Cyclooxygenase: Physilogical Effects, Inhibitors Action and Perspectives of Paracetamol Usage
DOI:
https://doi.org/10.22141/2224-0586.5.76.2016.76430Keywords:
cyclooxygenase, prostaglandins, thromboxanes, inflammation, non-steroidal anti-inflammatory drugs, paracetamolAbstract
The analytical review presents current approaches to the peculiarities of functioning of the enzyme ofcyclooxygenase (COX), prostanoids functioning as well as the mechanisms of the action of non-steroidal anti-inflammatory drugs targeting at COX. The paper also drills down the features of pharmaceutical effects of paracetamol, the drug which is still widely used in modern medicine to arrest a pain syndrome and to overcome fever. The main benefits and drawbacks of paracetamol usage have been indicated. The review deals with the issue of hepatotoxicity, its necessary preventive measures and up-to-date scheme of treatment of patients with acute toxic hepatitis caused by paracetamol overdose.
References
Norregaard R. Physiology and pathophysiology of cyclooxygenase‑2 and prostaglandin E2 in the kidney / R. Norregaard, T.H. Kwon, J. Frokiaer // Kidney Research and Clinical Practice. — 2015. — Vol. 34. — P. 194-200.
Rouzer C.A. Cyclooxygenases: structural and functional insights / C.A. Rouzer, L.J. Marnett // Journal of Lipid Research. — 2008. — Vol. 50. — S. 29-34.
Simmons D.L. Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition / D.L. Simmons, R.M. Botting, T. Hla // Pharmacological Reviews. — 2004. — Vol. 56, № 3. — P. 387-487.
Zreik T.G. The Prostaglandins: Basic Chemistry and Action / T.G. Zreik, H.R. Behrman / Glowm; A Free Resource for Medical Professionals [електронний ресурс] Update due 2016 / Режим доступу: http://www.glowm.com/section_view/heading/The%20Prostaglandins:%20Basic%20Chemistry%20and%20Action/item/312
King M.W. Introduction to the Eicosanoids / M.W. King / The Medical Biochemistry Page [електронний ресурс] Last modified: May 6, 2016 / Режим доступу: http://themedicalbiochemistrypage.org/eicosanoids.php
Serhan C.N. Pro-resolving lipid mediators are leads for resolution physiology / C.N. Serhan // Nature. — 2014. — Vol. 510, Issue 7503. — P. 92-101.
Claria J. Cyclooxygenase‑2 biology / J. Claria // Current Pharmaceutical Design. — 2003. — Vol. 9, № 27. — P. 2177-2190.
Roles of Cyclooxygenase (COX)-1 and COX‑2 in Prostanoid Production by Human Endothelial Cells: Selective Up-Regulation of Prostacyclin Synthesis by COX‑2 / G.E. Caughey, L.G. Cleland, P.S. Penglis [et al.] // Journal of Immunology. — 2001. — Vol. 167. — P. 2831-2838.
Cyclooxygenase and NSAIDs / University at Albany; State University of New York [електронний ресурс] / Режим доступу: http://www.albany.edu/faculty/cs812/bio366/Cyclooxygenase_ppt.pdf
Griffin R.M. Are Anti-Inflammatory Pain Relievers Safe for You? Here's help weighing the benefits and risks of NSAIDs, from aspirin to Celebrex / R.M. Griffin / WebMD [електронний ресурс] Medically updated August 2006 / Режим доступу: http://www.webmd.com/osteoarthritis/features/are-nsaids-safe-for-you
Medication Guide for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) (See the end of this Medication Guide for a list of prescription NSAID/ Food & Drug AdministrationUSA [електронний ресурс] August 2007 / Режим доступу: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089162.pdf
Managing the Adverse Effects of Nonsteroidal Anti-inflammatory Drugs / P. Patrignani, S. Tacconelli, A. Bruno [et al.] // Expert Rev. Clin. Pharmacol. — 2011. — Vol. 4, № 5. — P. 605-621.
