摘要:

背景  藥物-藥物相互作用(drug-drug interactions， DDIs)是導致藥物不良反應的因素，識別和避免DDIs對于優(yōu)化老年患者藥物治療效果十分必要。

目的   分析老年患者長期用藥中潛在的具有臨床意義的DDIs發(fā)生情況及相關影響因素，為老年藥物合理使用提供依據(jù)。

方法  2018年12月 - 2020年3月、2021年5月 - 2022年4月，在北京三個社區(qū)≥65歲的老年人群中開展橫斷面研究，使用《老年人潛在的具有臨床意義的DDIs國際共識清單》評估患者長期用藥中的DDIs發(fā)生情況，通過logistic回歸分析DDIs的危險因素。

結果  共納入老年患者683例，年齡[Md(IQR)：84(79 ~ 88)]歲，至少發(fā)生1種潛在DDIs的患者202例(29.6%)。其中藥品使用的種類越多，發(fā)生潛在DDIs的概率越高(與2 ~ 4種相比：5 ~ 9種，OR=2.751，95% CI：1.627 ~ 4.652，P＜0.001；10 ~ 14種，OR=5.006，95% CI：2.813 ~ 8.907，P＜0.001；≥15種，OR=11.27，95% CI：5.140 ~ 24.711，P＜0.001)，衰弱狀態(tài)(OR=1.757，95% CI：1.184 ~ 2.606，P=0.005)、有潛在不適當用藥(OR=2.722，95% CI：1.863 ~ 3.976，P＜0.001)、有心血管疾病(OR=6.759，95% CI：1.549 ~ 29.501，P=0.011)者發(fā)生潛在DDIs的概率更高。最常見的潛在DDIs為同時使用兩種以上保鉀藥，所有與非甾體抗炎藥有關的藥物相互作用中，患者均使用了阿司匹林。

結論  社區(qū)老年人用藥中潛在的具有臨床意義的DDIs多見，應特別關注多藥、衰弱、具有心血管疾病、有潛在不適當用藥的老年患者DDIs發(fā)生情況，加強潛在DDIs的相關風險監(jiān)測，以優(yōu)化藥物治療效果，減少不良結局。

Abstract:

Background  Drug-drug interactions (DDIs) are one of the factors for adverse drug reactions. It is necessary to identify and avoid DDIs to optimize the efficacy of drug therapy in elderly patients.

Objective  To study the prevalence of potentially clinically significant DDIs and related influencing factors in elderly patients in the communities, and provide evidence for rational drug use in the elderly.

Methods  A cross-sectional study was conducted from December 2018 to April 2022 in a cohort of older adults ≥65 years old in three communities in Beijing. The occurrence of potential DDIs in patients' long-term medication use was assessed using the International Consensus List of Potentially Clinically Significant DDIs in Older People, and risk factors for potential DDIs were analyzed by Logistic regression.

Results  A total of 683 elderly patients with a median age (interquartile spacing) of 84 (79 - 88) years were included, and 202 (29.6%) patients had at least one potential DDIs. The more the number of drugs used, the higher the probability of potential DDIs (compared with 2-4: 5-9, OR=2.751, 95%CI: 1.627-4.652, P<0.001; 10-14, OR=5.006, 95% CI: 2.813-8.907, P<0.001; ≥15, OR=11.27, 95% CI: 5.140-24.711, P<0.001). Patients in frail status (OR=1.757, 95% CI: 1.184-2.606, P=0.005), with PIM (OR=2.722, 95% CI: 1.863-3.976, P<0.001), and cardiovascular disease (OR=6.759, 95% CI: 1.549-29.501, P=0.011) had a higher risk of potential DDIs. The most common potential DDIs were the concomitant use of more than two potassium-preserving drugs, and aspirin was used by patients in all potential DDIs related to NSAIDs.

