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Hepatotoksik Antibiyotikler

Yıl 2015, Cilt: 8 Sayı: 1, 65 - 73, 01.06.2015

Öz

Tedavi sırasında ilacın en önemli yan etkilerinden biri karaciğer hasarıdır. Karaciğer, birçok ilaç ve değişik ajanların metabolizmasından sorumludur. İlaçların çoğu, intestinal emilimi kolaylaştıracak şekilde lipofilik yapıya sahiptir. İlaç, karaciğerde biyotransformasyon olarak bilinen, enzim sistemi aracılığıyla olan biyokimyasal olaylar ile safra ve idrardan atılımlarını mümkün kılan hidrofilik yapı kazanır. Biyotransformasyondan sorumlu ana organ olması karaciğeri aynı zamanda ilaç toksisitesinin hedefi haline getirir. Piyasada bulunan içlerinde çocuk ve yaşlı hastalarda da sıklıkla kullanılan antibiyotiklerin hepatotoksisite açısından önemli bir risk faktörü olduğu gözlenmiştir. Bu tür ilaçlar kullanılırken bu tehlike göz önünde bulundurulmalıdır. Enzim sisteminin genetik polimorfizmi, yaş cinsiyet farklılıkları, enfeksiyonlar, eşlik eden karaciğer hastalıkları ve birlikte kullanılan ilaçlar gibi nedenlerle aynı ilaca, eşit farmakolojik dozda verilmesine rağmen, kişiler farklı reaksiyon verebilirler. Karaciğer hasarı varlığında ise tedavide eliminasyonu öncelikle renal sistem üzerinden değişmemiş ilaç olarak yapılan antibiyotikler tercih edilmeli ve doz ayarlaması iyi yapılmalıdır.

