clinvestКачественная клиническая практикаKachestvennaya Klinicheskaya Praktika = Good Clinical Practice2588-05192618-8473ООО «Издательство ОКИ10.37489/2588-0519-2022-1-53-63clinvest-606Research ArticleБЕЗОПАСНОСТЬ ЛЕКАРСТВDRUG SAFETYЛекарственно-индуцированная лёгочная артериальная гипертензияDrug-induced pulmonary artery hypertensionhttps://orcid.org/0000-0002-0795-8225ОстроумоваО. Д.OstroumovaO. D.

Остроумова Ольга Дмитриевна - д. м. н., профессор, зав. кафедрой терапии и полиморбидной патологии имени академика М. С. Вовси ФГБОУ ДПО РМАНПО Минздрава РФ; профессор кафедры клинической фармакологии и пропедевтики внутренних болезней ФГАОУ ВО Первый МГМУ им. И. М. Сеченова Минздрава России (Сеченовский университет)SPIN-код: 3910-6585

Москва

Ostroumova Olga D. - Dr. Sci. (Med.), professor, head of the Department of Therapy and Polymorbid Pathology named after academician M. S. Vovsi FSBEI FPE RMACPE MOH Russia; professor of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases FSAEI HE I. M. Sechenov First MSMU MOH Russia (Sechenovskiy University)SPIN code: 3910-6585

Moscow

ostroumova.olga@mail.ruhttps://orcid.org/0000-0002-0401-1132ЛистратовА. И.ListratovA. I.

Листратов Александр Иванович - ординатор 2-го года кафедры терапии и полиморбидной патологии имени академика М. С. Вовси

Москва

Listratov Alexander I. - 2-year resident of the Department of Therapy and Polymorbid Pathology named after academician M. S. Vovsi

Moscow

alexanderlistratoff@yandex.ruhttps://orcid.org/0000-0001-5801-3742КочетковА. И.KochetkovA. I.

Кочетков Алексей Иванович - к. м. н., доцент кафедры терапии и полиморбидной патологии имени академика М. С. ВовсиSPIN-код: 9212-6010

Москва

Kochetkov Alexey I. - Cand. Sci. Med., Associate Professor of the Department of Department of Therapy and Polymorbid Pathology named after academician M. S. VovsiSPIN code: 9212-6010

Moscow

ak_info@list.ruБлизнюкС. А.BliznyukS. A.

Близнюк Светлана Александровна - к. м. н., врач-кардиолог, кардиологическое отделение для больных с острым инфарктом миокарда № 28

Москва

Bliznyuk Svetlana A. - Cand. Sci. Med., cardiologist, Cardiology Department for Patients with Acute Myocardial Infarction No. 28

Moscow

sabliznyuk@icloud.ruКомароваА. Г.KomarovaA. G.

Комарова Анна Григорьевна - к. м. н., зам. главного врачаSPIN-код: 3092-6789

Москва

Komarova Anna G. - Cand. Sci. Med., Deputy Chief PhysicianSPIN code: 3092-6789

Moscow

bellis-06@mail.ruhttps://orcid.org/0000-0002-4496-3680СычёвД. А.SychevD. A.

Сычёв Дмитрий Алексеевич - д. м. н., профессор, член-корр. РАН, ректор, зав. кафедрой клинической фармакологии и терапии имени академика Б. Е. Вотчала

SPIN-код: 4525-7556

Москва

Sychev Dmitry A. - Dr. Sci. (Med.), professor, Corresponding Member RAS, Rector, Head Department of the Clinical Pharmacology and Therapy named after academician B. E. VotchalSPIN code: 4525-7556

Moscow

dimasychev@mail.ruФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» МЗ РФ; ФГАОУ ВО Первый Московский государственный медицинский университет им. И. М. Сеченова Минздрава Российской Федерации (Сеченовский университет)РоссияFSBEI FPE “Russian Medical Academy of Continuous Professional Education” of the Ministry of Healthcare of the Russian Federation; FSAEI HE I. M. Sechenov First MSMU MOH Russia (Sechenovskiy University)Russian FederationФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» МЗ РФРоссияFSBEI FPE “Russian Medical Academy of Continuous Professional Education” of the Ministry of Healthcare of the Russian FederationRussian FederationГБУЗ ГКБ им. С. П. Боткина ДЗМРоссияBotkin City Clinical Hospital of the Moscow Department of HealthRussian Federation202201052022015363Copyright © Остроумова О.Д., Листратов А.И., Кочетков А.И., Близнюк С.А., Комарова А.Г., Сычёв Д.А., 20222022Остроумова О.Д., Листратов А.И., Кочетков А.И., Близнюк С.А., Комарова А.Г., Сычёв Д.А.Ostroumova O.D., Listratov A.I., Kochetkov A.I., Bliznyuk S.A., Komarova A.G., Sychev D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.clinvest.ru/jour/article/view/606

Лёгочная артериальная гипертензия (ЛАГ) — состояние, которое характеризуется повышением среднего давления в лёгочной артерии. Данная патология ассоциирована с высокой смертностью, а специфическая терапия лёгочной артериальной гипертензии не влияет на причину заболевания и является чрезвычайно дорогостоящей. В связи с этим особенно важно изучение модифицируемых этиологических факторов ЛАГ. К одним из таких факторов относятся лекарственные средства. Одной из ведущих групп препаратов-индукторов является группа анорексигенных средств. Именно представители данной группы, такие как аминорекс, были первыми индукторами ЛАГ. Причём эта нежелательная реакция была настолько значимой, что привела к отзыву с рынка данных препаратов. В настоящее время ведущую роль в контексте лекарственно-индуцированной лёгочной гипертензии играют такие средства, как противоопухолевые, противовирусные препараты, а также интерфероны. Данные препараты приводят к лёгочной гипертензии путём различных патофизиологических механизмов. Ведущими мерами профилактики данной патологии являются ограничение применения препаратов-индукторов, снижение распространения ВИЧ-инфекции, так как для лечения ВИЧ-инфицированных пациентов может применяться несколько групп лекарственных средств, приводящих к развитию лёгочной гипертензии.

