于第一线照护处方NSAIDs的建议


  【24drs.com】December 28, 2009 — 一篇发表于12月15日美国家庭医学科期刊(American Family Physician)的回顾文献,提出于第一线照护开立非抗发炎类固醇药物(NSAIDs)处方的建议。
  
  波特兰奥勒刚健康科学大学的Amanda Risser医师等人写道,藉由阻断环氧合酶(COX)而减少前列腺素合成,NSAIDs一般用于治疗发炎、疼痛、与发烧,两大类型的COX(COX-1和COX-2)都受到非选择性NSAIDs的抑制,COX-2也会受到选择性NSAIDs的抑制。所有的非选择性NSAIDs会透过抑制COX-1和血栓素A2(TXA2)路径而抑制血小板凝集。
  
  虽然NSAIDs被广为使用,但有一些风险,包括明显的上肠胃道出血(特别是年长者),使用抗凝血治疗者、有与使用NSAID相关上胃肠道出血病史之病患也有风险。并用NSAID与质子帮浦抑制剂(PPI)或组织胺H2受体拮抗剂可以降低消化不良、腹痛、胃肠道不适、胃肠道出血。
  
  尽管阿斯匹灵对心脏有保护性,其它的NSAIDs可能有心脏方面的副作用,包括恶化郁血性心衰竭、血压上升、心肌梗塞以及局部缺血。COX-2抑制剂的心肌梗塞风险增加,然而,美国目前唯一的COX-2抑制剂celecoxib,在心血管效果方面可能是安全的。
  
  NSAIDs不应用于肝硬化病患,因为这类病患的出血和肾衰竭风险更大。不过,NSAIDs很少引起肝损伤,对于肝脏的任何影响通常也是可逆的。比较会引起肝脏问题的NSAIDs有sulindac和diclofenac。
  
  当开立NSAIDs处方给使用抗凝血剂治疗者、血小板功能不佳者、或马上要进行手术者时需谨慎。
  
  NSAIDs的中枢神经系统副作用,包括无菌性脑膜炎、精神病与耳鸣,NSAIDs也会引起或恶化气喘。对于气喘病患,特别是那些鼻息肉或复发鼻窦炎者,应避免使用NSAIDs和阿斯匹灵。
  
  怀孕最后6到8周时,应避免使用NSAIDs,以免因为抑制前列腺素合成而延长妊娠、动脉导管过早关闭,血小板活化而引起母婴并发症。不过,多数的NSAIDs在怀孕期间是安全的,对于哺乳妇女,可以安全使用ibuprofen、indomethacin与naproxen。应教育病患正确的NSAID剂量信息,以及将其存放在孩童无法开启的容器,以免发生孩童NSAID过量风险。
  
  【主要建议】
  提供给开业医师的主要临床建议与相关证据等级如下:
  * 对于有NSAID相关溃疡但必须服用NSAIDs者,医师需考虑同时处方PPIs、加倍剂量的组织胺H2受体拮抗剂或misoprostol。这些病患也可以单独使用Celecoxib,但是心肌梗塞风险增加的病患应避免使用此药。可能怀孕的妇女也应避免服用misoprostol (证据等级C)。两篇系统性回顾指出,这类病患使用NSAIDs可以预防内视镜溃疡(endoscopic ulcers)。
  * 为了预防急性肾衰竭,肾脏病、郁血性心衰竭或肝硬化患者应避免使用NSAIDs (证据等级C,根据文献回顾以及共识指引之综述)。
  * 至于肾衰竭风险病患,以及服用血管收缩素转化酶抑制剂和血管张力素受器阻断剂者,医师在处方NSAIDs之后,应考虑监测血清肌酸酐浓度(证据等级C,根据共识指引之综述)。
  * 对于服用抗凝血剂的病患,如果可以的话,尽量避免NSAIDs与阿斯匹灵。如果需并用NSAIDs和抗凝血剂,则国际标准比(INR)预期会升高。这些病患应有适当的INR监测、调整warfarin剂量以及胃肠道方面的预防(证据等级C,根据系统性回顾)。
  * 至于哺乳妇女,可以安全地使用ibuprofen、indomethacin和naproxen(证据等级C,根据共识指引)。
  
