Background

By age 75, most of the population has some frailty or chronic process associated with pain. The American Geriatrics Society recently released a literature synthesis and expert consensus on best practices for pharmacologic management of pain in this complex group of patients.

Conclusions

Assessing pain in the older population can be difficult because of impaired cognition, minimization, or communication difficulties. A number of standardized screening tools can be used to assist in this undertaking.

Pain may not always be eliminated, even by aggressive management. Effective comfort goals may be a more realistic target, given the side effects and limits of existing medications. When using long-acting agents, provision should be made for treating breakthrough pain with short-acting medications.

Gastrointestinal absorption may be unpredictable in older patients because of slower transit times, surgically altered anatomy, or the side effects of medications.

Transdermal absorption is usually not affected by age.

An increased ratio of fat to lean body mass can result in a greater volume of distribution of fat-soluble drugs.

“Muscle relaxant” medications may inhibit polysynaptic myogenic reflexes in animal models, but their analgesic properties for muscle pain are unrelated to relief of muscle spasm.

Implementation

With its superior drug safety profile at lower doses, acetominophen is often recommended as a first-line agent for back and osteoarthritis pain. The 24-hour total dose should not exceed 4 g to minimize the risk of liver toxicity.

Nonsteroidal anti-inflammatory drugs have been associated with up to one-quarter of hospitalizations associated with drug toxicity; they should be used with caution because of potential toxicity to the renal, gastrointestinal, and cardiac systems. Patients receiving NSAIDs may have reduced GI toxicity if placed on proton pump inhibitors, high-dose H2-receptor blockers, or misoprostol. Patients should not take more than one nonselective anti-inflammatory agent or COX-2 inhibitor.

Naproxen is often the preferred NSAID because of its lower risk of cardiovascular toxicity. Although the Food and Drug Administration has warned that ibuprofen reduces the cardioprotective effects of aspirin, outcome data to support this recommendation remain uncertain. Diclofenac has the worst risk profile for cardiovascular events. Ketorolac is not recommended for chronic use and has a significant profile for renal and GI side effects.

The increasing evidence of the multisystem toxicity of nonsteroidal agents has increased the prescribing of opioid analgesics in the elderly. Data demonstrate short-term effectiveness for multiple persistent pain states, but long-term data are not available. Opioids should be administered cautiously on a trial basis with a mutual understanding of the limitations of the therapy. There are recent data suggesting hormonal changes with long-term use that can result in fatigue, depression, and lowered libido. Close monitoring of side effects, patient behavior, and therapeutic effect are core aspects of opioid prescribing.

Cyclobenzaprine has a therapeutic and side effect profile identical to that of amitriptyline. Carisoprodol has been removed from the European market because of its potential for abuse. Neither provide pain relief from true muscle spasm. Both are associated with a greater risk of falls in the elderly.

Baclofen is useful for severe spasticity from a variety of neurologic conditions. Titrating from low doses can minimize potential for dizziness and somnolence. Abrupt discontinuation can induce delirium and seizures.

While tricyclic antidepressants have been used for neuropathic pain for years, their potential for cardiovascular and anticholinergic side effects limits their application in geriatric care. Serotonin norepinephrine uptake inhibitors (SNRIs) such as duloxetine and venlafaxine are good alternatives for neuropathic pain and fibromyalgia. The SSRIs such as fluoxetine, citalopram, sertraline, and fluvoxamine have not been shown to be effective in combating pain.

Later-generation anticonvulsant agents such as gabapentin and pregabalin affect the voltage-gated calcium ion channels to improve neuropathic pain with fewer side effects, compared with tricyclic antidepressants and older anticonvulsants.

Topical lidocaine is effective for localized neuropathic pain. Localized nonneuropathic pain may respond to topical nonsteroidal agents. Topical capsaicin cream can provide some benefit by depleting substance P over time (potentially several weeks). Nearly a third of patients cannot tolerate the burning sensation, which can persist for several months.

Corticosteroids can be useful for pain from chronic inflammatory processes. They should not be used for osteoarthritis.

Calcitonin, by an unknown mechanism of action, can be useful for osteoporotic fracture pain of the vertebrae and pelvis. Side effects include nausea and abnormal serum calcium and phosphorus levels.

Reference

American Geriatrics Society Panel. Pharmacological management of persistent pain in older persons. J. Am. Ger. Soc. 2009;57:1331-46.