Kaynakça

  • Aapro MS, Martin C, Hatty S. Gemcitabine a safety review. Anticancer Drugs. 1998; 9: 191-201.
  • Aviles A, Herrera J, Ramos E. Hepatic injury during doxorubicin therapy. Arch Pathol Lab Med. 1984; 108: 912-913.
  • Aygün C, Kocaman O, Gürbüz Y, Şentürk Ö, Hülagü S. Clindamycin-induced acute cholestatic hepatitis. World J. Gastroenterol. 2007; 13(40): 5408-5410
  • Bakır M. Antimikobakteriyel ilaçlar. Infeksiyon Hastalıkları, Ed: Willke A, Söyletir G, Doğanay M, : Nobel Tıp Kitapevi, Ankara, 1996, pp.203-208.
  • Bergan T. Overview of acylureidopenicillin pharmacokinetics. Scandinavian Journal of Infectious Diseases. 1981; 29: 33-48.
  • Bouderaux JP, Hayes DH, Mizrahi S, Hussey S, Rengenstein F, Balart L. Fulminant hepatic failure, hepatorenal syndrome, and necrositing Pancreatitis after mynocycline hepatotoxicity. Tranplantation proceedings. 1993; 25(2): 1873.
  • Brown JH Kennedy BJ. Mithramycin in the treatment of disseminated testicular neoplasms. N Engl J Med. 1965; 272:.111-118.
  • Bullpit D, Potter CE, Jaderberg M. A lange scale generalpractice based investigation into clinical efficacy and tolerability of cefuroxime axetil in women with uncomplicated urinary tract infection. Curr Med Res. Opin. 1991; 12(5): 328-324.
  • Clay KD, Hanson JS, Pope SD, Rissmiller RW, Purdum PP, Banks PM. Brief communication:severe hepatotoxicity of telithromycin: three case reports and literature review. Ann Intern Med. 2006; 21: 144.
  • Cochet B, Belaieff J, Allaz F, Rudhart M, Bahant L. Serum levels and urinary excretion of cefoperazone in patients with hepatic insufficiency. Infection. 1981; 9 (suppl 1): 37-39.
  • Danan G, Mentay G, Cunci R, Erlinger S. Pefloxacin kinetics in cirrhosis. Clnical Pharmacology and Therapeutics 1983; 38: 439-442.
  • Davey PG. Pharmacokinetics in liver disease. J Antimicrob Chemother. 1998; 21(1): 1-8.
  • Derby LE, Jick H, Henry DA, Dean FD. Erytromycin-associated cholestatic hepatitis. The Medical Journal of Australia. 1993; 158: 600-603.
  • Farrell GC. Drug-Induced Liver Disease. New York: Churchill Livingstone, 1994, pp.20-34.
  • Fekety FR. (1990) Safety of parenteral third generation cephalosporins. American Journal of Medicine (suppl 4A ): 38-44.
  • Gabriel LP. Toxic Response of liver in Caserett and Doull’s Toxicology. Ed; Klassen CD, Amdur MO and Doull J, Third edition, Macmilan Publishing Company, New York, 1986, p:286-309.
  • Gönlügür U, Akkurt İ. Rifampisin ve Hepatotoksisite. İzmir göğüs hastanesi dergisi. 2003; 17: 45.
  • Jick J, Derby LE. A large population-based flow–up study of trimetoprim- sulphametoxazole , trimetoprim, and cephalexin for uncommon serious drug toxicity. Pharmacotherpy. 1995; 15(4): 4278-432.
  • Kandemir Ö, Kaya A. Hepatik ve renal yetmezlikte antibiyotik kullanımı. Klimik dergisi. 2000; 13: 3-7.
  • Kennedy BJ. Metabolic and toxic effects of mithramycin during tumor therapy. Am J Med. 1970; 49: 494-503.
  • Khuroo MS, Rustgi VK, Dawson GJ, Mushahwar TK, Yattoo GN, Kamili S, Khan BA. Spectrum of hepatitis E virus infection in India. J Med Virol. 1994; 43: 281-286.
  • Lav AH, Evans R, Chang CW, Selijsohn R. Pharmacokinetics of metronidazole in patients with alkolic liver disease. Antimicrobial Agents and Chemotherapy. 1987; 31: 1662-1664.
  • Leblebicioğlu H. Telitromisinin mikrobiyolojik etkinliği. Flora. 2003; 8(3):3-8.
  • Lienart F, Morissens M, Jacops P, Duccobu J. Doxycycline and hepatotoxicty. Acta Clinica Belgica. 1992; 47(3):205-208.
  • Lingren A, Olson R. Liver reactions from trimetoprim. Journal of internal medicine. 1994; 236: 281-284.
  • Maddrey WC, Boitrott JK. Drug induced chronic liver diseases. Gastroenterology. 1977; 72: 1348-53.
  • Madrey WC. Drug and chemical induced hepatic injury. Bockus Gastroenterology. Fourth 73
  • Edition, Ed; Berk JE, WB. Philadelphia: WB Saunders Company, 1985, pp: 2922-2951.
