nach oben

Drugs & Aging

Erschienen in:

01.02.2000 | Review Article

Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease in the Elderly

verfasst von: Chad M. VanDen Berg, Yusuf Kazmi, Professor Michael W. Jann

Erschienen in: Drugs & Aging | Ausgabe 2/2000

Einloggen, um Zugang zu erhalten

Abstract

The treatment of Alzheimer’s disease is of increasing importance as the population ages and the number of people with the disease increases. The aetiology of Alzheimer’s disease is complex and therefore treatment strategies rely on generalised pathological findings. Cholinesterase inhibitors enhance a generalised deficit of central nervous system acetylcholine and are the first class of agents specifically approved for the treatment of Alzheimer’s disease.

The clinical efficacy of the different cholinesterase inhibitors is similar; however, differences in pharmacodynamic and pharmacokinetic parameters can influence tolerability and safety in the elderly population. Concomitant disease states, significant drug interactions and the altered kinetics and dynamics seen in elderly patients can also affect treatment outcome.

Although cholinesterase inhibitors are not ‘curative’ for Alzheimer’s disease, clinical evidence indicates that these drugs can significantly delay the progress of cognitive impairment. Consequently, they represent a useful treatment for the symptoms of Alzheimer’s disease in the elderly.

Eggert A, Crismon ML, Ereshefsky L. Alzheimer’s disease. In: Dipiro J, Talbet RL, Yee GC, et al., editors. Pharmacotherapy. 3rd ed. New York: Elsiever, 1997: 1325–44

Brawn LA, Castleden CM. Adverse drug reactions: an overview of special considerations in the management of the elderly patient. Drug Saf 1990; 5(6): 421–35PubMedCrossRef

Hammerlein A, Derendorf H, Lowenthal DT. Pharmacokinetic and pharmacodynamic changes in the elderly. Clin Pharmacokinet 1998; 35(1): 49–64PubMedCrossRef

Catterson ML, Preskorn SH, Martin RL. Pharmacodynamic and pharmacokinetic considerations in geriatric psychopharmacology. Psychiatr Clin North Am 1997; 20(1): 205–18PubMedCrossRef

Crismon ML. Tacrine: the first drug approved for Alzheimer’s disease. Ann Pharmacother 1994; 28: 744–51PubMed

Rogers SL, Doody RS, Mohs RC, the Donepezil Study Group, et al. Donepezil improves the cognition and global function in Alzheimer’s disease: a 15-week, double-blind, placebocontrolled study. Arch Intern Med 1998; 58: 1021–31CrossRef

Rainer M. Galanthamine in Alzheimer’s disease: a new alternative to tacrine? CNS Drugs 1997; 7(2): 89–97CrossRef

Polinsky RJ. Clinical pharmacology of rivastigmine: a newgeneration acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease. Clin Ther 1998; 20(4): 634–47PubMedCrossRef

Unni LK, Hutt V, Imbimbo BP, et al. Kinetics of cholinesterase inhibition by eptastigmine in man. Eur J Clin Pharmacol 1991; 41: 83–4PubMedCrossRef

10.

Jann MW. Preclinical pharmacology of metrifonate. Pharmacotherapy 1998; 18 (2 Pt 2); 55–67SPubMed

11.

Rowland M, Tozer TN. Elimination. In: Clinical pharmacokinetics: concepts and applications. 2nd ed. Malvern (PA): Lea & Febiger, 1989: 148–76

12.

Williams L, Lowenthal DT. Drug therapy in the elderly. South Med J 1992; 85(2): 127–31PubMedCrossRef

13.

Chutka DS, Evans JM, Fleming KC, et al. Drug prescribing for elderly patients. Mayo Clin Proc 1995; 70: 685–93PubMedCrossRef

14.

O’Connell MB, Dwindell AM, Bannick-Mohrland SD. Predictive performance of equations to estimate creatinine clearance in hospitalized elderly patients. Ann Pharmacother 1992; 26: 627–35PubMed

15.

Nordberg A, Svensson AL. Cholinesterase inhibitors in the treatment of Alzheimer’s disease: a comparison of tolerability and pharmacology. Drug Saf 1998; 19(6): 465–80PubMedCrossRef

16.

Auteri A, Mosca A, Lattuada N, et al. Pharmacodynamics and pharmacokinetics of eptastigmine in elderly subjects. Eur J Clin Pharmacol 1993; 45(4): 373–6PubMedCrossRef

17.