Pulmonary arterial hypertension is a condition characterized by an increase in mean pressure in the pulmonary artery. This pathology is associated with high mortality, and specific therapy for pulmonary arterial hypertension does not affect the cause of the disease and is extremely expensive. In this regard, it is especially important to study the modifiable etiological factors of pulmonary arterial hypertension. One such factor is drugs. One of the leading groups of drugs-inductors is anorexigenic drugs. It was the representatives of this group, such as aminorex, who were the first inducers of pulmonary hypertension. Moreover, this adverse reaction was so significant that it led to the withdrawal of these drugs. Currently, the leading role in the context of drug-induced pulmonary hypertension is played by such drugs as anticancer, antiviral drugs, and interferons. These drugs lead to pulmonary hypertension through various pathophysiological mechanisms. The leading measures to prevent this pathology are to limit the use of culprit medications, reduce the spread of HIV infection, since several groups of drugs can be used to treat HIV-infected patients, leading to the development of pulmonary hypertension.

лёгочная артериальная гипертензиялекарственно-индуцированная лёгочная артериальная гипертензиялекарственные средстванежелательные реакциипротивоопухолевые препаратыpulmonary arterial hypertensiondrug-induced pulmonary arterial hypertensiondrugsadverse drug reactionsanticancer drugsReferencesАвдеев С. Н., Барбараш О. Л., Баутин А. Е., Волков А. В., Веселова Т. Н., Галявич А. С., Гончарова Н. С., Горбачевский С. В., Данилов Н. М., Еременко А. А., Мартынюк Т. В., Моисеева О. М., Саидова М. А., Сергиенко В. Б., Симакова М. А., Стукалова О. В., Чазова И. Е., Чернявский А. М., Шалаев С. В., Шмальц А. А., Царева Н. А. Легочная гипертензия, в том числе хроническая тромбоэмболическая легочная гипертензия. Клинические рекомендации 2020. Российский кардиологический журнал. 2021;26(12):4683. doi:10.15829/1560-4071-2021-4683Avdeev SN, Barbarash OL, Bautin AE, Volkov AV, Veselova TN, Galyavich AS, Goncharova NS, Gorbachevsky SV, Danilov NM, Eremenko AA, Martynyuk TV, Moiseeva OM, Saidova MA, Sergienko VB, Simakova MA, Stukalova OV, Chazova IE, Chernyavsky AM, Shalaev SV, Shmalts AA, Tsareva NA. 2020 Clinical practice guidelines for Pulmonary hypertension, including chronic thromboembolic pulmonary hypertension. Russian Journal of Cardiology. 2021;26(12):4683. (In Russ). doi:10.15829/1560-4071-2021-4683Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J. 2009;34(4):888–94. doi:10.1183/09031936.00145608Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J. 2009;34(4):888–94. doi:10.1183/09031936.00145608Thenappan T, Ryan JJ, Archer SL. Evolving epidemiology of pulmonary arterial hypertension [published correction appears in Am J Respir Crit Care Med. 2013;187(3):333]. Am J Respir Crit Care Med. 2012;186(8):707–9. doi:10.1164/rccm.201207-1266EDThenappan T, Ryan JJ, Archer SL. Evolving epidemiology of pulmonary arterial hypertension [published correction appears in Am J Respir Crit Care Med. 2013;187(3):333]. Am J Respir Crit Care Med. 2012;186(8):707–9. doi:10.1164/rccm.201207-1266EDGaliè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67–119. doi:10.1093/eurheartj/ehv317Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67–119. doi:10.1093/eurheartj/ehv317Zelt JGE, Sugarman J, Weatherald J, et al. Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS Guideline Era [published online ahead of print, 2021 Oct 21]. Eur Respir J. 2021;2101552. doi:10.1183/13993003.01552-2021Zelt JGE, Sugarman J, Weatherald J, et al. Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS Guideline Era [published online ahead of print, 2021 Oct 21]. Eur Respir J. 2021;2101552. doi:10.1183/13993003.01552-2021Thenappan T, Ormiston ML, Ryan JJ, Archer SL. Pulmonary arterial hypertension: pathogenesis and clinical management. BMJ. 2018;360:j5492. doi:10.1136/bmj.j5492Thenappan T, Ormiston ML, Ryan JJ, Archer SL. Pulmonary arterial hypertension: pathogenesis and clinical management. BMJ. 2018;360:j5492. doi:10.1136/bmj.j5492Anand V, Roy SS, Archer SL, et al. Trends and Outcomes of Pulmonary Arterial Hypertension-Related Hospitalizations in the United States: Analysis of the Nationwide Inpatient Sample Database From 2001 Th rough 2012. JAMA Cardiol. 2016;1(9):1021–9. doi:10.1001/jamacardio.2016.3591Anand V, Roy SS, Archer SL, et al. Trends and Outcomes of Pulmonary Arterial Hypertension-Related Hospitalizations in the United States: Analysis of the Nationwide Inpatient Sample Database From 2001 Th rough 2012. JAMA Cardiol. 