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1. Abstracts of papers and posters Meeting on Pharmaceutical Sciences

Author

Coile, Jr., Russell C., Wiedhaup, K., van Bommel, Ilva, Mol, Miriam, de Vries, Michiel, Massey, E. W., Biller, J., Davis, J. N., Adams, H. P., Marler, J. R., Magnani, H. N., Schotte, A., Janssen, P. F. M., Leysen, J. E., Skrabanja, A. T. P., Flendrig, L., van Iren, F., Schrijnemakers, E. W. M., Reinhoud, P. J., Kijne, J. W., Knevelman, A., de Wit, H. J. C., de Vries, J. D., Bult, A., Beijnen, J. H., van Winden, E. C. A., Talsma, H., Crommelin, D. J. A., Storm, G., Oussoren, C., Zuidema, J., Vingerhoeds, M. H., Smit, R. H. P., Dinther, F. v., Hultermans, T., Beumer, T., Fransz, A. N., Vromans, H., Bloemhof, D. A., van Mansvelt, F. J. W., Brouwers, J. R. B. J., Raemaekers, J., Boskma, R. J., Bloemhof, H., de Graaf, S. S. N., Uges, D. R. A., Kosterink, J. G. W., de Jonge, M. W. A., Smit, E. F., Kengen, R. A. M., de Leij, L., Piers, D. A., Shochat, D., The, T. H., Luurtsema, Gert, Franssen, Eric, Visser, Geb, Jeronimus-Stratingh, Margot, Bruins, Andries, Vaalburg, Wim, Luurtsema, G., Medema, J., Elsinga, P. H., Franssen, E. J. F., Visser, G. M., Vaalburg, W., Jmker, Jan I., Uges, Donald R. A., van der Paauw, Hugo, Maas, Max, de Vos, Henk, Hettelaar, Jenny, Slolk, L. M. L., van den Brand, W., Smit, B. J., Franssen, R. M. E., Vinks, A. A. T. M. M., Touw, D. J., Heijerman, H. G. M., Danhof, M., Bakker, W., Hermans, J., Driessen G. J., Wolters R., Go I. H., Fennis J., Gribnau F. W. J., Heerdink, Eibert R., Leufkens, Hubert G., Bakker, Albert, Heerdink, E. R., Lau, H. S., Bakker, A., Porsius, A. J., Beuning, K. S., Postma-Lim, E., de Boer, A., Nagtegaal, J. E., Stecher, N., Sturkenboom, M. C. J. M., de Jong-van den Berg, L. T. W., Cornel, M. C., Stricker, B. H. Ch., Wesseling, H., van den Bemt, P. M. L. A., Kil, P. J. M., Meyboom, R. H. B., de Koning, G. H. P., Herings, Ron M. C., Stricker, Bruno H. Ch., Leufkens, Hubert G. M., Urquhart, John, de Boer, Anthonius, Sturmans, Ferd, Middeibeek, Alma, Sturkenboom, Miriam C. J. M., de Jong-van den Berg, Lolkje T. W., Lammers, M. W., Hekster, Y. A., Keyser, A., Meinardi, H., Renier, W. O., Van Lier, H., Veehof, L., Stewart, R., Mevboom-de Jong, B., Haaijer-Ruskamp, F. M., Visser, L. E., van der Velden, J., Paes, A. H. P., van Mil, J. W. F., Tromp, Th. F. J., Casparie, M. K., Kuijpers, A., Stuvt, P. M. J., Dijkers, F. W., vd Ree, C. M., Ruben, B. A., Mokkink, H. G. A., Post, D., Gubbels, J. W., Stokx, L. J., Foets, M., Florax, C., van Dijk, A., Peters, E. T. J., van der Werf, G. T., Denig, P., Boerkamp, Ellis J. C., Haaijer-Ruskamp, Flora M., Reuyl, Jan C., Versluis, Albert, van Trigtv, Anke M., de Jong- vd Berg, Lolkie T. W., Willems, Jaap, Kaldeway, Hans, Wieringa, Nicolien, Herxheimer, Andrew, Vos, Rein, Heijman, Jennifer, Rikken, Floor, Omta S. W. F., Bouter L. M., van Engelen J. M. L., Leufkens, H. G. M., Steffens, B., Thijssen, J. J. H., de Boer, D., Tissot van Patot, H. A., Leusink, J. A., de Jongh, B. M., Reuvers, Inge H., van der Galiën, Trea A., Tromp, Dick F. J., Hendrikx, N. E. H. W., van der Werf, G. Th., Vos, R., Swart, J. A. A., Haisma, H. J., Borchert, J. C. H., Versantvoort, M. W., van Steenbergen, M. J., Hennink, W. E., Wolthuis, W. N. E., van Hooff, R. J. M., Wientjes, K. J. C., Schmidt, F. J., Schoonen, A. J. M., Te Wierik, G. H. P., Eissens, A. C., Lerk, C. F., Haas, M., Iwema Bakker, W. I., Reinhoudt, D. N., Mijer, D. K. F., de Zeeuw, D., Proost, J. H., Wierda, J. M. K. H., Meijer, D. K. F., Kuipers, M., Swart, P. J., Hendriks, M. M. W. B., Kamps, J. A. A. M., Struska, B., Thomas, C., Nijenhuis, A. M., Scherphof, G. L., Swaan, Peter W., Stehouwer, Marco C., Blok, Eric J. C., Tukker, Josef J., van Dijk, J., Gorissen, H. R. M., Groot-Padberg, Y. M., Olling M., van Gelderen C. E. M., Salomons P., Barends D. M., Meulenbelt J., Rauws A. G., Craane-van Hinsberg, W. H. M., Verhoef, J. C., Junginger, H., and Boddé, H. E.

