尽管每年都有数十种新药上市，但我们也不能忘了那些“久经考验”的老药。近年来，研究者经常会发现部分老药还有一些新用途和惊人的益处。华盛顿大学医学教授Douglas Paauw博士总结了7种药物的10种用途。来看一下，你都知道吗？
二甲双胍是最常用的口服降糖药物，有效，成本低，低血糖风险极低，对体重的影响是中性的。多项研究提出了它的另一个可能的获益——降低癌症的发病率和死亡率。
一项纳入超过20,000名女性2型糖尿病患者的巢式病例对照研究得出结论，使用二甲双胍超过5年与乳腺癌风险降低相关（OR 0.44; 95%CI 0.24-0.82）。
2017年发表的一项Meta分析纳入了9,000名服用二甲双胍的患者，结果显示结直肠腺瘤风险降低（pooled OR, 0.76; 95% CI, 0.63-0.92）。
二甲双胍还可能减缓某些癌症的进展并提高其生存率，包括头颈部、卵巢、胰腺和肺部的肿瘤。
不过这种效应在动物模型或流行病学研究中尚未得到一致的证实，目前正在对二甲双胍潜在的抗肿瘤作用进行大量的研究。
氯沙坦：降尿酸作用
对于高血压合并高尿酸血症的患者，服用氯沙坦除了降压还能降低血尿酸。氯沙坦具有碱化尿液的作用，可以增强尿酸排泄，降低尿酸结晶形成的风险。一项基于人群的病例对照研究发现，使用氯沙坦与痛风事件风险降低相关。
氯沙坦是唯一的显示尿酸水平显著降低的ARB类药物，对高尿酸血症患者是安全有效的。
噻嗪类利尿剂：预防骨质疏松性骨折
噻嗪类利尿剂可减少尿钙排泄，改善骨密度。在Framingham研究中，噻嗪类药物使用者的髋部骨折风险降低。其后的多项随机试验表明，噻嗪类利尿剂可维持骨密度。
在选择降压药物时，噻嗪类药物的这种益处值得考虑。
螺内酯：用于心衰和难治性高血压
RALES试验发现，对于左心室收缩功能障碍所致的严重心力衰竭患者，螺内酯联合标准治疗可显着降低并发症和死亡风险。
在过去10年中，螺内酯在治疗难治性高血压方面发挥了更大的作用。
螺内酯：抗雄激素作用
由于其抗雄激素作用，螺内酯也被用于女性多毛症、女性脱发、痤疮和多囊卵巢综合征（PCOS）皮肤改变的治疗。
关于多毛症和PCOS的证据最强，治疗痤疮和女性脱发的作用主要来自一些阳性研究和临床经验。
螺内酯：用于骨关节炎
螺内酯可阻断醛固酮。最近的两项研究评估了该药在骨关节炎中的潜在的治疗效果。
一项前瞻性随机研究纳入了200名符合美国风湿病学会膝关节骨性关节炎标准且存在新发膝关节积液的患者，结果显示，低剂量螺内酯组有66%的患者积液完全消失，效果优于布洛芬、冰和安慰剂。
但另一项针对老年人骨关节炎引起膝关节疼痛的随机、双盲、安慰剂对照得出结论，该药并未改善疼痛和身体功能。
硝酸甘油：外用，治疗肛裂
硝酸甘油最常用于预防或治疗心绞痛。外用硝酸甘油可以治疗肛裂。肛门括约肌压力高会减少该部位的血流量，局部使用硝酸甘油可以通过降低压力改善血流量。
2011年，美国食品和药品管理局（FDA）批准0.4%的硝酸甘油软膏用于治疗慢性肛裂的中重度疼痛。
硝酸甘油：外用，用于网球肘
局部硝酸甘油也被证明是治疗肱骨外上髁炎（俗称“网球肘”）的有效方法。一项随机对照试验中，局部使用硝酸甘油治疗成功率高达90％，6个月随访仍然效果显著。已经证实，使用硝酸甘油贴剂可减轻肱骨外上髁炎的疼痛症状并改善功能。
最近的系统评价发现，局部使用硝酸甘油6个月也可能是肌腱病的有效辅助治疗方法。
加巴喷丁：治疗慢性咳嗽
慢性咳嗽通常很难治疗。90%的慢性咳嗽患者有上呼吸道咳嗽综合征、哮喘、非哮喘性嗜酸细胞性支气管炎或胃食管反流病。针对这些疾病，咳嗽抑制剂几乎没有有效性证据；而神经调节剂加巴喷丁已被证明可以降低咳嗽频率并改善生活质量。
一项为期10周的安慰剂对照、随机、双盲试验纳入62名顽固性慢性咳嗽（持续超过8周）患者，发现加巴喷丁显著改善了咳嗽相关的生活质量，NNT 3.58。最新的慢性咳嗽指南认可了加巴喷丁用于慢性咳嗽是恰当的治疗选择。
甲氧氯普胺：用于偏头痛
抗多巴胺能药物甲氧氯普胺是急性偏头痛治疗的有效选择。部分偏头痛患者发作时表现为胃轻瘫，可出现恶心等症状。甲氧氯普胺可改善胃轻瘫，并促进口服药物的吸收，作为偏头痛的辅助治疗药物。
文献索引：
[1] Heckman-Stoddard BM, DeCensi A, Sahasrabuddhe VV, Ford LG. Repurposing metformin for the prevention of cancer and cancer recurrence. Diabetologia. 2017; 60: 1639-1647.
