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.

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Abstract— The photochemical reactivity of the non‐steroidal anti‐inflammatory drugs, naproxen and indomethacin, has been studied and compared with benoxaprofen, a similar compound of known cutaneous phototoxicity. Although indomethacin shows some phosphorescence at 77 K, flash photolysis at room temperature revealed only a weak photoionization process, and no photochemical reactivity was detected in steady state photolysis. Naproxen has strong fluorescence and phosphorescence, and in laser flash photolysis showed photoionization and a triplet state species in approximately equal yield. Naproxen and benoxaprofen produced singlet oxygen with similar quantum yield, as deduced from the sensitized rates of photooxidation of 2,5‐dimethylfuran. Naproxen underwent photodecarboxylation as detected by ESR‐spin trap experiments with 2‐methyl‐2‐nitrosopropane. The decarboxy‐naproxen radical combined readily with oxygen in aerated solution, and l‐(6‐methoxy‐2‐napthyl)ethanol and 2‐acetyl‐6‐methoxynaphthalene were formed as the oxidation products. In deaer‐ated solution, the major product was 2‐ethyI‐6‐methoxynaphthalene, with the alcohol also formed. In comparison, benoxaprofen also underwent decarboxylation, with much higher quantum yield, but the decarboxy‐benoxaprofen radical did not add oxygen. This difference in photoreactivity between naproxen and benoxaprofen, together with the much lower molar absorptivity of naproxen are the significant factors in relating to the differences in reported levels of clinical photosensitivity responses.

Abstract— Azathioprine is used as an immunosuppressant for renal transplant recipients, but is frequently associated with severe skin cancer as a side effect. 6‐Mercaptopurine, the primary metabolite of azathioprine. absorbs strongly in the UVA region and displays substantial photochemical reactivity. The primary photochemical processes in aqueous solution are triplet state formation and photoionization, as shown by flash photolysis. In oxygenated solution, singlet oxygen and superoxide are produced, and ground state 6MP appears to react with these species. Glutathione inhibits this reaction and is itself oxidized. In deoxygenated solution, reactions implicating the thiyl radical and hydrogen atom and electron transfer occur as shown by reaction with histidine and p‐nitrosodimethylaniline. Nitro Blue Tetrazolium or acrylamide.

Irradiation with UVA light of the anti-inflammatory drug diclofenac [2-(2,6-dichloroanilino)phenylacetic acid] in aqueous buffer or methanol solution leads to sequential loss of both chlorine substituents and ring closure to carbazole-1-acetic acid as the major product. Minor products result from substitution by the solvent. The photosensitizing properties of diclofenac and its major photoproduct were tested with singlet oxygen substrates and in the free radical polymerization of acrylamide. Although the major carbazole product is a weakly phototoxic agent, able to generate singlet oxygen more efficiently than diclofenac, the free radical photodechlorination process is postulated as the probable initiation step of in vivo photosensitivity responses.