Conclusion  Potentially clinically significant DDIs are common in elderly patients in the community. Special attention should be paid to the occurrence of DDIs in elderly patients with polypharmacy, frailty, cardiovascular disease, and PIM, and to enhancing the monitoring of risks associated with potential DDIs to optimize pharmacotherapy outcomes and reduce adverse outcomes.

表  1   研究對象基本特征(例，%)

Table  1   Characteristics of the participants (n, %)

　指標總體(n=683)無潛在DDIs (n=481)有潛在DDIs (n=202)χ2值P值 性別4.1740.041　女性445(65.2)325(73)120(27.0)　男性238(34.8)156(65.5)82(34.5)年齡Md(IQR)：84(79，88)歲27.1480.000　65 ~ 69歲93(13.6)82(88.2)11(11.8)　70 ~ 79歲90(13.2)72(80)18(20.0)　80 ~ 89歲410(60.0)275(67.1)135(32.9)　90 ~ 99歲90(13.2)52(57.8)38(42.2)BMI(24.34 ± 3.47) kg·m-20.9850.321?。?8.5 kg·m-2588(86.1)410(69.7)178(30.3)　≥28.5 kg·m-295(13.9)71(74.7)24(25.3)受教育程度0.3860.534　初中及以下496(72.6)346(69.8)150(30.2)　初中以下187(27.4)135(72.2)52(27.8)婚姻狀況0.2080.901　已婚438(64.2)311(71)127(29.0)　喪偶242(35.4)168(69.4)74(30.6)　離異分居3(0.4)2(66.7)1(33.3)照護情況4.4050.111　家人同住477(69.8)346(72.5)131(27.5)　專人照護133(19.5)84(63.2)49(36.8)　獨居73(10.7)51(69.9)22(30.1)收入6.3630.012　≤5000元169(24.7)132(78.1)37(21.9)?。?000元514(75.3)349(67.9)165(32.1)吸煙史1.5120.470　從不590(86.4)413(70)177(30)　已戒煙74(10.8)56(75.7)18(24.3)　吸煙19(2.8)12(63.2)7(36.8)1年內飲酒史0.0110.915　無620(90.8)437(70.5)183(29.5)　有63(9.2)44(69.8)19(30.2)藥品數(shù)量Md(IQR)：6(4，10)種104.2470.000　1 ~ 4種238(34.8)214(89.9)24(10.1)　5 ~ 9種260(38.1)181(69.6)79(30.4)　10 ~ 14種134(19.6)71(53)63(47)　≥15種51(7.5)15(29.4)36(70.6)1年內住院29.5620.000　無482(70.6)369(76.6)113(23.4)　有201(29.4)112(55.7)89(44.3)CCI評分Md(IQR)：3(1，4)10.2590.006　0 ~ 2330(48.3)245(74.2)85(25.8)　3 ~ 5257(37.6)181(70.4)76(29.6)　≥696(14.1)55(57.3)41(42.7)衰弱評分Md(IQR)：5(2，8)57.765＜0.001　　0 ~ 5355(52.0)289(81.4)66(18.6)　6 ~ 7136(19.9)92(67.6)44(32.4)　8 ~ 999(14.5)56(56.6)43(43.4)　10 ~ 1159(8.6)32(54.2)27(45.8)　≥1234(5.0)12(35.3)22(64.7)PIM48.618＜0.001　　無383(56.1)311(81.2)72(18.8)　有300(43.9)170(56.7)130(43.3)神經(jīng)系統(tǒng)疾病7.9800.005　無610(89.3)440(72.1)170(27.9)　有73(10.7)41(56.2)32(43.8)心腦血管疾病15.536＜0.001　　無47(6.9)45(95.7)2(4.3)　有636(93.1)436(68.6)200(31.4)消化系統(tǒng)疾病0.2530.615　無264(38.7)183(69.3)81(30.7)　有419(61.3)298(71.1)121(28.9)高血脂0.0510.821　無192(28.1)134(69.8)58(30.2)　有491(71.9)347(70.7)144(29.3)糖尿病4.1820.041　無351(51.4)235(67.0)116(33.0)　有332(48.6)246(74.1)86(25.9)　