Published
1993
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13. Poster Presentations

Author

Derijks, H. J., Meyboom, R. H. B., Heerdink, E. R., De Koning, G. H. P., Janknegt, R., and De Egberts, A. C. G.

Published
2007
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19. Dutch Pharmacological Meeting 1984

Author

Timmerman, H., Koeman, J. H., den Tonkelaar, E. H., Merkus, F. W. H. M., Struyker-Boudier, H. A. J., Bolt, G. R., Saxena, P. R., Bos, R. P., Breed, A. S. P. M., Theuws, J. L. G., Henderson, P. Th., de Brauw, L. M., de Bruijn, E. A., van de Velde, C. J. H., Tjaden, U. R., Kothuis, B. J. L., van Oosterom, A. T., Reeuwijk, H. J. E. M., Pinedo, H. M., van der Hoeven, R., Bultsma, T., Linschoten, M. R., Peter, J., Burbach, H., de Kloet, E. Ronald, Castelein, O., Verbeke, N., Leuven, K. U., Conings, L., Doods, H. N., Kalkman, H. O., de Jonge, A., Wilffert, B., Thoolen, M. J. M. C., Timmermans, P. B. M. W. M., van Zwieten, P. A., van Driel, J. B. M., Klaassen, A. B. M., Kuypers, W., Beld, A. J., Rodrigues de Miranda, J. F., Driessen, O., van der Velde, E. A., Engels, F., Oosting, R. S., Nijkamp, F. P., Evelo, C. T. A., Neis, J. M., Peters, J. G. P., ten Broeke, M. A. M., Vulders, C. A. J. M., Franssen, M. J. A. M., van Herwaarden, C. L. A., van de Putte, L. B. A., Gribnau, F. W. J., van der Graaff, M., Vermeulen, N. P. E., Hofman, P. H., Breimer, D. D., 't Hart, B. J., Wilting, J., de Gier, J. J., Hazelhoff, Bernard, de Vries, Jan B., Oijkstra, Durk, Mulder, Theo, Wynberg, Hans, Horn, Alan, van Doorn, R., Leijdekkers, Ch. -M., Anzion, R., Hengstum, M. v., Festen, J., Buijs, W., Broek, W. v. d., Groothedde, R., Corstens, F., van Heuven-Nolsen, P., de Wildt, D. J., Hillen, F. C., van Noordwijk, J., Janssen, Lambert H. M., Jansen, P. A. F., Meyboom, R. H. B., Vree, T. B., Jelinek, J., Schönbaum, E., Lomax, P., de Jong, W., Sandor, P., Cox van Put, J. J., Jongeneelen, F. J., Leijdekkers, Ch. M., Kerklaan, P. R. M., Zoetemelk, C. E. M., Mohn, G. R., Grote, J. J., Kuijpers, W., Kleinbloesem, C. H., van Brummelen, P., van Harten, J., Koopmans, P. P., Kateman, W., Tan, Y., van Ginneken, C. A. M., van Koppen, C. J., van der