Increased phototoxicity of hydrochlorothiazide by photodegradation

Abstract

The photodegradation products of hydrochlorothiazide produced by ultraviolet (UV) radiation were investigated for their phototoxicity utilizing the photohemolysis and Candida albicans tests. Hydrochlorothiazide was irradiated for 30, 60, 90 and 120 min with a 250 W xenon arc lamp using a WG295 cut‐off filter. Irradiation of hydrochlorothiazide resulted in the gradual decrease of all three absorption bands (225, 270 and 320 nm), the blue shift of the 225 nm band, and the appearance of a new band around 290 nm. Since previous results demonstrated that photosubstitution of chloride could occur, the main product of this photolysis most likely is ethoxyhydrochlorothiazide. The photohemolysis test revealed a significant increase in photohemolysis observed in the photodegradation products produced after 60, 90 and 120 min of UV irradiation. This increase in hemolysis value directly correlated with the UV‐irradiation time. However, there was no significant phototoxic killing of yeast in the Candida albicans test. This suggests photodegradation products of hydrochlorothiazide may play an important role in phototoxicity by acting on the cell membrane, but not on DNA. Considering the high in vitro phototoxicity observed in bendroflumethiazide and the data presented here, substitution of chloride seems to be responsible for the increased phototoxicity of hydrochlorothiazide.

Retinal Phototoxicity Induced by Hydrochlorothiazide After Exposure to a UV Tanning Device

“…Once excited to reactive states by UV or visible light, these compounds produce damage throughout mechanisms mediated by free radical or, directly, by oxygen (14). Thiazide and its derivates, such as hydrochlorothiazide, are able to induce photosensitization by both systems (15), and the retinal phototoxic damage induced by these compounds represents a well-recognized clinical condition (5)(6)(7)(8)(9)(10)(11)(12). Recently, Mauget-Fa et al have described four cases of incidental retinal phototoxicity in patients receiving photosensitizing drugs, after exposure to a light sources usually known to be harmless, such as camera flash, electric welding arc light and microscope light.…”

“…The photosensitivity reactions of hydrochlorothiazide were described shortly after their introduction for the treatment of hypertension as early as the end of the 1950s (5). Adverse reactions attributed to hydrochlorothiazide include cutaneous (lichenoid reaction, vasculitis, erythema multiforme, purpura) and ocular side effects (6). Both the anterior and the posterior segment of the eye may be affected (7).…”

Evaluation of the phototoxic potential of plants used in oriental medicine

“…Then both irradiated and nonirradiated plates were incubated at room temperature for 48 h and 29.67 Root the appearance of the clear zone around the plates was compared. If more than 3 mm of clear zone around the paper discs was found only in the UV-irradiated plate, it was regarded as a positive finding (Han et al, 2000).…”

“…C represents the absorbance of the supernatant which underwent hypotonic shock to produce maximal hemolysis (100% hemolysis). The mean hemolysis values of 5% or more were regarded as significant photohemolysis (Han et al, 2000).…”

An uncertainty and sensitivity analysis applied to the prioritisation of pharmaceuticals as surface water contaminants from wastewater treatment plant direct emissions

“…This last source of uncertainty may be relevant in the case of tamoxifen, as already mentioned; however, substances that do not appear in the ranking of compounds of most concern may have their comparative impact substantially increased by the inclusion of their derivative impact. For example, some researchers have suggested that the phototransformation products of triclosan, diclofenac or hydrochlorothiazide have a higher toxicity potential than their parent compounds (Han et al, 2000;Schmitt-Jansen et al, 2007). Nevertheless, the inclusion of phototransformation product impact is possible, if the chemical structures are identified, by applying the method proposed by van Zelm et al (2010).…”