  【编辑:增加心血管顾虑】
  丹麦哥本哈根大学Gentofte医院的Gunnar H. Gislason博士在编辑评论中表示,有关NSAIDs之心血管安全性的顾虑增加,在过去10年越趋明朗,虽然最初认为这些顾虑是与COX-2抑制剂有关,最近也发现非选择性NSAIDs与心血管风险的关联。
  
  因为总是有一些病患有需服用NSAIDs的疼痛状况,在开始NSAID治疗之前,应聚焦在风险与利益的平衡上。
  
  Gislason博士写道,这对于已经有心血管疾病的病患特别重要,这些人一定要优先考量使用心脏风险低的药物(例如acetaminophen、弱效鸦片类)来治疗疼痛。对于需要NSAID治疗者,应考量使用具有高度COX-1 选择性的NSAIDs(例如naproxen、ibuprofen、阿斯匹灵),且尽可能以最低剂量、最短期间治疗。若要较强的止痛效果,可以考虑并用其它类止痛药。
  
  至于辅助止痛治疗,Gislason博士建议考虑非药物疗法,例如物理治疗和运动。
  
  Gislason博士结论表示,流行病学研究显示,一般人广泛使用NSAIDs,已经有心脏疾病者也是,此外,在许多国家中,NSAIDs是以成药贩售,无须处方和专家建议,应限制它们的使用,或者提供可能的副作用的信息。这也表示需要再度评估目前有关使用NSAID的治疗策略,以及NSAIDs对于大家没有伤害的误解。
  
  回顾作者与编辑皆宣告没有相关财务关系。

Recommendations for Prescribing NSAIDs in the Primary Care Setting

By Laurie Barclay, MD
Medscape Medical News

December 28, 2009 — A review article published in the December 15 issue of the American Family Physician offers recommendations for prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) in the primary care setting.

"...NSAIDs are commonly used to treat inflammation, pain, and fever by decreasing prostaglandin synthesis through blockage of the cyclooxygenase (COX) enzyme," write Amanda Risser, MD, MPH, from Oregon Health and Science University in Portland, and colleagues. "The two major isoforms of COX (COX-1 and COX-2) are inhibited by nonselective NSAIDs. COX-2 is also inhibited by selective NSAIDs. All nonselective NSAIDs inhibit platelet aggregation through inhibition of COX-1 and the thromboxane A2 (TXA2) pathway."

Although NSAIDs are in widespread use, there are accompanying risks, including significant upper gastrointestinal (GI) tract bleeding (particularly in older persons), risks in those receiving anticoagulant therapy, and risks in patients with a history of upper GI tract bleeding associated with NSAID use. Dyspepsia, abdominal pain, GI discomfort, and GI bleeding may be reduced by combining the NSAID with a proton pump inhibitor (PPI) or histamine H2 blocker.

Despite the cardioprotective qualities of aspirin, other NSAIDs may have adverse cardiac effects, including worsening of congestive heart failure, increase in blood pressure, myocardial infarction, and ischemia. The risk for myocardial infarction is increased with COX-2 inhibitors, although celecoxib, which is the only COX-2 inhibitor still available in the United States, is somewhat safer regarding cardiovascular effects.

NSAIDs should not be used in patients with cirrhotic liver diseases because such patients are at greater risk of bleeding and for kidney failure. However, NSAIDs rarely cause hepatic damage, and any hepatic effects are usually reversible. NSAIDs with more potential for hepatic problems include sulindac and diclofenac.

Caution is advised when NSAIDs are prescribed in the setting of anticoagulant therapy, platelet dysfunction, or immediately before surgery.

