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Indomethacin: Can It Counteract Bradykinin Effects in COVID-19 Patients?

Alkotaji et al., Current Pharmacology Reports, doi:10.1007/s40495-021-00257-6
Apr 2021  
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Hypothesis that indomethacin will be beneficial for COVID-19 induced dry cough, via inhibition of the cyclooxygenase enzyme and reducing the level of inflammatory mediator bradykinin.
Alkotaji et al., 22 Apr 2021, peer-reviewed, 2 authors. Contact: radhwan.alzidan@uomosul.edu.iq.
This PaperIndomethacinAll
Indomethacin: Can It Counteract Bradykinin Effects in COVID-19 Patients?
Myasar Alkotaji, Radhwan N Al-Zidan
Current Pharmacology Reports, doi:10.1007/s40495-021-00257-6
COVID-19 represents the biggest health challenge. Although the mortality rate of COVID-19 is low, the high numbers of infected people and those with post-COVID-19 symptoms represent a real problem for the health system. A high number of patients with COVID-19 or people recovered from COVID-19 suffer from a dry cough and/or myalgia. Interestingly, an imbalance in bradykinin was observed in COVID-19 patients, which might be due to the accumulation of bradykinin as a result of a reduction in the degradation of bradykinin. This finding inspired the idea of possible similitude between the dry cough that is induced by angiotensin-converting enzyme inhibitors and the COVID-19-induced dry cough. Both of these types of cough are mediated, at least partially, by bradykinin. They both manifested as a persistent dry cough that is not responded to traditional dry cough remedies. However, several drugs were previously investigated for the treatment of angiotensin-converting enzyme inhibitor-induced dry cough. Here, we hypothesized that such treatment might be useful in COVID-19-induced dry cough and other bradykinin-related symptoms such as generalized pain and myalgia. In this article, evidence was presented to support the use of indomethacin as a potential treatment of COVID-19-induced dry cough. The choice of indomethacin was based on its ability to suppress the cyclooxygenase enzyme while also lowering the level of the inflammatory mediator bradykinin. Furthermore, indomethacin has been shown to be effective in treating angiotensin-converting enzyme inhibitor-induced dry cough. Moreover, indomethacin is a long-established, low-cost, effective, and readily available medication.
Declarations Ethics Approval and Consent to Participate Not applicable. Consent for Publication Not applicable. Conflict of Interest The authors declare that there is no conflict of interest.
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' '2019;20(1):1–15.', 'journal-title': 'Respir Res'}, { 'issue': '4', 'key': '257_CR34', 'doi-asserted-by': 'publisher', 'first-page': '212', 'DOI': '10.1159/000196201', 'volume': '60', 'author': 'M Cazzola', 'year': '1993', 'unstructured': 'Cazzola M, Matera MG, Liccardi G, De Prisco F, D’Amato G, Rossi F. ' 'Theophylline in the inhibition of angiotensin-converting enzyme ' 'inhibitor-induced cough. Respiration. 1993;60(4):212–5.', 'journal-title': 'Respiration.'