2016;1(9):1021–9. doi:10.1001/jamacardio.2016.3591Helgeson SA, Menon D, Helmi H, et al. Psychosocial and Financial Burden of Therapy in USA Patients with Pulmonary Arterial Hypertension. Diseases. 2020;8(2):22. doi:10.3390/diseases8020022Helgeson SA, Menon D, Helmi H, et al. Psychosocial and Financial Burden of Therapy in USA Patients with Pulmonary Arterial Hypertension. Diseases. 2020;8(2):22. doi:10.3390/diseases8020022McGee M, Whitehead N, Martin J, Collins N. Drug-associated pulmonary arterial hypertension. Clin Toxicol (Phila). 2018;56(9):801–9. doi:10.1080/15563650.2018.1447119McGee M, Whitehead N, Martin J, Collins N. Drug-associated pulmonary arterial hypertension. Clin Toxicol (Phila). 2018;56(9):801–9. doi:10.1080/15563650.2018.1447119Correale M, Tricarico L, Grazioli D, et al. Drug-Induced Pulmonary Arterial Hypertension: Mechanisms and Clinical Management. Cardiovasc Drugs Ther. 2019;33(6):725–38. doi:10.1007/s10557-019-06920-xCorreale M, Tricarico L, Grazioli D, et al. Drug-Induced Pulmonary Arterial Hypertension: Mechanisms and Clinical Management. Cardiovasc Drugs Ther. 2019;33(6):725–38. doi:10.1007/s10557-019-06920-xRamirez RL 3rd, Pienkos SM, de Jesus Perez V, Zamanian RT. Pulmonary Arterial Hypertension Secondary to Drugs and Toxins. Clin Chest Med. 2021;42(1):19–38. doi:10.1016/j.ccm.2020.11.008Ramirez RL 3rd, Pienkos SM, de Jesus Perez V, Zamanian RT. Pulmonary Arterial Hypertension Secondary to Drugs and Toxins. Clin Chest Med. 2021;42(1):19–38. doi:10.1016/j.ccm.2020.11.008Weigle DS. Pharmacological therapy of obesity: past, present, and future. J Clin Endocrinol Metab. 2003;88(6):2462–9. doi:10.1210/jc.2003-030151Weigle DS. Pharmacological therapy of obesity: past, present, and future. J Clin Endocrinol Metab. 2003;88(6):2462–9. doi:10.1210/jc.2003-030151Abenhaim L, Moride Y, Brenot F, et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group. N Engl J Med. 1996;335(9):609–16. doi:10.1056/NEJM199608293350901Abenhaim L, Moride Y, Brenot F, et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group. N Engl J Med. 1996;335(9):609–16. doi:10.1056/NEJM199608293350901Dempsie Y, MacRitchie NA, White K, et al. Dexfenfluramine and the oestrogen-metabolizing enzyme CYP1B1 in the development of pulmonary arterial hypertension. Cardiovasc Res. 2013;99(1):24–34. doi:10.1093/cvr/cvt064Dempsie Y, MacRitchie NA, White K, et al. Dexfenfluramine and the oestrogen-metabolizing enzyme CYP1B1 in the development of pulmonary arterial hypertension. Cardiovasc Res. 2013;99(1):24–34. doi:10.1093/cvr/cvt064Savale L, Chaumais MC, Cottin V, et al. Pulmonary hypertension associated with benfluorex exposure. Eur Respir J. 2012;40(5):1164–72. doi:10.1183/09031936.00188611Savale L, Chaumais MC, Cottin V, et al. Pulmonary hypertension associated with benfluorex exposure. Eur Respir J. 2012;40(5):1164–72. doi:10.1183/09031936.00188611Chen PI, Cao A, Miyagawa K, et al. Amphetamines promote mitochondrial dysfunction and DNA damage in pulmonary hypertension. JCI Insight. 2017;2(2):e90427. doi:10.1172/jci.insight.90427Chen PI, Cao A, Miyagawa K, et al. Amphetamines promote mitochondrial dysfunction and DNA damage in pulmonary hypertension. JCI Insight. 2017;2(2):e90427. doi:10.1172/jci.insight.90427Terra Filho M, Yen CC, Santos Ude P, Muñoz DR. Pulmonary alterations in cocaine users. Sao Paulo Med J. 2004;122(1):26–31. doi:10.1590/s1516-31802004000100007Terra Filho M, Yen CC, Santos Ude P, Muñoz DR. Pulmonary alterations in cocaine users. Sao Paulo Med J. 2004;122(1):26–31. doi:10.1590/s1516-31802004000100007Savale L, Sattler C, Günther S, et al. Pulmonary arterial hypertension in patients treated with interferon [published correction appears in Eur Respir J. 2015;46(6):1854]. Eur Respir J. 2014;44(6):1627–34. doi:10.1183/09031936.00057914Savale L, Sattler C, Günther S, et al. Pulmonary arterial hypertension in patients treated with interferon [published correction appears in Eur Respir J. 2015;46(6):1854]. Eur Respir J. 2014;44(6):1627–34. doi:10.1183/09031936.00057914Caravita S, Secchi MB, Wu SC, Pierini S, Paggi A. Sildenafil therapy for interferon-β-1a-induced pulmonary arterial hypertension: a case report. Cardiology. 2011;120(4):187–9. doi:10.1159/000335064Caravita S, Secchi MB, Wu SC, Pierini S, Paggi A. Sildenafil therapy for interferon-β-1a-induced pulmonary arterial hypertension: a case report. Cardiology. 2011;120(4):187–9. doi:10.1159/000335064Shah NP, Wallis N, Farber HW, et al. Clinical features of pulmonary arterial hypertension in patients receiving dasatinib. Am J Hematol. 2015;90(11):1060–4. doi:10.1002/ajh.24174Shah NP, Wallis N, Farber HW, et al. Clinical features of pulmonary arterial hypertension in patients receiving dasatinib. Am J Hematol. 