Central nervous system adverse effects of NSAIDs may include aseptic meningitis, psychosis, and tinnitus. NSAIDs may also trigger or exacerbate asthma. In patients with asthma, especially those with nasal polyps or recurrent sinusitis, NSAIDs and aspirin should be avoided.

During the last 6 to 8 weeks of pregnancy, NSAIDs should be avoided to prevent prolonged gestation from inhibition of prostaglandin synthesis, premature closure of the ductus arteriosus, and antiplatelet activity causing maternal and fetal complications. However, most NSAIDs are likely safe in pregnancy. In breast-feeding women, ibuprofen, indomethacin, and naproxen can be safely used. Parents should be educated regarding correct NSAID dosing and storage in childproof containers to prevent accidental NSAID overdose in children.

Key Recommendations

Specific key clinical recommendations for practice, and their accompanying level of evidence rating, are as follows:

  • Physicians should consider prescribing PPIs, double-dose histamine H2 blockers, or misoprostol with NSAIDs for persons who must take NSAIDs, although they have had an NSAID-associated ulcer. Celecoxib may also be used alone in these patients, but this drug should be avoided in patients at increased risk for myocardial infarction. Women who might become pregnant should not take misoprostol (level of evidence, C). Two systematic reviews describe the use of NSAIDs in this setting for the prevention of endoscopic ulcers.
  • For prevention of acute renal failure, NSAIDs should be avoided whenever possible in patients with preexisting kidney disease, congestive heart failure, or cirrhosis (level of evidence, C, based on a literature review and a summary of consensus guidelines).
  • For patients at risk for renal failure, and in those taking angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, physicians should consider monitoring serum creatinine levels after prescribing treatment with NSAIDs (level of evidence, C, based on a summary of consensus guidelines).
  • In patients taking anticoagulants, NSAIDs and aspirin should be avoided if possible. An increase in international normalized ratio (INR) should be expected if concurrent use of NSAIDs and anticoagulants is required. These patients should have appropriate INR monitoring, dosage adjustments of warfarin, and GI prophylaxis (level of evidence, C, based on a systematic review).
  • In breast-feeding women, ibuprofen, indomethacin, and naproxen can be safely used (level of evidence, C, based on a consensus guideline).

Editorial: Increased Cardiovascular Concerns

In an accompanying editorial, Gunnar H. Gislason, MD, PhD, from Copenhagen University Hospital Gentofte in Copenhagen, Denmark, describes increased concerns regarding the cardiovascular safety profile of NSAIDs, which have come to light during the last decade. Although these concerns were first recognized for COX-2 inhibitors, increased cardiovascular risk associated with nonselective NSAIDs has recently been identified.

Because there will always be groups of patients with pain conditions who must take NSAIDs, there is a need to focus on the balance between risk and benefit before NSAID therapy is started.

"This is especially important in persons with established cardiovascular disease in whom alternative pain treatment with lower cardiac risk (e.g., acetaminophen, weak opiates) should always be the first choice," Dr. Gislason writes. "In persons needing NSAID treatment, NSAIDs with the highest COX-1 selectivity (e.g., naproxen, ibuprofen, aspirin) should be preferred and used in the lowest dosages and for the shortest durations possible. For stronger analgesic effect, a combination with other types of analgesics should be considered."

As supplements to analgesic therapy, Dr. Gislason also recommends considering nonpharmacologic treatment, such as physiotherapy and physical exercise.

"Epidemiologic studies have demonstrated extensive use of prescription NSAIDs in the general population, as well as in persons with established cardiac disease," Dr. Gislason concludes. "Also, in many countries, NSAIDs are sold without a prescription, expert advice, limits on their use, or information on potential adverse effects. This indicates the need for reevaluation of current treatment strategies regarding NSAID use and the misconception that NSAIDs are harmless for everyone."

The review authors and editorialist have disclosed no relevant financial relationships.

Am Fam Physician. 2009;80:1371-1378.

    
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