Ricciotti E. Prostaglandins and inflammation / E. Ricciotti, G.A. Fitzgerald // Arteriosclerosis, Thrombosis & Vascular Biology. — 2011. — Vol. 31, № 5. — P. 986-1000.
Anti-inflammatory effects of PGE2 in the lung: role of the EP4 receptor subtype / M.A. Birrell, S.A. Maher, B. Dekkak [et al.] // Thorax. — 2015. — Vol. 70, № 8. — P. 740-747.
Scher J.U. The anti-inflammatory effects of prostaglandins / J.U. Scher, M.H. Pillinger // Journal of Investigative Medicine. — 2009. — Vol. 57, № 6. — P. 703-708.
Non-Steroidal Anti-Inflammatory Drugs Comparison / eMed Expert [електронний ресурс] Last updated: April 01, 2016 / Режим доступу: http://www.emedexpert.com/compare/nsaids.shtml
Страчунский Л.С. Нестероидные противовоспалительные средства / Л.С. Страчунский, С.Н. Козлов / Смоленская государственная медицинская академия [електронний ресурс] / Режим доступу: http://www.antibiotic.ru/rus/all/metod/npvs/npvs.shtml
Cryer B. Cyclooxygenase‑1 and cyclooxygenase‑2 selectivity of widely used nonsteroidal anti-inflammatory drugs / B. Cryer, M. Feldman // American Journal of Medicine. — 1998. — Vol. 104, № 5. — P. 413-421.
Насонов Е.Л. Современное учение о селективных ингибиторах ЦОГ‑2: новые аспекты применения мелоксикама (Мовалиса) / Е.Л. Насонов // Научно-практическая ревматология. — 2003. — № 4 (68). — С. 87-91.
Solomon D.H. COX‑2 selective inhibitors: Adverse cardiovascular effects / D.H. Solomon / UpToDate [електронний ресурс] Literature review current through: May 2016 / Режим доступу: http://www.uptodate.com/contents/cox‑2-selective-inhibitors-adverse-cardiovascular-effects
Cardiovascularsafetyof non-steroidal anti-inflammatorydrugs: network meta-analysis / S. Trelle, S. Reichenbach, S. Wandel [et al.] // British Medical Journal. — 2011. — Vol. 342. — P. 7086.
Role of prostacyclin in the cardiovascular response to thromboxane A2 / Y. Cheng, S.C. Austin, B. Rocca [et al.] // Science. — 2002. — Vol. 296. — P. 539.
Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs and risk of stroke / M.D. Haag, M.J. Bos, A. Hofman [et al.] // Arch. Intern. Med. — 2008. — Vol. 168, № 11. — P. 1219-1224.
Nonaspirin NSAIDs, cyclooxygenase 2 inhibitors, and the risk for stroke / C.L. Roumie, E.F. Mitchel, L. Kaltenbach [et al] // Stroke. — 2008. — Vol. 39, № 7. — P. 2037-2045.
Non-aspirin NSAIDs, cyclooxygenase‑2 inhibitors and risk for cardiovascular events-stroke, acute myocardial infarction, and death from coronary heart disease / C.L. Roumie, N.N. Choma, L. Kaltenbach [et al.] // Pharmacoepidemiology & Drug Safety. — 2009. — Vol. 18, № 11. — P. 1053-1063.
Dajani E.Z. Cardiovascular and gastrointestinal toxicity of selective cyclo-oxygenase‑2 inhibitors in man / E.Z. Dayani, K. Islam // Journal of Physiology & Pharmacology. — 2008. — Vol. 59, Suppl. 2. — P. 117-133.
Risk of death or reinfarction associated with the use of selective cyclooxygenase‑2 inhibitors and nonselective nonsteroidalantiinflammatory drugs after acute myocardial infarction / G.H. Gislason, S. Jacobsen, J.N. Rasmussen [et al.] // Circulation. — 2006. — Vol. 113, № 25. — P. 2906-2913.