2015;90(11):1060–4. doi:10.1002/ajh.24174Minami M, Arita T, Iwasaki H, et al. Comparative analysis of pulmonary hypertension in patients treated with imatinib, nilotinib and dasatinib. Br J Haematol. 2017;177(4):578–87. doi:10.1111/bjh.14608Minami M, Arita T, Iwasaki H, et al. Comparative analysis of pulmonary hypertension in patients treated with imatinib, nilotinib and dasatinib. Br J Haematol. 2017;177(4):578–87. doi:10.1111/bjh.14608Hickey PM, Thompson AA, Charalampopoulos A, et al. Bosutinib therapy resulting in severe deterioration of pre-existing pulmonary arterial hypertension. Eur Respir J. 2016;48(5):1514–6. doi:10.1183/13993003.01004-2016Hickey PM, Thompson AA, Charalampopoulos A, et al. Bosutinib therapy resulting in severe deterioration of pre-existing pulmonary arterial hypertension. Eur Respir J. 2016;48(5):1514–6. doi:10.1183/13993003.01004-2016Quilot FM, Georges M, Favrolt N, et al. Pulmonary hypertension associated with ponatinib therapy. Eur Respir J. 2016;47(2):676–9. doi:10.1183/13993003.01110-2015Quilot FM, Georges M, Favrolt N, et al. Pulmonary hypertension associated with ponatinib therapy. Eur Respir J. 2016;47(2):676–9. doi:10.1183/13993003.01110-2015Low AT, Howard L, Harrison C, Tulloh RM. Pulmonary arterial hypertension exacerbated by ruxolitinib. Haematologica. 2015;100(6):e244–5. doi:10.3324/haematol.2014.120816Low AT, Howard L, Harrison C, Tulloh RM. Pulmonary arterial hypertension exacerbated by ruxolitinib. Haematologica. 2015;100(6):e244–5. doi:10.3324/haematol.2014.120816Gagnadoux F, Capron F, Lebeau B. Pulmonary veno-occlusive disease after neoadjuvant mitomycin chemotherapy and surgery for lung carcinoma. Lung Cancer. 2002;36(2):213–5. doi:10.1016/s0169-5002(01)00479-2Gagnadoux F, Capron F, Lebeau B. Pulmonary veno-occlusive disease after neoadjuvant mitomycin chemotherapy and surgery for lung carcinoma. Lung Cancer. 2002;36(2):213–5. doi:10.1016/s0169-5002(01)00479-2Ranchoux B, Günther S, Quarck R, et al. Chemotherapyinduced pulmonary hypertension: role of alkylating agents. Am J Pathol. 2015;185(2):356–71. doi:10.1016/j.ajpath.2014.10.021Ranchoux B, Günther S, Quarck R, et al. Chemotherapyinduced pulmonary hypertension: role of alkylating agents. Am J Pathol. 2015;185(2):356–71. doi:10.1016/j.ajpath.2014.10.021Lafaras C, Mandala E, Verrou E, et al. Non-thromboembolic pulmonary hypertension in multiple myeloma, after thalidomide treatment: a pilot study. Ann Oncol. 2008;19(10):1765–9. doi:10.1093/annonc/mdn287Lafaras C, Mandala E, Verrou E, et al. Non-thromboembolic pulmonary hypertension in multiple myeloma, after thalidomide treatment: a pilot study. Ann Oncol. 2008;19(10):1765–9. doi:10.1093/annonc/mdn287Liotta M, Rose PG, Escobar PF. Pulmonary hypertension in two patients treated with bevacizumab for recurrent ovarian cancer. Gynecol Oncol. 2009;115(2):308–9. doi:10.1016/j.ygyno.2009.08.003Liotta M, Rose PG, Escobar PF. Pulmonary hypertension in two patients treated with bevacizumab for recurrent ovarian cancer. Gynecol Oncol. 2009;115(2):308–9. doi:10.1016/j.ygyno.2009.08.003Hainsworth JD, Fang L, Huang JE, et al. BRIDGE: an open-label phase II trial evaluating the safety of bevacizumab + carboplatin/paclitaxel as first-line treatment for patients with advanced, previously untreated, squamous non-small cell lung cancer. J Thorac Oncol. 2011;6(1):109–14. doi:10.1097/JTO.0b013e3181f94ad4Hainsworth JD, Fang L, Huang JE, et al. BRIDGE: an open-label phase II trial evaluating the safety of bevacizumab + carboplatin/paclitaxel as first-line treatment for patients with advanced, previously untreated, squamous non-small cell lung cancer. J Thorac Oncol. 2011;6(1):109–14. doi:10.1097/JTO.0b013e3181f94ad4Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension [published correction appears in J Am Coll Cardiol. 2014;63(7):746]. J Am Coll Cardiol. 2013;62(25 Suppl):D34–D41. doi:10.1016/j.jacc.2013.10.029Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension [published correction appears in J Am Coll Cardiol. 2014;63(7):746]. J Am Coll Cardiol. 2013;62(25 Suppl):D34–D41. doi:10.1016/j.jacc.2013.10.029Mathew R, Huang J, Katta US, Krishnan U, Sandoval C, Gewitz MH. Immunosuppressant-induced endothelial damage and pulmonary arterial hypertension. J Pediatr Hematol Oncol. 2011;33(1):55–8. doi:10.1097/MPH.0b013e3181ec0edeMathew R, Huang J, Katta US, Krishnan U, Sandoval C, Gewitz MH. Immunosuppressant-induced endothelial damage and pulmonary arterial hypertension. J Pediatr Hematol Oncol. 2011;33(1):55–8. doi:10.1097/MPH.0b013e3181ec0edeAlvarez PA, Saad AK, Flagel S, Mazzocchi O, Blanco MV. Leflunomide-induced pulmonary hypertension in a young woman with rheumatoid arthritis: a case report. Cardiovasc Toxicol. 