Moore Douglas E
Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia.
Drug Saf. 2002;25(5):345-72. doi: 10.2165/00002018-200225050-00004.
The interaction of sunlight with drug medication leads to photosensitivity responses in susceptible patients, and has the potential to increase the incidence of skin cancer. Adverse photosensitivity responses to drugs occur predominantly as a phototoxic reaction which is more immediate than photoallergy, and can be reversed by withdrawal or substitution of the drug. The bias and inaccuracy of the reporting procedure for these adverse reactions is a consequence of the difficulty in distinguishing between sunburn and a mild drug photosensitivity reaction, together with the patient being able to control the incidence by taking protective action. The drug classes that currently are eliciting a high level of adverse photosensitivity are the diuretic, antibacterial and nonsteroidal anti-inflammatory drugs (NSAIDs). Photosensitising chemicals usually have a low molecular weight (200 to 500 Daltons) and are planar, tricyclic, or polycyclic configurations, often with heteroatoms in their structures enabling resonance stabilisation. All absorb ultraviolet (UV) and/or visible radiation, a characteristic that is essential for the chemical to be regarded as a photosensitiser. The photochemical and photobiological mechanisms underlying the adverse reactions caused by the more photoactive drugs are mainly free radical in nature, but reactive oxygen species are also involved. Drugs that contain chlorine substituents in their chemical structure, such as hydrochlorthiazide, furosemide and chlorpromazine, exhibit photochemical activity that is traced to the UV-induced dissociation of the chlorine substituent leading to free radical reactions with lipids, proteins and DNA. The photochemical mechanisms for the NSAIDs that contain the 2-aryl propionic acid group involve decarboxylation as the primary step, with subsequent free radical activity. In aerated systems, the reactive excited singlet form of oxygen is produced with high efficiency. This form of oxygen is highly reactive towards lipids and proteins. NSAIDs without the 2-arylpropionic acid group are also photoactive, but with differing mechanisms leading to a less severe biological outcome. In the antibacterial drug class, the tetracyclines, fluoroquinolones and sulfonamides are the most photoactive. Photocontact dermatitis due to topically applied agents interacting with sunlight has been reported for some sunscreen and cosmetic ingredients, as well as local anaesthetic and anti-acne agents. Prevention of photosensitivity involves adequate protection from the sun with clothing and sunscreens. In concert with the preponderance of free radical mechanisms involving the photosensitising drugs, some recent studies suggest that diet supplementation with antioxidants may be beneficial in increasing the minimum erythemal UV radiation dose.
阳光与药物相互作用会使易感患者产生光敏反应，并有可能增加皮肤癌的发病率。药物引起的不良光敏反应主要表现为光毒性反应，比光过敏反应更为迅速，停药或更换药物后反应可逆转。这些不良反应报告程序存在偏差和不准确之处，原因在于难以区分晒伤与轻度药物光敏反应，而且患者能够通过采取防护措施来控制发病率。目前引发高度不良光敏反应的药物类别有利尿剂、抗菌药和非甾体抗炎药（NSAIDs）。光敏化学物质通常分子量较低（200至500道尔顿），呈平面、三环或多环构型，其结构中常含有杂原子以实现共振稳定。所有这些物质都能吸收紫外线（UV）和/或可见光，这一特性是该化学物质被视为光敏剂的关键。活性较高的药物引发不良反应的光化学和光生物学机制主要是自由基性质，但也涉及活性氧物种。化学结构中含有氯取代基的药物，如氢氯噻嗪、呋塞米和氯丙嗪，其光化学活性源于紫外线诱导氯取代基解离，进而引发与脂质、蛋白质和DNA的自由基反应。含有2-芳基丙酸基团的NSAIDs的光化学机制以脱羧为主要步骤，随后产生自由基活性。在通气系统中，能高效产生活性激发单线态氧。这种形式的氧对脂质和蛋白质具有高度反应性。不含2-芳基丙酸基团的NSAIDs也具有光活性，但作用机制不同，导致的生物学后果较轻。在抗菌药物类别中，四环素、氟喹诺酮类和磺胺类药物光活性最强。据报道，一些防晒剂和化妆品成分以及局部麻醉剂和抗痤疮药物等局部应用的制剂与阳光相互作用会引起光接触性皮炎。预防光敏反应需要通过穿着衣物和使用防晒霜来充分防晒。与涉及光敏药物的自由基机制占主导地位相一致，一些近期研究表明，补充抗氧化剂的饮食可能有助于增加最小红斑紫外线辐射剂量。