Ohnishi A, Mihara M, Kamakura H, et al. Comparison of the pharmacokinetics of E2020, a new compound for Alzheimer’s disease, in healthy young and elderly subjects. J Clin Pharmacol 1993; 33: 1086–91PubMed

18.

Schran HF, Habucky K, Mancione LC, et al. The effects of renal and hepatic impairment on the disposition of the acetylcholinesterase (AChE) inhibitor SDX ENA 713 [abstract]. Pharmacol Res 1996; 13: S428

19.

Tiseo PJ, Varga R, Perdomo CA, et al. An evaluation of the pharmacokinetics of donepezil HCl in patients with impaired hepatic function. Br J Clin Pharmacol 1998; 46 Suppl. 1: 51–5PubMed

20.

Tiseo PJ, Foley K, Friedhoff LT. An evaluation of the pharmacokinetics of donepezil HCl in patients with moderately to severely impaired renal function. Br J Clin Pharmacol 1998; 46 Suppl. 1: 56–60PubMed

21.

Parke-Davis. Cognex (tacrine hydrochloride): prescribing information. Morris Plains (NJ): Parke-Davis, 1993

22.

Masters CL, Beyreuther K. Alzheimer’s disease. BMJ 1998; 316: 446–8PubMedCrossRef

23.

Goedert M. Tau protein and the neurofibrillary pathology of Alzheimer’s disease. Trends Neurosci 1993; 16: 460–5PubMedCrossRef

24.

Iqbal K, Alonso AC, Gong CX, et al. Alzheimer neurofibrillary degeneration: a feasible and key target for therapeutics. In: Becker R, Giacobini E, editors. Alzheimer disease: from molecular biology to therapy. Boston (MA): Birkhauser, 1996: 31–6

25.

Vogel G. Tau protein mutations confirmed as neuron killers. Science 1998; 280: 1524–5PubMedCrossRef

26.

Cordell B. β-Amyloid formation as a potential therapeutic target for Alzheimer’s disease. Annu Rev Pharmacol Toxicol 1994; 34: 69–89PubMedCrossRef

27.

Selkoe D. Amyloid protein and Alzheimer’s disease. Sci Am 1991; 265: 68–78PubMedCrossRef

28.

Oltersdorf T, Fritz LC, Schen DB, et al. The secreted form of the Alzheimer’s amyloid precursor protein with the Kunitz domain is the protease nexin-II. Nature 1989; 341: 144–7PubMedCrossRef

29.

Smith RP, Higuchi DA, Broze GJ. Platelet coagulation factor Xia-inhibitor, a form of Alzheimer amyloid precursor protein. Science 1990; 248: 1126–8PubMedCrossRef

30.

Qiu WQ, Ferreira A, Miller C, et al. Cell-surface β-amyloid precursor protein stimulates neurite outgrowth of hippocampal neurons in an isoform-dependent manner. J Neurosci 1995; 15: 2157–67PubMed

31.

Saitoh T, Sundsmo M, Roch JM, et al. Secreted form of amyloid α protein precursor is involved in the growth regulation of fibroblasts. Cell 1989; 58: 615–22PubMedCrossRef

32.

Mattson MP, Cheng B, Culwell AR, et al. Evidence for excitoprotective and intraveuronal calcium-regulating roles for secreted forms of the beta-amyloid precursor protein. Neuron 1993; 10: 243–54PubMedCrossRef

33.

Geerts H, Nuydens R, de Jong M, et al. A new focus on cytoskeletal therapy in Alzheimer’s disease. In: Becker R, Giacobini E, editors. Alzheimer disease: from molecular biology to therapy. Boston (MA): Birkhauser, 1996: 61–5

34.

Chevallier N, Marambaud P, Vincent JP, et al. Novel cathepsin D inhibitors prevent the β-secretase-derived intracellular formation of a 12 kDa potentially amyloidogenic product in human cells. In: Becker R, Giacobini E, editors. Alzheimer disease: from molecular biology to therapy. Boston (MA): Birkhauser, 1996: 67–73

35.

Cacabelos R, Hofman A, Mullan M, et al. Alzheimer’s disease: scientific progress for future trends. DN&P 1993; 6: 242–4

36.

Cacabelos R, Nordberg A, Caamaño J, et al. Therapeutic strategies in Alzheimer’s disease. Ann Psychiatry 1995; 4: 221–79

37.