表  2   社區(qū)老年人群潛在具有臨床意義的DDIs的發(fā)生例次及風險(n=202)

Table  2   Incidence and risk of potentially clinically significant DDIs (n=202)

共識編號DDI組合發(fā)生例次/(例次，%)相互作用風險 DDI-21同時使用≥2種保鉀藥物105(51.98)高血鉀癥DDI-23ACEI/ARB + 口服NSAIDs90(44.55)腎功能惡化及高血鉀血壓控制改變DDI-37阿普唑侖或地西泮或咪達唑侖或三唑侖
或唑吡坦或佐匹克隆 + CYP3A4抑制劑76(37.62)過度的鎮(zhèn)靜和長時間的催眠作用DDI-24利尿劑 + 口服NSAIDs36(17.82)腎功能惡化、高鉀血癥和充血性心力衰竭改變了血壓控制DDI-27辛伐他汀 + 氨氯地平29(14.36)嚴重的肌病和橫紋肌溶解，可導致急性腎衰竭和死亡DDI-18利伐沙班 + P-gp抑制劑或CYP3A4-抑制劑12(5.94)出血DDI-20抗血小板藥物 + 口服NSAIDs9(4.45)出血、胃腸道毒性(炎癥、潰瘍、穿孔)
降低了阿司匹林的心臟保護作用DDI-12口服抗凝劑 + 抗血小板藥物6(2.97)出血DDI-30鈣通道阻滯劑 + CYP3A4抑制劑6(2.97)鈣通道阻滯劑作用增強DDI-36同時使用3種中樞作用藥物6(2.97)摔倒和骨折的風險增加，認知能力受損DDI-11口服抗凝劑 + 口服NSAIDs4(1.98)出血、胃腸道出血和毒性(如炎癥、潰瘍和穿孔)DDI-26阿托伐他汀或辛伐他汀
或洛伐他汀 + 維拉帕米或地爾硫卓3(1.49)嚴重的肌病和橫紋肌溶解，
可導致急性腎衰竭和死亡DDI-50乙酰膽堿酯酶抑制劑 + 降低心率的藥物3(1.49)心跳過緩DDI-57同時使用≥2種抗膽堿能藥物3(1.49)抗膽堿能效應包括認知能力下降DDI-6地高辛 + 噻嗪類或袢利尿劑2(0.99)地高辛毒性；可能導致嚴重的致命心律失常后果DDI-22ACEI或ARB或保鉀利尿劑 + 鉀補充劑2(0.99)高血鉀癥DDI-25他汀類藥物 + 吉非貝齊2(0.99)嚴重的肌病和橫紋肌溶解，可導致急性腎衰竭和死亡DDI-32β -阻滯劑 + 維拉帕米或地爾硫卓2(0.99)潛在的嚴重心血管不良反應，包括
充血性心力衰竭、嚴重低血壓、心絞痛加重、
心室停搏、竇性停搏、心臟傳導阻滯DDI-39口服NSAIDs + SSRI或SNRI2(0.99)出血、消化道出血DDI-65同時使用2種降鉀藥物(如b2激動劑、噻嗪類、
環(huán)型利尿劑、皮質類固醇)2(0.99)低鉀血癥、QT間期延長和尖端扭轉型心動過速DDI-7維生素k拮抗劑 + 貝特類1(0.50)出血DDI-10維生素k拮抗劑 + 胺碘酮1(0.50)出血DDI-16達比加群 + P-gp抑制劑1(0.50)出血DDI-56口服或腸外皮質類固醇
+ 口服NSAIDs1(0.50)胃腸道潰瘍或出血DDI-66SSRI + 袢利尿劑或噻嗪類利尿劑1(0.50)低鈉血癥，直立性低血壓

