SECONDARY AMINO GROUPS IN ACE INHIBITORS/CALCIUM CHANNEL BLOCKERS, ANTIARRHYTHMICS AND ANTICOAGULANTS AS DONORS FOR DRUG RELATED PHOTOTOXICITY/CARCINOGENICITY: NUTRITIONAL NITROSOGENESIS AS SUBSTANTIAL/ADDITIONAL COFACTOR FOR SKIN CARCINOGENESIS.

Drug-mediated phototoxicity and photocarcinogenicity have long remained poorly understood. One of the most significant dilemmas surrounding this issue is the sporadic nature of these reactions. This sporadic occurrence may be explained by modern and newly introduced concepts such as drug-mediated nitrosogenesis of skin cancer, as well as nitroso-photocarcinogenesis of skin cancer. Regardless of their carcinogenic potential, all nitrosamines may exhibit phototoxic properties and may therefore act as photocarcinogenic substances, because of the instability of the nitroso group under UV radiation. Drug-related Nitroso Photocarcinogenesis represents a new and innovative concept that seeks to provide a logical explanation for the phenomenon of nitroso-photocarcinogenicity. Various groups of medications, including antihypertensive agents (beta-blockers, ACE inhibitors, calcium antagonists, centrally acting sympatholytics, and sartans), anticoagulants, antidiabetic drugs, and several other classes, possess secondary amino groups. Under gastric conditions - an acidic environment and in the presence of nitrite-rich food - these amino groups may lead to the formation of nitrosamines, which are well known carcinogens and established photocarcinogens. The subsequent resorption of these drug-mediated nitroso compounds may result in their subsequent deposition in the skin. The decomposition of nitrosamines under the influence of ultraviolet radiation may lead to the release of nitric oxide and/or procarcinogenic mediators capable of damaging DNA of keratinocytes and melanocytes. Thus, in practice, malignant cellular branches may be initiated even when the relevant groups of medications are not externally contaminated with nitrosamines. In this sense, generic drugs from heterogenous classes may effectively act as donors of photocarcinogenic compounds to the human skin. In this context, and in support of the aforementioned modern concept of skin cancer, we present another case of keratinocyte cancer (basal cell carcinoma) that developed relatively shortly after combined intake of four drugs (apixaban, flecainide, amlodipine, and perindopril), each containing a secondary amino group in its structure - serving as a potential precursor for the generation of photocarcinogens in the stomach. The skin cancer has been removed surgically. The defect has been treated via nasal tip rotation flap as dermatosurgical approach. The role of endogenous, gastric related Nitrosogenesis during intake of potentially completely uncontaminated drugs (containing secondary amino groups in their chemical structure), in relation to nitroso-photocacinogenesis and the subsequent development of skin cancer, is discussed.