2012;12(2):180–3. doi:10.1007/s12012-012-9153-3Alvarez PA, Saad AK, Flagel S, Mazzocchi O, Blanco MV. Leflunomide-induced pulmonary hypertension in a young woman with rheumatoid arthritis: a case report. Cardiovasc Toxicol. 2012;12(2):180–3. doi:10.1007/s12012-012-9153-3Lazarevic VLj, Liljeholm M, Forsberg K, et al. Fludarabine, cyclophosphamide and rituximab (FCR) induced pulmonary hypertension in Waldenstrom macroglobulinemia. Leuk Lymphoma. 2008;49(6):1209–11. doi:10.1080/10428190802007718Lazarevic VLj, Liljeholm M, Forsberg K, et al. Fludarabine, cyclophosphamide and rituximab (FCR) induced pulmonary hypertension in Waldenstrom macroglobulinemia. Leuk Lymphoma. 2008;49(6):1209–11. doi:10.1080/10428190802007718Montrone D, Correale M, Franzese MG, Ieva R, Di Biase M, Capalbo SF. Pulmonary arterial hypertension in a chronic lymphocytic leukemia patient in treatment with rituximab. J Cardiovasc Med (Hagerstown). 2015;16(Suppl 1):S65. doi:10.2459/JCM.0b013e3283621adfMontrone D, Correale M, Franzese MG, Ieva R, Di Biase M, Capalbo SF. Pulmonary arterial hypertension in a chronic lymphocytic leukemia patient in treatment with rituximab. J Cardiovasc Med (Hagerstown). 2015;16(Suppl 1):S65. doi:10.2459/JCM.0b013e3283621adfHo RC, Ho EC, Tan CH, Mak A. Pulmonary hypertension in first episode infective endocarditis among intravenous buprenorphine users: case report. Am J Drug Alcohol Abuse. 2009;35(3):199–202. doi:10.1080/00952990902939719Ho RC, Ho EC, Tan CH, Mak A. Pulmonary hypertension in first episode infective endocarditis among intravenous buprenorphine users: case report. Am J Drug Alcohol Abuse. 2009;35(3):199–202. doi:10.1080/00952990902939719Garrett PM. Tramadol overdose and serotonin syndrome manifesting as acute right heart dysfunction. Anaesth Intensive Care. 2004;32(4):575–7. doi:10.1177/0310057X0403200417Garrett PM. Tramadol overdose and serotonin syndrome manifesting as acute right heart dysfunction. Anaesth Intensive Care. 2004;32(4):575–7. doi:10.1177/0310057X0403200417Freitas CF, Faro R, Dragosavac D, Clozel M, De Nucci G, Antunes E. Role of endothelin-1 and thromboxane A2 in the pulmonary hypertension induced by heparin-protamine interaction in anesthetized dogs. J Cardiovasc Pharmacol. 2004;43(1):106–12. doi:10.1097/00005344-200401000-00016Freitas CF, Faro R, Dragosavac D, Clozel M, De Nucci G, Antunes E. Role of endothelin-1 and thromboxane A2 in the pulmonary hypertension induced by heparin-protamine interaction in anesthetized dogs. J Cardiovasc Pharmacol. 2004;43(1):106–12. doi:10.1097/00005344-200401000-00016Evrard F, Dupuis M, Muller T, Jacquerye P. Hypertension artérielle pulmonaire isolée et pergolide [Isolated pulmonary hypertension and pergolide]. Rev Neurol (Paris). 2008;164(3):278–9. doi:10.1016/j.neurol.2007.09.005Evrard F, Dupuis M, Muller T, Jacquerye P. Hypertension artérielle pulmonaire isolée et pergolide [Isolated pulmonary hypertension and pergolide]. Rev Neurol (Paris). 2008;164(3):278–9. doi:10.1016/j.neurol.2007.09.005Walker AM, Langleben D, Korelitz JJ, et al. Temporal trends and drug exposures in pulmonary hypertension: an American experience. Am Heart J. 2006;152(3):521–6. doi:10.1016/j.ahj.2006.02.020Walker AM, Langleben D, Korelitz JJ, et al. Temporal trends and drug exposures in pulmonary hypertension: an American experience. Am Heart J. 2006;152(3):521–6. doi:10.1016/j.ahj.2006.02.020Misumi K, Ogo T, Ueda J, et al. Development of Pulmonary Arterial Hypertension in a Patient Treated with Qing-Dai (Chinese Herbal Medicine). Intern Med. 2019;58(3):395–9. doi:10.2169/internalmedicine.1523-18Misumi K, Ogo T, Ueda J, et al. Development of Pulmonary Arterial Hypertension in a Patient Treated with Qing-Dai (Chinese Herbal Medicine). Intern Med. 2019;58(3):395–9. doi:10.2169/internalmedicine.1523-18Tisdale JE, Miller DA. Drug Induced Diseases: Prevention, Detection, and Management. 3rd Ed. Bethesda, Md.: American Society of Health-System Pharmacists, 2018. 1399 рр.Tisdale JE, Miller DA. Drug Induced Diseases: Prevention, Detection, and Management. 3rd Ed. Bethesda, Md.: American Society of Health-System Pharmacists, 2018. 