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13. Abstracts of papers clinical pharmacological meeting

Author

Brink, H., Derkx, F., Kolstee, H., Merkus, P., Smits, J., Man in 't Veld, A., Schslekamp, M., Postma, C. T., Hoefnagels, W. H. L., Thien, Th., van Bortel, L. M. A. B., Böhm, R. O. B., Mooy, J. M. V., Schiffers, P. M. H., Rahn, K. H., Donker, A. J. M., Frydman, A., van Leerdam, F. J. H., de Vries, P. M. J. H., Oe, P. L., Chang, P. C., van Veen, S., Vermey, P., van Brummelen, P., Molema, J., Lammers, J. -W. J., Folgering, H. Th. M., van Herwaarden, C. L. A., de Boer, A., Stiekema, J. C. J., Danhof, M., Boei jinga, J. K., Breimer, D. D., Blauw, G. J., van Zwieten, P. A., Doorenbos, C. J., Daha, M. R., Hermans, W. A. J. J., Schüsler-van Hees, M. T. I. W., Merkus, F. W. H. M., Oldenhof, H. G. J., de Jong, M., Steenhoek, A., Janknegt, R., Koelman, J. H., Nube, M. J., Franssen, C., Wollersheim, H., Veering, B. Th., Burm, A. G. L., van Kleef, J. W., Hennis, P. J., Spierdijk, Joh, Bovill, J. G., Breimer, L. T. M., de Bruijn, E. A., Schouten, J., Smits, P., van 't Laar, A., van Baak, M. A., Koene, F., Verstappen, F. T. J., van der Krogt, J. A., and van Brumelen, P.

Published
1987
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16. 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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19. Abstracts of papers

Author

Wesseling, H., Veur, E. v. d., Berge, B. S. ten, Donker, A. J. M., May, J. F., Schuurman, F. H., van Schaik, B. A. M., Geyskes, G. G., Petri, H., Böhm, R., Mooy, J., van Kemenade, J., van Baak, M., Rahn, K. H., van Heereveld, H. A. E. M., Wollersheim, H., Thien, Th., Lammers, J. W. J., Folgering, H. Th. M., van Herwaarden, C. L. A., Graafsma, S. J., Snijders, P. J. F., de Miranda, J. F. Rodrigues, de Bruijn, E. A., van Oosterom, A. T., Kuppen, P. J. K., Jol, C., Tjaden, U. R., Trimbos, J. B., Runhaar, E. A., Nooij, H. A., van de Loo, A. A. J., Speth, P. A. J., Linssen, P. C. M., Haanen, C., Leeuwenkamp, O. R., Neyt, J. H., van der Vijgh, W. J. F., Pinedo, H. M., Schellens, J. H. M., Danhof, M., Breimer, D. D., Overdiek, J. W. P. M., Merkus, F. W. H. M., Teeuwen, H. W. A., de Schepper, P., Tjandramaga, T. B., van Rossum, J. M., Tukker, J. J., Blankenstein, M. A., Nortier, J. W. R., Zantvoort, F. A., Wagonvoort, J. H. T., Derkx, F. H. M., Michel, M. F., Wijnands, W. J. A., Baars, A. M., Vree, T. B., van Dalen, R., Termond, E. S. F., Boekema, P., Smits, P., de Abreu, R., Thlen, Th., van 't Laar, A., Böhm, R. O. B., Arends, B. G., van Hooff, H. E. J., van Baak, M. A., Derkx F., Tan-Tjiong H., Wenting G., Manin't Veld A., Schalekamp M., van Harten, J., van Brummelen, P., Danhof, H., Lodewijks, M. Th. M., Jansen, P. A. F., van Ginneken, C. A. M., Gribnau, F. W. J., Lohman, J. J. H. M., Hooymans, P. M., Merkus, F. W. H. H., Mol, M. J. T. M., Stalenhoef, A. F. H., Demacker, P. N. M., van't Laar, A., Raaijmakers, J. A. M., Terpstra, G. K., and Holdrinet, R. S. G.

Published
1986
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20. Invloed van 3 afzonderlijke saneringsmaatregelen tegen de huisstofmijt op de respiratoire conditie van astmapatienten

Author

Cloosterman, S. G. M., Schermer, T. R. J., Hofland, I. D., Heide, S., bert brunekreef, Den Elshout, F. J. J., Folgering, H. Th M., and Schayck, C. P.

Subjects
Interactie tussen bronchusverwijding en allergeenexpositie in allergisch astma, Interaction between bronchodilatation and allergen exposure in allergic asthma, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Contains fulltext : 26121___.PDF (Publisher’s version ) (Open Access)

Published
1997

22. Effects of inhaled beclomethasone dipropionate on beta2-receptor function in the airways and adrenal responsiveness in bronchial asthma

Author

Molema, J., Lammers, J. -W. J., Herwaarden, C. L. A., and Folgering, H. Th. M.