Dr. Golden (left) is professor of medicine and public health and Dr. Hopkins is program director for the internal medicine/pediatrics combined residency program at the University of Arkansas, Little Rock.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

背景

 

大多数人到75岁时都多少会出现虚弱或与疼痛相关的慢性疾病。最近，美国老年医学会(American Geriatrics Society)发布了一份探讨老年人疼痛药物治疗最佳方案的文献合集及专家共识。

 

结论

 

由于老年人的认知功能受损、麻木或存在沟通方面的困难，因此对老年人进行疼痛评估较为困难。可采用一系列标准筛查方法辅助这种评估工作。

 

疼痛通常不能完全消除，甚至积极治疗也不能达到这一目标。考虑到现有药物的副作用和局限性，设定达到有效缓解的目标可能更为切合实际。应用长效药物时，应同时准备用于治疗突发性疼痛(breakthrough pain)的短效药物。

 

药物在老年患者胃肠道中的吸收情况较难预测，因为可能存在以下情况：通过时间较慢、存在手术引起的解剖结构改变或药物副作用。

 

透皮吸收通常不受年龄影响。

 

肥瘦体重比率越大，脂溶性药物的分布容积越大。

 

在动物模型中，“肌肉松弛”药物可抑制多突触肌源性反射，但这些药物对肌肉疼痛的止痛作用与肌肉痉挛缓解无关。

 

实施

 

对乙酰氨基酚低剂量使用时的安全性高，因此经常被推荐作为背部和骨关节炎疼痛的一线治疗药物。为了尽量降低肝毒性危险，24小时总剂量不应超过4 g。

 

非甾体类抗炎药(NSAID)与1/4的药物毒性相关住院率有关。由于这类药物对肾脏、胃肠道和心脏系统具有潜在毒性，因此应慎用。服用NSAID的患者如果同时服用质子泵抑制剂、高剂量H2受体阻滞剂或米索前列醇，则可降低胃肠道毒性。患者不应服用1种以上的非选择性抗炎药或COX-2抑制剂。

 

NSAID治疗通常首选萘普生，因为其心血管毒性危险较低。尽管美国食品药品管理局(FDA)警告，布洛芬可降低阿司匹林的心脏保护作用，但尚未有明确的的结局数据支持这一说法。双氯芬酸引起心血管事件的危险性最大。酮咯酸的肾和胃肠道副作用明显，不建议长期使用。

 

有关非甾体类药物的多系统毒性的证据日益增加，由此促进了阿片类镇痛药在老年患者中的应用。研究显示，阿片类镇痛药可在短期内有效缓解多发性持续性疼痛状态，但尚缺乏相关长期疗效数据。应在了解阿片类药物治疗优缺点的基础上，试验性地慎用这类药物。近期研究表明，长期应用阿片类药物引起的激素变化可导致疲劳、抑郁及性欲下降。阿片类药物治疗的关键在于严密监测副作用、患者行为和疗效。

 

环苯扎林与阿米替林具有相同的疗效谱和副作用谱。由于存在滥用的可能，卡立普多已撤出欧洲市场。这两种药物均不能缓解真正肌肉痉挛引起的疼痛。两者均可增加老年人摔倒的危险。

 

巴氯芬能够有效缓解各种神经病变引起的严重痉挛状态。从低剂量开始滴定，能够最大程度地降低发生头晕和嗜睡的可能性。突然停药可引起谵妄和癫痫发作。

 

虽然三环类抗抑郁药已用于治疗神经病理性疼痛多年，但这类药物的心血管和抗胆碱能副作用限制了其在老年患者中的应用。诸如度洛西汀和文拉法辛等5-羟色胺去甲肾上腺素摄取抑制剂(SNRI)是治疗神经病理性疼痛和纤维肌痛的有效替代药物。诸如氟西汀、西酞普兰、舍曲林和 氟伏沙明等选择性5-羟色胺再摄取抑制剂(SSRI)已被证实可有效缓解疼痛。

 

如加巴喷丁和普瑞巴林等的新一代抗惊厥药主要通过影响电压门控性钙离子通道来缓解神经病理性疼痛，并且与三环类抗抑郁药和传统抗惊厥药相比，副作用更少。

 

外用利多卡因可有效缓解局部神经病理性疼痛。外用非甾体类药物可有效治疗局部非神经病理性疼痛。外用辣椒素乳膏可通过在一段时间(约数周)内耗损P物质而产生一定止痛作用。涂敷该乳膏所产生的烧灼感可持续几个月，近1/3的患者不能耐受这种烧灼感。

 

皮质类固醇可有效缓解慢性炎性疾病引起的疼痛。这类药不应用于治疗骨关节炎。

 

降钙素可有效治疗椎体和骨盆的骨质疏松性骨折疼痛，但作用机制尚不清楚。副作用包括恶心及血清钙和磷水平异常。

 

参考文献

 

American Geriatrics Society Panel. Pharmacological management of persistent pain in older persons. J. Am. Ger. Soc. 2009;57:1331-46.

 

Golden博士(左)是阿肯色大学小石城分校(University of Arkansas, Little Rock)的内科学和公共卫生学教授，Hopkins博士是该校内科和儿科联合实习项目的项目主任。

 

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