Aisen PS, Davis KL. Inflammatory mechanisms in Alzheimer’s disease: implications for therapy. Am J Psychiatry 1994; 151: 1105–13PubMed

38.

Cummings JL, Kaufer D. Neuropsychiatric aspects of Alzheimer’s disease: the cholinergic hypothesis revisited. Neurology 1996; 47: 876–83PubMedCrossRef

39.

Young AB, Penney JB. Neurotransmitter receptors in Alzheimer’s disease. In: Terry RD, Katzman R, Bick KL, editors. Alzheimer’s disease. New York (NY): Raven Press, 1994: 293–303

40.

Steele CD, Steinberg M, Milles G, et al. Recognition and management of early Alzheimer’s disease. J Clin Outcomes Manage 1999; 6(3): 52–68

41.

Parnetti L, Senin U, Mecocci P. Cognitive enhancement therapy for Alzheimer’s disease. Drugs 1997; 53(3): 752–68PubMedCrossRef

42.

Farlow M, Gracon SI, Hershey LA, et al. A controlled trial of tacrine in Alzheimer’s disease. JAMA 1992; 268: 2523–9PubMedCrossRef

43.

Knapp MJ, Knopman DS, Soloman PR, et al. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. JAMA 1994; 271: 985–91PubMedCrossRef

44.

Rogers SL, Farlow MR, Doody RS, et al. A 24-week, doubleblind, placebo-controlled, trial of donepezil in patients with Alzheimer’s disease. Neurology 1998; 50: 136–45PubMedCrossRef

45.

Corey-Bloom J, Anand R, Veach J. A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer’s disease. Int J Geriatr Psychopharmacol 1998; 1: 55–65

46.

Rosler M, Anand R, Cicin-Sain A, et al. Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: international randomised controlled trial. BMJ 1999; 318: 633–40PubMedCrossRef

47.

Cummings JL, Cyrus PA, Bierber F, et al. Metrifonate treatment of the cognitive deficits of Alzheimer’s disease: the Metrifonate Study Group. Neurology 1998; 50: 1214–21PubMedCrossRef

48.

Morris JC, Cyrus PA, Orazem J, et al. Metrifonate benefits cognitive, behavioral, and global function in patients with Alzheimer’s disease. Neurology 1998; 50: 1222–30PubMedCrossRef

49.

Thal LJ, Schwartz G, Sano M, et al. A multicenter double-blind study of controlled-release physostigmine for the treatment of symptoms secondary to Alzheimer’s disease. Neurology 1996; 47: 1389–95PubMedCrossRef

50.

Small GW, Rabins PV, Barry PP, et al. Diagnosis and treatment of Alzheimer disease and related disorders. JAMA 1997; 278(16): 1363–71PubMedCrossRef

51.

Food, Drug and Cosmetic Reports. FDA guidance on Alzheimer’s drug clinical utility assessments. FDC Rep 1992: 13–5

52.

Davis KL, Thal LJ, Gamzu ER, et al. A double-blind, placebocontrolled multicenter study of tacrine for Alzheimer’s disease. N Engl J Med 1992; 327: 1253–9PubMedCrossRef

53.

Kluger A, Ferris H. Scales for the assessment of Alzheimer’s disease. Psychiatr Clin North Am 1991; 14(2): 309–26PubMed

54.

Morgan CD, Baade LE. Neuropsychological testing and assessment scales for dementia of the Alzheimer’s type. Psychiatr Clin North Am 1997; 20(1): 25–43PubMedCrossRef

55.

Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer’s disease. Am J Psychiatry 1984; 141: 1356–64PubMed

56.

Dal-Bianco P, Maly J, Wober C, et al. Galanthamine treatment in Alzheimer’s disease. J Neural Transm 1991; Suppl. 33: 59–63

57.

Wilcock G, Wilkinson D. Galanthamine hydrobromide: interim results of a group comparative, placebo-controlled study of the efficacy and safety in patients with a diagnosis of senile dementia of the Alzheimer’s type. Neurobiol Aging 1996; 17 Suppl. 4: S144CrossRef

58.

Knopman DS, Knapp MJ, Gracon SI, et al. The clinician interview based impression (CIBI): a clinician’s global change rating scale in Alzheimer’s disease. Neurology 1994; 44: 2315–21PubMedCrossRef

59.

