on the effects of aging on the pharmacology of commonly used sedative drugs in the ICU is scarce. For the general population, we found that for midazolam, propofol, fentanyl and remifentanil aging is associated with an increased susceptibility of the patients for the pharmacodynamic properties of these agents. This effect is confirmed for some of these drugs in ICU patients. In addition, a reduction in drug clearance was observed for propofol and remifentanil.

CONCLUSION

Based on these findings, we suggest to start with lower dosages for midazolam, propofol, fentanyl and remifentanil in elderly ICU patients and to re-evaluate frequently and adjust the therapy by clinical effect if necessary.

Rubriek: Overzichtsartikel
Identificatie: 2017;2:a1659
Datum: 15 december 2017

Contact

Redacteur / secretaris
Arjan Polderman

(070) 373 73 14 npfo@npfo.nl