Drug-Induced Cutaneous Photosensitivity

Abstract

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.

Generation of reactive aryl radical intermediates in the reductive photodehalogenation of itraconazole

“…This reaction pathway is reminiscent of covalent photobinding between drugs and proteins, which is the triggering step of photoallergy. [31][32][33][34] Thus, the attention was focused on the ability of radical 1 c to react with proteins, and in particular with the aromatic amino acid residues, for instance the indole heterocycle of tryptophan (Trp). With this aim, a model dyad (5) was designed by linking Trp methyl ester with 2,4-dichlorophenylacetic acid, which contains the reactive moiety of 1 (Fig.…”

Recall of indoor tanning salon warnings and safety guidelines among a national sample of tanners

“…Of concern, 35 % of the sample reported never being warned about photosynthesizing medications (i.e., medications that increase risk of sunburn). Photosynthesizing medications include-but are not limited to-commonly prescribed antibiotics, non-steroidal anti-inflammatories including naproxen and ibuprofen (common to treat pain, swelling, menstrual cramps, and inflammation), and some acne medications [32,33]. Thus, it is important that this risk information is communicated to IT users.…”

Photo-Onycholysis Caused by Olanzapine and Aripiprazole

“…6 Although several classical antipsychotics such as the phenothiazines and the butyrophenones have been incriminated for phototoxic reactions, olanzapine and aripiprazole have not been associated with photo-onycholysis or phototoxic reactions. 7 Our patient was using chlorpromazine hydrochloride for 3.5 years and never observed phototoxic cutaneous or nail reactions. This indicates that photoonycholysis is more possible to be attributable to olanzapine and/or aripiprazole than being a delayed reaction to chlorpromazine.…”

“…8 All of the chlorine-containing drugs figure strongly in the list of photosensitizers such as chlorpromazine and hydrochlorothiazide. 7 Olanzapine's chemical structure does not feature prominent photosensitizing parts, and its mode of photosensitization might be even more obscure. It has been described as cause for hyperpigmentation on the dorsal aspect of the hands of 1 patient, with clear demarcation from the forearms.…”