表  3   社區(qū)老年人群涉及潛在的DDIs最多的藥物類別和具體藥物

Table  3   The most frequent drug classes and drugs involved in potential DDIs

　藥品類別使用人數(shù)/例發(fā)生相關DDIs例數(shù)/(例，%)涉及DDIs最多的藥品/例 鈣離子通道阻滯劑337105(31.16)氨氯地平(79)，硝苯地平(21)血管緊張素Ⅱ受體拮抗劑19084(44.21)厄貝沙坦(33)，氯沙坦鉀(20)口服非甾體抗炎藥23791(38.40)阿司匹林(91)，塞來昔布(2)利尿劑 8846(52.27)氫氯噻嗪(25)，螺內酯(15)他汀類14934(22.82)辛伐他汀(30)，阿托伐他汀(4)血管經(jīng)張素轉化酶抑制劑 2919(65.52)貝那普利(9)，培哚普利(4)

表  4   老年長期用藥潛在DDIs關聯(lián)因素的logistics分析

Table  4   Logistics analysis of potential DDIs for long-term use in the elderly

　變量OR95% CIP值 藥品數(shù)量　2 ~ 4種1.000　5 ~ 9種2.7511.627 ~ 4.652＜0.001　10 ~ 14種5.0062.813 ~ 8.907＜0.001　≥15種11.2705.140 ~ 24.711＜0.001衰弱(衰弱評分≥5)1.7571.184 ~ 2.6060.005有PIM2.7221.863 ~ 3.976＜0.001有心血管疾病6.7591.549 ~ 29.5010.011有糖尿病0.5950.405 ~ 0.8750.008 [1]

Leal Rodríguez C,Kaas-Hansen BS,Eriksson R,et al. Drug interactions in hospital Prescriptions in Denmark:prevalence and associations with adverse outcomes[J]. Pharmacoepidemiol Drug Saf,2022,31(6): 632-642.

[2]

Niu J,Straubinger RM,Mager DE. Pharmacodynamic drug-drug interactions[J]. Clin Pharmacol Ther,2019,105(6): 1395-1406.

[3]

Poly TN,Islam MM,Yang HC,et al. Appropriateness of overridden alerts in computerized physician order entry:systematic review[J]. JMIR Med Inform,2020,8(7): e15653.

[4]

Davies LE,Spiers G,Kingston A,et al. Adverse outcomes of polypharmacy in older people:systematic review of reviews[J]. J Am Med Dir Assoc,2020,21(2): 181-187.

[5]

Sánchez-Fidalgo S,Guzmán-Ramos MI,Galván-Banqueri M,et al. Prevalence of drug interactions in elderly patients with multimorbidity in primary care[J]. Int J Clin Pharm,2017,39(2): 343-353.

[6] 陳張勇,劉利剛,吐達洪,等. 基于3種標準的社區(qū)老年患者潛在不適當用藥評估[J]. 中國新藥與臨床雜志,2018,37(12): 700-706. doi: 10.14109/j.cnki.xyylc.2018.12.009 [7]

By the American Geriatrics Society Beers Criteria? Update Expert Panel. American geriatrics society 2019 updated AGS beers criteria? for potentially inappropriate medication use in older adults[J]. J Am Geriatr Soc,2019,67(4): 674-694.

[8]

O'Mahony D,O'Sullivan D,Byrne S,et al. STOPP/START criteria for potentially inappropriate prescribing in older people:version 2[J]. Age Ageing,2015,44(2): 213-218.

[9]

Anrys P,Petit AE,Thevelin S,et al. An international consensus list of potentially clinically significant drug-drug interactions in older people[J]. J Am Med Dir Assoc,2021,22(10): 2121-2133.