Beek, E. M., Lammers, J. W. J., Krielaart, M. J., Laban, E., Charbon, G. A., Folgering, H. Th. M., Lenders, J. W. M., Sluiter, H. E., Willemsen, J., Thien, Th., Mooy, J., Schols, M., Baak, M. v., Hooff, M. v., Rahn, K. H., Mulder, Theo B. A., Grol, Cor J., Dijkstra, Durk, Horn, Alan S., Neef, C., Meijer, D. K. F., van Gemert, P. J. L., Roelofs, H. M. J., Osterhuis, B. O, ten Berge, R. J. M., Schellekens, P. T. A., van Boxtel, C. J., Peeters, P. A. M., Raghoebar, M., Tiemessen, H. L. G. H., Raaijmakers, J. A. M., van Rozen, A. J., Terpstra, G. K., Wassink, G. A., Kreukniet, J., Remeyer, L. R., Reeuwijk, H. J. E., Touw, D. J., Rollema, Hans, Mastebroex, Dora, Russel, F. G. M., Wouterse, A. C., Rijk, M. C. M., Salden, H. J. M., De Schaepdryver, A. F., Lefebvre, R. A., Bogaert, M. G., Scheres, H. M. E., Salden, H. J. H., Siero, H. L. M., Slee, P. H. Th. J., van den Berg, L., Huysmans, F. Th. M., Koene, R. A. P., Smits, J. F. M., Nievelstein, H. M. N., Struyker Boudier, H. A. J., Raaijmakers, J. A. H., Huidekoper, H. J., Thljssen, H. H. W., Baars, L. C. M., Mathy, M. J., Veldhoven, C. M. M., AriËns, E. J., Ruland, C. M., de Vos, Cor, de Graaf, Joop, van Aalst, Gerard, Steenbergen, Hans, Hekster, Y. A., Tijhuis, M. W., Nouws, J. F. M., Wollersheim, H., Fennis, J., van 't Laar, A., Wijnands, W. J., van der Gen, A., Jzerman, A. P. I., Aué, G., Dorlas, R., Krajnc, E. I., Loeber, J. G., van Leeuwen, F. X. R., Wester, P. W., Vos, J. G., Vaessen, H. A. M. G., Heijden, C. A. v. d., Canton, J. H., de Klerk, A., Krajc, E. I., Kruizinga, W., van Ommen, B., Rozing, J., van der Heijden, C. A., van der Voet, G. B., de Wolff, F. A., Edelbroek, Peter M., de Reus, Margot J. H., van den Berg, Tjeerd, and de Wolff, Frederik A.

Published
1984
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20. Risk of drug-induced photosensitivity: focus on spectroscopic and molecular characteristics

Author

Verdel, B. M., Souverein, P. C., Meyboom, R. H. B., Kardaun, S. H., Leufkens, H. G. M., and Egberts, A. C. G.

Subjects
spectroscopy, ultraviolet radiation, pharmacovigilance, EXOGENOUS AGENTS, molecular drug characteristics, photosensitivity, CUTANEOUS PHOTOSENSITIVITY
Abstract

