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Confusion about measuring central nervous system effects

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Abstract

Anticholinergic therapy together with behavioral treatment are the main stays of treatment for the overactive bladder. Successful therapy and patient compliance depend very much on side effects. In the past, little attention has been paid to anticholinergic side effects in the central nervous system (CNS), which can be critical, especially for elderly patients. Incidence and intensity of CNS effects depend on the pharmacokinetic and pharmacodynamic properties that are decisive whether anticholinergics pass the blood-brain barrier as a result of passive and active transport mechanisms. To measure potential CNS side effects of anticholinergic drugs, rapid eye movement sleep analysis, quantitative-topographic electroencephalogram studies, and psychometric tests were performed. Structural changes in brain morphology resulting from anticholinergics also were analyzed in a post-mortem study.

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References and Recommended Reading

  1. Milsom I, Abrams P, Cardozo L, et al.: How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. Br J Urol Int 2001, 87:760–766.

    CAS  Google Scholar 

  2. Stewart W, Herzog R, Wein A, et al.: The NOBLE Program Research Team: prevalence and impact of overactive bladder in the US: Results from the NOBLE program. Neurourol Urodyn 2001, 20:403–422.

    Article  Google Scholar 

  3. Igawa Y: Discussion: functional role of M1, M2, and M3 muscarinic receptors in overactive bladder. Urology 2000, 55(suppl 5A):47–49. Provides data on muscarinic receptor research and discusses the significance of receptor subtypes and effects on OAB pharmacotherapy.

    Article  PubMed  CAS  Google Scholar 

  4. Schwantes U, Topfmeier P: Importance of pharmacological and physiochemical properties for tolerance of antimuscarinic drugs in the treatment of detrusor instability and detrusor hyperreflexia: chances for improvement of therapy. Int J Clin Pharmacol Ther 1999, 37:209–218. Reviews and highlights the importance of chemical structure in kinetic and dynamic properties.

    PubMed  CAS  Google Scholar 

  5. Dmochowski RR, Appell RA: Advancements in pharmacologic management of the overactive bladder. Urology 2000, 56(suppl 6A):41–49. Cutting-edge analysis of pharmacologic therapy by leading minds in the field of urology.

    Article  PubMed  CAS  Google Scholar 

  6. Friebe TP, Mutschler E, Lambrecht G: Muskarinrezeptor-subtypen: pharmakologische charakterisierung, molekulare struktur lokglisation, function and receptor-effector-kopplung. Pharm Z Wiss 1993, 1:3–11.

    Google Scholar 

  7. Hoffman BB, Lefkowitz RJ, Taylor P: Neurotransmission: the autonomic and somatic motor nervous system. In Goodman & Gilman’s The Pharmacological Basis of Therapeutics, edn 9. Edited by Hardman JG, Limbird LL. New York: McGraw-Hill; 1996:105–139.

    Google Scholar 

  8. Nies AS, Spielberg SP: Principle of therapeutics. In Goodman & Gilman’s The Pharmacological Basis of Therapeutics, edn 9. Edited by Hardman JG, Limbird LL. New York: McGraw-Hill; 1996:43–62.

    Google Scholar 

  9. Pak RW, Petrou SP, Staskin D: Trospium chloride: a quaternary amine with unique pharmacologic properties. Curr Urol Rep 2003, 4:436–440. Highlights advantages of trospiumchloride, a quaternary amine minimally metabolized, not highly protein-bound, and theoretically unable to cross the blood-brain barrier, in comparison with other standard anticholinergic treatment.

    Article  PubMed  Google Scholar 

  10. Fricker G, Miller DS: Modulation of drug transporters at the blood-brain barrier. Pharmacology 2004, 70:169–176. An excellent review of knowledge about the active transport proteins including ABC and organic anion transporters, which function at the blood-brain barrier.

    Article  PubMed  CAS  Google Scholar 

  11. Van de Waterbeemd H, Camenisch G, Folkers G, et al.: Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors. J Drug Target 1998, 6:151–155.

    Article  PubMed  Google Scholar 

  12. Mahar Doan KM, Humphreys JE, Webster LO, et al.: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther 2000, 303:1029–1037.

    Google Scholar 

  13. Bendayan R, Lee G, Bendayan M: Functional expression and localization of P-glycoprotein at the blood-brain barrier. Microsc Res Tech 2002, 57:327–349.

    Article  PubMed  CAS  Google Scholar 

  14. Zhang Y, Han H, Elmquist WF, Miller DW: Expression of various multidrug resistance-associated protein homologues in brainmicrovessel endothelial cells. Brain Res 2000, 876:148–153.