[10] 中國老年保健醫(yī)學研究會老年合理用藥分會,中華醫(yī)學會老年醫(yī)學分會,中國藥學會老年藥學專業(yè)委員會,等. 中國老年人潛在不適當用藥判斷標準(2017年版)[J]. 藥物不良反應雜志,2018,20(1): 2-8. [11]

Rolfson DB,Majumdar SR,Tsuyuki RT,et al. Validity and reliability of the Edmonton frail scale[J]. Age Ageing,2006,35(5): 526-529.

[12]

Charlson M,Szatrowski TP,Peterson J,et al. Validation of a combined comorbidity index[J]. J Clin Epidemiol,1994,47(11): 1245-1251. doi: 10.1016/0895-4356(94)90129-5

[13] 中國老年保健醫(yī)學研究會老年內分泌與代謝病分會,中國毒理學會臨床毒理專業(yè)委員會. 老年人多重用藥安全管理專家共識[J]. 中國全科醫(yī)學,2018,21(29): 3533-3544. [14] 國家重點研發(fā)項目(YFC)課題組,中國老年醫(yī)學學會醫(yī)養(yǎng)結合促進委員會. 高齡老年共病患者多重用藥安全性管理專家共識[J]. 中華保健醫(yī)學雜志,2021,23(5): 548-554. [15]

Tommelein E,Petrovic M,Somers A,et al. Older patients' Prescriptions screening in the community pharmacy:development of the Ghent Older People’s Prescriptions community Pharmacy Screening (GheOP3S) tool[J]. J Public Health (Oxf),2016,38(2): e158-e170.

[16]

Nyborg G,Straand J,Klovning A,et al. The Norwegian General Practice:nursing Home criteria (NORGEP-NH) for potentially inappropriate medication use:a web-based Delphi study[J]. Scand J Prim Health Care,2015,33(2): 134-141.

[17]

Monteith S,Glenn T. Comparison of potential psychiatric drug interactions in six drug interaction database programs:a replication study after 2 years of updates[J]. Hum Psychopharmacol,2021,36(6): e2802.

[18]

Abbas A,Al-Shaibi S,Sankaralingam S,et al. Determination of potential drug-drug interactions in prescription orders dispensed in a community pharmacy setting using Micromedex? and Lexicomp?:a retrospective observational study[J]. Int J Clin Pharm,2022,44(2): 348-356.

[19] 王思蒙,張晨,孫雪,等. 社區(qū)老年人潛在不適當用藥及其應對模式的研究進展[J]. 中國全科醫(yī)學,2022,25(13): 1551-1556. [20]

Bories M,Bouzillé G,Cuggia M,et al. Drug-drug interactions in elderly patients with potentially inappropriate medications in primary care,nursing home and hospital settings:a systematic review and a preliminary study[J]. Pharmaceutics,2021,13(2): 266.

[21]

Albertsen N,Sommer TG,Olsen TM,et al. Polypharmacy and potential drug-drug interactions among Greenland’s care home residents[J]. Ther Adv Drug Saf,2022,13: 20420986221103918.

[22]

Hanlon JT,Perera S,Newman AB,et al. Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults[J]. J Clin Pharm Ther,2017,42(2): 228-233.

[23]

Hughes JE,Russo V,Walsh C,et al. Prevalence and factors associated with potential drug-drug interactions in older community-dwelling adults:a prospective cohort study[J]. Drugs Aging,2021,38(11): 1025-1037. doi: 10.1007/s40266-021-00898-8

[24]

Burato S,Leonardi L,Antonazzo IC,et al. Comparing the prevalence of polypharmacy and potential drug-drug interactions in nursing homes and in the community dwelling elderly of Emilia Romagna region[J]. Front Pharmacol,2021,11: 624888. doi: 10.3389/fphar.2020.624888

[25]

Beckey NP,Parra D,Colon A. Retrospective evaluation of a potential interaction between azithromycine and warfarin in patients stabilized on warfarin[J]. Pharmacotherapy,2000,20(9): 1055-1059.

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