Около 90% всех заболеваний связано с болью. При болевых синдромах разной этиологии нестероидные противовоспалительные препараты (НПВП) относятся по уровню потребления к наиболее популярным лекарствам в мире. Кеторолак (Кеторол®) – это НПВП, доступный в парентеральной, таблетированной формах, а также в виде геля, который обладает мощным обезболивающим потенциалом, а его эффективность хорошо изучена для лечения умеренной и сильной боли во многих клинических ситуациях, подтвержденная в ряде исследований. Кеторолак относится к группе неселективных ингибиторов циклооксигеназы, производных гетероарильной уксусной кислоты. Нежелательные эффекты кеторолака сходны с таковыми при применении других НПВП. Клинически важные побочные эффекты включают желудочно-кишечные кровотечения, пептические язвы, почечную недостаточность, гематологическую дисфункцию, которые нивелируются при соблюдении дозировок и количестве дней приема (до 5 дней). Кеторолак обладает обезболивающей эффективностью, аналогичной морфину. Кеторолак эффективно применяется при некоторых неотложных состояниях, таких как приступ желчнокаменной болезни, мигрень, у пациентов с опиоидной зависимостью, серповидно-клеточным кризом и костно-мышечной болью.
Ключевые слова: кеторолак, механизм действия, нежелательные побочные явления, эффективность.
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About 90% of all diseases associated with pain. When pain syndromes of different etiologies nonsteroidal anti-inflammatory drugs (NSAIDs) are on the level of consumption of the most popular drugs in the world. Ketorolac (Ketorol) – NSAIDs is available in parenteral, tablet form, as well as in the form of a gel, which has a powerful analgesic potential and its effectiveness has been well studied for the treatment of moderate to severe pain in many clinical situations, confirmed in several studies. Ketorolac refers to a group of non-selective cyclooxygenase inhibitors, heteroaryl acetic acid derivatives. Adverse effects of ketorolac are similar to those when using other NSAIDs. Clinically important side effects include gastrointestinal bleeding, peptic ulcer, renal insufficiency, hematologic dysfunction, which are offset in compliance with the dosage and number of days of treatment (up to 5 days). Ketorolac has analgesic efficacy similar to morphine. Ketorolac is effectively used in some emergencies, such as an attack of gallstones, migraines, patients with opioid dependence, a crisis of sickle cell and musculoskeletal pain.
Key words: ketorolac, mechanism of action, unwanted side effects, effectiveness.
1. Алексеев В.В. Нестероидный противовоспалительный препарат кетопрофен в лечении неврогенных болевых синдромов. Справ. поликлин. врача. 2007; 5 (7): 23–5. / Alekseev V.V. Nesteroidnyi protivovospalitel'nyi preparat ketoprofen v lechenii nevrogennykh bolevykh sindromov. Sprav. poliklin. vracha. 2007; 5 (7): 23–5. [in Russian]
2. Котова О.В., Акарачкова Е.С. Острые болевые синдромы в неврологической практике. Эффективная фармакотерапия. 2014; 31: 40–5. / Kotova O.V., Akarachkova E.S.Ostrye bolevye sindromy v nevrologicheskoi praktike. Effektivnaia farmakoterapiia. 2014; 31: 40–5. [in Russian]
3. Pirmohamed M, James S, Meakin S et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004; 329: 15–8.
4. Котова О.В. Применение кеторолака при острых болевых синдромах. Фарматека. 2013; 13 (266): 41–4. / Kotova O.V. Primenenie ketorolaka pri ostrykh bolevykh sindromakh. Farmateka. 2013; 13 (266): 41–4. [in Russian]
5. Larkin GL, Peacock WF et al. Efficacy of ketorolac tromethamine versus meperidine in the ED treatment of acute renal colic. Am J Emerg Med 1999; 17 (1): 6–10.
6. Pérez-Urizar J, Granados-Soto V et al. Analgesic efficacy and bioavailability of ketorolac in postoperative pain: a probability analysis. Arch Med Res 2000; 31 (2): 191–6.