[2] Bodmer M, Meier C, Krähenbühl S, et al. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care. 2010; 33: 1304-1308.
[3] Jung YS, Park CH, Eun CS, et al. Metformin use and the risk of colorectal adenoma: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2017; 32: 957-965.
[4] Curry J, Johnson J, Tassone P, et al. Metformin effects on head and neck squamous carcinoma microenvironment: window of opportunity trial. Laryngoscope. 2017; 127: 1808-1815.
[5] Wang SB, Lei KJ, Liu JP, Jia YM. Continuous use of metformin can improve survival in type 2 diabetic patients with ovarian cancer: a retrospective study. Medicine (Baltimore). 2017; 96: e7605.
[6] Wan G, Sun X, Li F, et al. Survival benefit of metformin adjuvant treatment for pancreatic cancer patients: a systematic review and meta-analysis. Cell Physiol Biochem. 2018; 49: 837-847.
[7] Zeng S, Gan HX, Xu JX, Liu JY. Metformin improves survival in lung cancer patients with type 2 diabetes mellitus: a meta-analysis. Med Clin (Barc). 2018 Aug 30.
[8] Heckman-Stoddard BM, Gandini S, Puntoni M, et al. Repurposing old drugs to chemoprevention: the case of metformin. Semin Oncol. 2016; 43: 123-133.
[9] Würzner G, Gerster JC, Chiolero A, et al. Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout. J Hypertens. 2001; 19: 1855-1860.
[10] Naritomi H, Fujita T, Ito S, et al. Efficacy and safety of long-term losartan therapy demonstrated by a prospective observational study in Japanese patients with hypertension: the Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) study. Hypertens Res. 2008; 31: 295-304.
[11] Katsiki N, Tsioufis K, Ural D, Volpe M. Fifteen years of LIFE (Losartan Intervention for Endpoint Reduction in Hypertension)—lessons learned for losartan: an \"old dog playing good tricks.\" J Clin Hypertens (Greenwich). 2018 Jun 15.
[12] Wolff ML, Cruz JL, Vanderman AJ, Brown JN. The effect of angiotensin II receptor blockers on hyperuricemia. Ther Adv Chronic Dis. 2015; 6: 339-346.
[13. Choi HK, Soriano LC, Zhang Y, Rodríguez LA. Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study. BMJ. 2012; 344: d8190.
[14] Madison JM, Irwin RS. Cough: a worldwide problem. Otolaryngol Clin North Am. 2010; 43: 1-13.
[15] Ryan NM, Vertigan AE, Birring SS. An update and systematic review on drug therapies for the treatment of refractory chronic cough. Expert Opin Pharmacother. 2018; 19: 687-711.
[16] Ryan NM, Birring SS, Gibson PG. Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial. Lancet. 2012; 380: 1583-1589.
[17] Gibson P, Wang G, McGarvey L, et al. Treatment of unexplained chronic cough: CHEST guideline and expert panel report. Chest. 2016;149:27-44.
[18] Tokola RA, Neuvonen PJ. Effects of migraine attack and metoclopramide on the absorption of tolfenamic acid. Br J Clin Pharmacol. 1984; 17: 67-75.
[19] Schulman EA, Dermott KF. Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs. Headache. 2003; 43: 729-733.