1399 рр.Hoeper MM, Ghofrani HA, Grünig E, et al. Pulmonary Hypertension. Dtsch Arztebl Int. 2017;114(5):73–84. doi:10.3238/arztebl.2017.0073Hoeper MM, Ghofrani HA, Grünig E, et al. Pulmonary Hypertension. Dtsch Arztebl Int. 2017;114(5):73–84. doi:10.3238/arztebl.2017.0073Quezada M, Martin-Carbonero L, Soriano V, et al. Prevalence and risk factors associated with pulmonary hypertension in HIV-infected patients on regular follow-up. AIDS. 2012;26(11):1387–92. doi:10.1097/QAD.0b013e328354f5a1Quezada M, Martin-Carbonero L, Soriano V, et al. Prevalence and risk factors associated with pulmonary hypertension in HIV-infected patients on regular follow-up. AIDS. 2012;26(11):1387–92. doi:10.1097/QAD.0b013e328354f5a1Rasoulinejad M, Moradmand Badie S, Salehi MR, et al. Echocardiographic assessment of systolic pulmonary arterial pressure in HIV-positive patients. Acta Med Iran. 2014;52(11):827–30.Rasoulinejad M, Moradmand Badie S, Salehi MR, et al. Echocardiographic assessment of systolic pulmonary arterial pressure in HIV-positive patients. Acta Med Iran. 2014;52(11):827–30.Orcholski ME, Yuan K, Rajasingh C, et al. Drug-induced pulmonary arterial hypertension: a primer for clinicians and scientists. Am J Physiol Lung Cell Mol Physiol. 2018;314(6):L967–L983. doi:10.1152/ajplung.00553.2017Orcholski ME, Yuan K, Rajasingh C, et al. Drug-induced pulmonary arterial hypertension: a primer for clinicians and scientists. Am J Physiol Lung Cell Mol Physiol. 2018;314(6):L967–L983. doi:10.1152/ajplung.00553.2017MacLean MMR. The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series). Pulm Circ. 2018;8(2):2045894018759125. doi:10.1177/2045894018759125MacLean MMR. The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series). Pulm Circ. 2018;8(2):2045894018759125. doi:10.1177/2045894018759125Hood KY, Mair KM, Harvey AP, et al. Serotonin Signaling Through the 5-HT1B Receptor and NADPH Oxidase 1 in Pulmonary Arterial Hypertension. Arterioscler Thromb Vasc Biol. 2017;37(7):1361–70. doi:10.1161/ATVBAHA.116.308929Hood KY, Mair KM, Harvey AP, et al. Serotonin Signaling Through the 5-HT1B Receptor and NADPH Oxidase 1 in Pulmonary Arterial Hypertension. Arterioscler Thromb Vasc Biol. 2017;37(7):1361–70. doi:10.1161/ATVBAHA.116.308929Maclean MR, Dempsie Y. Th e serotonin hypothesis of pulmonary hypertension revisited. Adv Exp Med Biol. 2010;661:309–22. doi:10.1007/978-1-60761-500-2_20Maclean MR, Dempsie Y. Th e serotonin hypothesis of pulmonary hypertension revisited. Adv Exp Med Biol. 2010;661:309–22. doi:10.1007/978-1-60761-500-2_20Брегель Л. В., Белозеров Ю. М., Новиков П. В., Школьникова М. А. Генетика легочной гипертензии. Российский вестник перинатологии и педиатрии. 2014;59(1):22–7.Bregel LV, Belozerov YuM, Novikov PV, Shkolnikova MA. The genetics of pulmonary hypertension. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2014;59(1):22–7. (In Russ).Pleym H, Greiff G, Mjorndal T, et al. Effect of serotonin reuptake inhibitors on pulmonary hemodynamics in humans. J Clin Med Res. 2011;3(5):230–8. doi:10.4021/jocmr654wPleym H, Greiff G, Mjorndal T, et al. Effect of serotonin reuptake inhibitors on pulmonary hemodynamics in humans. J Clin Med Res. 2011;3(5):230–8. doi:10.4021/jocmr654wGuignabert C, Izikki M, Tu LI, et al. Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension. Circ Res. 2006;98(10):1323–30. doi:10.1161/01.RES.0000222546.45372.a0Guignabert C, Izikki M, Tu LI, et al. Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension. Circ Res. 2006;98(10):1323–30. doi:10.1161/01.RES.0000222546.45372.a0Adnot S, Houssaini A, Abid S, et al. Serotonin transporter and serotonin receptors. Handb Exp Pharmacol. 2013;218:365–80. doi:10.1007/978-3-642-38664-0_15Adnot S, Houssaini A, Abid S, et al. Serotonin transporter and serotonin receptors. Handb Exp Pharmacol. 2013;218:365–80. doi:10.1007/978-3-642-38664-0_15Dempsie Y, MacLean M. Role of the serotonin transporter in pulmonary arterial hypertension. Expert Rev Clin Pharmacol. 2008;1(6):749–57. doi:10.1586/17512433.1.6.749Dempsie Y, MacLean M. Role of the serotonin transporter in pulmonary arterial hypertension. Expert Rev Clin Pharmacol. 2008;1(6):749–57. doi:10.1586/17512433.1.6.749Eddahibi S, Adnot S. Anorexigen-induced pulmonary hypertension and the serotonin (5-HT) hypothesis: lessons for the future in pathogenesis. Respir Res. 2002;3(1):9. doi:10.1186/rr181Eddahibi S, Adnot S. Anorexigen-induced pulmonary hypertension and the serotonin (5-HT) hypothesis: lessons for the future in pathogenesis. Respir Res. 2002;3(1):9. doi:10.1186/rr181MacLean MR. Pulmonary hypertension, anorexigens and 5-HT: pharmacological synergism in action? Trends Pharmacol Sci. 1999;20(12):490–5. doi:10.1016/s0165-6147(99)01389-9MacLean MR. Pulmonary hypertension, anorexigens and 5-HT: pharmacological synergism in action? Trends Pharmacol Sci. 1999;20(12):490–5. doi:10.1016/s0165-6147(99)01389-9Hendricks-Munoz KD, Gerrets RP, Higgins RD, et al. Cocaine-stimulated endothelin-1 release is decreased by angiotensin-converting enzyme inhibitors in cultured endothelial cells. Cardiovasc Res. 1996;31(1):117–23. doi:10.1016/s0008-6363(95)00168-9Hendricks-Munoz KD, Gerrets RP, Higgins RD, et al. Cocaine-stimulated endothelin-1 release is decreased by angiotensin-converting enzyme inhibitors in cultured endothelial cells. Cardiovasc Res. 1996;31(1):117–23. doi:10.1016/s0008-6363(95)00168-9Pradhan L, Mondal D, Chandra S, et al. Molecular analysis of cocaineinduced endothelial dysfunction: role of endothelin-1 and nitric oxide. Cardiovasc Toxicol. 