7. Barber FA, Gladu DE. Comparison of oral ketorolac and hydrocodone for pain relief after anterior cruciate ligament reconstruction. Arthroscopy 1998; 14 (6): 605–12.
8. Watcha MF, Jones MB, Lagueruela RG et al. Comparison of ketorolac and morphine as adjuvants during pediatric surgery. Anesthesiology1992; 76 (3): 368–72.
9. Dula DJ, Anderson R, Wood GC. A prospective study comparing i.m. ketorolac with i.m. meperidine in the treatment of acute biliary colic. J Emerg Med 2001; 20 (2): 121–4.
10. Henderson SO, Swadron S, Newton E. Comparison of intravenous ketorolac and meperidine in the treatment of biliary colic. J Emerg Med 2002; 23 (3): 237–41.
11. Mroszczak EJ, Jung D, Yee J et al. Ketorolac tromethamine pharmacokinetics and metabolism after intravenous, intramuscular, and oral administration in humans and animals. Pharmacotherapy 1990; 10 (Pt. 2): 33S–39S.
12. Boyer KC, McDonald P, Zoetis T. A novel formulation of ketorolac tromethamine for intranasal administration: preclinical safety evaluation. Int J Toxicol 2010; 29: 467–78.
13. Rooks WH II, Tomolonis AJ, Maloney PJ et al. The analgesic and anti-inflammatory profile of (+/−)-5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2a]pyrrole-1-carboxylic acid (RS-37619). Agents Actions 1982; 12 (5–6): 684–90.
14. Sotgiu ML, Biella G, Formaglio F, Marchettini P. Central effect of ketorolac involving NMDA receptors activity. Brain Res 1998; 813 (1): 223–6.
15. McAleer SD, Majid O, Venables E et al. Pharmacokinetics and safety of ketorolac following single intranasal and intramuscular administration in healthy volunteers. J Clin Pharmacol 2007; 47: 13–8.
16. Jung D, Mroszczak E, Bynum L. Pharmacokinetics of ketorolac tromethamine in humans after intravenous, intramuscular and oral administration. Eur J Clin Pharmacol 1988; 35: 423–5.
17. He A, Hersh EV. A review of intranasal ketorolac tromethamine for the short-term management of moderate to moderately severe pain that requires analgesia at the opioid level. Curr Med Res Opin 2012; 28: 1873–80.
18. Litvak KM, McEvoy GK. Ketorolac, an injectable nonnarcotic analgesic. Clin Pharm 1990; 9: 921–35.
19. Forrest JB, Camu F, Greer IA et al. Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery. Br J Anaesth 2002; 88: 227–33.
20. Singla N, Singla S, Minkowitz HS et al. Intranasal ketorolac for acute postoperative pain. Curr Med Res Opin 2010; 26: 1915–23.
21. Joishy SK, Walsh D. The opioid-sparing effects of intravenous ketorolac as an adjuvant analgesic in cancer pain: application in bone metastases and the opioid bowel syndrome. J Pain Symptom Manage 1998; 16: 334–9.
22. Brown CR, Mazzulla JP, Mok MS et al. Comparison of repeat doses of intramuscular ketorolac tromethamine and morphine sulfate for analgesia after major surgery. Pharmacotherapy 1990; 10 (Pt. 2): 45S–50S.
23. Gillis JC, Brogden RN. Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Drugs 1997; 53: 139–88.
24. Kenny GN, McArdle CS, Aitken HH. Parenteral ketorolac: opiate-sparing effect and lack of cardiorespiratory depression in the perioperative patient. Pharmacotherapy 1990; 10 (Pt. 2): 127S–131S.
25. Grimsby GM, Conley SP, Trentman TL et al. A double-blind randomized controlled trial of continuous intravenous Ketorolac vs. placebo for adjuvant pain control after renal surgery. Mayo Clin Proc 2012; 87: 1089–97.
26. Yee MK, Evans WD, Facey PE et al. Gastric emptying and small bowel transit in male volunteers after i.m. ketorolac and morphine. Br J Anaesth 1991; 67: 426–31.