[20] Najjar M, Hall T, Estupinan B. Metoclopramide for acute migraine treatment in the emergency department: an effective alternative to opioids. Cureus. 2017;9:e1181.
[21] Felson DT, Sloutskis D, Anderson JJ, et al. Thiazide diuretics and the risk of hip fracture. Results from the Framingham Study. JAMA. 1991; 265: 370-373.
[22] LaCroix AZ, Ott SM, Ichikawa L, et al. Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000; 133: 516-526.
[23] Dalbeth N, Gamble GD, Horne A, Reid IR. Relationship between changes in serum urate and bone mineral density during treatment with thiazide diuretics: secondary analysis from a randomized controlled trial. Calcif Tissue Int. 2016; 98: 474-478.
[24] Xiao X, Xu Y, Wu Q. Thiazide diuretic usage and risk of fracture: a meta-analysis of cohort studies. Osteoporos Int. 2018; 29: 1515-1524.
[25] Gorfine SR. Topical nitroglycerin therapy for anal fissures and ulcers. N Engl J Med. 1995; 333: 1156-1157.
[26] Lund JN, Scholefield JH. A randomised, prospective, double-blind, placebo-controlled trial of glyceryl trinitrate ointment in treatment of anal fissure. Lancet. 1997; 349: 11-14.
[27] Fenton C, Wellington K, Easthope SE. 0.4% nitroglycerin ointment : in the treatment of chronic anal fissure pain. Drugs. 2006; 66: 343-349.
[28] Ozden R, Uruç V, Doğramaci Y, et al. Management of tennis elbow with topical glyceryl trinitrate. Acta Orthop Traumatol Turc. 2014; 48: 175-180.
[29] Paoloni JA, Appleyard RC, Nelson J, Murrell GA. Topical nitric oxide application in the treatment of chronic extensor tendinosis at the elbow: a randomized, double-blinded, placebo-controlled clinical trial. Am J Sports Med. 2003; 31: 915-920.
[30] Paoloni JA, Murrell GA, Burch RM, Ang RY. Randomised, double blind, placebo-controlled clinical trial of a new topical glyceryl trinitrate patch for chronic lateral epicondylosis. Br J Sports Med. 2009; 43: 299-302.
[31] Challoumas D, Kirwan PD, Borysov D, et al. Topical glyceryl trinitrate for the treatment of tendinopathies: A systematic review. Br J Sports Med. 2018 Oct 9.
[32] Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999; 341: 709-717.
[33] de Souza F, Muxfeldt E, Fiszman R, Salles G. Efficacy of spironolactone therapy in patients with true resistant hypertension. Hypertension. 2010; 55: 147-152.
[34] Carey RM, Calhoun DA, Bakris GL, et al; American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council. Resistant hypertension: detection, evaluation, and management: a scientific statement from the American Heart Association. Hypertension. 2018; 72: e53-e90.
[35] Brown J, Farquhar C, Lee O, et al. Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne. Cochrane Database Syst Rev. 2009; CD000194.
[36] Rathnayake D, Sinclair R. Innovative use of spironolactone as an antiandrogen in the treatment of female pattern hair loss. Dermatol Clin. 2010; 28: 611-618.
[37] Layton AM, Eady EA, Whitehouse H, et al. Oral spironolactone for acne vulgaris in adult females: a hybrid systematic review. Am J Clin Dermatol. 2017; 18: 169-191.
[38] Isvy-Joubert A, Nguyen JM, Gaultier A, et al. Adult female acne treated with spironolactone: a retrospective data review of 70 cases. Eur J Dermatol. 2017; 27: 393-398.
[39] Goodman NF, Cobin RH, Futterweit W, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome—part 1. Endocr Pract. 2015; 21: 1291-1300.
[40] Elsaman AM, Radwan AR, Mohammed WI, Ohrndorf S Low-dose spironolactone: treatment for osteoarthritis-related knee effusion. A prospective clinical and sonographic-based study. J Rheumatol. 2016; 43: 1114-1120.
[41] Mcmurdo ME, Sumukadas D, Donnan PT, et al. Spironolactone for people age 70 years and older with osteoarthritic knee pain: a proof-of-concept trial. Arthritis Care Res (Hoboken). 2016; 68 :716-721.
医脉通编译自：Douglas S. Paauw. 10 Little Known Uses for Common, Everyday Drugs. Medscape. December 3, 2018