Background Drug-induced photosensitivity is difficult to predict and remains a challenge for both the dermatological clinical practice and pharmacovigilance. Purpose To assess the association between spectroscopic and molecular characteristics and the occurrence of photosensitivity reactions. Methods For 143 well-known photosensitisers (e.g. tetracyclines, diuretics), we retrieved information on spectroscopic and molecular parameters, including: absorption maximum lambda(max), molar absorption coefficient epsilon, area under the absorption curve (AUC), molecular weight and configuration, hetero and aromatic halogen atoms, lipophilicity (log P) and acid/base status (pKa). In the WHO-ADR database, all reports with suspected adverse drug reactions of the study drugs were selected. We identified all reports on photosensitivity reactions and defined them as cases. All other reports were selected as non-cases. A case-non-case approach was performed to assess the spectroscopic and molecular exposure variables as a factor for photosensitivity reactions. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). Results A lambda(max) between 290 and 320 nm (OR 3.74, 95% CI 3.45-4.06), and an epsilon > 20000 M(-1) cm(-1) (OR 5.49, 95% CI 5.10-5.92) were highly associated with the reporting of photosensitivity reactions. Risk of the photosensitivity reactions was significantly increased among intermediate or high AUCs compared to low AUC. Low molecular weight and aromatic halogen atoms were associated with photosensitivity reactions (OR 2.37, 95% CI 2.07-2.71 resp. OR 3.37, 95% CI 3.15-3.61) as were log p

Published
2009

21. Can intranasal corticosteroids cause migraine-like headache?

Author

Pokladnikova, J., Meyboom, R. H. B., Vlcek, J., and Edwards, R. I.

Subjects
*CORTICOSTEROIDS, *INTRANASAL medication, *MIGRAINE, *MEDICAL research, *RHINITIS
Abstract

Intranasal corticosteroids (INCs) act predominantly locally and are considered to exert minimal systemic effects. On reviewing the international data collected in the World Health Organization's global pharmacovigilance programme an unexpected cluster was found of 38 case reports of migraine in suspected connection with INCs. These reports came from five countries (May 2007) and concerned six different drugs. In all reports the INC was the sole suspect drug. In nine cases re-exposure to the drug had taken place, leading to the recurrence of the event in eight of these patients. However, INCs are mainly used for rhinitis, and there is a known connection between rhinitis and migraine. Although representing only 0.6% of the total of case reports, international pharmacovigilance data suggest that the use of INCs may cause or trigger migraine or migraine-like headache. Further study is needed to determine if the reported association is true or not and, if so, what the possible mechanism is. [ABSTRACT FROM AUTHOR]

Published
2009
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24. CONGESTIVE HEART FAILURE DUE TO NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN THE ELDERLY.

Author

VAN DEN OUWELAND, F. A., GRIBNAU, F. W. J., and MEYBOOM, R. H. B.

Abstract

Congestive heart failure in the elderly which might be due to treatment with nonsteroidal anti-inflammatory drugs was studied by means of a questionnaire sent to the participants of a postgraduate course on locomotor disease in the elderly, and also by analysis of the hospital records of 600 elderly subjects diagnosed with congestive heart failure. The questionnaire revealed 22 possible cases, reported by 20 physicians (84 physicians out of 243 responded). In the hospital population five probable cases were detected. Details of these patients are presented. In contrast with findings in the literature, solute retention was in no case the result of kidney function impairment. The specific problems regarding the attribution of this adverse effect are discussed. The results of our study provide further evidence that congestive heart failure due to nonsteroidal anti-inflammatory drug treatment is a probable adverse drug reaction in elderly individuals with or without a history of impaired cardiac performance. It may result from drug toxicity following (relative) overdosing in this age group, from reduced effectiveness of concomitant diuretic treatment or from effects on cardiovascular homoeostasis. [ABSTRACT FROM PUBLISHER]

Published
1988
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25. ANTIHYPERTENSIVE TREATMENT AS A POSSIBLE CAUSE OF STROKE IN THE ELDERLY.

Author

JANSEN, P. A. F., SCHULTE, B. P. M., MEYBOOM, R. H. B., and GRIBNAU, F. W. J.

Abstract

There have been a few reports on stroke as a side-effect of antihypertensive treatment. To study the occurrence of this side-effect, a questionnaire was sent to all Dutch nursing homes (n=322). Thirty patients were reported with signs of cerebral ischaemia shortly after starting antihypertensive and diuretic drugs. Nine of these cases were well documented with full data on blood pressure, measured immediately after the event and compared with pretreatment levels. A review of cases reported in the literature is presented. It is concluded that, especially in elderly patients, an abrupt fall in blood pressure may induce cerebral ischaemia, sometimes resulting in stroke. Antihypertensive treatment in the elderly should therefore start with a small dose, the aim being to reduce blood pressure gradually. [ABSTRACT FROM PUBLISHER]

Published
1986
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30. Risk of drug-induced photosensitivity: focus on spectroscopic and molecular characteristics.