27. Eriksson H, Tenhunen A, Korttila K. Balanced analgesia improves recovery and outcome after outpatient tubal ligation. Acta Anaesthesiol Scand 1996; 40: 151–5.
28. Smith LA, Carroll D, Edwards JE et al. Single-dose ketorolac and pethidine in acute postoperative pain: systematic review with meta-analysis. Br J Anaesth 2000; 84: 48–58.
29. Taggart E, Doran S, Kokotillo A et al. Ketorolac in the treatment of acute migraine: a systematic review. Headache 2013; 53: 277–87.
30. Olsen JC, McGrath NA, Schwarz DG et al. A double-blind randomized clinical trial evaluating the analgesic efficacy of ketorolac versus butorphanol for patients with suspected biliary colic in the emergency department. Acad Emerg Med 2008; 15: 718–22.
31. Котова О.В. Опыт применения кеторолака в терапии острой боли. Фарматека. 2012; 9 (242): 52–5. / Kotova O.V. Opyt primeneniia ketorolaka v terapii ostroi boli. Farmateka. 2012; 9 (242): 52–5. [in Russian]
32. Vadivelu N, Gowda AM, Urman RD et al. Ketorolac tromethamine – routes and clinical implications. Pain Pract 2015; 15 (2): 175–93. Doi: 10.1111/papr.12198. Epub 2014 Apr 16.
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1. Alekseev V.V. Nesteroidnyi protivovospalitel'nyi preparat ketoprofen v lechenii nevrogennykh bolevykh sindromov. Sprav. poliklin. vracha. 2007; 5 (7): 23–5. [in Russian]
2. Kotova O.V., Akarachkova E.S.Ostrye bolevye sindromy v nevrologicheskoi praktike. Effektivnaia farmakoterapiia. 2014; 31: 40–5. [in Russian]
3. Pirmohamed M, James S, Meakin S et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004; 329: 15–8.
4. Kotova O.V. Primenenie ketorolaka pri ostrykh bolevykh sindromakh. Farmateka. 2013; 13 (266): 41–4. [in Russian]
5. Larkin GL, Peacock WF et al. Efficacy of ketorolac tromethamine versus meperidine in the ED treatment of acute renal colic. Am J Emerg Med 1999; 17 (1): 6–10.
6. Pérez-Urizar J, Granados-Soto V et al. Analgesic efficacy and bioavailability of ketorolac in postoperative pain: a probability analysis. Arch Med Res 2000; 31 (2): 191–6.
7. Barber FA, Gladu DE. Comparison of oral ketorolac and hydrocodone for pain relief after anterior cruciate ligament reconstruction. Arthroscopy 1998; 14 (6): 605–12.
8. Watcha MF, Jones MB, Lagueruela RG et al. Comparison of ketorolac and morphine as adjuvants during pediatric surgery. Anesthesiology1992; 76 (3): 368–72.
9. Dula DJ, Anderson R, Wood GC. A prospective study comparing i.m. ketorolac with i.m. meperidine in the treatment of acute biliary colic. J Emerg Med 2001; 20 (2): 121–4.
10. Henderson SO, Swadron S, Newton E. Comparison of intravenous ketorolac and meperidine in the treatment of biliary colic. J Emerg Med 2002; 23 (3): 237–41.
11. Mroszczak EJ, Jung D, Yee J et al. Ketorolac tromethamine pharmacokinetics and metabolism after intravenous, intramuscular, and oral administration in humans and animals. Pharmacotherapy 1990; 10 (Pt. 2): 33S–39S.
12. Boyer KC, McDonald P, Zoetis T. A novel formulation of ketorolac tromethamine for intranasal administration: preclinical safety evaluation. Int J Toxicol 2010; 29: 467–78.
13. Rooks WH II, Tomolonis AJ, Maloney PJ et al. The analgesic and anti-inflammatory profile of (+/−)-5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2a]pyrrole-1-carboxylic acid (RS-37619). Agents Actions 1982; 12 (5–6): 684–90.
14. Sotgiu ML, Biella G, Formaglio F, Marchettini P. Central effect of ketorolac involving NMDA receptors activity. Brain Res 1998; 813 (1): 223–6.