2008;8(4):161–71. doi:10.1007/s12012-008-9025-zPradhan L, Mondal D, Chandra S, et al. Molecular analysis of cocaineinduced endothelial dysfunction: role of endothelin-1 and nitric oxide. Cardiovasc Toxicol. 2008;8(4):161–71. doi:10.1007/s12012-008-9025-zGeorge PM, Cunningham ME, Galloway-Phillipps N, et al. Endothelin-1 as a mediator and potential biomarker for interferon induced pulmonary toxicity. Pulm Circ. 2012;2(4):501–4. doi:10.4103/2045-8932.105039George PM, Cunningham ME, Galloway-Phillipps N, et al. Endothelin-1 as a mediator and potential biomarker for interferon induced pulmonary toxicity. Pulm Circ. 2012;2(4):501–4. doi:10.4103/2045-8932.105039Moslehi JJ, Deininger M. Tyrosine Kinase Inhibitor-Associated Cardiovascular Toxicity in Chronic Myeloid Leukemia. J Clin Oncol. 2015;33(35):4210–8. doi:10.1200/JCO.2015.62.4718Moslehi JJ, Deininger M. Tyrosine Kinase Inhibitor-Associated Cardiovascular Toxicity in Chronic Myeloid Leukemia. J Clin Oncol. 2015;33(35):4210–8. doi:10.1200/JCO.2015.62.4718Groeneveldt JA, Gans SJ, Bogaard HJ, Vonk-Noordegraaf A. Dasatinibinduced pulmonary arterial hypertension unresponsive to PDE-5 inhibition. Eur Respir J. 2013;42(3):869–70. doi:10.1183/09031936.00035913Groeneveldt JA, Gans SJ, Bogaard HJ, Vonk-Noordegraaf A. Dasatinibinduced pulmonary arterial hypertension unresponsive to PDE-5 inhibition. Eur Respir J. 2013;42(3):869–70. doi:10.1183/09031936.00035913Ranchoux B, Meloche J, Paulin R, et al. DNA Damage and Pulmonary Hypertension. Int J Mol Sci. 2016;17(6):990. doi:10.3390/ijms17060990Ranchoux B, Meloche J, Paulin R, et al. DNA Damage and Pulmonary Hypertension. Int J Mol Sci. 2016;17(6):990. doi:10.3390/ijms17060990Brown JM, Yamamoto BK. Effects of amphetamines on mitochondrial function: role of free radicals and oxidative stress. Pharmacol Ther. 2003;99(1):45–53. doi:10.1016/s0163-7258(03)00052-4Brown JM, Yamamoto BK. Effects of amphetamines on mitochondrial function: role of free radicals and oxidative stress. Pharmacol Ther. 2003;99(1):45–53. doi:10.1016/s0163-7258(03)00052-4Orcholski ME, Khurshudyan A, Shamskhou EA, et al. Reduced carboxylesterase 1 is associated with endothelial injury in methamphetamineinduced pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2017;313(2):L252–L266. doi:10.1152/ajplung.00453.2016Orcholski ME, Khurshudyan A, Shamskhou EA, et al. Reduced carboxylesterase 1 is associated with endothelial injury in methamphetamineinduced pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2017;313(2):L252–L266. doi:10.1152/ajplung.00453.2016Guignabert C, Phan C, Seferian A, et al. Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension. J Clin Invest. 2016;126(9):3207–18. doi:10.1172/JCI86249Guignabert C, Phan C, Seferian A, et al. Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension. J Clin Invest. 2016;126(9):3207–18. doi:10.1172/JCI86249Li S, Yu Y, Yang P, et al. Trichloroethylene Alters Th 1/Th 2/Th 17/Treg Paradigm in Mice: A Novel Mechanism for Chemically Induced Autoimmunity. Int J Toxicol. 2018;37(2):155–63. doi:10.1177/1091581818757036Li S, Yu Y, Yang P, et al. Trichloroethylene Alters Th 1/Th 2/Th 17/Treg Paradigm in Mice: A Novel Mechanism for Chemically Induced Autoimmunity. Int J Toxicol. 2018;37(2):155–63. doi:10.1177/1091581818757036Burton VJ, Ciuclan LI, Holmes AM, et al. Bone morphogenetic protein receptor II regulates pulmonary artery endothelial cell barrier function. Blood. 2011;117(1):333–41. doi:10.1182/blood-2010-05-285973Burton VJ, Ciuclan LI, Holmes AM, et al. Bone morphogenetic protein receptor II regulates pulmonary artery endothelial cell barrier function. Blood. 2011;117(1):333–41. doi:10.1182/blood-2010-05-285973Huertas A, Perros F, Tu L, et al. Immune dysregulation and endothelial dysfunction in pulmonary arterial hypertension: a complex interplay. Circulation. 2014;129(12):1332–40. doi:10.1161/CIRCULATIONAHA.113.004555Huertas A, Perros F, Tu L, et al. Immune dysregulation and endothelial dysfunction in pulmonary arterial hypertension: a complex interplay. Circulation. 2014;129(12):1332–40. doi:10.1161/CIRCULATIONAHA.113.004555Joselson R, Warnock M. Pulmonary veno-occlusive disease after chemotherapy. Hum Pathol. 1983;14(1):88–91. doi:10.1016/s0046-8177(83)80052-5Joselson R, Warnock M. Pulmonary veno-occlusive disease after chemotherapy. Hum Pathol. 