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Skin photosensitization

Japanese Ministry of Health and Welfare (Former Ministry of Health, Labor and Welfare), Guidelines for Toxicity Studies of Drugs (7) Skin Photosensitization Studies, Tokyo,... [Pg.31]

The antidepressant protriptyline (116) causes skin photosensitization in man. Jones and Sharpies irradiated an aqueous solution of the hydrochloride with a medium-pressure mercury lamp for 16 h and separated the products by preparative TLC. First formed was the epoxide (117) which photohydrated to the diol (118). Also isolated was the enol (119) [84], Earlier, Gasparro and Kochevar had shown that only the hydrochloride was photodegraded under nitrogen in water or ethanol. Three products were isolated and all lysed erythrocytes, but the structure of only one was suggested. This was a cyclobutyl dimer as shown by its mass spectrum and its photolysis back to protriptyline by light of 254 nm. Presumably, a [2 + 2] cycloaddition of the olefine bonds had occurred [85]. [Pg.76]

Adverse Effects. Common side effects of griseofulvin administration include headaches—which may be severe—and gastrointestinal disturbances (nausea, vomiting, diarrhea). Some individuals may exhibit hypersensitivity to this drug as evidenced by skin rashes. Skin photosensitivity (increased reaction to ultraviolet light) may also occur. [Pg.549]

The deaths of breast-fed infants in the mid-fifties in Turkey, and an epidemic of skin sores and discolorations (porphyria cutanea tarda) were associated with the accidental consumption of HCB-contaminated seed grain (refs. 93-910 Clinical symptoms included weight loss, enlargement of lymph nodes and thyroid, abnormal growth of body hair and skin photosensitization. [Pg.326]

Another drug, ALA, has been used to treat restenosis of the superficial femoral artery. These have been small, uncontrolled studies. In one report, ALA was given orally in a clinical study of adjuvant PDT in patients undergoing femoral angioplasty (61). Patients left the hospital after an overnight stay and there were no reports of skin photosensitivity. The authors suggested a benefit and no evident safety concerns, leading... [Pg.387]

SAFETY PROFILE Poison by intravenous route. Moderately toxic by ingestion. Mutation data reported. A human skin photosensitizer. Questionable carcinogen with experimental neoplastigenic and tumorigenic data by skin contact. Combustible when exposed to heat or flame can react vigorously with oxidizing materials. To fight fire, use water, foam,... [Pg.1089]

Dermatologiccil preparations, with a chemical structure similar to well known photosensitizes in humans and those which are inferred to have a possibility of skin photosensitivity, are applied (Notification No. 24 of the PAB, 1989). [Pg.298]

Rodighiero, G., Musajo, L., Dall Acqua, F., Marciani, S., Caporale, G., Ciavatta, I. Mechanism of skin photosensitization by furocoumarins. Photoreactivity of various furocoumarins with native DNA and with ribosomal RNA. Biochim. Biophys. Acta 217, 40 (1970). [Pg.55]

Finally, it must be pointed out that the extensive and long-term therapeutic use of phenothiazines might often cause several unwanted or side effects, such as skin photosensitization, disorders in the lipid status, reproductive toxicity and cardiac arrhythmia. Therefore, it is very important to understand better the biochemical mechanisms responsible for the different side effects of phenothiazines and their toxicity. [Pg.225]

For example, the photochemistry of non-steroidal anti-inflammatory drugs (NSAIDs) derived from 2-arylpropionic acid, has been studied because these compounds are known to exhibit phototoxicity (see Special Topic 6.22) and skin photosensitivity in some patients. The photodecarboxylation of ketoprofen (325), a benzophenone... [Pg.331]

Certain other porphyrins have shown improved in vivo photodynamic activity over Hpd and Photofrin, for example, the meso-tetra(hydroxyphenyl) porphyrin examined by Berenbaum et al. (Figure 19). The meta derivative was some 25-30 times more potent (in terms of comparative tumoricidal doses) than Hpd in an in vivo mouse tumor with apparently less skin photosensitivity [56]. [Pg.304]

Richter AM, Yip S, Waterfield E, Logan PM, Slonecker CE, Levy JG. Mouse skin photosensitization with benzoporphyrin derivatives and Photofrin macroscopic and microscopic evaluation. Photochem Photobiol 1991 53 281-286. [Pg.139]

Golpashin, F., Weiss, B., and Durr, H., 1984, Photochemical model studies on skin photosensitizing drugs sulfonamides and sulfonylureas, Arch. Pharm. (Weinheim) 317, 906-913. [Pg.104]

Boyle, D.G. and Potter, W.R. (1987) Photobleaching of photofrin B as a means of eliminating skin photosensitivity, Photochem. Photobiol., 46 997-1001. [Pg.202]

Roberts, W.G., Smith, K.M., McCullough, J.L., and Bems, M.W. (1989) Skin photosensitivity and photodestruction of several potential photodynamic sensitizers, Photochem. Photobiol., 49 431-438. [Pg.209]

Possible side effects such as skin photosensitization associated with the diuretic hydrochlorothiazide (61 R = Cl) may be linked to photoactivation of the chloro group <87Mi 6i4-02>. Irradiation... [Pg.653]

Early studies with PDT employed complex mixtures of poorly defined porphyrins known as hemato-porphyrin derivative (photofrin I) or a partially purified mixture known as porfimer sodium (PHOTOFRIN II) that was administered parenterally with subsequent irradiation using polychromatic light sources. The major problem with this approach was the prolonged period (4-6 weeks) of photosensitivity caused by skin retention of the porphyrin formulations. This led to a search for compounds that could be administered topically and that were eliminated more readily from the skin. The porphyrin precursor S-aminolevulinic acid (ALA) is converted to various porphyrins, particularly protoporphyrin (proto), in tissues including the skin (see below). Protoporphyrin subsequently is eliminated rapidly from the body, thereby minimizing the period of skin photosensitivity to a few hours. Topically applied ALA HCl (20% wA>) and, more recently, the methyl ester of ALA have been used successfully for the PDT of various types of nonmelanoma skin cancers and premalignant lesions. [Pg.1082]

Unlike MC540, most of the cyanins used in PDT are compounds which easily penetrate the membrane. The kryptocyanins have a high tumor selectivity, a strong absorption in the red, a minimal toxicity in darkness, a low skin photosensitivity and a single action mode, properties which make them interesting photosensitizers. [Pg.74]

In 1956, it was reported that of four volunteers who ingested ALA as part of a study of porphyrin metabolism, those who took the largest doses experienced transient photosensitization of the skin [105,106]. These experiments took place at a time when it was generally believed that the capacity for excessive synthesis of porphyrins was restricted to the liver and the bone marrow, because it was these organs which produced the porphyrins responsible for the skin photosensitization associated with certain types of porphyria [107]. Consequently, the skin photosensitization induced by ingestion of ALA was interpreted in similar terms. Despite this erroneous assumption about the mechanism involved, these researchers had established that systemic administration of ALA to humans could cause skin photosensitization. We verified these observations in mice given ALA... [Pg.89]


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