  • Mayama T, Koyama Y, Sebata K, Tanaka Y, Shirai S, Sakai H. Postmarketing surveillance on side effects of cefminox sodium. İnt. J. Clin. Pharmacol. Ther. 1995; 33(3). 149-155.
  • Meredith MJ, Reed DJ. Depletion in vitro of mitochondrial glutathione in rat hepatocytes and enhancement of lipid peroxidation by Adriamycin and 1,3 chloroethyl-nitrosurea(BCNU). Biochem Pharmacol. 1983; 32: 1383-1388.
  • Munoz SJ, Hernandez AM, Maddrey WC. İntrahepatic cholestatisis and phospholipidozis associated with the use of tirimethoprim-sulfhamethoxazole. Hepatology. 1990; 12: 342-347.
  • Olsson R, Wiholm BE, Sand C, Zettergen L, Hultcrsntz R, Myrhed M. Liver damage from cloxacillin flucloxacillin and dicloxaxillin. J. Hepatol. 1992; 15(1-2): 154-156.
  • Pieron R, Marien C, Jagueux M. Jaundice et rifampicin. Sem Hop.1971; 47: 1286-95.
  • Robert H, Alford H. Antimycobacterial Agents, Principles and Practice of Infectious Diseases, Ed; Gerald L. Mandell, R. Gordon Douglas, John E. Bennet, Churchill Livingstone, New York, Edinburg, London, Melbourne, 1990, pp.350-354.
  • Roger M, Des Prez Cralıs R. Mycobacterium Tuberculosis. Principles and Practice of ınfectious Diseases, Ed; Gerald L. Mandell, R. Gordon Douglas, John E. Bennet, Churchill Livingstone, New York, Edinburg, London, Melbourne: 1990, pp.1890.
  • Rolando N, Wyke RJ. İnfections. Gut. 1991; Suplement:25-28.
  • Ryan J, Dudley FJ. Cholestazis with ticarsillin-pottasium clavulanate (Timentin). The Medical Journal of Australia. 1992; 156:291.
  • Ryback MJ, Albrecht LM, Boike SC, Chandrasekar PH. Nefrotoxicity of vancomycin, alone and with aminoglycoside. Journal of Antimicrobial Chemotherapy. 1990; 25: 679-687.
  • Ryley NG, Fleming KA, Chapman, RW.Focal destructive colangiopathy associated with amoxycillin-clavulanic acid (Augmentin). J. Hepatol. 1995; 23(3): 278-282.
  • Sgro C, Clinard F, Ouazir K. Incidence of drug-induced hepatic injuries: A French population-based study. Hepatology. 2002; 36: 451–5.
  • Sivapalasingam S, Steigbigel NH. Macrolides, clindamycin, and ketolides, Principles and Practice of Infectious Disease, Eds; “Mandell GL, Bennett JE, Dolin R, Elsevier Inc, New York, 2005, pp.396-417.
  • Smith PM, Wilton A, Routledge PA. Jaundice associated with amoxicillin-clavulanate potassium therapy. Eur J Gastroenterol Hepatol. 1991; 3: 95-96.
  • Ulutan F. Karaciğer hastalarında antimikrobiyal ilaçların kullanımı, Antimikrobiyal Kemoterapi -Klinik Uygulamalar ve Yenilikler, Ed; Meço O, Türk Miktrobiyoloji Cemiyeti Yayınları, Ankara. 1992. pp.27.
  • Umstead GS, Neumann KH. Erythromycin ototoxcity and acute psychotic reaction in cancer patients with hepatic dysfunction. Archieves of Internal Medicine1986; 146: 897-899.
  • Vasko AJM, Ligia M, Rui, MM. Lymphocyte reactivity to ex-vivo drug antigens in drug induced hepatitis. J. Hepatol 1994; 21:151-158.
  • Vial,T., Biour, M., Descotes, j, Trepo, C. Antibiotic-associated hepatitis: Update 1990. The Annals of Pharmacotheraphy. 1997; 31: 204-220.
  • Williams R. New directions in acute liver failure. J R Coll Physicians Lond. 1994; 28: 552-559.
  • Willke A, Çokca F. Linkozamidler. Infeksiyon Hastalıkları, Ed; Willke A, Söyletir G, Doğanay M, Nobel Tıp Kitapevi, Ankara, 1996, pp.178-180.
  • Willke A. Diğer Beta Laktamlar. Infeksiyon hastalıkları,.Ed: Willke A, Söyletir G, Doğanay M, Nobel Tıp Kitapevi, Ankara, 1996, pp.141-143.
  • Wilson WR, Cockerill FR. Tetracyclines, chloramphenicol, eritromycin, and clindamisin. Mayo. Clin. Proc. 1987; 62: 906-915.
  • Yazar E, Traş B. Hepatotoksik Antibiyotikler. Türk Veteriner Hekimliği Dergisi. 2000; 12:128.
  • Zimmerman HT, Maddrey WC. Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: Analysis of instances of therapeutic misadventure. Hepatology. 1998; 22: 767-773

