Academic Criticims: Antihypertensives, Nitrosamines And Melanoma- Beyond The Medical Aspects of The Socially Significant Human Problem. Current State and Future Directions
Authors: Tchernev Georgi , Ivanov Lyudmil , Kordeva Simona , Broshtilova Valentina , Khanom Shafali , Henry Casey Sabrina , Joseph Jenisa Mary 
Published: September 2024

The rapid reversal of the direction of thought, of the general attitude, focus and vision on a problem or task, is not new and has been known since biblical times, the Middle Ages or the recent past, but in various forms, such as : ˝The King is dead, long live the King!˝ It is for this reason that abrupt shifts of perception and behaviour or receptor sensitivity in a cell or tissue should not be seen as unusual for the human race either. Similarly, the moral and ethical behavior of the scientific community at the moment has suddenly announced an abrupt change in its outlook, interpretation, and interpretive attitudes-namely: it had another point of view concerning the pathogenesis of skin cancer in general (but so also for prostate cancer, lymphomas, etc.). And the reason for this was the medication intake for high blood pressure. On the intake of the pure medications. Also defined as cancer associative pathogenetic intake. This change, or total metamorphosis, concerning the academic insight, growth, and awareness, is occurring massively and universally only in 2024, linking thiazide diuretic use (according to the most recent German study) to the occurrence of at least 4 heterogeneous forms of skin cancer: basal cell carcinomas, squamous cell carcinomas, atypical fibroxanthoma, and dermal pleomorphic sarcoma. ˝The understanding turns out to be even quite contagious˝, encompassing in parallel an American study (published in the form of a meta-analysis/ 2024), which announces that there is a change of everything mentioned so far as understanding (or concerning Oncopharmacogenesis) and there is a significant association between the intake of most of the known worldwide antihypertensive drugs and the occurrence of keratinocytic tumors and melanomas subsequently. A third study, again by an American collective (2024), linked the intake of photosensitizing drugs in postmenopausal women, again with the development of keratinocytic tumors and melanomas, and found a definite association with the patients’ exposure to solar radiation as well (photocarcinogenesis/nitroso-photocarcinogenesis?). And calcium antagonists are associated once again (2024) with the potential generation of prostate cancer, while renin angiotensin antagonists: rather with a lower risk or better prognosis of patients, however, already developed this type of tumor. But let us note that this type of carcinoma occurs within the already mentioned antihypertensive medication , which has been available for years (on sartans or on calcium antagonists) before the tumor even arises! And whether the prognosis of patients is better afterwards depends rather on other factors. Interpretation of clinical as well as certain prognostic data is and remains in practice a play on words or refraction through a particular (different) mental, ideological or ˝light prism˝. But the most general thesis is and remains the following: the intake of these two classes of medication (sartans and calcium antagonists) is followed by the subsequent occurrence of prostate cancer, although this is not clearly expressed in any line of the referenced work. Interesting how even the academic community in Taiwan, only now, in 2024, is ˝suddenly impressed˝ that taking antihypertensives/ and diuretics during pregnancy is associated with a rather high, significantly associated risk of developing acute lymphocytic lymphoma and non-Hodgkin’s lymphoma in newborns. Refracting all the mentioned scientific information through the prism of Oncopharmacogenesis and drug-initiated Nitrosogenesis, the following could be shared: it is unlikely that these follow-ups (formalized in 2024) are random, episodic and manipulated. But everything formalized so far finds its reasonable explanation in the following: 1) there is no way that a single drug in the form of a pure/active substance can lead to the development of heterogeneous forms of cancer: be it skin, prostate, blood, lymph gland or a number of others. These drugs are described by regulators as containing heterogeneous nitrosamines/carcinogens or mutagens, each one individually or in combination, capable of inducing heterogeneous cancers! And 2) There is no way that in Germany , France, America and Bulgaria for example, the same tumours can be registered after taking the same drugs and this not be catalogued as a carcinogenic side effect for years. Regardless (or even dependent) of whether it is caused by the contaminant in the form of a particular nitrosamine or the active ingredient, the generic. And 3): the unifier in these publications (concerning cancer) remains to be the one and only or rather: the drug related Nitrosocontamination, the Oncopharmacogenesis/ Pharmacooncogenesis. Or the contamination with a heterogeneous/monomorphic type of carcinogens in the form of nitrosamines and their derivatives, which remain, however, completely uncommented as a cause of cancer and melanomas in particular, and that too, and very unfortunately, in none of the international publications presented. Nitrosamines could also be considered as bicarcinogens or polycarcinogens. A typical example therefore remains NDMA: it activates RAS oncogenes before its metabolism, and its metabolites after metabolisation in the liver , are in fact other, radically different mutagens. From another point of view, contamination of certain preparations is possible with up to several nitrosamines or NDSRIS at the same time (in the context of mono or polycontamination of one or more drugs). Precisely because of the above-shared facts, the association between the intake of a particular contaminated antihypertensive drug and the subsequent development of melanoma or other cancers does not require such in-depth analyses or future, prospective follow-up. Polycarcinogenic intake could also lead to the development of melanomas , even if this intake is not formally indicated on drug packaging worldwide. It is this lack of formalisation that casts serious shadows of doubt over the pure substance and could prove to be a subsequent or relatively short-term deterrent to the spread of even uncontainted drug production and the resulting global drug shortage. The labelling of the Nitroso-component and its complete elimination afterwards, remains the only guarantee for : 1) the protection of the health of patients worldwide , 2) the guarantee of their legal right to be informed of what products they consume as final consumers and 3) the guarantee of the survival of companies in the conditions of reasonable and fair competition and not on the basis of a hidden distribution of nitrosamines in medicines ensuring 3. 1) the development of melanomas (but also a high incidence of cancer in general) but also 3.2) government subsidies in the billions by law. Crossing this ˝devil’s circle˝ would ensure that the ˝much desired progress˝ is achieved: a rapid and explainable decrease in cancer incidence in general, but also in melanoma incidence in particular. In this context, we report on another or next two patients who were taking a particular antihypertensive medication and developed melanomas again subsequently. In patient 1 we discuss the role of beta blockers in the face of bisoprolol and the subsequent development of cutaneous melanomas, and discuss the weakness/manipulative aspect of certain international data on the subject: such as a protective effect of beta blockers in melanomas, for example, which does not exist , but is rather attributable. In the second patient described, a nevus associated melanoma developed on the basis of multimedication with perindopril, amlodipine and moxonidine. Modern scenarios of cancer generation in the context of Nitrosogenesis, Oncopharmacogenesis and Nitroso-photocarcinogenesis are commented. Clearly defined new concepts in medicine would be able to rewrite soon the history and textbooks concerning skin cancer and melanoma in particular. The vision of new horizons, however, requires a rapid rethinking and imposition of new concepts and standards based on a new perspective rather than on lobbyistic, inadequate in action and design coercive regimens for universal tolerance of carcinogens in the most commonly distributed antihypertensive (but no only) drugs worldwide. The scientific worldview and insights remain, to date, the only guiding but also saving light in that direction. Keywords: perindopril;amlodipine; moxonidine; bisoprolol; NDMA; nitrosogenesis; oncopharmacogenesis; photonitrosogenesis; melanoma