}, { 'issue': '8941', 'key': '257_CR35', 'doi-asserted-by': 'publisher', 'first-page': '13', 'DOI': '10.1016/S0140-6736(95)91151-0', 'volume': '345', 'author': 'M Hargreaves', 'year': '1995', 'unstructured': 'Hargreaves M, Benson M. Inhaled sodium cromoglycate in ' 'angiotensin-converting enzyme inhibitor cough. Lancet. ' '1995;345(8941):13–6.', 'journal-title': 'Lancet'}, { 'issue': '3', 'key': '257_CR36', 'doi-asserted-by': 'publisher', 'first-page': '121', 'DOI': '10.1016/S0011-393X(00)88520-3', 'volume': '60', 'author': 'R Fogari', 'year': '1999', 'unstructured': 'Fogari R, Zoppi A, Mugellini A, Preti P, Banderali A, Salvetti A. ' 'Effects of amlodipine, nifedipine GITS, and indomethacin on ' 'angiotensin-converting enzyme inhibitor-induced cough: a randomized, ' 'placebo-controlled, double-masked, crossover study. Curr Ther Res. ' '1999;60(3):121–8.', 'journal-title': 'Curr Ther Res'}, { 'issue': '1', 'key': '257_CR37', 'first-page': '161', 'volume': '255', 'author': 'JR McEWAN', 'year': '1990', 'unstructured': 'McEWAN JR, Choudry NB, Fuller RW. The effect of sulindac on the abnormal ' 'cough reflex associated with dry cough. J Pharmacol Exp Ther. ' '1990;255(1):161–4.', 'journal-title': 'J Pharmacol Exp Ther'}, { 'issue': '7', 'key': '257_CR38', 'doi-asserted-by': 'publisher', 'first-page': '776', 'DOI': '10.1016/S0895-7061(00)00268-5', 'volume': '13', 'author': 'A Tenenbaum', 'year': '2000', 'unstructured': 'Tenenbaum A, Grossman E, Shemesh J, Fisman EZ, Nosrati I, Motro M. ' 'Intermediate but not low doses of aspirin can suppress ' 'angiotensin-converting enzyme inhibitor-induced cough. Am J Hypertens. ' '2000;13(7):776–82.', 'journal-title': 'Am J Hypertens'}, { 'issue': '2', 'key': '257_CR39', 'doi-asserted-by': 'publisher', 'first-page': '166', 'DOI': '10.1161/01.HYP.38.2.166', 'volume': '38', 'author': 'S-C Lee', 'year': '2001', 'unstructured': 'Lee S-C, Park SW, Kim D-K, Lee SH, Hong KP. Iron supplementation ' 'inhibits cough associated with ACE inhibitors. Hypertension. 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Scand J Gastroenterol. 2000;35(9):957–9.', 'journal-title': 'Scand J Gastroenterol'}, { 'issue': '9', 'key': '257_CR45', 'doi-asserted-by': 'publisher', 'first-page': '1391', 'DOI': '10.1111/cmi.12446', 'volume': '17', 'author': 'C Amici', 'year': '2015', 'unstructured': 'Amici C, La Frazia S, Brunelli C, Balsamo M, Angelini M, Santoro MG. ' 'Inhibition of viral protein translation by indomethacin in vesicular ' 'stomatitis virus infection: role of eif2α kinase PKR. Cell Microbiol. ' '2015;17(9):1391–404.', 'journal-title': 'Cell Microbiol'}, { 'issue': '2', 'key': '257_CR46', 'doi-asserted-by': 'publisher', 'first-page': '436', 'DOI': '10.1111/head.12769', 'volume': '56', 'author': 'S Lucas', 'year': '2016', 'unstructured': 'Lucas S. The pharmacology of indomethacin. Headache Head Face Pain. ' '2016;56(2):436–46.', 'journal-title': 'Headache Head Face Pain'}, { 'issue': '6', 'key': '257_CR47', 'doi-asserted-by': 'publisher', 'first-page': '219', 'DOI': '10.22270/jddt.v10i6.4383', 'volume': '10', 'author': 'RN Al-Zidan', 'year': '2020', 'unstructured': 'Al-Zidan RN. Potential drug-drug and drug-disease interactions of ' 'selected experimental therapies used in treating COVID-19 patients. J ' 'Drug Deliv Ther. 2020;10(6):219–30.', 'journal-title': 'J Drug Deliv Ther'}, { 'issue': '7', 'key': '257_CR48', 'doi-asserted-by': 'publisher', 'first-page': '2291', 'DOI': '10.3390/ph3072291', 'volume': '3', 'author': 'WH Hörl', 'year': '2010', 'unstructured': 'Hörl WH. Nonsteroidal anti-inflammatory drugs and the kidney. 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