Onkoderma - Clinic for Dermatology, Venereology and Dermatologic Surgery, Sofia; Department of Dermatology and Venereology, Medical Institute of Ministry of Interior, Sofia, Bulgaria.
Georgian Med News. 2023 Sep(342):152-155.
The data on the polycontamination of multimedication in polymorbid patients with a heterogeneous class of carcinogens/nitrosamines, NDSRIs (classified according to the FDA regulation to the companies of 2023 to those with a carcinogenic potency between 1 and 5), are one of the most important steps to clarify the concept of skin cancer nitrosogenesis/ pathogenesis. The FDA is the first regulatory institution in the world to courageously declare that a problem exists and should be addressed. The main and currently unexplained and somewhat controversial issue lies in 1) the sporadic nature of polycontamination in different geographical regions, and 2) the lack of official data from the established international, but also regional pharmaceutical market regulators on the results of the checks conducted for nitrosamine contamination of the respective batches. It is this that leads scientists to the idea of (albeit seemingly) speculative but entirely possible controlled contamination of the production in certain geographical regions. This (hypo)thesis is supported, albeit indirectly, by the fact that: a recent regional check for possible contamination of sartans in a particular geographical region was not indicative of the presence of any nitrosamines/NDSRIs. But this fact is indicative of several extremely important things: 1) contamination is not ubiquitous, its genesis is heterogeneous; 2) contamination could be completely avoided at production level in certain geographical regions; 3) ˝controlled contamination˝ or carelessness of a heterogeneous nature should be excluded by the relevant regulators. Regular inspection and certification of medicinal products in relevant geographical regions to exclude contamination with nitrosamines/NDSRIs would be the surest method to protect public health globally. The initial parameters of the restrictive processes for the availability of nitrosamines in medicines have been established by the most powerful regulator globally in the face of the FDA, with the hope being that manufacturers will find a short-term solution to the problem. We report another patient who simultaneously developed 2 cutaneous tumors under potentially/actually nitrosamine contaminated drugs such as: beta blockers- atenolol, calcium antagonists- nifedipine/amlodipine, sartans- valsartan and antiarrhythmics- propafenone. One of the tumors was localized in the upper lip area (keratoacanthoma) and the other in the right shoulder area (basal cell carcinoma). Successful surgical treatment of the tumors was performed in the form of upper lip advancement rotation flap and elliptical excision of the second lesion. The evolution/growth rate of the tumors in relation to the potential mutagens/carcinogens heterogeneous in their potency contained in the drugs is commented.
多药治疗的多污染物数据在患有异质类致癌剂/亚硝胺的多病态患者中，NDSRIs（根据 2023 年 FDA 规定分类为对致癌潜力在 1 到 5 之间的公司）是阐明皮肤癌亚硝胺发生/发病机制概念的最重要步骤之一。FDA 是世界上第一个勇敢地宣布存在问题并应予以解决的监管机构。主要且目前尚未解释且有些争议的问题在于 1）不同地理区域的多污染物的散发性，以及 2）在各自批次的亚硝胺污染检查结果方面，国际上但也包括区域制药市场监管机构缺乏官方数据。正是这一点导致科学家们产生了（尽管看似）推测性但完全可能的在某些地理区域对生产进行受控污染的想法。尽管间接，但这种假设得到了以下事实的支持：最近在特定地理区域对沙坦类药物进行的区域性污染检查并未表明存在任何亚硝胺/NDSRIs。但这一事实表明了一些极其重要的事情：1）污染并非无处不在，其发生是异质的；2）在某些地理区域，污染完全可以在生产层面上避免；3）相关监管机构应排除“受控污染”或异质性质的粗心大意。在相关地理区域定期检查和认证药品以排除亚硝胺/NDSRIs 污染将是保护全球公众健康的最可靠方法。在面对 FDA 的情况下，全球最强大的监管机构已经确定了限制药品中亚硝胺可用性的初始参数，希望制造商能够找到短期解决问题的方法。我们报告了另一位患者，他同时在可能/实际上受到亚硝胺污染的药物下发展出 2 种皮肤肿瘤，例如：β受体阻滞剂-阿替洛尔、钙通道阻滞剂-硝苯地平/氨氯地平、沙坦类-缬沙坦和抗心律失常药-普罗帕酮。其中一个肿瘤位于上唇区域（角化棘皮瘤），另一个位于右肩区域（基底细胞癌）。对肿瘤进行了成功的手术治疗，形式为上唇推进旋转皮瓣和第二个病变的椭圆形切除。对肿瘤的进化/生长速度与药物中异质潜在诱变剂/致癌剂的关系进行了评论。
