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Photosensitizing: psoralens and porfimer

Photosensitizing products have the feature to be converted under the influence of natural or artificial light into molecules having a great chemical reactivity and likely to give adverse effects but also to have, under particular conditions, a therapeutic interest. The main products are psoralens and porfimer.

Psoralens

The psoralens used in therapeutics are methoxsalen or 8-methoxypsoralene and bergapten or 5-methoxypsoralen,which are two position isomers. Methoxsalen (Meladinine*, Oxsoralen*, Puvasoralen*) is more used than bergapten, ingredient of bergamot oil.

Psoralens intercalate in DNA, but do not establish covalent bonds in absence of light. Under the effect of light, the psoralens intercalated in DNA are activated, even in absence of oxygen, and establish intrastrand or interstrand covalent bonds with bases, forming adducts. In the presence of oxygen, there is, in addition, formation of superoxide radicals which damage DNA. By these two mechanisms, psoralens, under the influence of light, inhibit replication and transcription. They can also increase pigmentation by acting on melanocytes.

Generally, a long-wavelenght ultraviolet radiation (wavelength ranging between 320 and 380 nanometers) called UVA is used to activate psoralens (the wavelength UVB lies between 290 and 320 nm). The treatment combining psoralens and exposure to light is called photochemotherapy and named PUVA (P = psoralen and UVA).

The clinical uses of psoralens are psoriasis and vitiligo. In the treatment of psoriasis, it is the damage of DNA under the effect of psoralen and light which damage epidermal cells causing the skin flakes. In the treatment of vitiligo, it is the stimulation of melanocytes which is involved (in absence of melanocytes, there is no tanning but burns).

The effect of light is more important when the concentration of psoralens in the epidermal cells is high. This concentration is at its maximum on average two to four hours after the intake of psoralens by oral route and persists approximately eight hours.

The intake by oral route or the cutaneous application of psoralens followed by a noncontrolled exposure to light can cause severe burns. In addition, psoralens, through various mechanisms, stimulate melanogenesis, which results in a tanning of the skin. The importance of the tanning is variable according to the individuals.

Psoralens are compounds very little toxic in absence of sun. In single administration or of short duration, the danger of the psoralens are burns which can be extremely severe and, after repeated use, an increased risk of skin cancers.

Porfimer

Photosensitizing products having an affinity for internal cancers accessible to a beam of light can be given before irradiation by a wavelength light suitable for activation. This method is named photodynamic therapy or photochemotherapy. Haematoporphyrin was one of the compounds used. 5-aminolevulinic acid, not photosensitizing itself, is also used because it is metabolized to protoporphyrin IX, a strongly photosensitizing molecule.

A porphyrin polymer of porcine origin, porfimer (Photofrin*), was marketed recently. It is proposed in the treatment of certain bronchial or esophageal cancers. Its administration is followed by an exposure of tumor tissues to a light of 630 nm wavelength provided by a laser source and led to the tumor by an optical fiber.

Precautions must be taken to limit the body exposure to sunlight or to an intense artificial light after administration of photosensitizing products, until thir elimination.

Verteporfin (VISUDYNE*), benzoporphyrine derivative, is used in ophthalmology for the treatment of the neovascular age-related macular degeneration, its administration being followed by an activation by a laser light (Laser photocoagulation alone is the usual treatment).

Photosensitizing drugs

A certain number of drugs, because of their chemical structure, have unwanted photosensitizing properties and can sometimes elicit in patients serious cutaneous reactions after exposure to light. Among these drugs, are fluoroquinolones in particular sparfloxacin, amiodarone, tetracyclines… etc.

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