Abstract

Sixteen patients suffering from bronchial astham, with or without chronic bronchitits, sufficiently severe to be treated with inhaled corticosteroids, were studied in a single-blind trial (blind observer) of beclomethasone dipropionate (BDP) given in three randomized dosage regimens: 500, 1000 and 2000 µg per day, each for 4 weeks. The ß2-adrenergic agoinst response curve showed a dose-dependent increase in FEV1 which was not affected by different doses of BDP. A small but significant reduction in basal cortisol levels was observed after BDP 500 µg/day. There was no significant difference between the various doses of BDP in reducting cortisol level and stimulation with tetracosactide remained unchanged. The study showed a gradual, dose-dependent improvement in lung function, statistically significant for morning peak expiratory flow rate at BDP 2000 µg/day. Dyspnoea score and ß2-agonist use decreased, reflecting the anti-asthmatic effects. An increase in total leukocyte count was observed, together with a decrease in the eosinophil count. Oral candidiasis was seen in 2 out of 16 patients. It is concluded that the clinical anti-asthmatic effects of corticosteroid treatment by inhalation are not due to modulation of ß2-receptor function in the airways.

Published
1988
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23. Ventilatory effects of beta1-receptor-selective blockade with bisoprolol and metoprolol in asthmatic patients

Author

Lammers, J. W. J., Folgering, H. Th. M., and Herwaarden, C. L. A.

Abstract

In a double blind, placebo-controlled study the ventilatory effects of the beta1-selective receptor blockers bisoprolol (EMD 33512) and metoprolol and their interactions with the beta2-adrenoceptor agonist terbutaline were investigated in 8 asthmatic patients. Both beta-blockers, in all the doses given, caused a significant decrease in peak expiratory flow rate (PEFR). Vital capacity (VC) and forced expiratory volume in one second (FEV1) were significantly decreased only after 10 mg bisoprolol. Terbutaline inhalation caused the same significant improvements in FEV1 and PEFR during placebo as during bisoprolol 10 mg, bisoprolol 20 mg and metoprolol 100 mg. Both beta-blockers caused equal changes in heart rate (HR) at rest. Systolic and diastolic blood pressure (BP) decreased significantly after bisoprolol 20 mg and metoprolol 100 mg, but not after bisoprolol 10 mg. Inhalation of terbutaline up to a dose of 3.5 mg had no influence on HR and BP. The results point to good beta1-selectivity of bisoprolol 10 mg and 20 mg and metoprolol 100 mg in asthmatic patients. No correlation was found between the plasma levels of the beta-blockers and the changes in the ventilatory indices, HR or BP.

Published
1984
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25. Metabolic acidosis improves airway conductance in patients with asthma.

Author

Brijker F, van den Elshout FJ, Bosch FH, Heijdra YF, and Folgering HT

Subjects
Administration, Oral, Adult, Airway Resistance physiology, Ammonium Chloride administration & dosage, Ammonium Chloride pharmacology, Asthma physiopathology, Bronchial Hyperreactivity drug therapy, Bronchial Hyperreactivity physiopathology, Double-Blind Method, Female, Forced Expiratory Volume drug effects, Forced Expiratory Volume physiology, Humans, Hydrogen-Ion Concentration drug effects, In Vitro Techniques, Male, Middle Aged, Peak Expiratory Flow Rate drug effects, Peak Expiratory Flow Rate physiology, Treatment Outcome, Acidosis chemically induced, Airway Resistance drug effects, Ammonium Chloride therapeutic use, Asthma drug therapy
Abstract

The objective was to investigate whether acute metabolic acidosis could cause bronchodilation in patients with asthma. Twelve patients with asthma (8 females, mean age 39 (+/- SD 12) years, forced expiratory volume in 1 second [FEV(1)] 93 [+/-9] % predicted, PC(20) 1.9 (+/-1.0) mg/mL) participated in a double-blind, placebo-controlled trial. Subjects ingested calculated amounts of ammonium chloride to induce acidosis or saline as placebo, in random order, each on a separate day. Airway resistance (R(aw)), specific airway conductance (sG(aw)), FEV(1), and PEF were measured as primary variables. To evaluate the consequences of alterations in bronchial contractility on the airway responsiveness, the histamine provocation test (PC(20)) was measured as secondary variable. The intervention resulted in a mean (SD) decrease in base excess from -0.5 (+/-1.4) to -3.9 (+/-1.1) mmol/L (p < 0.01) and a decrease in pH from 7.41 (+/-0.02) to 7.36 (+/-0.02) (p < 0.01). This caused a statistically significant increase in sG(aw) from 1.15 (+/-0.16) to 1.26 (+/-0.13) 1/kPa.s) (p < 0.05). Tendencies towards increase were found in PEF (7.79 (+/-2.2) versus 8.09 (+/-1.9) (NS, p = 0.10) and in FEV(1) (2.98 (+/-0.9) versus 3.06 (+/-0.9) (NS, p = 0.15). PC(20) did not change significantly. It was concluded that acute metabolic acidosis has a modest bronchodilating effect in patients with asthma.

Published
2009
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26. Tremor side effects of salbutamol, quantified by a laser pointer technique.

