Phototoxic effects

Because LF(Ls are potent photoactive compounds, they have been used clinically to treat human skin disorders such as skin depigmentation (vitiligo), psoriasis, mycosis fungoides, polymorphous photodermatitis and eczema. About 40 mg of psoralen (79) administered 

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Serious side-effects have been associated with the important psychotherapeutic agent, chlorpromazine (358), almost since its introduction. High sensitivity to sunburn, pigmentation of the skin and ocular opacity are common phototoxic effects [ 196]. In a series of phenothiazines, the chloro-substituted compounds, particularly chlorpromazine, prochlorperazine and perphenazine, showed by far the greatest phototoxic activity [197, 198]. 

All these derivatives showed significant photocytotoxic activity, with a phototoxic effect lower than the one observed with the commercial formulation Photofrin , when the dead cells were counted immediately after irradiation. 

Our further studies were devoted to the C60 phototoxic effect on the different cell lines. Earlier we have got preliminary data on the opposite effect of a C60/PVP complex on some cell lines of tumor and non-tumor origin the life span of the former in the presence of 5 mg/ml of the complex (30-40 pg/ml of C60) diminished during three consecutive passages while of the later - slightly augmented (data not published). 

This test enables to identify compounds which show a phototoxic effect in vivo... 

FIGURE 11.17 Phototoxic effects of plant compounds on mammalian herbivores. 

These recommendations are based on the published phototoxic effects of bergapten and the established dose-effect relationships Young at a I., J. Photochem. Photobiol. B, 7, 231 (1990) Dubertret et al. ibid 7, 251 (1990), idem, ibid, 7, 362 (1990). 

Dayhaw-Barker R The eye as a unique target for toxic and phototoxic effects. In Korte R, Weinbauer GF, eds. Towards New Horizons in Primate Toxicology. Muen-ster Waxmann, 2000 145-58. 

What is the potential phototoxic effect on the eyes and skin of rodents after a single dose followed by exposure to radiation from a xenon lamp (simulate sunlight) ... 

Free of lingering phototoxicity effects, cutaneous or otherwise. 

The release of cyanide and ferricyanide ions in photodecomposed solutions of sodium nitroprusside is considered to be a great health hazard (15). One of the photoproducts of benzydamine hydrochloride is reported to be responsible for its reported phototoxic effect (16). 

Some of the dyes that are photolabile have been reported to cause phototoxic effects. For example, curcumin has demonstrated phototoxicity to mammalian cells (20). Methylene blue in eye solutions was reported to induce toxic effects (21). It is important, therefore, that drugs and excipients used in product formulations be screened for their photostability as well as photosensitizing effects. 

Adverse effects of tetracyclines include resistant bacteria, folliculitis, candidiasis, gastrointestinal upset, and phototoxic effects. Tetracyclines must not be combined with systemic retinoids because of the increased probability for development of intracranial hypertension. Tetracycline is used in the treatment of moderate to severe acne vulgaris. It is the least expensive of the tetracyclines and therefore often prescribed for initial therapy. A common initial approach includes tetracycline 1 g daily (500 mg twice daily), 1 hour before meals after 1 or 2 months, when marked improvement of inflammatory lesions is observed, the dose may be decreased to 500 mg every day, for another 1 or 2 months. Drawbacks to the use of tetracycline include also a drug-food interaction with dairy prodncts. 

Doxycycline is commonly used in the treatment of moderate to severe acne vulgaris. It is more effective and produces less resistance than tetracycline. The initial dosage is usually 100 or 200 mg daily, followed after improvement by 50 mg/day as a maintenance dose it may be taken with food even thongh it is more effective when taken 30 minutes before meals. Subantimicrobial-dose doxycycline (20 mg) has been investigated in a double-blind, placebo-controlled trial in the treatment of moderate facial acne. Positive ontcomes were achieved with no development of resistant organisms or change in normal skin flora. Adverse effects include resistant bacteria, folliculitis, candidiasis, gastrointestinal upset, and phototoxic effects such as photo-onycholysis. ... 

In addition to gaps in knowledge for currently existing classes of chemicals and ecotoxicological effects, other mechanisms of actions that are currently not yet studied, or other processes, may require further studies. For example, recently it has become clear that phototoxic effects may be a realistic problem for polycylic aromatic hydrocarbons (PAHs) in aquatic and benthic organisms. The amount of UV-light which is required for phototoxicity, is thus an example of a parameter which was not introduced earlier as an important environmental parameter to describe or predict toxicity [148]. Other examples are if the internal effect concept can be used for metals and organometals in risk assessment [149,150]. 

PDT as a therapeutic modality. Antibody-based targeting is one method currently under investigation. In vitro studies using various tumor cell lines have shown that photosensitizers conjugated to monoclonal antibodies can achieve a higher phototoxic effect at lower doses than with drug or antibody alone (44,45). In vivo work in a mouse rhabomyosarcoma model yielded similar results (46). 

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