Author

Verdel BM, Souverein PC, Meyboom RH, Kardaun SH, Leufkens HG, and Egberts AC

Subjects
Databases, Factual statistics & numerical data, Humans, Prescription Drugs analysis, Risk Factors, Seasons, Ultraviolet Rays adverse effects, World Health Organization, Photosensitivity Disorders chemically induced, Photosensitivity Disorders epidemiology, Prescription Drugs adverse effects, Prescription Drugs chemistry, Spectrum Analysis statistics & numerical data
Abstract

Background: Drug-induced photosensitivity is difficult to predict and remains a challenge for both the dermatological clinical practice and pharmacovigilance., Purpose: To assess the association between spectroscopic and molecular characteristics and the occurrence of photosensitivity reactions., Methods: For 143 well-known photosensitisers (e.g. tetracyclines, diuretics), we retrieved information on spectroscopic and molecular parameters, including: absorption maximum lambda(max), molar absorption coefficient epsilon, area under the absorption curve (AUC), molecular weight and configuration, hetero and aromatic halogen atoms, lipophilicity (log P) and acid/base status (pKa). In the WHO-ADR database, all reports with suspected adverse drug reactions of the study drugs were selected. We identified all reports on photosensitivity reactions and defined them as cases. All other reports were selected as non-cases. A case-non-case approach was performed to assess the spectroscopic and molecular exposure variables as a factor for photosensitivity reactions. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI)., Results: A lambda(max) between 290 and 320 nm (OR 3.74, 95% CI 3.45-4.06), and an epsilon > 20,000 M(-1) cm(-1) (OR 5.49, 95% CI 5.10-5.92) were highly associated with the reporting of photosensitivity reactions. Risk of the photosensitivity reactions was significantly increased among intermediate or high AUCs compared to low AUC. Low molecular weight and aromatic halogen atoms were associated with photosensitivity reactions (OR 2.37, 95% CI 2.07-2.71 resp. OR 3.37, 95% CI 3.15-3.61) as were log p < 1 and pKa < 7., Conclusion: The reporting of photosensitivity reactions to established phototoxic drug classes is strongly influenced by spectroscopic and physicochemical characteristics of individual drugs., ((c) 2009 John Wiley & Sons, Ltd.)

Published
2009
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31. Deep vein thromboembolism in malignant diseases.

Author

Zemková M, Meyboom RH, Blazek M, Kotlárová J, Vlcek J, and Jebavý L

Subjects
Anticoagulants therapeutic use, Heparin, Low-Molecular-Weight therapeutic use, Humans, Risk Factors, Thromboembolism etiology, Thromboembolism prevention & control, Vitamin K adverse effects, Neoplasms complications, Thromboembolism drug therapy
Abstract

Tumourous diseases are associated with haemorrhagic as well as thrombotic complications. Trousseau described in 1865 a mutual association between tumourous diseases and venous thromboembolism. As many as 15-20% patients with venous thromboembolism have an undetected malignity, which equals a prevalence of 2-3% in the population. From this ensues the relative risk of a newly diagnosed malignity which is higher during the first year after venous thromboembolism. Migrating thrombophlebitis is a relatively specific sign in tumours, in particular in pancreatic tumours. In the pathogenesis of venous thromboembolisms in tumourous diseases, the following factors play a significant part: elevated coagulation parameters, reduced fibrinolysis, frequent immobilization, surgical operations in the case history, chemotherapy, hormonal therapy and central venous catheters. Conventional long term management of VTE involves the use of vitamin K antagonists, such as warfarin, to reduce the risk of recurrence. Recent evidence-based approach in long term management of VTE in patients with tumorous disease shows that the use of LMWH offers an effective alternative to VKAs with higher efficacy, without a significantly increased risk of bleeding, and without the need for regular laboratory monitoring.

