Chew Marci L, Mulsant Benoit H, Pollock Bruce G, Lehman Mark E, Greenspan Andrew, Mahmoud Ramy A, Kirshner Margaret A, Sorisio Denise A, Bies Robert R, Gharabawi Georges
Department of Pharmaceutical Sciences, School of Pharmacy, Geriatric Psychopharmacology Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Am Geriatr Soc. 2008 Jul;56(7):1333-41. doi: 10.1111/j.1532-5415.2008.01737.x. Epub 2008 May 26.
The objective of this study was to measure the anticholinergic activity (AA) of medications commonly used by older adults. A radioreceptor assay was used to investigate the AA of 107 medications. Six clinically relevant concentrations were assessed for each medication. Rodent forebrain and striatum homogenate was used with tritiated quinuclidinyl benzilate. Drug-free serum was added to medication and atropine standard-curve samples. For medications that showed detectable AA, average steady-state peak plasma and serum concentrations (C(max)) in older adults were used to estimate relationships between in vitro dose and AA. All results are reported in pmol/mL of atropine equivalents. At typical doses administered to older adults, amitriptyline, atropine, clozapine, dicyclomine, doxepin, L-hyoscyamine, thioridazine, and tolterodine demonstrated AA exceeding 15 pmol/mL. Chlorpromazine, diphenhydramine, nortriptyline, olanzapine, oxybutynin, and paroxetine had AA values of 5 to 15 pmol/mL. Citalopram, escitalopram, fluoxetine, lithium, mirtazapine, quetiapine, ranitidine, and temazepam had values less than 5 pmol/mL. Amoxicillin, celecoxib, cephalexin, diazepam, digoxin, diphenoxylate, donepezil, duloxetine, fentanyl, furosemide, hydrocodone, lansoprazole, levofloxacin, metformin, phenytoin, propoxyphene, and topiramate demonstrated AA only at the highest concentrations tested (patients with above-average C(max) values, who receive higher doses, or are frail may show AA). The remainder of the medications investigated did not demonstrate any AA at the concentrations examined. Psychotropic medications were particularly likely to demonstrate AA. Each of the drug classifications investigated (e.g., antipsychotic, cardiovascular) had at least one medication that demonstrated AA at therapeutic doses. Clinicians can use this information when choosing between equally efficacious medications, as well as in assessing overall anticholinergic burden.
本研究的目的是测量老年人常用药物的抗胆碱能活性（AA）。采用放射受体分析法研究了107种药物的AA。对每种药物评估了六个临床相关浓度。使用啮齿动物前脑和纹状体匀浆与氚标记的奎尼丁苄酯。将无药物血清添加到药物和阿托品标准曲线样本中。对于显示可检测到AA的药物，使用老年人的平均稳态血浆和血清峰值浓度（C(max)）来估计体外剂量与AA之间的关系。所有结果均以阿托品等效物的pmol/mL报告。在给予老年人的典型剂量下，阿米替林、阿托品、氯氮平、双环胺、多塞平、L-莨菪碱、硫利达嗪和托特罗定的AA超过15 pmol/mL。氯丙嗪、苯海拉明、去甲替林、奥氮平、奥昔布宁和帕罗西汀的AA值为5至15 pmol/mL。西酞普兰、艾司西酞普兰、氟西汀、锂盐、米氮平、喹硫平、雷尼替丁和替马西泮的值小于5 pmol/mL。阿莫西林、塞来昔布、头孢氨苄、地西泮、地高辛、地芬诺酯、多奈哌齐、度洛西汀、芬太尼、呋塞米、氢可酮、兰索拉唑、左氧氟沙星、二甲双胍、苯妥英、丙氧芬和托吡酯仅在测试的最高浓度下显示出AA（C(max)值高于平均水平、接受更高剂量或身体虚弱的患者可能显示出AA）。其余研究的药物在所检查的浓度下未显示出任何AA。精神药物特别容易显示出AA。所研究的每种药物类别（如抗精神病药、心血管药物）至少有一种药物在治疗剂量下显示出AA。临床医生在选择等效疗效的药物时以及评估总体抗胆碱能负担时可以使用这些信息。