    Article  PubMed  CAS  Google Scholar 

  15. Lorico A, Rappa G, Finch RA, et al.: Disruption of the murine MRP (multidrug resistance protein) gene leads to increased sensitivity to etoposide (VP-16) and increased levels of glutathione. Cancer Res 1997, 57:5238–5242.

    PubMed  CAS  Google Scholar 

  16. Valsecia ME, Malgor LA, Espindola JH, et al.: New adverse effect of oxybutynin: “night terror” [Letter]. Ann Pharmacother 1998, 32:506.

    Article  PubMed  CAS  Google Scholar 

  17. Appell R: Clinical efficacy and safety of tolterodine in the treatment of overactive bladder: a pooled analysis. Urology 1997, 50(suppl 6A):90–99.

    Article  PubMed  CAS  Google Scholar 

  18. Guay DR: Tolterodine, a new antimuscarinic drug for treatment of bladder overactivity. Pharmacotherapy 1999, 19:267–280.

    Article  PubMed  CAS  Google Scholar 

  19. Diefenbach K, Donath F, Maurer A, et al.: Randomized, doubleblind study of the effects of oxybutynin, tolterodine, trospium chloride and placebo on sleep in healthy young volunteers. Clin Drug Invest 2003, 23:395–404.

    Article  CAS  Google Scholar 

  20. Diefenbach K, Arold G, Wollny A, et al.: The influence of anticholinergics used in incontinence on sleep in healthy volunteers aged 50 years and older. Abstract presented at the ICS/IUGA Annual Meeting. Paris: August 25–27, 2004. From these two studies, it is obvious that there already are differences between young healthy volunteers and healthy volunteers over the age of 50 years; in the young volunteers only, oxybutynin changed their sleep structure and in healthy volunteers over the age of 50 years, oxybutynin and tolterodine, not trospumchloride, change sleep structure.

  21. Perry EK, Kilford L, Lees AJ, et al.: Increased Alzheimer pathology in Parkinson’s disease related to antimuscarinic drugs. Ann Neurol 2003, 54:235–238.

    Article  PubMed  CAS  Google Scholar 

  22. Pietzko A, Dimpfel W, Schwantes U, Topfmeier P: Influences of trospium chloride and oxybutynin on quantitative EEG in healthy volunteers. Clin Pharmacol 1994, 47:337–343.

    CAS  Google Scholar 

  23. Todorova A, Vonderheit-Guth B, Dimpfel W: Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous system. J Clin Pharmacol 2001, 41:636–644. Compares the potential CNS adverse effects of tolterodine, oxybutynin, trospium chloride, and placebo in a randomized, single-blind, parallel-group with qEEG study. Oxybutynin caused a significantly greater number of EEG changes than did tolterodine or trospium.

    Article  PubMed  CAS  Google Scholar 

  24. Herberg KW, Füsgen I: Effect of trospium chloride, oxybutynin-HCl, and propiverine-HCl on traffic related performance with respect of safety. Geriatrie Forschung 1997, 7:77–83.

    Google Scholar 

  25. Donnellan CA, Fook L, Mc Donald P, et al.: Oxybutynin and cognitive dysfunction. BMJ 1997, 315:1363–1364.

    PubMed  CAS  Google Scholar 

  26. In T’Veld BA, Kwee-Zuiderwijk WJ, Van Puijenbroek EP, et al.: Neuropsychiatrische bijwerkingen toegeschreven aan her gebruik van oxybutynin. Ned Tijschr Geneeskd 1998, 142:590–592.

    Google Scholar 

  27. Malone-Lee JG, Walsh JB, Maugourd MF: Tolterodine: a safe and effective treatment for older patients with overactive bladder. J Am Geriatr Soc 2001, 49:700–770.

    Article  PubMed  CAS  Google Scholar 

  28. Edwards KR, O’Connor J: Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors [Letter]. Jag S 2002, 50:1165–1166.

    Article  Google Scholar 

  29. Moore AR, O’Keefe ST: Drug-induced cognitive impairment in the elderly. Drugs Aging 1999, 15:15–28.

    Article  PubMed  CAS  Google Scholar 

  30. Brickenkamp R, Zillner E: The d2 Test of Attention (d2). In Testkatalog 2000/2001. Testzentrale, Göttingen, Bern: Hogrefe-Verlag; 2000:60.

    Google Scholar 

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Madersbacher, H.G. Confusion about measuring central nervous system effects. Curr Urol Rep 5, 442–446 (2004). https://doi.org/10.1007/s11934-004-0068-9

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  • DOI: https://doi.org/10.1007/s11934-004-0068-9

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