Author

Nizet TA, Broeders ME, and Folgering HT

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Asthma complications, Asthma drug therapy, Child, Child, Preschool, Diagnostic Techniques, Neurological instrumentation, Female, Humans, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive complications, Pulmonary Disease, Chronic Obstructive drug therapy, Reference Values, Reproducibility of Results, Sensitivity and Specificity, Surveys and Questionnaires, Tremor diagnosis, Albuterol adverse effects, Bronchodilator Agents adverse effects, Lasers, Tremor chemically induced
Abstract

Objective: To study tremor side effects of salbutamol an easily applicable, quick and low-priced method is needed. A new method using a commercially available, pen-shaped laser pointer was developed. Aim of the study was to determine sensitivity, reproducibility, reference values and the agreement with a questionnaire., Methods: Tremor was measured using a laser pointer technique. To determine sensitivity we assessed tremor in 44 patients with obstructive lung disease after administration of cumulative doses of salbutamol. Subjects were asked to aim at the centre of a target, subdivided in concentric circles, from 5 m distance. The circle in which the participant succeeded to aim was recorded in millimetres radius. In another series of measurements, reproducibility and reference values of the tremor was assessed in 65 healthy subjects in three sessions, at 9 a.m., 4 p.m. and 9 a.m., respectively, 1 week later. Postural tremor was measured with the arm horizontally outstretched rest tremor with the arm supported by an armrest and finally tremor was measured after holding a 2-kg weight until exhaustion. Inter-observer variability was measured in a series of 10 healthy subjects. Tremor was measured simultaneously by two independent observers., Results: Salbutamol significantly increased tremor severity in patients in a dose-dependent way. Within healthy adults no age-dependency could be found (b = 0.262 mm/year; P = 0.72). There was no agreement between the questionnaire and tremor severity (r = 0.093; P = 0.53). Postural tremor showed no significant difference between the first and third session (P = 0.07). Support of the arm decreased tremor severity, exhaustion increased tremor severity significantly. A good agreement was found between two independent observers (interclass correlation coefficient 0.72)., Discussion: Quantifying tremor by using an inexpensive laser pointer is, with the exception of children (<12 years) a sensitive and reproducible method.

Published
2004
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27. Is the increase in bronchial responsiveness or FEV1 shortly after cessation of beta2-agonists reflecting a real deterioration of the disease in allergic asthmatic patients? A comparison between short-acting and long-acting beta2-agonists.

Author

van Schayck CP, Cloosterman SG, Bijl-Hofland ID, van den Hoogen H, Folgering HT, and van Weel C

Subjects
Adrenergic beta-Agonists therapeutic use, Adult, Albuterol therapeutic use, Asthma physiopathology, Bronchial Hyperreactivity, Double-Blind Method, Female, Forced Expiratory Volume drug effects, Formoterol Fumarate, Histamine, Humans, Male, Time Factors, Adrenergic beta-Agonists adverse effects, Asthma drug therapy, Ethanolamines therapeutic use
Abstract

Regular use of beta2-agonists might result in increased bronchial hyper-responsiveness (BHR) and decreased forced expiratory volume in 1 sec (FEV1). It has been suggested that these possible detrimental effects are not a real deterioration of the disease, but that it might be only a transient (rebound) effect shortly after discontinuing this regular use. Moreover, these effects are thought to occur especially during short-acting and not during long-acting beta2-agonists use. The aim of this study was to invest gate whether a rebound effect (a pharmacological deterioration effect diminishing after several hours) in FEV1 and PC20 (concentration of histamine causing a 20% fall in FEV1 with regard to baseline) occurred after cessation of regular use of beta2-agonists, and whether this occurred both after short-acting and long-acting beta2-agonists. Allergic asthmatic patients (n = 134) were randomly allocated to the use of a short-acting (salbutamol), a long-acting beta2-agonist (formoterol) or placebo for 12 weeks (double-blind, double-dummy). No other asthma medication was allowed, including inhaled corticosteroids. At the start and every 4 weeks later FEV and PC20 were measured, each time at least 12 h after the last doses of study medication, which is in the possible rebound period. To investigate whether a (transient) rebound effect occurred, parameters were additionally measured at least 72 h later after discontinuation of the study medication. After 12 weeks of short-acting beta2-agonist use, a drop was seen in FEV1 from 85.6 (+/- 2.21)% predicted to 78.8 (+/- 2.9)% predicted, measured 15 h (median) after the last doses of medication. This was significantly different compared to placebo. When measured 168 h (median) later FEV1 recovered to 85.5 (+/- 2.4)% predicted, comparable to baseline. PC20 decreased with -1.17 (+/- 0.44) doubling dose after 12 weeks of short-acting beta2-agonist use, measured 15 h after the last doses of medication, which was significantly different compared to placebo. However, 168 h later PC20 recovered slightly with +0.55 (+/- 0.34) doubling dose, but this value was still lower compared to placebo. In contrast, during long-acting beta2-agonist and placebo use no significant changes were seen. In conclusion, the use of short-acting beta2-agonists resulted in a transient (rebound) effect in FEV while the effects on PC20 may point to a real deterioration of the disease. Long-acting beta2-agonist and placebo use showed no changes. We conclude that a mono-therapy of short-acting and not of long-acting beta2-agonists might have deleterious effects in asthma.

Published
2002
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