Karaciğer Fonksiyon Bozukluğu Olan Hastalarda İlaç Kullanımı
Özet
Karaciğer fonksiyon bozukluğu, kritik yoğun bakım hastalarının yaklaşık yarısında görülen ve ilaç klirensinin azalmasıyla toksisite riskini artıran kritik bir klinik tablodur. İlaç kaynaklı karaciğer hasarı (DILI); doz bağımlı intrinsik veya dozdan bağımsız idiyosenkratik olarak sınıflandırılırken, tanısında ALT, AST, ALP, bilirubin, albümin düzeyleri ve protrombin zamanı gibi laboratuvar parametreleri kritik rol oynar. Karaciğer yetmezliği olan hastalarda ilaçların emilimi, dağılım hacmi, proteinlere bağlanma oranları ve metabolizmaları (özellikle ilk geçiş etkisi) önemli ölçüde değişmektedir. Bu hastalarda ilaç yönetimi için Child-Pugh sınıflandırması rehberliğinde bireyselleştirilmiş doz ayarlamaları yapılması, tedavinin düşük dozda başlanması ve yakından takip edilmesi önerilir. Yoğun bakımda sık kullanılan analjezikler (parasetamol, opioidler), sedatifler (propofol, benzodiazepinler), antikoagülanlar, proton pompası inhibitörleri, antiepileptikler, antipsikotikler ve antibiyotiklerin farmakokinetik değişimleri nedeniyle dozları hassasiyetle optimize edilmelidir. Karaciğerde metabolize olan ilaçlardan mümkün olduğunca kaçınılmalı, dar terapötik aralıklı ajanlar için risk-fayda analizi yapılmalı ve gerektiğinde uzman desteği veya klinik eczacı iş birliğiyle tedavi rejimleri optimize edilerek hasta güvenliği en üst düzeye çıkarılmalıdır.
Liver dysfunction is a critical clinical condition observed in approximately half of critically ill intensive care patients, which increases the risk of toxicity by reducing drug clearance. Drug-induced liver injury (DILI) is classified as dose-dependent intrinsic or dose-independent idiosyncratic, and laboratory parameters such as ALT, AST, ALP, bilirubin, albumin levels, and prothrombin time play a crucial role in its diagnosis. In patients with liver impairment, drug absorption, volume of distribution, protein binding rates, and metabolism (especially the first-pass effect) undergo significant changes. For drug management in these patients, it is recommended to perform individualized dose adjustments guided by the Child-Pugh classification, initiate therapy at low doses, and monitor closely. Due to pharmacokinetic alterations, the dosages of analgesics (paracetamol, opioids), sedatives (propofol, benzodiazepines), anticoagulants, proton pump inhibitors, antiepileptics, antipsychotics, and antibiotics frequently used in intensive care must be precisely optimized. Drugs metabolized by the liver should be avoided where possible, risk-benefit analyses should be conducted for narrow therapeutic index agents, and when necessary, treatment regimens should be optimized through specialist support or clinical pharmacist collaboration to maximize patient safety.
Referanslar
Power BM, Forbes AM, van Heerden PV, Ilett KF. Pharmacokinetics of drugs used in critically ill adults. Clin Pharmacokinet. 1998;34(1):25-56.
Lescot T, Karvellas C, Beaussier M, Magder S, Riou B. Acquired liver injury in the intensive care unit. Anesthesiology. 2012;117(4):898-904.
Longo D, Fauci A. Harrison's gastroenterology and hepatology (2nd Edition). McGraw-Hill Education; 2013.
Franz CC, Hildbrand C, Born C, Egger S, Bravo AER, Krähenbühl S. Dose adjustment in patients with liver cirrhosis: impact on adverse drug reactions and hospitalizations. Eur J Clin Pharmacol. 2013;69(8):1565-73.
Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. American J Gastroenterol ACG. 2017;112(1):18-35.
Andrade RJ, Aithal GP, Björnsson ES, Kaplowitz N, Kullak-Ublick GA, Larrey D, et al. EASL clinical practice guidelines: drug-induced liver injury. J Hepatol. 2019;70(6):1222-61.
Andrade RJ, Chalasani N, Björnsson ES, Suzuki A, Kullak-Ublick GA, Watkins PB, et al. Drug-induced liver injury. Nat Rev Dis Primers. 2019;5(1):1-22.
Vaja R, Ghuman N. Drugs and the liver. Anaesth Intensive Care. 2015;16(1):30-4.