Daily aspirin therapy: Understand the benefits and risks / Diseases and Conditions. Heart disease / Mayo Clinic [електронний ресурс] Nov. 03, 2015 / Режим доступу: http://www.mayoclinic.org/diseases-conditions/heart-disease/in-depth/daily-aspirin-therapy/art‑20046797
Kama P.C.A. COX‑3: uncertainties and controversies / P.C.A. Kama, A. Sob // South African Journal of Regional Anaesthesia, Pain. — 2011. — № 1 / SAJRAP [електронний ресурс] / Режим доступу: http://www.edoc.co.za/modules.php?name = News&file = article&sid = 3349
COX‑3, a cyclooxygenase‑1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression / N. Chandrasekharan, H. Dai, K. Roos [et al.] // Proc. Nat. Acad. Sci. USA. — 2002. — Vol. 99, № 21. — P. 13926-13931.
Flower R.J. Inhibition of Prostaglandin Synthetase in Brain explains the Anti-pyretic Activity of Paracetamol (4-Acetamidophenol) / R.J. Flower, J.R. Vane // Nature. — 1972. — Vol. 240. — P. 410-411.
Botting R.M. Mechanism of action of acetaminophen: is there a cyclooxygenase 3? / R.M. Botting // Clin. Infect. Dis. — 2000. — Vol. 31, Suppl. 5. — S. 202-210.
Bovill J.G. Mechanisms of actions of opioids and non-steroidal anti-inflammatory drugs / J.G. Bovill // Eur. J. Anaesthesiol. — 1997. — P. 9-15.
Effect of aminophylline on aspirin penetration into the central nervous system in rats / V. Vasovic, B. Banic, V. Jakovljevic [et al.] // Eur. J. Drug. Metab. Pharmacokinet. — 2008. — Vol. 33. — P. 23-30.
Mannila A.H. Central Nervous System Permeation of Ibuprofen, Ketoprofen and Indomethacin. In Vivo and In Situ Studies in Rats and Clinical Trials in Children / Doctoral dissertation [електронний ресурс] 2009 / Faculty of Pharmacy of the University of Kuopio / Режим доступу: http://epublications.uef.fi/pub/urn_isbn_978-951-27-1147-5/urn_isbn_978-951-27-1147-5.pdf
How readily does ketorolac penetrate cerebrospinal fluid in children? / E. Kumpulainen, H. Kokki, M. Laisalmi [et al.] // J. Clin. Pharmacol. — 2008. — Vol. 48, № 4. — P. 495-501.
Acetaminophen distribution in the rat central nervous system / J.P. Courad, D. Besse, C. Delchambre [et al.] // Life Sci. — 2001. — Vol. 69. — P. 1455-1464.
Cerebrospinal fluid and plasma concentrations of dipyrone metabolites after a single oral dose of dipyrone / O. Cohen, E. Zylber-Katz, Y. Caraco [et al.] // Eur. J. Clin. Pharmacol. — 1998. — Vol. 54, № 7. — P. 549-553.
Bernareggi A. The pharmacokinetic profile of nimesulide in healthy volunteers / A. Bernareggi // Drugs. — 1993. — Vol. 46. — P. 64-72.
Botting R. COX‑3 and the mechanism of action of paracetamol / R. Botting, S. Ayoub // Prostaglandins Leukotrienes and Essential Fatty Acids. — 2005. — Vol. 72, № 2. — P. 85-87.
Graham G.G. Mechanism of action of paracetamol / G.G. Graham, K.F. Scott // Am. J. Ther. — 2005. — Vol. 12. — P. 46-55.
Kis B. Acetaminophen and the Cyclooxygenase‑3 Puzzle: Sorting out Facts, Fictions, and Uncertainties / B. Kis, J.A. Snipes, D.W. Busija // Journal of Pharmacology & Experimental Therapeutics. — 2005. — Vol. 315. — P. 1-7.