Kaufer DI, Cummings JL, Christine D. Effect of tacrine on behavioral symptoms in Alzheimer’s disease: an open-label study. J Geriatr Psychiatry Neurol 1996; 9: 1–6PubMed

60.

Cummings JL. The neuropsychiatric inventory: assessing psychopathology in dementia patients. Neurology 1997; 48 Suppl. 6: S10–16PubMedCrossRef

61.

Riter RN, Fries BE. Predictors of the placement of cognitively impaired residents on special care units. Gerontologist 1992; 32: 184–90PubMedCrossRef

62.

DeJong R, Osterlund OW, Roy GW. Measurement of quality of life changes in patients with Alzheimer’s disease. Clin Ther 1989; 11(4): 545–54PubMed

63.

Cutler NR, Sramek JJ. The bridging study: optimizing the dose for phase II/III. In: Becker R, Giacobini E, et al. Alzheimer disease: from molecular biology to therapy. Boston (MA): Birkhauser, 1996: 387–91

64.

Cutler NR, Jhee SS, Cyrus P, et al. Safety and tolerability of metrifonate in patients with Alzheimer’s disease: results of a maximum tolerated dose study. Life Sci 1998; 62(16): 1433–41PubMedCrossRef

65.

Mant T, Troetel WM, Imbimbo BP. Maximum tolerated dose and pharmacodynamics of eptastigmine in elderly healthy volunteers. J Clin Pharmacol 1998; 38: 610–7PubMed

66.

Ford JM, Truman CA, Wilcock GK, et al. Serum concentrations of tacrine hydrochloride predict its adverse effects in Alzheimer’s disease. Clin Pharmacol Ther 1993; 53: 691–5PubMedCrossRef

67.

Rogers SL, Cooper NM, Sukavaty R, et al. Pharmacokinetic and pharmacodynamic profile of donepezil HC1 following multiple oral doses. Br J Pharmacol 1998; 46 Suppl. 1: 7–12

68.

Cutler NR, Anand R, Hartman RD, et al. Antiemetic therapy for Alzheimer’s patients receiving the cholinesterase inhibitor SDZ ENA 713 [abstract]. Clin Pharmacol Ther 1998; 63(2): 188

69.

Sarin S, Gill KD. Biochemical and behavioral deficits in adult rat following chronic dichlorvos exposure. Pharmacol Biochem Behav 1998; 59(4): 1081–6PubMedCrossRef

70.

Glynn P, Holton JL, Nolan CC, et al. Neuropathy target esterase: immunolocalization to neuronal cell bodies and axons. Neuroscience 1998; 83(1): 295–302PubMedCrossRef

71.

Ehrich M, Correll L, Veronesi B. Acetylcholinesterase and neuropathy target esterase inhibitions in neuroblastoma cells to distinguish organophosphorus compounds causing acute and delayed neurotoxicity. Fundam Appl Toxicol 1997; 38(1): 55–63PubMedCrossRef

72.

Fournier L, Musard D, Lecorsier A. Lymphocyte esterases and hydroxylases in neurotoxicology. Vet Hum Toxicol 1996; 38(3): 190–5PubMed

73.

Sterri SH, Lyngaas S, Fonnum F. Toxicity of soman after repetitive injection of sublethal doses in guinea-pig and mouse. Acta Pharmacol Toxicol (Copenh) 1981; 49: 8–13CrossRef

74.

Williams FM, Charlton C, de Blaquiere GE, et al. The effects of multiple low doses of organophosphates on target enzymes in brain and diaphragm in the mouse. Hum Exp Toxicol 1997; 16: 67–71PubMedCrossRef

75.

Mennear JH. Dichlorvos carcinogenicity: an assessment of the weight of experimental evidence. Regul Toxicol Pharmacol 1994; 20 (3 Pt 1): 354–61PubMedCrossRef

76.

Anonymous. Bayersuspends metrifonate trials. Scrip 1998 Sep 30; 2374: 19

77.

Watkins PB, Zimmerman HJ, Knapp MJ, et al. Hepatotoxic effects of tacrine administration in patients with Alzheimer’s disease. JAMA 1994; 271: 992–8PubMedCrossRef

78.

Chan PC, Huff J, Haseman JK, et al. Carcinogenesis studies of dichlorvos in Fischer rats and B6C3F1 mice. Jpn J Cancer Res 1991; 82(2): 157–64PubMedCrossRef

79.

Blair D, Dix KM, Hunt PF, et al. Dichlorvos: a two-year inhalation carcinogenesis study in rats. Arch Toxicol 1976: 281–94

80.