Lin S, Smith BS. Drug dosing considerations for the critically ill patient with liver disease. Crit Care Nurs Clin North Am. 2010;22(3):335-40.
Teschke R, Danan G. Drug-induced liver injury: is chronic liver disease a risk factor and a clinical issue? Expert Opin Drug Metabol Toxicol. 2017;13(4):425-38.
Diep U, Chudow M, Sunjic KM. Pharmacokinetic changes in liver failure and impact on drug therapy. AACN Adv Crit Care. 2017;28(2):93-101.
Soleimanpour H, Safari S, Nia KS, Sanaie S, Alavian SM. Opioid drugs in patients with liver disease: a systematic review. Hepat Mon. 2016;16(4).
Bittencourt PL, Terra C, Parise ER, Farias AQ, Arroyo V, Fernandez J, et al. Intensive care management of patients with liver disease: proceedings of a single-topic conference sponsored by the Brazilian Society of Hepatology. Arq Gastroenterol. 2015;52 Suppl 1:55-72.
Devlin JW, Mallow-Corbett S, Riker RR. Adverse drug events associated with the use of analgesics, sedatives, and antipsychotics in the intensive care unit. Crit Care Med. 2010;38:231-43.
Qamar A, Vaduganathan M, Greenberger NJ, Giugliano RP. Oral anticoagulation in patients with liver disease. J Am Coll Cardiol. 2018;71(19):2162-75.
Dhar A, Mullish BH, Thursz MR. Anticoagulation in chronic liver disease. J Hepatol. 2017;66(6):1313-26.
Lisman T, Kamphuisen PW, Northup PG, Porte RJ. Established and new-generation antithrombotic drugs in patients with cirrhosis–Possibilities and caveats. J Hepatol. 2013;59(2):358-66.
Gish RG, Regenstein FG, Flamm SL, Stravitz RT, Brothers JM. Guidance for Coagulation Management in Patients With Acute or Chronic Liver Failure. Gastroenterol Hepatol (N Y). 2021;17.
Barkun A, Bardou M. Proton-pump inhibitor prophylaxis in the ICU-Benefits worth the risks? : N Engl J Med. 2018;379(23):2263-2264
Ye Z, Blaser AR, Lytvyn L, Wang Y, Guyatt GH, Mikita JS, et al. Gastrointestinal bleeding prophylaxis for critically ill patients: a clinical practice guideline. BMJ. 2020;6;368:l6722.
Shin JM, Kim N. Pharmacokinetics and pharmacodynamics of the proton pump inhibitors. J Neurogastroenterol Motil. 2013;19(1):25.
Weersink RA, Bouma M, Burger DM, Drenth JP, Harkes-Idzinga SF, Hunfeld NG, et al. Evidence-based recommendations to improve the safe use of drugs in patients with liver cirrhosis. Drug Saf. 2018;41(6):603-13.
Cotta M, Roberts J, Lipman J. Antibiotic dose optimization in critically ill patients. Med Intensiva. 2015;39(9):563-72.
Halilovic J, Heintz BH. Antibiotic dosing in cirrhosis. Am J Health-Syst Pharm. 2014;71(19):1621-34.
Vidaurre J, Gedela S, Yarosz S. Antiepileptic drugs and liver disease. Pediatr Neurol. 2017;77:23-36.
Anderson GD, Hakimian S. Pharmacokinetic of antiepileptic drugs in patients with hepatic or renal impairment. Clin Pharmacokinet. 2014;53(1):29-49.
Marshall J, Herzig SJ, Howell MD, Le SH, Mathew C, Kats JS, et al. Antipsychotic utilization in the intensive care unit and in transitions of care. J Crit Care. 2016;33:119-24.
Telles-Correia D, Barbosa A, Cortez-Pinto H, Campos C, Rocha NB, Machado S. Psychotropic drugs and liver disease: a critical review of pharmacokinetics and liver toxicity. World J Gastrointest Pharmacol Ther. 2017;8(1):26.
Gardner KN, Bostwick JR. Medication prescribing in liver dysfunction. Ment Health Clin. 2014;4(3):131-7.
Slim M, Medina-Caliz I, Gonzalez-Jimenez A, Cabello MR, Mayoral-Cleries F, Lucena MI, et al. Hepatic safety of atypical antipsychotics: current evidence and future directions. Drug Saf. 2016;39(10):925-43.