Published
2007

32. Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death.

Author

De Bruin ML, Pettersson M, Meyboom RH, Hoes AW, and Leufkens HG

Subjects
Adverse Drug Reaction Reporting Systems, Aged, Anti-Arrhythmia Agents therapeutic use, Databases, Factual, ERG1 Potassium Channel, Ether-A-Go-Go Potassium Channels, Female, Gender Identity, Heart Ventricles, Humans, Long QT Syndrome chemically induced, Male, Middle Aged, Odds Ratio, Potassium Channel Blockers blood, Potassium Channel Blockers therapeutic use, Risk, World Health Organization, Arrhythmias, Cardiac chemically induced, Death, Sudden etiology, Potassium Channel Blockers adverse effects, Potassium Channels, Voltage-Gated antagonists & inhibitors
Abstract

Aims: Drug-induced QTc-prolongation, resulting from inhibition of HERG potassium channels may lead to serious ventricular arrhythmias and sudden death. We studied the quantitative anti-HERG activity of pro-arrhythmic drugs as a risk factor for this outcome in day-to-day practice., Methods and Results: All 284,426 case reports of suspected adverse drug reactions of drugs with known anti-HERG activity received by the International Drug Monitoring Program of the World Health Organization (WHO-UMC) up to the first quarter of 2003, were used to calculate reporting odds ratios (RORs). Cases were defined as reports of cardiac arrest, sudden death, torsade de pointes, ventricular fibrillation, and ventricular tachycardia (n = 5591), and compared with non-cases regarding the anti-HERG activity, defined as the effective therapeutic plasma concentration (ETCPunbound) divided by the HERG IC50 value, of suspected drugs. We identified a significant association of 1.93 (95% CI: 1.89-1.98) between the anti-HERG activity of drugs, measured as log10 (ETCPunbound/IC50), and reporting of serious ventricular arrhythmias and sudden death to the WHO-UMC database., Conclusion: Anti-HERG activity is associated with the risk of reports of serious ventricular arrhythmias and sudden death in the WHO-UMC database. These findings are in support of the value of pre-clinical HERG testing to predict pro-arrhythmic effects of medicines.

Published
2005
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33. Data-mining analyses of pharmacovigilance signals in relation to relevant comparison drugs.

Author

Bate A, Lindquist M, Orre R, Edwards IR, and Meyboom RH

Subjects
Captopril adverse effects, Clozapine adverse effects, Databases, Factual, Drug Monitoring methods, Humans, Pharmaceutical Preparations classification, Practolol adverse effects, Terfenadine adverse effects, World Health Organization, Adverse Drug Reaction Reporting Systems standards, Adverse Drug Reaction Reporting Systems statistics & numerical data, Bayes Theorem, Drug-Related Side Effects and Adverse Reactions, Information Storage and Retrieval
Abstract

Objective: The aim of this paper is to demonstrate the usefulness of the Bayesian Confidence Propagation Neural Network (BCPNN) in the detection of drug-specific and drug-group effects in the database of adverse drug reactions of the World Health Organization Programme for International Drug Monitoring., Methods: Examples of drug-adverse reaction combinations highlighted by the BCPNN as quantitative associations were selected. The anatomical therapeutic chemical (ATC) group to which the drug belonged was then identified, and the information component (IC) was calculated for this ATC group and the adverse drug reaction (ADR). The IC of the ATC group with the ADR was then compared with the IC of the drug-ADR by plotting the change in IC and its 95% confidence limit over time for both., Results: The chosen examples show that the BCPNN data-mining approach can identify drug-specific as well as group effects. In the known examples that served as test cases, beta-blocking agents other than practolol are not associated with sclerosing peritonitis, but all angiotensin-converting enzyme inhibitors are associated with coughing, as are antihistamines with heart-rhythm disorders and antipsychotics with myocarditis. The recently identified association between antipsychotics and myocarditis remains even after consideration of concomitant medication., Conclusion: The BCPNN can be used to improve the ability of a signal detection system to highlight group and drug-specific effects.

Published
2002
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