Hepatotoxic Antibiotics

Yıl 2015, Cilt: 8 Sayı: 1, 65 - 73, 01.06.2015

Öz

Drug induced hepatotoxicity is one of the most important side effects in treatment. Liver is responsible for metabolism of many drugs and xenobiotics. Most drugs are lipophilic, enabling them to cross the membranes of intestinal cells. They gain a hydropylic structure through steps known as biotransformation by many enzyme systems in the liver. These transactions yields water soluble molecules and these are easily secreted in the urine or bile. Being the main organ of biotransformation, the liver is also the target organ for drug toxicity. The most handlig antibiotics in pediatric and geriatric clinical use are a big risc factor on hepatotoxiciy. Clinicians must be careful when using these antibiotics. Due to genetic polimorfizm of enzyme system, age, gender differences, infections, coexisting liver pathology and coadministered agents, different individuals exhibit different reactions to the same drug although given the same pharmacological doses. When liver injury exists, in the treatment the antibiyotics whose elimination has not been altered trough renal system should be chosen and the dose regulation should be done well.

Kaynakça

  • Aapro MS, Martin C, Hatty S. Gemcitabine a safety review. Anticancer Drugs. 1998; 9: 191-201.
  • Aviles A, Herrera J, Ramos E. Hepatic injury during doxorubicin therapy. Arch Pathol Lab Med. 1984; 108: 912-913.
  • Aygün C, Kocaman O, Gürbüz Y, Şentürk Ö, Hülagü S. Clindamycin-induced acute cholestatic hepatitis. World J. Gastroenterol. 2007; 13(40): 5408-5410
  • Bakır M. Antimikobakteriyel ilaçlar. Infeksiyon Hastalıkları, Ed: Willke A, Söyletir G, Doğanay M, : Nobel Tıp Kitapevi, Ankara, 1996, pp.203-208.
  • Bergan T. Overview of acylureidopenicillin pharmacokinetics. Scandinavian Journal of Infectious Diseases. 1981; 29: 33-48.
  • Bouderaux JP, Hayes DH, Mizrahi S, Hussey S, Rengenstein F, Balart L. Fulminant hepatic failure, hepatorenal syndrome, and necrositing Pancreatitis after mynocycline hepatotoxicity. Tranplantation proceedings. 1993; 25(2): 1873.
  • Brown JH Kennedy BJ. Mithramycin in the treatment of disseminated testicular neoplasms. N Engl J Med. 1965; 272:.111-118.
  • Bullpit D, Potter CE, Jaderberg M. A lange scale generalpractice based investigation into clinical efficacy and tolerability of cefuroxime axetil in women with uncomplicated urinary tract infection. Curr Med Res. Opin. 1991; 12(5): 328-324.
  • Clay KD, Hanson JS, Pope SD, Rissmiller RW, Purdum PP, Banks PM. Brief communication:severe hepatotoxicity of telithromycin: three case reports and literature review. Ann Intern Med. 2006; 21: 144.
  • Cochet B, Belaieff J, Allaz F, Rudhart M, Bahant L. Serum levels and urinary excretion of cefoperazone in patients with hepatic insufficiency. Infection. 1981; 9 (suppl 1): 37-39.
  • Danan G, Mentay G, Cunci R, Erlinger S. Pefloxacin kinetics in cirrhosis. Clnical Pharmacology and Therapeutics 1983; 38: 439-442.
  • Davey PG. Pharmacokinetics in liver disease. J Antimicrob Chemother. 1998; 21(1): 1-8.
  • Derby LE, Jick H, Henry DA, Dean FD. Erytromycin-associated cholestatic hepatitis. The Medical Journal of Australia. 1993; 158: 600-603.
  • Farrell GC. Drug-Induced Liver Disease. New York: Churchill Livingstone, 1994, pp.20-34.
  • Fekety FR. (1990) Safety of parenteral third generation cephalosporins. American Journal of Medicine (suppl 4A ): 38-44.
  • Gabriel LP. Toxic Response of liver in Caserett and Doull’s Toxicology. Ed; Klassen CD, Amdur MO and Doull J, Third edition, Macmilan Publishing Company, New York, 1986, p:286-309.
  • Gönlügür U, Akkurt İ. Rifampisin ve Hepatotoksisite. İzmir göğüs hastanesi dergisi. 2003; 17: 45.
  • Jick J, Derby LE. A large population-based flow–up study of trimetoprim- sulphametoxazole , trimetoprim, and cephalexin for uncommon serious drug toxicity. Pharmacotherpy. 1995; 15(4): 4278-432.
  • Kandemir Ö, Kaya A. Hepatik ve renal yetmezlikte antibiyotik kullanımı. Klimik dergisi. 2000; 13: 3-7.
  • Kennedy BJ. Metabolic and toxic effects of mithramycin during tumor therapy. Am J Med. 1970; 49: 494-503.
  • Khuroo MS, Rustgi VK, Dawson GJ, Mushahwar TK, Yattoo GN, Kamili S, Khan BA. Spectrum of hepatitis E virus infection in India. J Med Virol. 1994; 43: 281-286.
  • Lav AH, Evans R, Chang CW, Selijsohn R. Pharmacokinetics of metronidazole in patients with alkolic liver disease. Antimicrobial Agents and Chemotherapy. 1987; 31: 1662-1664.