Zeiger E, Erexson G, Mortelmans K, et al. Genetic toxicity studies of 1,2,3,4-tetrahydro-9-acridinamine (tacrine). Mutat Res 1997; 393(3): 189–97PubMedCrossRef

81.

Seymour RM, Routledge PA. Important drug-drug interactions in the elderly. Drugs Aging 1998; 12(6): 485–94PubMedCrossRef

82.

Crismon ML. Pharmacokinetics and drug interactions of cholinesterase inhibitors administered in Alzheimer’s disease. Pharmacotherapy 1998; 18 (2 Pt 2): 47–54SPubMed

83.

Becquemont L, Ragueneau I, Le Bot MA, et al. Influence of the CYP1A2 inhibitor fluvoxamine on tacrine pharmacokinetics in humans. Clin Pharmacol Ther 1997; 61: 619–27PubMedCrossRef

84.

Becquemont L, Le Bot MA, Riche C, et al. Use of heterologously expressed human cytochrome P450 1A2 to predict tacrine-fluvoxamine drug interaction in man. Pharmacogenetics 1998; 8: 101–8PubMedCrossRef

85.

Michalets EL. Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 1998; 18: 84–112PubMed

86.

Welty D, Pool W, Woolf T, et al. The effect of smoking on the pharmacokinetics and metabolism of Cognex® in healthy volunteers [abstract]. Pharmacol Res 1993; 10: S334

87.

Tiseo PJ, Perdomo CA, Friedhoff LT. Concurrent administration of donepezil HCl and ketoconazole: assessment of pharmacokinetic changes following single and multiple doses. Br J Clin Pharmacol 1998; 46 Suppl. 1: 30–4PubMed

88.

Tiseo PJ, Rogers SL, Perdomo CA, et al. The effect of cimetidine and ketoconazole on the pharmacokinetics of donepezil HCl [abstract]. Clin Pharmacol Ther 1998; 63(2): 234

89.

Tiseo PJ, Perdomo CA, Friedhoff LT. Concurrent administration of donepezil HCl and cimetidine: assessment of pharmacokinetic changes following single and multiple doses. Br J Clin Pharmacol 1998; 46 Suppl. 1: 25–9PubMed

90.

Eisai Inc. Aricept (donepezil hydrochloride): prescribing information. Teaneck (NJ): Eisai Inc., 1998

91.

Tiseo PJ, Perdomo CA, Friedhoff LT. Concurrent administration of donepezil HCl and digoxin: assessment of pharmacokinetic changes. Br J Clin Pharmacol 1998; 46 Suppl. 1: 40–4PubMed

92.

Tiseo PJ, Foley K, Friedhoff LT. Concurrent administration of donepezil HCl and theophylline: assessment of pharmacokinetic changes following multiple-dose administration in healthy volunteers. Br J Clin Pharmacol 1998; 46 Suppl. 1: 35–9PubMed

93.

Tiseo PJ, Foley K, Friedhoff LT. The effect of multiple doses of donepezil HCl on the pharmacokinetic and pharmacodynamic profile of warfarin. Br J Clin Pharmacol 1998; 46 Suppl. 1: 45–50PubMed

94.

Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer’s disease in the United States and the public health impact on delaying disease onset. Am J Public Health 1998; 88: 1337–42PubMedCrossRef

95.

Lamb HM, Faulds D. Metrifonate. Drugs Aging 1997; 11(6): 490–6PubMedCrossRef

96.

Pettigrew LC, Bieber F, Lettieri J, et al. Pharmacokinetics, pharmacodynamics, and safety of metrifonate in patients with Alzheimer’s disease. J Clin Pharmacol 1998; 38: 236–45PubMed

Titel: Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease in the Elderly
verfasst von: Chad M. VanDen Berg
Yusuf Kazmi
Professor Michael W. Jann
Publikationsdatum: 01.02.2000
Verlag: Springer International Publishing
Erschienen in: Drugs & Aging / Ausgabe 2/2000
Print ISSN: 1170-229X
Elektronische ISSN: 1179-1969
DOI: https://doi.org/10.2165/00002512-200016020-00004

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren.

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2000

Optimising Management of Patients with Advanced Heart Failure

Verteporfin

Recognition and Treatment of Dysthymia in Elderly Patients

Photodynamic Therapy in Gastrointestinal Cancer