15. McAleer SD, Majid O, Venables E et al. Pharmacokinetics and safety of ketorolac following single intranasal and intramuscular administration in healthy volunteers. J Clin Pharmacol 2007; 47: 13–8.
16. Jung D, Mroszczak E, Bynum L. Pharmacokinetics of ketorolac tromethamine in humans after intravenous, intramuscular and oral administration. Eur J Clin Pharmacol 1988; 35: 423–5.
17. He A, Hersh EV. A review of intranasal ketorolac tromethamine for the short-term management of moderate to moderately severe pain that requires analgesia at the opioid level. Curr Med Res Opin 2012; 28: 1873–80.
18. Litvak KM, McEvoy GK. Ketorolac, an injectable nonnarcotic analgesic. Clin Pharm 1990; 9: 921–35.
19. Forrest JB, Camu F, Greer IA et al. Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery. Br J Anaesth 2002; 88: 227–33.
20. Singla N, Singla S, Minkowitz HS et al. Intranasal ketorolac for acute postoperative pain. Curr Med Res Opin 2010; 26: 1915–23.
21. Joishy SK, Walsh D. The opioid-sparing effects of intravenous ketorolac as an adjuvant analgesic in cancer pain: application in bone metastases and the opioid bowel syndrome. J Pain Symptom Manage 1998; 16: 334–9.
22. Brown CR, Mazzulla JP, Mok MS et al. Comparison of repeat doses of intramuscular ketorolac tromethamine and morphine sulfate for analgesia after major surgery. Pharmacotherapy 1990; 10 (Pt. 2): 45S–50S.
23. Gillis JC, Brogden RN. Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Drugs 1997; 53: 139–88.
24. Kenny GN, McArdle CS, Aitken HH. Parenteral ketorolac: opiate-sparing effect and lack of cardiorespiratory depression in the perioperative patient. Pharmacotherapy 1990; 10 (Pt. 2): 127S–131S.
25. Grimsby GM, Conley SP, Trentman TL et al. A double-blind randomized controlled trial of continuous intravenous Ketorolac vs. placebo for adjuvant pain control after renal surgery. Mayo Clin Proc 2012; 87: 1089–97.
26. Yee MK, Evans WD, Facey PE et al. Gastric emptying and small bowel transit in male volunteers after i.m. ketorolac and morphine. Br J Anaesth 1991; 67: 426–31.
27. Eriksson H, Tenhunen A, Korttila K. Balanced analgesia improves recovery and outcome after outpatient tubal ligation. Acta Anaesthesiol Scand 1996; 40: 151–5.
28. Smith LA, Carroll D, Edwards JE et al. Single-dose ketorolac and pethidine in acute postoperative pain: systematic review with meta-analysis. Br J Anaesth 2000; 84: 48–58.
29. Taggart E, Doran S, Kokotillo A et al. Ketorolac in the treatment of acute migraine: a systematic review. Headache 2013; 53: 277–87.
30. Olsen JC, McGrath NA, Schwarz DG et al. A double-blind randomized clinical trial evaluating the analgesic efficacy of ketorolac versus butorphanol for patients with suspected biliary colic in the emergency department. Acad Emerg Med 2008; 15: 718–22.
31. Котова О.В. Опыт применения кеторолака в терапии острой боли. Фарматека. 2012; 9 (242): 52–5. / Kotova O.V. Opyt primeneniia ketorolaka v terapii ostroi boli. Farmateka. 2012; 9 (242): 52–5. [in Russian]
32. Vadivelu N, Gowda AM, Urman RD et al. Ketorolac tromethamine – routes and clinical implications. Pain Pract 2015; 15 (2): 175–93. Doi: 10.1111/papr.12198. Epub 2014 Apr 16.
Авторы
О.В.Котова*, Е.С.Акарачкова
ГБОУ ВПО Первый Московский государственный медицинский университет им. И.М.Сеченова Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 1
*ol_kotova@mail.ru
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O.V.Kotova*, E.S.Akarachkova
I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 119991, Russian Federation, Moscow, ul. Trubetskaia d. 8, str. 1
*ol_kotova@mail.ru