  • Leblebicioğlu H. Telitromisinin mikrobiyolojik etkinliği. Flora. 2003; 8(3):3-8.
  • Lienart F, Morissens M, Jacops P, Duccobu J. Doxycycline and hepatotoxicty. Acta Clinica Belgica. 1992; 47(3):205-208.
  • Lingren A, Olson R. Liver reactions from trimetoprim. Journal of internal medicine. 1994; 236: 281-284.
  • Maddrey WC, Boitrott JK. Drug induced chronic liver diseases. Gastroenterology. 1977; 72: 1348-53.
  • Madrey WC. Drug and chemical induced hepatic injury. Bockus Gastroenterology. Fourth 73
  • Edition, Ed; Berk JE, WB. Philadelphia: WB Saunders Company, 1985, pp: 2922-2951.
  • Mayama T, Koyama Y, Sebata K, Tanaka Y, Shirai S, Sakai H. Postmarketing surveillance on side effects of cefminox sodium. İnt. J. Clin. Pharmacol. Ther. 1995; 33(3). 149-155.
  • Meredith MJ, Reed DJ. Depletion in vitro of mitochondrial glutathione in rat hepatocytes and enhancement of lipid peroxidation by Adriamycin and 1,3 chloroethyl-nitrosurea(BCNU). Biochem Pharmacol. 1983; 32: 1383-1388.
  • Munoz SJ, Hernandez AM, Maddrey WC. İntrahepatic cholestatisis and phospholipidozis associated with the use of tirimethoprim-sulfhamethoxazole. Hepatology. 1990; 12: 342-347.
  • Olsson R, Wiholm BE, Sand C, Zettergen L, Hultcrsntz R, Myrhed M. Liver damage from cloxacillin flucloxacillin and dicloxaxillin. J. Hepatol. 1992; 15(1-2): 154-156.
  • Pieron R, Marien C, Jagueux M. Jaundice et rifampicin. Sem Hop.1971; 47: 1286-95.
  • Robert H, Alford H. Antimycobacterial Agents, Principles and Practice of Infectious Diseases, Ed; Gerald L. Mandell, R. Gordon Douglas, John E. Bennet, Churchill Livingstone, New York, Edinburg, London, Melbourne, 1990, pp.350-354.
  • Roger M, Des Prez Cralıs R. Mycobacterium Tuberculosis. Principles and Practice of ınfectious Diseases, Ed; Gerald L. Mandell, R. Gordon Douglas, John E. Bennet, Churchill Livingstone, New York, Edinburg, London, Melbourne: 1990, pp.1890.
  • Rolando N, Wyke RJ. İnfections. Gut. 1991; Suplement:25-28.
  • Ryan J, Dudley FJ. Cholestazis with ticarsillin-pottasium clavulanate (Timentin). The Medical Journal of Australia. 1992; 156:291.
  • Ryback MJ, Albrecht LM, Boike SC, Chandrasekar PH. Nefrotoxicity of vancomycin, alone and with aminoglycoside. Journal of Antimicrobial Chemotherapy. 1990; 25: 679-687.
  • Ryley NG, Fleming KA, Chapman, RW.Focal destructive colangiopathy associated with amoxycillin-clavulanic acid (Augmentin). J. Hepatol. 1995; 23(3): 278-282.
  • Sgro C, Clinard F, Ouazir K. Incidence of drug-induced hepatic injuries: A French population-based study. Hepatology. 2002; 36: 451–5.
  • Sivapalasingam S, Steigbigel NH. Macrolides, clindamycin, and ketolides, Principles and Practice of Infectious Disease, Eds; “Mandell GL, Bennett JE, Dolin R, Elsevier Inc, New York, 2005, pp.396-417.
  • Smith PM, Wilton A, Routledge PA. Jaundice associated with amoxicillin-clavulanate potassium therapy. Eur J Gastroenterol Hepatol. 1991; 3: 95-96.
  • Ulutan F. Karaciğer hastalarında antimikrobiyal ilaçların kullanımı, Antimikrobiyal Kemoterapi -Klinik Uygulamalar ve Yenilikler, Ed; Meço O, Türk Miktrobiyoloji Cemiyeti Yayınları, Ankara. 1992. pp.27.
  • Umstead GS, Neumann KH. Erythromycin ototoxcity and acute psychotic reaction in cancer patients with hepatic dysfunction. Archieves of Internal Medicine1986; 146: 897-899.
  • Vasko AJM, Ligia M, Rui, MM. Lymphocyte reactivity to ex-vivo drug antigens in drug induced hepatitis. J. Hepatol 1994; 21:151-158.
  • Vial,T., Biour, M., Descotes, j, Trepo, C. Antibiotic-associated hepatitis: Update 1990. The Annals of Pharmacotheraphy. 1997; 31: 204-220.
  • Williams R. New directions in acute liver failure. J R Coll Physicians Lond. 1994; 28: 552-559.
  • Willke A, Çokca F. Linkozamidler. Infeksiyon Hastalıkları, Ed; Willke A, Söyletir G, Doğanay M, Nobel Tıp Kitapevi, Ankara, 1996, pp.178-180.
  • Willke A. Diğer Beta Laktamlar. Infeksiyon hastalıkları,.Ed: Willke A, Söyletir G, Doğanay M, Nobel Tıp Kitapevi, Ankara, 1996, pp.141-143.
  • Wilson WR, Cockerill FR. Tetracyclines, chloramphenicol, eritromycin, and clindamisin. Mayo. Clin. Proc. 1987; 62: 906-915.
  • Yazar E, Traş B. Hepatotoksik Antibiyotikler. Türk Veteriner Hekimliği Dergisi. 2000; 12:128.
  • Zimmerman HT, Maddrey WC. Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: Analysis of instances of therapeutic misadventure. Hepatology. 1998; 22: 767-773
Toplam 52 adet kaynakça vardır.