1983;14(1):88–91. doi:10.1016/s0046-8177(83)80052-5Wu KY, Wang HZ, Hong SJ. Mechanism of mitomycin-induced apoptosis in cultured corneal endothelial cells. Mol Vis. 2008;14:1705–12.Wu KY, Wang HZ, Hong SJ. Mechanism of mitomycin-induced apoptosis in cultured corneal endothelial cells. Mol Vis. 2008;14:1705–12.Kanmogne GD, Kennedy RC, Grammas P. Analysis of human lung endothelial cells for susceptibility to HIV type 1 infection, coreceptor expression, and cytotoxicity of gp120 protein. AIDS Res Hum Retroviruses. 2001;17(1):45–53. doi:10.1089/088922201750056771Kanmogne GD, Kennedy RC, Grammas P. Analysis of human lung endothelial cells for susceptibility to HIV type 1 infection, coreceptor expression, and cytotoxicity of gp120 protein. AIDS Res Hum Retroviruses. 2001;17(1):45–53. doi:10.1089/088922201750056771Mehta PM, Grainger TA, Lust RM, et al. Effect of cocaine on left ventricular function. Relation to increased wall stress and persistence after treatment. Circulation. 1995;91(12):3002–9. doi:10.1161/01.cir.91.12.3002Mehta PM, Grainger TA, Lust RM, et al. Effect of cocaine on left ventricular function. Relation to increased wall stress and persistence after treatment. Circulation. 1995;91(12):3002–9. doi:10.1161/01.cir.91.12.3002Российское кардиологическое общество (РКО). Хроническая сердечная недостаточность. Клинические рекомендации 2020. Российский кардиологический журнал. 2020;25(11):4083. doi:10.15829/1560-4071-2020-4083Russian Society of Cardiology (RSC). 2020 Clinical practice guidelines for Chronic heart failure. Russian Journal of Cardiology. 2020;25(11):4083. (In Russ). doi:10.15829/1560-4071-2020-4083Savale L, Chaumais MC, O’Connell C, et al. Interferon-induced pulmonary hypertension: an update. Curr Opin Pulm Med. 2016;22(5):415–20. doi:10.1097/MCP.0000000000000307Savale L, Chaumais MC, O’Connell C, et al. Interferon-induced pulmonary hypertension: an update. Curr Opin Pulm Med. 2016;22(5):415–20. doi:10.1097/MCP.0000000000000307Renard S, Borentain P, Salaun E, et al. Severe Pulmonary Arterial Hypertension in Patients Treated for Hepatitis C With Sofosbuvir. Chest. 2016;149(3):e69–e73. doi:10.1016/j.chest.2015.09.018Renard S, Borentain P, Salaun E, et al. Severe Pulmonary Arterial Hypertension in Patients Treated for Hepatitis C With Sofosbuvir. Chest. 2016;149(3):e69–e73. doi:10.1016/j.chest.2015.09.018Dhillon S, Kaker A, Dosanjh A, et al. Irreversible pulmonary hypertension associated with the use of interferon alpha for chronic hepatitis C. Dig Dis Sci. 2010;55(6):1785–90. doi:10.1007/s10620-010-1220-7Dhillon S, Kaker A, Dosanjh A, et al. Irreversible pulmonary hypertension associated with the use of interferon alpha for chronic hepatitis C. Dig Dis Sci. 2010;55(6):1785–90. doi:10.1007/s10620-010-1220-7Funakoshi-Hirose I, Aki T, Unuma K, et al. Distinct effects of methamphetamine on autophagy-lysosome and ubiquitin-proteasome systems in HL-1 cultured mouse atrial cardiomyocytes. Toxicology. 2013;312:74–82. doi:10.1016/j.tox.2013.07.016Funakoshi-Hirose I, Aki T, Unuma K, et al. Distinct effects of methamphetamine on autophagy-lysosome and ubiquitin-proteasome systems in HL-1 cultured mouse atrial cardiomyocytes. Toxicology. 2013;312:74–82. doi:10.1016/j.tox.2013.07.016Humbert M, Deng Z, Simonneau G, et al. BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives. Eur Respir J. 2002;20(3):518–23. doi:10.1183/09031936.02.01762002Humbert M, Deng Z, Simonneau G, et al. BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives. Eur Respir J. 2002;20(3):518–23. doi:10.1183/09031936.02.01762002Naranjo C, Busto U, Sellers E, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239–45. doi:10.1038/clpt.1981.154Naranjo C, Busto U, Sellers E, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239–45. doi:10.1038/clpt.1981.154Сычев Д. А., Остроумова О. Д., Переверзев А. П. и др. Лекарственно-индуцированные заболевания: подходы к диагностике, коррекции и профилактике. Фармаконадзор. Фарматека. 2020;(6):113–26. doi:10.18565/pharmateca.2020.6.113-126Sychev DA, Ostroumova OD, Pereverzev AP, et al. Drug-induced diseases: approaches to diagnosis, correction and prevention. Pharmacovigilance. Farmateka. 2020;(6):113–26. (In Russ). doi:10.18565/pharmateca.2020.6.113-126Лекарственнo-индуцированные заболевания. Том I: монография / В. А. Дё, К. А. Загородникова, Д. В. Иващенко и др.; под науч. ред. Сычева Д. А., Остроумовой О. Д., Переверзева А. П. – М.: Прометей, 2022. – 540 с.Lekarstvenno-inducirovannye zabolevaniya. Tom I: monografiya / VA Dyo, KA Zagorodnikova, DV Ivashchenko, et al.; Ed. by Sychev DA, Ostroumova OD, Pereverzev AP. Moscow: Prometej, 2022. (In Russ).

The authors declare that there are no conflicts of interest present.