Sharma C.V. Paracetamol: mechanisms and updates / C.V. Sharma / Continuing Education in Anaesthesia, Critical Care & Pain (2013) [електронний ресурс] / Режим доступу: http://ceaccp.oxfordjournals.org/content/early/2013/10/10/bjaceaccp.mkt049.full
Mattia C. What anesthesiologists should know about paracetamol (acetaminophen) / C. Mattia, F. Coluzzi // Minerva Anestesiol. — 2009. — Vol. 75. — P. 644-653.
Jahr J.S. Intravenous acetaminophen: a review of pharmacoeconomic science for perioperative use / J.S. Jahr, P. Filocamo, S. Singh // Am. J. Ther. — 2013. — Vol. 20. — P. 189-199.
Onset of acetaminophen analgesia: comparison of oral and intravenous routes after third molar surgery / P.L. Moller, S. Sindet-Pedersen, C.T. Petersen [et al.] // British Journal of Anaesthesia. — 2005. — Vol. 94. — P. 642-648.
Smith H.S. Potential analgesic mechanism of acetaminophen / H.S. Smith // Pain Physician. — 2009. — Vol. 12. — P. 269-320.
Paracetamol: new vistas of an old drug / A. Bertolini, A. Ferrari, A. Ottani [et al.] // CNS Drug Rev. — 2006. — Vol. 12. — P. 250-275.
Пероксидаза / Лекции по ферментам / Joomla! Open Source Content Management [електронний ресурс] / Режим доступу: http://food-chem.ru/lektsii-po-fermentam/27-peroksidaza.html
Randomised comparison of intravenous paracetamol and intravenous morphine for acute traumatic limb pain in the emergency department / M. Craig, R. Jeavons, J. Probert [et al.] // Emerg. Med. J. — 2012. — Vol. 29. — P. 37-39.
Intravenous acetaminophen reduces postoperative nausea and vomitting: a systematic review and meta-analysis / C.C. Arfel, A. Turan, K. Souza [et al.] // Pain. — 2013. — Vol. 154. — P. 677-689.
Георгиянц М.А. Опыт использования внутривенного парацетамола после ортопедических оперативных вмешательств / М.А. Георгиянц, Н.И. Волошин, В.И. Кривобок // Травма. — 2012. — Т. 13, № 4. — С. 77-80.
Secoli S.R. Cost-effectiveness analysis of the analgesic therapy of postoperative pain / S.R. Secoli, K.G. Padilha, J. Litvoc // Revista Latino-Americana de Enfermagem. — 2008. — Vol. 16, № 1 / SciFLOBrasil [електронний ресурс] / Режим доступу: http://www.scielo.br/scielo.php?script = sci_arttext&pid = S0104-11692008000100007
O’Malley G.F. Acetaminophen Poisoning / G.F. O’Malley, R. O’Malley / Merck Manual. Professional Version [електронний ресурс] Last full review/revision May 2015 / Режим доступу: http://www.merckmanuals.com/professional/injuries-poisoning/poisoning/acetaminophen-poisoning
Lancaster E.M. Acetaminophen hepatotoxicity: an updated review / E.M. Lancaster, J.R. Hiatt, A. Zarrinpar // Arch. Toxicol. — 2015. — Vol. 89, Issue 2. — P. 193-199.
FDA Drug Safety Communication: Prescription Acetaminophen Products to be Limited to 325 mg Per Dosage Unit; Boxed Warning Will Highlight Potential for Severe Liver Failure / FDA, U.S. Food & Drug Administration [електронний ресурс] / Режим доступу: http://www.fda.gov/Drugs/DrugSafety/ucm239821.htm
Farrell S.E. AcetaminophenToxicity / S.E. Farrell / Medscape [електронний ресурс] Updated: May 18, 2016 / Режим доступу: http://emedicine.medscape.com/article/820200-overview
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