Ayrıntılar

Bölüm DERLEME
Yazarlar

Hakan Demir Bu kişi benim

Yavuz Osman Birdane Bu kişi benim

Yayımlanma Tarihi 1 Haziran 2015
Kabul Tarihi 19 Kasım 2014
Yayımlandığı Sayı Yıl 2015 Cilt: 8 Sayı: 1

Kaynak Göster

APA Demir, H., & Birdane, Y. O. (2015). Hepatotoxic Antibiotics. Kocatepe Veterinary Journal, 8(1), 65-73.
AMA Demir H, Birdane YO. Hepatotoxic Antibiotics. kvj. Ocak 2015;8(1):65-73.
Chicago Demir, Hakan, ve Yavuz Osman Birdane. “Hepatotoxic Antibiotics”. Kocatepe Veterinary Journal 8, sy. 1 (Ocak 2015): 65-73.
EndNote Demir H, Birdane YO (01 Ocak 2015) Hepatotoxic Antibiotics. Kocatepe Veterinary Journal 8 1 65–73.
IEEE H. Demir ve Y. O. Birdane, “Hepatotoxic Antibiotics”, kvj, c. 8, sy. 1, ss. 65–73, 2015.
ISNAD Demir, Hakan - Birdane, Yavuz Osman. “Hepatotoxic Antibiotics”. Kocatepe Veterinary Journal 8/1 (Ocak 2015), 65-73.
JAMA Demir H, Birdane YO. Hepatotoxic Antibiotics. kvj. 2015;8:65–73.
MLA Demir, Hakan ve Yavuz Osman Birdane. “Hepatotoxic Antibiotics”. Kocatepe Veterinary Journal, c. 8, sy. 1, 2015, ss. 65-73.
Vancouver Demir H, Birdane YO. Hepatotoxic Antibiotics. kvj. 2015;8(1):65-73.

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